Articles de revues : « HU Jie »

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Stover Gingerich, Barbara. « Introducing Special Issue Editor Jie Hu, PhD, RN ». Home Health Care Management & ; Practice 22, n^o 7 (19 août 2010) : 543. http://dx.doi.org/10.1177/1084822310375498.

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Hu, Jie, Tian Zhao, Wei Geng, Yi Lu, Xiao-Fang Zhao, Yuan-Zhou Li, Yu-Qian Tang et al. « Correction : Synthesis of hydrophobic and hydrophilic TiO2 nanofluids for transformable surface wettability and photoactive coating ». Chemical Communications 55, n^o 77 (2019) : 11642. http://dx.doi.org/10.1039/c9cc90390a.

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Correction for ‘Synthesis of hydrophobic and hydrophilic TiO₂ nanofluids for transformable surface wettability and photoactive coating’ by Jie Hu et al., Chem. Commun., 2019, 55, 9275–9278.

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Hu, Jie, Tao Chen, Moye Wang, Hue Sun Chan et Zhuqing Zhang. « Correction : A critical comparison of coarse-grained structure-based approaches and atomic models of protein folding ». Physical Chemistry Chemical Physics 19, n^o 27 (2017) : 18102. http://dx.doi.org/10.1039/c7cp90146a.

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Kerlan, Anne. « Le cinéma documentaire de Hu Jie : pour une contre-histoire de la Chine maoïste ». La Revue Documentaires N° 26-27, n^o 1 (1 avril 2016) : 87–97. http://dx.doi.org/10.3917/docu.026.0087.

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CIM, Editor. « Letter of Retraction ». Clinical & ; Investigative Medicine 38, n^o 3 (31 mai 2015) : 142. http://dx.doi.org/10.25011/cim.v38i3.22708.

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It has come to our attention that the a manuscript published in CIM: JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S “GOLP3 is a predictor of survival in patients with hepatocellular carcinoma” Clin Invest Med. 2014 Aug 1;37(4):E233-42 contains text identical to a manuscript published in Tumour Biology: Hu GS, Li YQ, Yang YM, Shi W, Liao AJ, Yao YH, Zeng B, Yuan J “High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma” Tumour Biol. 2014 Sep;35(9):8625-32. doi: 10.1007/s13277-014-2105-8. Epub 2014 May 28. For this reason, the publication in CIM has been retracted. Jonathan Angel, MD Editor, CIM

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Editorial, E. « Retraction : Li Y, Li D, Ren B, Hu J, Li B, Krzton A, Li M. Determinants of differences in the activity budgets of Rhinopithecus bieti by age/sex class at Xiangguqing in the Baimaxueshan nature reserve, China. Arch Biol Sci. 2015;67(2):675-83. DOI : 10.2298/ABS140917033L ». Archives of Biological Sciences 68, n^o 1 (2016) : 237. http://dx.doi.org/10.2298/abs160112009e.

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This is a notice of retraction of the article: Determinants of differences in the activity budgets of Rhinopithecus bieti by age/sex class at Xiangguqing in the Baimaxueshan nature reserve, China by Li Yanhong, Li Dayong, Ren Baoping, Hu Jie, Li Baoguo, Krzton Ali, Li Ming, published in the Archives of Biological Sciences Vol. 67, Issue 2, 2015. Due to inadequate exchange of information between the previous and new Editor-in-Chief of the Archives of Biological Sciences, the new Editor-in-Chief was not informed of the authors? request for withdrawal of the article. After obtaining the written request, signed by all of the authors, the Editor-in-Chief has decided to withdraw the article. Link to the retracted article <a href="http://dx.doi.org/10.2298/ABS140917033L">10.2298/ABS140917033L</a>

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Shi, Jie, Rui Zhou, Shuo Wang, Yuxin Liu, Baorui Tian, Yanhua Liu, YaNan Chen et al. « Abstract 1564 : NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 1564. http://dx.doi.org/10.1158/1538-7445.am2024-1564.

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Abstract Background: Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Method: Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. What’s more, we also identified membrane proteins whose sialylation was able to be modified by NEU4 in OC cells by pull down and mass spectrum to investigate the functional significance of NEU4-mediated desialylation. Results: In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N196 residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Conclusion: Our results provide new insights into how the OC glycome is dysregulated by NEU4 during OC progression and reveals a functionally important glycosite on EGFR for its abnormal activation in cancer. Citation Format: Jie Shi, Rui Zhou, Shuo Wang, Yuxin Liu, Baorui Tian, Yanhua Liu, YaNan Chen, Taoyu Hu, Yuhao Mu, Shufan Wang, Xintao Shao, Jie Yan, Pengpeng Qu, Wei Ding, Shuang Yang, Yi Shi, Jia Li, Longlong Wang. NEU4-mediated desialylation ignites the oncogenic receptors for the dissemination of ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1564.

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Miao, Kun, Wei Kuang et Lifeng Wu. « Discussion of “Maximum Gradient Decision-Making for Railways Based on Convolutional Neural Network” by Hao Pu, Hong Zhang, Paul Schonfeld, Wei Li, Jie Wang, Xianbao Peng, and Jianping Hu ». Journal of Transportation Engineering, Part A : Systems 147, n^o 4 (avril 2021) : 07021001. http://dx.doi.org/10.1061/jtepbs.0000507.

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Liu, Zhijun, Yucun Zhou, Weilin Zhang, Jie Hou, Xueyu Hu et Meilin Liu. « Sulfur- and Coking-Tolerant Anodes for Solid Oxide Fuel Cells ». ECS Meeting Abstracts MA2022-02, n^o 47 (9 octobre 2022) : 1761. http://dx.doi.org/10.1149/ma2022-02471761mtgabs.

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Sulfur- and Coking-tolerant Anodes for Solid Oxide Fuel Cells Zhijun Liu,1 Yucun Zhou,1 Weilin Zhang,1 Jie Hou,1 Xueyu Hu,1 Meilin Liu1, * 1 School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332-0245, United States Abstract Solid oxide fuel cells (SOFCs) have potential to be one of the most efficient systems for direct conversion of a wide variety of chemical fuels into electricity. 1-3 However, the lack of sulfur- and coking-tolerant anodes still hinders the development of direct hydrocarbon-fueled SOFCs for efficient and cost-effective operation. The conventional Ni-based anodes may suffer from carbon deposition and sulfur poisoning when they are directly exposed to sulfur-containing hydrocarbon fuels, resulting in degradation in performance or even destruction of the anodes. 4-6 In this presentation, we will report a conventional Ni-Zr0.84Y0.16O2-δ (YSZ) anode decorated with Ce and Ba-based catalyst coatings to significantly enhance the sulfur and coking tolerance. Results suggest that the enhanced sulfur tolerance is attributed to the evenly distributed Ce-based catalyst on the inner surface of the porous Ni-YSZ anode while the enhanced coking tolerance is benefited from the Ba-based catalyst layer on the top of the anode. SOFCs with the catalysts-modified Ni-YSZ anodes show minimal degradation when hydrogen with 100 ppm H2S is used as the fuel. More importantly, stable operation is demonstrated for direct utilization of sulfur-containing liquid fuels (e.g., octane and gasoline). This work demonstrates the great potential of catalyst coatings for enhancing contaminant tolerance and durability of SOFC electrodes. Z. Wang, Y. Wang, D. Qin, Y. Gu, H. Yu, S. Tao, B. Qian and Y. Chao, J. Eur. Ceram. Soc. (2022). S. Sengodan, M. Liu, T.-H. Lim, J. Shin, M. Liu and G. Kim, J. Electrochem. Soc., 161, F668 (2014). Z. Cheng, J.-H. Wang, Y. Choi, L. Yang, M. C. Lin and M. Liu, Energy Environ. Sci., 4, 4380 (2011). T. Hays, A. M. Hussain, Y.-L. Huang, D. W. McOwen and E. D. Wachsman, ACS Appl. Energy Mater., 1, 1559 (2018). Y. Chen, B. deGlee, Y. Tang, Z. Wang, B. Zhao, Y. Wei, L. Zhang, S. Yoo, K. Pei, J. H. Kim, Y. Ding, P. Hu, F. F. Tao and M. Liu, Nat. Energy, 3, 1042 (2018). L. Yang, S. Wang, K. Blinn, M. Liu, Z. Liu, Z. Cheng and M. Liu, Science, 326, 126 (2009).

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Lu, Lina, Jennifer Rui Wang, Ying C. Henderson, Shanshan Bai, Jie Yang, Min Hu, Yuanqing Yan et al. « Abstract 3131 : Anaplastic transformation model in thyroid cancer revealed by single cell lineage and fate analysis ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 3131. http://dx.doi.org/10.1158/1538-7445.am2023-3131.

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Abstract The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC), however the complex intra-tumor transformation process is poorly understood. We investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single cell transcriptomes and genetic alterations data of patients with different subtypes of thyroid cancer. The resulting model started from stress-responsive DTC cells to inflammatory ATC cells, to mitotic defective ATC cells and extended all the way to mesenchymal ATC cells. In parallel with tumor cell evolution, macrophages shifted from anti-tumor to tumor-promoting states and T cells reprogrammed from cytotoxic to exhausted states. Further, our analysis identified two important milestones: 1) diploid stage, where ATC cells were commonly diploids with non-RAS mutations and inflammatory phenotypes. 2) aneuploid stage, where ATC cells gained aneuploidy with frequent RAS mutations and mesenchymal phenotypes leading to the extreme lethal stage of ATC progression. Citation Format: Lina Lu, Jennifer Rui Wang, Ying C. Henderson, Shanshan Bai, Jie Yang, Min Hu, Yuanqing Yan, Tuan M Tran, Jianzhuo Li, Cheng-Kai Shiau, Rachel Kieser, Xiao Zhao, Jiping Wang, Roza Nurieva, Michelle D. Williams, Maria E. Cabanillas, Ramona Dadu, Naifa Lamki Busaidy, Mark Zafereo, Nicholas Navin, Stephen Y. Lai, Ruli Gao. Anaplastic transformation model in thyroid cancer revealed by single cell lineage and fate analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3131.

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Wang, Kaile, Zhenna Xiao, Yiyun Lin, Runmin Wei, Jie Ye, Rui Ye, Min Hu et al. « Abstract 76 : Reprogramming of the preinvasive breast microenvironment identified by spatial nucleus barcoding ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 76. http://dx.doi.org/10.1158/1538-7445.am2023-76.

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Abstract Ductal-carcinoma-in-situ (DCIS) is the most common early-stage breast cancer and a non-obligate precursor to invasive breast cancer. However our understanding of the spatial microenvironment and the reprogramming of cell types in DCIS remains limited. To address this question, we developed a Spatial Nucleus Barcoding (SNuBar) method that utilizes a single oligonucleotide adaptor to preserve spatial information followed by performing single nucleus RNA sequencing. We validated the accuracy and scalability of SNuBar in cell lines and applied this method to investigate the spatial microenvironment of 4 normal breast tissues, 7 normal adjacent DCIS tissues, and 8 DCIS cancers. The analysis of single cells isolated from 596 macrodissected spatial regions identified 13 major cell types and 43 cell states, that co-localized in different combinations across four main topographic areas. Spatial analysis revealed that vascular and myoepithelial cells were reprogrammed in localized zones near the premalignant cells, while fibroblasts, T-cells and myeloid cells were reprogrammed across broader fields. Our data shows that many diverse cell types are reprogrammed in spatially-defined areas in the DCIS microenvironment, relative to the normal breast tissue regions. Citation Format: Kaile Wang, Zhenna Xiao, Yiyun Lin, Runmin Wei, Jie Ye, Rui Ye, Min Hu, Shanshan Bai, Emi Sei, Aatish Thennavan, Bora Lim, Andrew Futreal, Alastair Thompson, Savitri Krishnamurthy, Nicholas Navin. Reprogramming of the preinvasive breast microenvironment identified by spatial nucleus barcoding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 76.

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Wang, Kaile, Zhenna Xiao, Yiyun Lin, Runmin Wei, Shanshan Bai, Jie Ye, Rui Ye et al. « Abstract 5483 : Macrospatial ecotype heterogeneity in early-stage breast cancer identified by spatial nucleus barcoding ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 5483. http://dx.doi.org/10.1158/1538-7445.am2024-5483.

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Abstract Ductal carcinoma in situ (DCIS), the predominant form of early-stage breast cancer and a precursor to invasive breast cancer, remains inadequately understood in terms of spatial microenvironment reprogramming. In this study, we developed a Spatial Nucleus Barcoding (SNuBar) approach for single-nucleus RNA sequencing (SNuBar-RNA) that utilizes a single oligonucleotide adaptor to preserve spatial information. The accuracy and scalability of SNuBar was validated using cell line mixture experiments. We then applied SNuBar-RNA to investigate the macrospatial ecotype heterogeneity in early-stage breast cancer. By analyzing single cells from different macrodissected spatial regions in normal breast tissues, matched normal and DCIS tissues, we identified 13 major cell types and 43 distinct cell states, co-localizing in diverse combinations across four primary topographic areas (adipose-enriched, normal epithelial, activated stroma and tumor). Spatial analysis revealed the reprogramming of vascular and myoepithelial cells in localized zones near premalignant cells, while fibroblasts, T-cells, and myeloid cells exhibited reprogramming across broader fields. Validation using the MERSCOPE assay confirmed stromal heterogeneity between tumor and normal areas. Collectively, our data shows that many diverse cell types are reprogrammed in spatially-defined areas in the early-stage breast cancer microenvironment, relative to the normal breast tissue regions. Citation Format: Kaile Wang, Zhenna Xiao, Yiyun Lin, Runmin Wei, Shanshan Bai, Jie Ye, Rui Ye, Min Hu, Aatish Thennavan, Emi Sei, Alastair Thompson, Savitri Krishnamurthy, Nicholas Navin. Macrospatial ecotype heterogeneity in early-stage breast cancer identified by spatial nucleus barcoding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5483.

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Khatri, Ujjwol, Neetu Dayal, Tao Shen, Xueqing Hu, Herman Sintim et Jie Wu. « Abstract 4660 : Characterization of a nicotinamide-based kinase inhibitor HSN748 for inhibition of RET-driven tumors ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 4660. http://dx.doi.org/10.1158/1538-7445.am2024-4660.

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Abstract Rearranged during transfection (RET) is a protein tyrosine kinase that is aberrantly activated by gene fusions or mutations in many types of human cancer including thyroid cancer and non-small cell lung cancer (NSCLC). Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are FDA approved RET-selective tyrosine kinase inhibitors (TKIs) being used to treat RET-altered cancer. However, these tumors develop selpercatinib/pralsetinib-resistance via acquisition of RET(G810C/R/S) mutations located at the solvent front of the ATP binding pocket. The overall goal of our research is to discover next-generation of RET kinase inhibitors to inhibit selpercatinib/pralsetinib-resistant RET solvent-front mutants. In this study, we characterized one of the nicotinamide-based RET kinase inhibitor, HSN748, in vitro and in vivo. HSN748 was able to inhibit selpercatinib/pralsetinib-resistant RET(G810C/R) solvent-front mutations. In BaF3/KIF5B-RET(G810C) tumor xenograft experiment, HSN748 treatment resulted in tumor regression. In immune competent transgenic mice, KIF5B-RET-induced lung tumors regressed after HSN748 treatment by oral gavage for one month (10-15 mg/kg, QD) without affecting body weight. These results identify HSN748 as an orally available RET inhibitor capable of inhibiting KIF5B-RET and its solvent-front mutant-driven tumors. Citation Format: Ujjwol Khatri, Neetu Dayal, Tao Shen, Xueqing Hu, Herman Sintim, Jie Wu. Characterization of a nicotinamide-based kinase inhibitor HSN748 for inhibition of RET-driven tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4660.

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Wang, Kaile, Tapsi Kumar, Junke wang, Darlan Minussi, Emi Sei, Jianzhuo li, Tuan Tran et al. « Abstract 125 : Archival single cell sequencing reveals persistent subclones over years to decades of DCIS progression ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 125. http://dx.doi.org/10.1158/1538-7445.am2023-125.

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Abstract Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer (IBC), yet the genomic progression to recurrent disease remains poorly understood. A main contributor to this gap in knowledge arises from technical challenges with genomic profiling of formalin-fixed paraffin-embedded (FFPE) materials. To address this challenge, we developed Arc-well, the first high-throughput method that can perform single cell DNA sequencing of thousands of cells from FFPE materials and frozen tissues. Using Arc-well, we profiled genomic copy number in 27,851 single cells from 26 archival FFPE tissues that were stored for 3-31 years. Analysis of genomic evolution in 10 patients with matched DCIS and recurrent cancers (DCIS or IBC) separated by 2-16 years showed that many primary DCIS lesions had already undergone whole-genome-doubling and had extensive clonal diversity, similar to the paired recurrence. The data from most patients (8/10) suggest an evolutionary bottleneck model of progression, in which a single subclone persisted during the progression to the recurrent disease, revealing copy number aberrations associated with invasion and recurrence. Citation Format: Kaile Wang, Tapsi Kumar, Junke wang, Darlan Minussi, Emi Sei, Jianzhuo li, Tuan Tran, Aatish Thennavan, Min Hu, Anna Casasent, Zhenna Xiao, Shanshan Bai, Yuehui Zhao, Amado Zurita, Ana Aparicio, Brian Chapin, Jie ye, Jianjun Zhang, Don Gibbons, Andrew Futreal, Lorraine King, Jeffrey Marks, E. Shelley Hwang, Vandna Shah, Ellinor Sawyer, Petra Kristel, Jelle Wesseling, Esther H. Lips, Nicholas Navin. Archival single cell sequencing reveals persistent subclones over years to decades of DCIS progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 125.

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Khatri, Ujjwol, Neetu Dayal, Xueqing Hu, Elizabeth Larocque, Nimishetti Naganna, Tao Shen, Xuan Liu et al. « Abstract 3851 : Targeting RET solvent-front mutants with an alkynyl nicotinamide-based inhibitor ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 3851. http://dx.doi.org/10.1158/1538-7445.am2023-3851.

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Abstract Selpercatinib (LOXO-292, LY3527723) and pralsetinib (BLU-667) are first-in-class RET-targeted cancer therapy drugs. However, secondary RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation RET Tyrosine kinase inhibitors (TKIs). While the G810C/R/S/V mutations located at the RET kinase solvent-front site were detected in selpercatinib-treated patients, it was unclear whether all of these and other potential G810 mutants are resistant to selpercatinib and pralsetinib. We profiled selpercatinib and pralsetinib on all six possible G810 mutants derived from single nucleotide substitution. Surprisingly, the G810V mutant found in a clinical study was not resistant to selpercatinib or pralsetinib. Besides G810C/R/S, G810D also conferred selpercatinib/pralsetinib resistance. We found that alkynyl nicotinamide compounds such as HSN608 have better drug-like properties than alkynyl benzamides. HSN608 inhibited RET and RET V804M gatekeeper mutant, and all six G810 mutants with low nanomolar IC50s in the BaF3/KIF5B-RET mutant cell model. In cell derived xenograft (CDX) tumors driven by KIF5B-RET(G810C), HSN608 caused regression of the selpercatinib-resistant tumors. This study clarifies the sensitivities of different RET solvent-front mutants to selpercatinib and pralsetinib, and identifies an alkylnyl nicotinamide-based RET TKI for inhibiting selpercatinib/pralsetinib-resistant G810 mutants. Citation Format: Ujjwol Khatri, Neetu Dayal, Xueqing Hu, Elizabeth Larocque, Nimishetti Naganna, Tao Shen, Xuan Liu, Frederick W. Holtsberg, M. Javad Aman, Herman O. Sintim, Jie Wu. Targeting RET solvent-front mutants with an alkynyl nicotinamide-based inhibitor. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3851.

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Whittingham, Stan, BEN PEI, Isik Buyuker, Krystal Lee, Fengxia Xin et Hui Zhou. « (Invited, Digital Presentation) Pushing the Limits of High Nickel NMC Cathodes ». ECS Meeting Abstracts MA2022-01, n^o 2 (7 juillet 2022) : 334. http://dx.doi.org/10.1149/ma2022-012334mtgabs.

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Lithium-ion batteries now dominate electrochemical energy storage for vehicle propulsion and grid storage in addition to portable electronics. In 2022, they celebrate their 50th anniversary, and yet still achieve only 25% of their theoretical energy density. The dominant anode and cathode today are graphitic carbon and the layered NMC oxides, LI[NiMnCoAl]O2. Both need improving. Most of the carbon in the anode must go, and the NMCs need pushing to their limit and at the same time eliminating cobalt. I will today discuss the challenges faced as we push the limits of the NMCs to their limits, > 80% lithium cycling, and Ni>0.8 and Co <<0.1. The higher the Ni content the lower the charging voltage needed for a given cycling capacity, but the greater its surface and bulk reactivity. The issues discussed will include 1stcycle loss [1], high rate capability [2], cathode stability [3], and surface/bulk reactivity and the impact of surface/bulk modification [4,5] and the micron-size single crystals vs meatballs on these [6]. This work is being supported by DOE-EERE-BMR-Battery500 consortium. [1]. Hui Zhou, Fengxia Xin, Ben Pei, M. Stanley Whittingham, “What Limits the Capacity of Layered Oxide Cathodes in Lithium Batteries?”, ACS Energy Lett. 2019, 4: 1902−1906. [2]. Chunmei Ban, Zheng Li, Zhuangchun Wu, Melanie J. Kirkham, Le Chen, Yoon Seok Jung, E. Andrew Payzant, Yanfa Yan, M. Stanley Whittingham, and Anne C. Dillon “Extremely Durable High-Rate Capability of a LiNi0.4Mn0.4Co0.2O2 Cathode Enabled by Single–Wall Carbon Nanotubes”, Advanced Energy Materials, 2011, 1: 58-62. [3]. Hyung-Joo Noh, Sungjune Youn, Chong Seung Yoon, Yang-Kook Sun “Comparison of the structural and electrochemical properties of layered Li[NixCoyMnz]O2 (x = ¼ 1/3, 0.5, 0.6, 0.7, 0.8 and 0.85) cathode material for lithium-ion batteries”, J. Power Sources, 2013, 233: 121-130. [4]. Fengxia Xin, Hui Zhou, Yanxu Zong, Mateusz Zuba, Yan Chen, Natasha A. Chernova, Jianming Bai, Ben Pei, Anshika Goel, Jatinkumar Rana, Feng Wang, Ke An, Louis F. J. Piper, Guangwen Zhou, and M. Stanley Whittingham, “What is the Role of Nb in Nickel-Rich Layered Oxide Cathodes for Lithium-Ion Batteries?”, ACS Energy Letters, 2021, 6: 1377-1382. [5]. Ben Pei, Hui Zhou, Anshika Goel, Mateusz Zuba, Hao Liu, Fengxia Xin, and M. Stanley Whittingham, “Al Substitution for Mn during Co-Precipitation Boosts the Electrochemical Performance of LiNi0.8Mn0.1Co0.1O2”, J. Electrochemical Society, 2021, 68: 050532. [6]. Yujing Bi, Jinhui Tao, Yuqin Wu, Linze Li, Yaobin Xu, Enyuan Hu, Bingbin Wu, Jiangtao Hu, Chongmin Wang, JiGuang Zhang, Yue Qi and Jie Xiao, “Reversible planar gliding and microcracking in a single-crystalline Ni-rich cathode”, Science, 2020, 370: 1313-1317.

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Zhang, Li, Heng Wu, Karyssa Palopo, Jie Hu, Marvin Cadiente, Anh Nguyen, Teodelinda Mirabella et Dongxu Sun. « Abstract 1147 : A novel anti-Galectin-3 antibody therapeutic for the treatment of triple negative breast cancer ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 1147. http://dx.doi.org/10.1158/1538-7445.am2022-1147.

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Abstract About 43,600 women in the U.S. are expected to die in 2021 from breast cancer. Triple negative breast cancer (TNBC), which accounts for approximately 15% of all breast cancers, is diagnosed by exclusion of expression and/or amplification of three biomarkers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]).Characterized by a high risk of relapse (one half of patients with early stages experience recurrence), short overall survival and progression-free survival (life expectancy of few months after failure of first-line chemotherapy), TNBC represents a high unmet medical need. Galectin-3 plays multiple roles in tumor initiation and development via a variety of cellular processes, spanning from angiogenesis to tumor migration. Galectin-3 (Gal3) expression is induced in TNBC patients and highly correlates with poor survival, as shown by our and others’ bioinformatics analysis from public database. We recently discovered and patented a series of antibodies with high specificity and affinity for Gal3, one of which is currently tested in human volunteers. This clinical candidate has shown superior pharmacokinetic properties and clean toxicity profile in GLP studies on non-human primates. Here, we show that anti-Gal3 inhibit both anchorage dependent and independent growth of TNBC cells, as well as Gal3-induced escape from NK cell killing. Also, anti-Gal3 proved to be efficacious in in vivo studies, where TNBC cells were implanted in mammary fat pads of mice and tumor progression, measured as growth of primary mass and presence of metastatic nodules in the lungs, was followed during the two months of treatment. The results presented herein support the conclusion that our therapeutic modality could offer an alternative promising treatment of TNBC. Citation Format: Li Zhang, Heng Wu, Karyssa Palopo, Jie Hu, Marvin Cadiente, Anh Nguyen, Teodelinda Mirabella, Dongxu Sun. A novel anti-Galectin-3 antibody therapeutic for the treatment of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1147.

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Fu, Michael C. « Simulation-Based Algorithms for Markov Decision Processes : Monte Carlo Tree Search from AlphaGo to AlphaZero ». Asia-Pacific Journal of Operational Research 36, n^o 06 (décembre 2019) : 1940009. http://dx.doi.org/10.1142/s0217595919400098.

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AlphaGo and its successors AlphaGo Zero and AlphaZero made international headlines with their incredible successes in game playing, which have been touted as further evidence of the immense potential of artificial intelligence, and in particular, machine learning. AlphaGo defeated the reigning human world champion Go player Lee Sedol 4 games to 1, in March 2016 in Seoul, Korea, an achievement that surpassed previous computer game-playing program milestones by IBM’s Deep Blue in chess and by IBM’s Watson in the U.S. TV game show Jeopardy. AlphaGo then followed this up by defeating the world’s number one Go player Ke Jie 3-0 at the Future of Go Summit in Wuzhen, China in May 2017. Then, in December 2017, AlphaZero stunned the chess world by dominating the top computer chess program Stockfish (which has a far higher rating than any human) in a 100-game match by winning 28 games and losing none (72 draws) after training from scratch for just four hours! The deep neural networks of AlphaGo, AlphaZero, and all their incarnations are trained using a technique called Monte Carlo tree search (MCTS), whose roots can be traced back to an adaptive multistage sampling (AMS) simulation-based algorithm for Markov decision processes (MDPs) published in Operations Research back in 2005 [Chang, HS, MC Fu, J Hu and SI Marcus (2005). An adaptive sampling algorithm for solving Markov decision processes. Operations Research, 53, 126–139.] (and introduced even earlier in 2002). After reviewing the history and background of AlphaGo through AlphaZero, the origins of MCTS are traced back to simulation-based algorithms for MDPs, and its role in training the neural networks that essentially carry out the value/policy function approximation used in approximate dynamic programming, reinforcement learning, and neuro-dynamic programming is discussed, including some recently proposed enhancements building on statistical ranking & selection research in the operations research simulation community.

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Huang, Huaizhi (Gilbert), Chunling Hu, Jie Na, Mohamed Abozaid, Amik Munankarmy, Tara Rao, Carolyn A. Dunn Lumby et al. « Abstract PR09 : Functional and clinical characterization of hypomorphic missense variants in the BRCA2 cancer predisposition gene ». Cancer Research 84, n^o 3_Supplement_1 (1 février 2024) : PR09. http://dx.doi.org/10.1158/1538-7445.advbc23-pr09.

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Abstract Many germline BRCA2 missense variants of uncertain significance (VUS) remain to be clinically classified as pathogenic or benign. Here we identify 70 missense VUS in the DNA binding domain (DBD) of BRCA2 that partially reduced homologous recombination DNA repair activity of the protein in a homology directed DNA repair cell-based assay. CRISPR/cas9-based knockin of these variants reduced cell survival of haploid cells and conferred increased sensitivity to the PARP inhibitor Olaparib. Sequence alignment analysis found that the variants were highly conserved across species from pufferfish to human. Structural analysis showed that these variants are located predominantly in unstructured regions of the DBD. Case-control association studies showed that the hypomorphic variants conferred moderate risks of breast (OR:2.85; 95%CI:1.43-5.88) and ovarian cancer (OR:3.37; 95%CI:1.30-8.54) that were significantly different from risks associated with known pathogenic and benign variants. Cumulative lifetime risks of breast and ovarian cancer among carriers were estimated at 25% and 4.7%, respectively. Age at diagnosis of breast cancer among hypomorphs carriers was 55 years of age as opposed to 48 years of age for carriers of pathogenic variants. In addition, the combination of functional and other genetic data in an ACMG/AMP-like variant classification model reclassified 39 variants as likely pathogenic. This novel group of low penetrance missense variants further calibrate BRCA2 variant classification methods and have significant implications for the management of variant carriers. Citation Format: Huaizhi (Gilbert) Huang, Chunling Hu, Jie Na, Mohamed Abozaid, Amik Munankarmy, Tara Rao, Carolyn A. Dunn Lumby, Paulo Cilas Morais Lyra, Ronan E. Couch, Benjamin R. Persons, Eric C. Polley, Rachid Karam, Tina Pesaran, Siddhartha Yadav, Alvaro N.A. Monteiro, Nicholas J. Boddicker, Susan M. Domchek, Marcy E. Richardson, Fergus J. Couch. Functional and clinical characterization of hypomorphic missense variants in the BRCA2 cancer predisposition gene [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr PR09.

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NURALIEV, MAXIM S., ANDREY N. KUZNETSOV, SVETLANA P. KUZNETSOVA et CHI-MING HU. « Ardisia patentiradiosa (Primulaceae), a new species from southern Vietnam ». Phytotaxa 522, n^o 1 (5 octobre 2021) : 63–67. http://dx.doi.org/10.11646/phytotaxa.522.1.7.

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Ardisia patentiradiosa C.M. Hu & Nuraliev (Primulaceae) collected from montane forest of Gia Lai Province, Vietnam, is described and illustrated. Its distinguishing characters from its closest relatives, Ardisia gracilenta C.M. Hu & J.E. Vidal and A. pitardii C.M. Hu & J.E. Vidal, are discussed.

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Hu, Jie, Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia et Jian Zhou. « Abstract 1020 : Tissue-informed ctDNA MRD assay detects post-surgery minimal residual disease in HCC patients ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 1020. http://dx.doi.org/10.1158/1538-7445.am2023-1020.

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Abstract Introduction: Residual disease detection is a significant clinical need in post-surgery treatment of resectable hepatocellular carcinoma (HCC) patients. Previous NGS-based studies targeting fixed genomic regions had reported that circulating tumor DNA (ctDNA) could provide evidence for prognosis prediction during HCC treatment. However, the sensitivity of methods was limited and could not reach the threshold of minimal residual disease (MRD) test. Here we reported a baseline tissue -informed ctDNA NGS assay, detecting MRD in HCC patients who received hepatectomy and predicted prognosis in MRD positive patients. Methods: The study retrospectively enrolled 200 early-stage HCC patients who received surgical resections. Tumor and normal tissue samples were collected respectively through surgery. Plasma samples were collected 7 days or more post-surgery. In the completed pilot study, samples from 17 patients were tested by a baseline tissue-informed MRD assay (PredicineBEACON). Tumor-specific mutations were identified by whole exon sequencing on baseline tumor and normal tissue samples. For each patient, up to 50 mutations were selected through bioinformatics pipelines for personalized MRD panel design, in combination with a fixed panel of 500 tumor actionable hotspots. The post-surgery plasma samples were then tested for MRD with the panel through ultra-deep sequencing(100,000X). Afterward, genomic tumor fraction proportions were calculated. Results: In the completed pilot study, 12 of 17 patients (70.6%) were called MRD positive based on tests of post-surgery plasma. Among MRD positive patients, 3 were identified as MRD risk high (proportion of tumor fraction≥0.1%) and MRD risk of others were moderate (proportion of tumor fraction<0.1%). The tumor fraction proportion of MRD positive patients varied from 0.013% to 17.84% (median 0.042%). The recurrence free survival (RFS) and overall survival (OS) probabilities were significantly correlated with MRD risk: the median RFS of two groups(risk-high vs. risk-moderate) was 10.1 months vs. 57.4 months (p-value<0.001), while the median OS of two groups (risk-high vs. risk-moderate) was 31.2 months vs. 57.4 months(p-value=0.028). Conclusions: Baseline-informed ctDNA NGS assay showed ultra-sensitive capability of MRD detection on early-stage HCC patients, with outstanding positive rate through plasma samples collected 7 days post-surgery. The MRD risk provided significant prognostic evidence for patient survival and disease relapse. Citation Format: Jie Hu, Haoran Tang, Feng Xie, Yue Zhang, Shidong Jia, Jian Zhou. Tissue-informed ctDNA MRD assay detects post-surgery minimal residual disease in HCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1020.

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Yang, Cuiqing, Xiaohui Shao, Feng Zhou, Lei Zhou, Qi Deng, Yun Zhang, Guangcun Cheng et al. « Abstract 6343 : A multispecific T cell engager binding to both membrane proximal and membrane distal epitopes of MSLN with low affinity CD3 for the treatment of AML and solid tumors ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 6343. http://dx.doi.org/10.1158/1538-7445.am2022-6343.

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Abstract Purpose: The effective treatment of AML and solid tumors remains an unmet medical need. Mesothelin (MSLN) is a glycophosphatidylinositol-linked tumor antigen overexpressed in a variety of malignancies, including AML and solid tumors, such as mesothelioma, cholangiocarcinoma, ovarian, pancreatic, lung, esophageal, gastric, colorectal, endometrial and triple-negative breast cancer. Early signs of clinical efficacy with MSLN-targeting agents have validated MSLN as a promising target for therapeutic intervention, but therapies with improved efficacy are still needed. CD3-based T cell engagers are highly potent therapeutic molecules with T cell cytotoxicity activities in the picomolar range. But high CRS risk and T cell exhaustion has been observed for high affinity CD3-based T cell engagers in clinicals, so we used high affinity MSLN and low affinity CD3 to improve efficacy of T cell engager. Experimental Design: We designed SMTE-001, a 78-kDa, tetra-specific, T-cell-activating protein molecule, which binds to two epitopes (membrane proximal and membrane distal) of MSLN, CD3ε on T cells, and to serum albumin. Experiments were conducted to assess the potency, activity, and half-life of HPN536 in in vitro assays, rodent models, and in nonhuman primates (NHP). This molecule was tested in a cytotoxicity assay using human PBMCs co-cultured with OVCAR3, Hela and NCI-H292 cells, which express different levels of MSLN. Soluble MSLN and CA125 (ligand of MSLN) was added to determine effects on cytotoxicity. In vivo xenograft mouse studies were conducted using a PBMC model. Results: Here we report the design and the promising preclinical activity of SMTE-001 molecule in vitro and in vivo. We demonstrate that the bivalent MSLN T cell engager has increased in vitro potency in T cell activation and tumor cell killing, as compared to a monovalent counterpart on high MSLN expressing cells. We also demonstrate that T cell exhaustion is reduced for the low-affinity CD3, compared to the low-affinity CD3 molecule. Because soluble MSLN and CA125 is shed from cancer cells into cancer patient serum, we also demonstrate that soluble MSLN and CA125 does not interfere with the cytotoxic activity of SMTE-001. Importantly, we demonstrate in vivo that SMTE-001 significantly inhibits tumor growth in a dose-dependent manner, while high-affinity CD3 molecule’ efficacy reduces when higher dosing. In cynomolgus monkeys, SMTE-001 shows pharmacokinetics in support of weekly dosing in humans. Conclusions: Collectively, these data demonstrate strong anti-tumor efficacy by this novel multispecific bivalent T cell engager. These data indicate the therapeutic potential of this molecule to activate T cells and improve the clinical efficacy in AML and MSLN-expressing solid tumors. Citation Format: Cuiqing Yang, Xiaohui Shao, Feng Zhou, Lei Zhou, Qi Deng, Yun Zhang, Guangcun Cheng, Yingying Hu, Huaiyuan Ma, Yadan Wu, Shuai Wang, Jie Zang, Lei Liu, Wenqing Yang, Yang Liu, Chunlei Xia, Jianzhong Hu, Ande Luo, Yayuan Fu, Zhuoxiao Cao, Renhong Tang. A multispecific T cell engager binding to both membrane proximal and membrane distal epitopes of MSLN with low affinity CD3 for the treatment of AML and solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6343.

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Li, Jiaxin. « Research on the Origin and Evolution of Hu Jia ». Lecture Notes in Education Psychology and Public Media 39, n^o 1 (22 janvier 2024) : 82–87. http://dx.doi.org/10.54254/2753-7048/39/20240677.

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The Silk Road originated from the Western Han Dynasty. The word Silk indicates that it was originally a trade route, which eventually developed into a bridge for economic, cultural, and artistic exchanges between the East and the West. It connected Central Asia, West Asia, and countries around the Mediterranean, allowing different countries and different styles of music and dance to collide, promoting music exchanges and development in the surrounding countries along the Silk Road. As for the introduction of musical instruments and music into the Central Plains, the Silk Road has undoubtedly had a positive impact on the development of Chinese music. It can be said to be a music canal that runs through the East and the West. Jia, with its mournful sound, is originally a musical instrument played by the Hu people. The wooden Hu Jia of the Han Dynasty was introduced to the Central Plains by Zhang Qian's expedition to the Western Regions, while the reed Hu Jia was popular in Mongolian ethnic regions. This ancient ethnic musical instrument has almost disappeared and has gone through a legendary journey. Its structure and changes are of great research value. This paper uses methods of literature analysis and case analysis to study the playing techniques of Hu Jia and its evolution from the Western Han Dynasty to the present. Through the argumentation in this paper, it is discovered that the three-hole Hu Jia used in the Xinjiang Altay region in 1985 was still the same as those used in the Western Jin Dynasty and the Qing Dynasty, indicating that Hu Jia has not been lost.

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Cheng, Ka Ming, Gui yun Wu, Kowk Kuen Cheung, Xiao-Ling Shen, Ying-Jie Hu et Ki Lui. « Abstract 4676 : 11α-O-2-methylbutanoyl-12β-O-tigloyl-tenacigenin B (MT2) is a novel paclitaxel chemosensitizer to inhibit growth in Taxol non-resistant and Taxol resistant cancers ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 4676. http://dx.doi.org/10.1158/1538-7445.am2024-4676.

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Abstract 11α-O-2-methylbutanoyl-12β-O-tigloyl-tenacigenin B (MT2) is a single molecule isolated from a traditional Chinese Medicinal herb Marsdenia tenacissima (MT). Recently, our group has isolated a few single molecules from the MT herb, they have shown significant anti-tumor activity in vitro and MT2 has the highest potential among all. We have performed MTT viability assay and clonogenic assay to demonstrate that MT2-alone is non-cytotoxic, but the cytotoxicity of the paclitaxel+MT2 combination treatment was more significant than that of paclitaxel, a microtubule stabilizing chemotherapeutic agent. The underlying mechanism of such growth inhibition is contributed by the down-regulation of the pro-survival signaling and up-regulation of the apoptotic signaling such as an increase in cleaved caspase 3 and decrease in anti-apoptotic Bcl-2 proteins when cancer cells are co-treated with MT2+paclitaxel. More importantly, intraperitoneal administration of the combination treatment 5 times of MT2+paclitaxel (30mg/kg, 8mg/kg) has a more significant anti-tumor effect than the paclitaxel-alone (8mg/kg) or MT2-alone (30mg/kg) treatments using the wild-type hepatic HepG2 xenograft model in nude mice. Besides the wild-type HepG2 cancer cells, we have further demonstrated that MT2 is able to resensitize paclitaxel-resistant HepG2 cancer cells by inhibiting the activity of p-glycoprotein (Pgp), a key drug efflux transporter in chemotherapy resistance cancer cells. Also, the combination treatment has shown a significant anti-tumor effect in HepG2/DOX Pgp-overexpressed xenograft in nude mice. Taken together, MT2 is a novel chemosensitiser in combination use with paclitaxel to treat cancer. It enhances cancer apoptosis by suppressing the anti-apoptotic and survival signaling pathways in cancer cells. Citation Format: Ka Ming Cheng, Gui yun Wu, Kowk Kuen Cheung, Xiao-Ling Shen, Ying-Jie Hu, Ki Lui. 11α-O-2-methylbutanoyl-12β-O-tigloyl-tenacigenin B (MT2) is a novel paclitaxel chemosensitizer to inhibit growth in Taxol non-resistant and Taxol resistant cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4676.

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Chen, Jie-yao, Shi-jun Chen, Wei-bin Huang et Guang-wen Ma. « Erratum for “Discussion of ‘New Flood Early Warning and Forecasting Method Based on Similarity Theory’ by Zhangling Xiao, Zhongmin Liang, Binquan Li, Bo Hou, Yiming Hu, and Jun Wang” by Jie-yao Chen, Shi-jun Chen, Wei-bin Huang, and Guang-wen Ma ». Journal of Hydrologic Engineering 26, n^o 1 (janvier 2021) : 08220003. http://dx.doi.org/10.1061/(asce)he.1943-5584.0002024.

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Yadav, Siddhartha, Nicholas J. Boddicker, Jie Na, Eric C. Polley, Chunling Hu, Steven N. Hart, Rohan D. Gnanaolivu et al. « Abstract GS4-04 : Population-based Estimates of contralateral Breast Cancer Risk among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 ». Cancer Research 83, n^o 5_Supplement (1 mars 2023) : GS4–04—GS4–04. http://dx.doi.org/10.1158/1538-7445.sabcs22-gs4-04.

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Abstract Purpose To estimate the risk of contralateral breast cancer (CBC) among women in the general population with germline pathogenic variants (PVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2. Methods Among 15,104 prospectively followed women within the CARRIERS study treated with ipsilateral surgery for invasive breast cancer, a subset of 14,237 women were identified from population-based studies. The risk of CBC was estimated for PV carriers in each gene compared to women without PVs in a multivariate proportional hazard regression analysis accounting for the competing risk of death and adjusting for patient and tumor characteristics. The primary analyses focused on the overall cohort and on women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor status. Results Germline BRCA1, BRCA2, and CHEK2 PV carriers with breast cancer were at significantly elevated risk (Hazard ratio ≥ 1.9, p< 0.05) of CBC, whereas only the PALB2 PV carriers with ER-negative breast cancer had elevated risks. In contrast, ATM PV carriers did not have significantly increased CBC risks. African American PV carriers had similarly elevated risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 15-year cumulative incidence of CBC was >20% for BRCA1, BRCA2 and CHEK2 PV carriers with breast cancer, and for PALB2 PV carriers with ER-negative breast cancer. The 15-year cumulative incidence of CBC among postmenopausal PV carriers was < 20% for PV carriers in any of the 5 genes. Conclusions Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 are at substantially increased risk of CBC and may benefit from enhanced surveillance and risk-reduction strategies. Citation Format: Siddhartha Yadav, Nicholas J. Boddicker, Jie Na, Eric C. Polley, Chunling Hu, Steven N. Hart, Rohan D. Gnanaolivu, Nicole Larson, Carolyn Dunn, Susan Holtegaard, Huaizhi Huang, Lauren R. Teras, Alpa V. Patel, James V. Lacey Jr., Susan Neuhausen, Leslie Bernstein, Elena Martinez, Christopher Haiman, Fei Chen, Kathryn Ruddy, Janet Olson, Esther John, Allison W. Kurian, Dale P. Sandler, Katie M. O’Brien, Jack A. Taylor, Clarice R. Weinberg, Hoda Anton-Culver, Argyrios Ziogas, Gary R. Zirpoli, David E. Goldgar, Katherine L. Nathanson, Susan Domchek, Julie R. Palmer, Jeffrey Weitzel, Peter Kraft, Fergus J. Couch. Population-based Estimates of contralateral Breast Cancer Risk among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-04.

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Li, Jie, Nan Hu, Yilu Zhang, Xiaolong Yang, Minjuan Deng, Wenfeng Gong, Longbo Yin et al. « Abstract 6158 : BGB-24714, a novel oral IAP antagonist, displayed significant anti-tumor activities in preclinical models as a monotherapy and in combination with paclitaxel ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 6158. http://dx.doi.org/10.1158/1538-7445.am2023-6158.

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Abstract Background: Evasion of apoptosis is identified as one of the essential hallmarks of cancer and upregulation of inhibitor of apoptosis proteins (IAPs) is one of the mechanisms by which tumor cells evade apoptosis. An oral SMAC mimetic and antagonist of cellular IAP1 (cIAP1) and X-linked IAP (XIAP), BGB-24714, is currently investigated in a phase 1a/1b oncology trial in patients with advanced or metastatic solid tumors (NCT05381909). Here, we evaluated the anti-tumor activity of BGB-24714 as a single agent or in combination with paclitaxel in preclinical models. Results: BGB-24714 effectively inhibited cIAP1 by inducing its degradation in MDA-MB-231 cells, with an EC50 of 2.5 nM. BGB-24714 also potently antagonized the inhibitory interaction of XIAP with caspase-9 and induced caspase-9 autoactivation in MDA-MB-231 cells, with an EC50 of 23 nM. In a total of 25 breast cancer cell lines treated with TNFα, BGB-24714 potently inhibited the in vitro proliferation of 5 breast cancer cells with EC50 < 100 nM. In pharmacodynamics studies, single dose administration of BGB-24714 significantly induced degradation of cIAP1 and antagonism of the XIAP: Smac interaction in the MDA-MB-231 xenograft model in a dose dependent manner. Using the same model, BGB-24714 exhibited dose-dependent anti-tumor activities as a single agent. The tumor growth inhibition rates were 30%, 52% and 73% in low to high dosage treatment groups. Furthermore, BGB-24714 at medium dosage level demonstrated synergized anti-tumor activity in HCC1806 xenograft model when used in combination with paclitaxel. In intermittent dosing study, BGB-24714 with the intermittent dosing schedule demonstrated significant but slightly less effective anti-tumor activity than the continuous dosing schedule. In summary, BGB-24714, as a novel oral IAP antagonist, showing significant anti-tumor activities in preclinical models, which is promising and warrants the testing of the compound in human. Citation Format: Jie Li, Nan Hu, Yilu Zhang, Xiaolong Yang, Minjuan Deng, Wenfeng Gong, Longbo Yin, Yong Liu, Yajuan Gao, Wei Wei, Xing Wang, Xinyi Liang, Yanwen Ma, Xuxing Sang, Chang Liu, Jingyuan Wang, Qianqian Lu, Fengtao Song, Xi Yuan, Yibing Wang, Jing Li, Wei Jin, Xuesong Liu, Xiaomin Song. BGB-24714, a novel oral IAP antagonist, displayed significant anti-tumor activities in preclinical models as a monotherapy and in combination with paclitaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6158.

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Huang, Huaizhi, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na et al. « Abstract A003 : Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes ». Cancer Prevention Research 15, n^o 12_Supplement_1 (1 décembre 2022) : A003. http://dx.doi.org/10.1158/1940-6215.dcis22-a003.

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Abstract Introduction: The relationship between germline pathogenic variants (PVs) in cancer predisposition genes and ductal carcinoma in situ (DCIS) is not well established. The objective of this study is to determine the risks of DCIS and contralateral breast cancer among women with DCIS associated with germline PVs in cancer predisposition genes. Methods: Associations between pathogenic variants in 11 cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MSH6, PALB2, RAD51C, and RAD51D) and DCIS were determined in case control analyses of a population-based cohort of 3876 women with DCIS and age-matched unaffected women, and in a clinical cohort of 9887 DCIS cases undergoing clinical genetic testing at Ambry Genetics and unaffected reference controls. The incidence of contralateral breast cancer risk in BRCA1, BRCA2, and PALB2 PV carriers with DCIS was also evaluated in a time-to-event analysis. Results: The mean age at diagnosis of DCIS was 50 years in the clinical testing cohort and 59 years in the population-based cohort. The frequency of PVs in 11 predisposition genes among DCIS cases was 6.9% in the clinical testing cohort and 4.9% in the population-based cohort. PVs in ATM, BRCA1, BRCA2, CHEK2, MSH6, PALB2, and RAD51D were associated with significantly increased risks (Odds Ratio (OR) >2) of DCIS in the clinical testing cohort whereas only PVs in BRCA1, CHEK2, PALB2, and ATM were associated with significantly increased risks of DCIS in the population-based cohort. The cumulative incidence of contralateral breast cancer among BRCA1, BRCA2, and PALB2 PV carriers with DCIS was 11% in 5-years and 20% in 15-years. Conclusions: This study provides new insights into PVs that predispose to DCIS. In addition, it establishes an increased risk of contralateral breast cancer risk among women with DCIS who are carriers of PVs in BRCA1, BRCA2, or PALB2. These findings will guide surveillance and risk reducing strategies in germline PV carriers with DCIS. Citation Format: Huaizhi Huang, Ronan E. Couch, Holly LaDuca, Siddhartha Yadav, Eric C. Polley, Nicholas J. Boddicker, Jie Na, Rohan D. Gnanaolivu, David E. Goldgar, Tina Pesaran, Steven N. Hart, Jill S. Dolinsky, Julie R. Palmer, Lauren Teras, Alpa V. Patel, Kathryn J. Ruddy, Janet E. Olson, Celine M. Vachon, Peter Kraft, Song Yao, Amy Trentham-Dietz, Katherine L. Nathanson, Jeffrey N. Weitzel, Susan M. Domchek, Fergus J. Couch, Chunling Hu. Risks of ductal carcinoma in situ of the breast associated with pathogenic variants in cancer predisposition genes [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr A003.

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An, Wonyoung, Sung Ryul Choi et Jun-Young Park. « Transition Metal Doped-Chalcogenide Based Electrocatalysts for Oxygen Evolution Reaction ». ECS Meeting Abstracts MA2022-02, n^o 64 (9 octobre 2022) : 2370. http://dx.doi.org/10.1149/ma2022-02642370mtgabs.

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Hydrogen, which possesses high gravimetric energy density, has recently received great attentions to respond to the seriousness of global climate change [1, 2]. In particular, the alkaline water electrolysis cells (AECs) that can produce hydrogen through electrochemical reactions without greenhouse gas emissions are substantially promising as renewable next-generation energy storage and conversion devices. In AECs, oxygen evolution reactions (OERs) occur at the anode, while hydrogen evolution reactions take place at the cathode [3, 4]. However, the sluggish kinetics of the multi-electron transfer process is a paramount challenge for efficient OER activity. Furthermore, precious metal catalysts such as iridium and ruthenium are still mainly used as an OER catalyst, and their low economic efficiency and durability are acting as major problems in the commercialization stage. Therefore, the reduction of reaction overpotential is crucial to boost catalytic efficiency for OER in AECs. In this study, the OER catalyst study is performed on sulfide-based chalcogenide materials. It has been reported that the sulfide-based chalcogenide materials have shown the excellent catalytic activity because the covalent characteristics between transition metal and chalcogenide is stronger than that of oxide-based catalysts [5]. In particular, among various sulfide-based chalcogenide materials, nickel sulfide-based catalysts have actively studied because they can simply synthesize using a hydrothermal method. Additionally, nickel sulfides have a structurally Ni-Ni metal bond that makes it easy to transfer charge species for OERs. Herein, various transition metals are doped into the nickel sulfide to improve the catalytic activity and electrical conductivity via generation of extra defects in the crystal structure. The crystal structure and catalytic activity of chalcogenide catalysts are analyzed through various physicochemical and electrochemical analysis methods. References [1] Hainan Sun, Xiaomin Xu, Zhiwei Hu, Liu Hao Tjeng, Jie Zhao, Qin Zhang, Hong-Ji Lin, Chien-Te Chen, Ting-Shan Chan, Wei Zhou, Zongping Shao, Journal of Materials Chemistry A 7 (2019) 9924. [2] Thomas E. Mallouk, Nature Chemistry 5 (2013) 362–363. [3] Muhammad Saqib, In-Gyu Choi, Hohan Bae, Kwangho Park, Ji-sup Shin, You-Dong Kim, John-In Lee, Minkyeong Jo, Yeong-Cehol Kim, Kug-Seung Lee, Sun-Ku Song, Eric D. Wachsman and Jun-Young Park, Energy & Environmental Science 14 (2021) 2472–2484. [4] Sung Ryul Choi, John-In Lee, Hyunyoung Park, Sung Won Lee, Dong Yeong Kim, Won Young An, Jung Hyun Kim, Jongsoon Kim, Hyun-seok Cho, Jun-Young Park, Chemical Engineering Journal 409 (2021) 128226. [5] Hatem M. A. Amin, UIf-Peter Apfel, European Journal of Inorganic Chemistry 2020 (2020) 2679–2690. Keywords: Oxygen evolution reaction, Alkaline electrolysis cell, Water splitting, Transition metal, Post-transition metal, Chalcogenide. * Corresponding author: jyoung@sejong.ac.kr (J. Y. Park)

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Zhang, Qichun, Wenping Hu, Thuc-Quyen Nguyen, Qibing Pei et Jia Zhu. « Professor Daoben Zhu : a giant in organic solids in China ». Journal of Materials Chemistry C 10, n^o 7 (2022) : 2311–13. http://dx.doi.org/10.1039/d2tc90014a.

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Guest editors Qichun Zhang, Wenping Hu, Thuc-Quyen Nguyen, Qibing Pei and Jia Zhu introduce this Journal of Materials Chemistry C issue in honour of Professor Daoben Zhu on the occasion of his 80th birthday.

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Wang, Jian, Hongzhen Lin et Stefano Passerini. « Construction of Dendrite-Free Metallic Lithium Anodes : From Static Lithiophilic Adsorption to Dynamic Electrochemical Diffusion Kinetics ». ECS Meeting Abstracts MA2023-02, n^o 5 (22 décembre 2023) : 831. http://dx.doi.org/10.1149/ma2023-025831mtgabs.

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Lithium metal batteries (LMBs) possess high theoretical energy density, becoming a promising next-generation energy storage system.1, 2 However, the applications of Li metal anodes are restricted by the Li dendrite formation, repeated formation and fracturing of solid electrolyte interphase (SEI), and large volume expansion, resulting in severe “dead lithium” and subsequent short circuiting.3, 4 Herein, differing from conventional interfacial engineering or current-collector designs with numerous lithiophilic site, fundamental novel insights of Li plating kinetics via using single-atomic catalyst (SAC) activators to boost Li diffusion behaviors is proposed to realize delocalized deposition.5, 6 Specifically, via the aid of series of characterizations and theoretical simulations, the SACs have the ability in decreasing barriers of desolvation, Li ion transport or Li atom diffusion and we have unambiguously depicted that the SACs serve as kinetic activators in propelling the surface spreading and lateral redistribution of the lithium atoms for achieving dendrite-free plating morphology. Reference: Wang, J.; Hu, H.; Zhang, J.; Li, L.; Jia, L.; Guan, Q.; Hu, H.; Liu, H.; Jia, Y.; Zhuang, Q.; Cheng, S.; Huang, M.; Lin, H. Hydrophobic lithium diffusion-accelerating layers enables long-life moisture-resistant metallic lithium anodes in practical harsh environments. Energy Storage Mater. 2022, 52, 210-219. Zhang, J.; He, R.; Zhuang, Q.; Ma, X.; You, C.; Hao, Q.; Li, L.; Cheng, S.; Lei, L.; Deng, B.; Li, X.; Lin, H.; Wang, J. Tuning 4f-Center Electron Structure by Schottky Defects for Catalyzing Li Diffusion to Achieve Long-Term Dendrite-Free Lithium Metal Battery. Adv. Sci. (Weinh) 2022, 9, (23), e2202244. Wang, J.; Li, L.; Hu, H.; Hu, H.; Guan, Q.; Huang, M.; Jia, L.; Adenusi, H.; Tian, K. V.; Zhang, J.; Passerini, S.; Lin, H. Toward Dendrite-Free Metallic Lithium Anodes: From Structural Design to Optimal Electrochemical Diffusion Kinetics. ACS Nano 2022, 16, 17729−17760. Zhang, J.; You, C.; Lin, H.; Wang, J. Electrochemical Kinetic Modulators in Lithium–Sulfur Batteries: From Defect‐Rich Catalysts to Single Atomic Catalysts. Energy & Environmental Materials 2022, 5, (3), 731-750. Wang, J.; Zhang, J.; Cheng, S.; Yang, J.; Xi, Y.; Hou, X.; Xiao, Q.; Lin, H. Long-Life Dendrite-Free Lithium Metal Electrode Achieved by Constructing a Single Metal Atom Anchored in a Diffusion Modulator Layer. Nano Lett. 2021, 21, (7), 3245-3253. Wang, J.; Zhang, J.; Duan, S.; Jia, L.; Xiao, Q.; Liu, H.; Hu, H.; Cheng, S.; Zhang, Z.; Li, L.; Duan, W.; Zhang, Y.; Lin, H. Lithium Atom Surface Diffusion and Delocalized Deposition Propelled by Atomic Metal Catalyst toward Ultrahigh-Capacity Dendrite-Free Lithium Anode. Nano Lett. 2022, 22, (19), 8008-8017.

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Lu, Shun, Jie Wang, Yan Yu, Xinmin Yu, Yanping Hu, Zhiyong Ma, Xingya Li et al. « Abstract CT552 : RATIONALE 304 : Tislelizumab (TIS) plus chemotherapy versus chemotherapy alone as first-line (1L) treatment for non-squamous (non-sq) NSCLC in patients (pts) aged 65-75 years ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : CT552. http://dx.doi.org/10.1158/1538-7445.am2022-ct552.

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Abstract Background: Primary results from the Phase 3 RATIONALE-304 study (NCT03663205) showed efficacy and a manageable safety/tolerability profile for TIS, an anti-programmed cell protein 1 monoclonal antibody, plus chemotherapy, as 1L treatment for non-sq NSCLC. We report results from pts aged 65-75 years. Methods: In RATIONALE-304, eligible pts (18-75 years) were treatment-naïve and had locally advanced or metastatic non-sq NSCLC. Pts were stratified by disease stage and programmed death-ligand 1 expression, and randomized 2:1 to receive TIS (200 mg intravenously [IV]) plus platinum (carboplatin AUC 5 or cisplatin 75 mg/m2 IV) plus pemetrexed 500 mg/m2 every three weeks for 4-6 cycles followed by maintenance TIS plus pemetrexed (Arm A), or platinum pemetrexed for 4-6 cycles followed by maintenance pemetrexed (Arm B). Progression-free survival (PFS) by independent review committee (IRC), objective response rate (ORR), and safety were assessed in pts aged 65-75 years. Results: In total, 97 pts aged 65-75 years were randomized to Arm A (60 pts) or Arm B (37 pts). The median age of pts was 68.0 years, and 76 pts (78.4%) were male. PFS was longer, and ORR higher, in Arm A vs Arm B (Table). Overall, 59 pts in Arm A, and 37 pts in Arm B experienced ≥ 1 treatment-emergent adverse event (TEAE). In Arm A, Grade ≥ 3 TEAEs occurred in 43 (72.9%) pts aged 65-75 years vs 150 (67.6%) aged ≥ 18 years, and in Arm B, 18 (48.6%) pts aged 65-75 years vs 59 (53.6%) pts aged ≥ 18 years. TEAEs leading to permanent discontinuation of any component of study treatment occurred in 19 (32.2%) pts in Arm A, and 5 (13.5%) pts in Arm B. 21 (35.6%) pts receiving TIS experienced ≥ 1 immune-related TEAE. Conclusions: Observed improvements in PFS and ORR support the treatment benefits of TIS in combination with platinum and pemetrexed chemotherapy in pts aged 65-75 with advanced non-squamous NSCLC. The safety profile of TIS in pts aged 65-75 years was similar to the safety profile for all pts in the overall study population. Table Arm A (N=60) Arm B (N=37) PFS Events (%) 27 (45.0) 20 (54.1) HR (95% CI) 0.727 (0.407, 1.297) - Median, months (95% CI) 9.7 (5.75, 11.53) 7.7 (4.21, 9.76) ORR, % (95% CI) 53.3 (40.0, 66.3) 40.5 (24.8, 57.9) HR, hazard ratio Citation Format: Shun Lu, Jie Wang, Yan Yu, Xinmin Yu, Yanping Hu, Zhiyong Ma, Xingya Li, Wu Zhuang, Yunpeng Liu, Weidong Li, Jiuwei Cui, Dong Wang, Wangjun Liao, Mengzhao Wang, Jianying Zhou, Zhehai Wang, Yuping Sun, Wanyu He, Yuanyuan Bao. RATIONALE 304: Tislelizumab (TIS) plus chemotherapy versus chemotherapy alone as first-line (1L) treatment for non-squamous (non-sq) NSCLC in patients (pts) aged 65-75 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT552.

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Ou, Yang, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi et al. « Abstract 4556 : USP51-GRP78-ABCB1 axis promotes chemoresistance of triple negative breast cancer by decreasing the accumulation of doxorubicin in cells ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 4556. http://dx.doi.org/10.1158/1538-7445.am2024-4556.

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Abstract Background: Resistance to chemotherapy remains an obstacle for triple-negative breast cancer (TNBC) patients. The core components of the ubiquitin-proteasome system have been demonstrated to regulate chemoresistance of TNBC. As a novel deubiquitinase (DUB), ubiquitin-specific peptidase 51 (USP51) plays a pivotal role in chemotherapeutic resistance in multiple malignancies. Herein, we sought to better understand how USP51 performs a cell-intrinsic role in mediating chemotherapeutic resistance in TNBC. Methods: Western blotting, RNA-sequencing and CCK8 assays were used to identify the DUBs for chemoresistance of breast cancer. Coimmunoprecipitation, GST-pulldown, protein deubiquitination and immunohistochemistry assays were then used to determine the biological phenotypes of ectopic USP51 in TNBC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin-7-amido-4-methylcoumarin (Ub-AMC)-based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors. Results: To identify the critical DUBs involved in breast cancer chemoresistance, we established doxorubicin-resistant Cal51 and MDA-MB-231 TNBC cell lines by multiple dose exposure. We found ectopic USP51 in doxorubicin-resistant cells compared with their parental cells. Moreover, USP51-interfered chemoresistant tumor cells exhibited impaired cell viability as well as increased DNA damage and cell apoptosis upon treatment with doxorubicin. On the contrary, overexpression of USP51 performed the opposite effects to enhance cell viability but decrease DNA damage and apoptosis in response to doxorubicin; however, these outcomes were not shown for its catalytically inactive mutant USP51C372S. At the molecular level, GRP78 was identified as a bona fide substrate of USP51. Importantly, knockdown USP51 increased doxorubicin-induced DNA damage and apoptosis, which was rescued by overexpression of GRP78 in vitro and in vivo. In addition, the activity of ABCB1, the main efflux pump of doxorubicin, was enhanced by GRP78. Consistently, the expression of USP51, GRP78 and ABCB1 were correlated with chemoresistant phenotypes in TNBC patients. Of note, we also explored a small molecular inhibitor of USP51, WCY-4-1, which conferred chemosensitization in TNBC. Conclusion: These findings collectively indicated that ectopic USP51 enhances the activity of ABCB1 by deubiquitinating and stabilizing GRP78, which leads to decreased accumulation of doxorubicin as well as decreased DNA damage and cell apoptosis in TNBC. Our results also revealed that specific inhibition of USP51 significantly impairs doxorubicin-resistance in TNBC. Citation Format: Yang Ou, Kun Zhang, Qiuying Shuai, Chenyang Wang, Huayu Hu, Lixia Cao, Chunchun Qi, Min Guo, Zhaoxian Li, Jie Shi, Yuxin Liu, Siyu Zuo, Xiao Chen, Yanjing Wang, Mengdan Feng, Hang Wang, Yi Shi, Guang Yang, Shuang Yang. USP51-GRP78-ABCB1 axis promotes chemoresistance of triple negative breast cancer by decreasing the accumulation of doxorubicin in cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4556.

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Liu, Renyan, Nicole L. Solimini, Patrick Bhola, Timothy B. Branigan, Jie Hao, Xin Wang, Roshen Alharthi et al. « Abstract 604 : Targeting casein kinase 1 alpha (CK1 alpha) and transcriptional CDKs (CDK7/9) in human liposarcomas ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 604. http://dx.doi.org/10.1158/1538-7445.am2024-604.

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Abstract Introduction: Liposarcomas (LPS) are rare mesenchymal cell malignancies of adipocytic origin that are diagnosed in more than 3500 patients in the US each year. The two most common subtypes, well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS), are characterized by extrachromosomal DNA amplifications harboring the MDM2 (100%) and CDK4 (90+%) genes, generally with wild type TP53. Management of metastatic or surgically unresectable LPS remains purely palliative. Recent clinical trials targeting MDM2 or CDK4/6 with small-molecule inhibitors have shown promise but have been hampered by dose-limiting toxicities. The development of new therapeutics is greatly needed to improve outcomes for patients with LPS. Results: To identify unique liposarcoma-specific vulnerabilities, we screened multiple human LPS cell lines for transcriptional CDK expression and found high levels of CDK7 and CDK9. We demonstrate that CDK9 inhibitors suppress LPS cell growth and induce apoptosis by decreasing MDM2 levels while inducing expression of p53. To enhance p53 activation in these cells, we screened for expression of known regulators of p53, including CK1α, whose inhibition has previously been shown to activate p53. We demonstrate that LPS cells express CK1α and that the cytotoxic effects of CDK9 inhibitors are enhanced upon CK1α depletion. These data led us to examine combined targeting of CK1α and CDK9 in LPS with the novel agent BTX-A51, which has previously been shown to inhibit CK1α, CDK9, as well as CDK7 with nanomolar efficacy in AML models. BTX-A51 potently reduces expression of MDM2 with marked induction of p53, resulting in profound apoptosis of LPS cells. Through CRISPR/Cas9-mediated p53 knockout, we establish that BTX-A51-mediated apoptosis is primarily p53-dependent. However, BTX-A51 also reduces expression of MCL1 and primes LPS cell lines and primary LPS cells for BIM-induced apoptosis, as demonstrated by BH3 profiling. Importantly, preliminary in vivo data in an LPS patient-derived xenograft model reveal that BTX-A51 is well-tolerated with tumor growth inhibition. Conclusions: Our results suggest that BTX-A51 has potent preclinical efficacy in treating LPS, primarily through inhibition of CK1α and CDK9. Future mechanistic studies will further clarify mechanisms of BTX-A51-mediated apoptosis, as well as the contribution of CDK7 inhibition to anti-tumor activity. Our data justify a planned clinical trial that will evaluate the efficacy of BTX-A51 in patients with advanced WDLPS or DDLPS. Citation Format: Renyan Liu, Nicole L. Solimini, Patrick Bhola, Timothy B. Branigan, Jie Hao, Xin Wang, Roshen Alharthi, Michael Yorsz, Shaili Soni, Cing-siang Hu, Irit Snir-Alkalay, Prafulla Gokhale, Anthony Letai, Yinon Yinon Ben-Neriah, George D. Demetri, Geoffrey I. Shapiro. Targeting casein kinase 1 alpha (CK1 alpha) and transcriptional CDKs (CDK7/9) in human liposarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 604.

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ZHU, Yan. « Sustainable groundwater development and management in the Quaternary Hang-Jia-Hu Plain, China ». Journal of Zhejiang University SCIENCE 3, n^o 2 (2002) : 205. http://dx.doi.org/10.1631/jzus.2002.0205.

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Zhu, Yan. « Sustainable groundwater development and management in the Quaternary Hang-Jia-Hu Plain, China ». Journal of Zhejiang University-SCIENCE A 3, n^o 2 (avril 2002) : 205–8. http://dx.doi.org/10.1631/bf03396439.

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Taherkhani, Negar, Hossein Piri, Azadeh Hekmat et Kamahldin Haghbeen. « Humic and Fulvic Acids Induced Thermodynamic and Structural Instability of Tyrosinase With Antiproliferative Effect on A375 Melanoma Cancer Cell Line ». Journal of Inflammatory Diseases 26, n^o 4 (1 janvier 2023) : 183–92. http://dx.doi.org/10.32598/jid.26.4.3.

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Background: The tyrosinase enzyme catalysis monophenols to melanin pigments through the melanogenesis process. For this reason, various inhibitors have been studied for enzyme regulations in melanogenesis abnormalities in both the food and cosmetics industries. In this study, the effect of humic acid (Hu) and fulvic acid (Fu) on the structure, activity, and stability of mushroom tyrosinase (MT) was investigated. Methods: These two organic acids are the main components of soil humus. Assessment of the thermodynamic and structural stability of enzymes was obtained through thechemical and thermal denaturations and (8-anilino-naphthalene sulfonic acid) ANS fluorescence analysis. The Hu and Fu impact on A375 melanoma cancer cell viability was achieved by MTT assay. Findings: The results of enzyme half denaturation concentration (Cm), melting points (Tm), ΔG0 values and external fluorescence emissions in the presence of Hu and FA proved the reduction of the thermodynamic and structural stability of MT by these compounds. The anti-proliferation effects of the compounds were confirmed by the inhibitory concentrations of 50% (IC50) of 31.5 and 42.7 µM and 12.5 and µM at time points of 24 and 48 hours treatments of the A375 melanoma cell line by Hu and Fu, respectively. Conclusion: Humic and fulvic acids can be expected to contribute to advancing skin disorder science play a crucial role in tyrosinase related disorders and anti-cancer effects, and good candidates for medical applications.

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Wong, Jason Yat-Yang, Richard Cawthon, Wei Hu, Somayina Ezennia, Shahinaz Gadalla, Charles Breeze, Batel Blechter et al. « Abstract 2251 : Alu retroelement copy number, leukocyte telomere length, and lung cancer risk in the prospective Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 2251. http://dx.doi.org/10.1158/1538-7445.am2022-2251.

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Abstract Prospective cohort and genome-wide association studies have found consistent associations between longer leukocyte telomere length (LTL) and increased lung cancer risk. These findings present a paradox in the traditional expectations of telomere dynamics in cancer development, as longer telomeres are generally considered to be reflective of less advanced age and greater genomic stability. We posited that longer LTL may reflect or lead to delayed cellular senescence allowing cells to accumulate genomic abnormalities that drive lung carcinogenesis. Furthermore, increased copy number of Alu retroelements, repetitive mobile DNA sequences that are approximately 300 base pairs in length, could also reflect genomic instability. We previously found that exposure to diesel exhaust, a known lung carcinogen, was associated with increased Alu copy number and suspect that increased Alu retrotransposition could influence lung carcinogenesis. However, the interrelationship between Alu retroelements, LTL, and lung cancer is unknown. Therefore, we investigated associations between Alu copy number, LTL, and lung cancer risk in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We conducted a nested case-control study of 410 confirmed incident lung cancer cases and 416 controls individually matched on age, sex, race/ethnicity, study center, and blood draw date. Quantitative PCR was used to measure Alu copy number and telomere length relative to albumin (Alb) copy number (Alu/Alb and T/S ratio, respectively) in pre-diagnostic leukocytes. Conditional logistic regression was used to estimate associations between quartiles (Q) of Alu/Alb ratio (reference=Q1) and lung cancer risk, adjusted for matching factors, smoking status and packyears, and LTL. Additionally, we dichotomized Alu/Alb ratio and LTL at their medians and created a cross-combination variable to assess combined effects. We found a positive dose-response relationship between Alu/Alb ratio and lung cancer risk (odds ratio (OR), 95% confidence intervals (CI): Q2: 1.34 (0.73, 2.48); Q3:1.89 (0.94, 3.84); Q4: 2.66 (1.03, 5.63); p-trendordinal=0.02). The association was apparent for lung adenocarcinoma (LUAD) (Q2: 1.32 (0.46, 3.77); Q3: 2.88 (0.90, 9.25); Q4: 5.07 (1.29, 19.87); p-trendordinal=0.02). We have previously reported that longer measured LTL was also associated with an increased risk of LUAD (Q4: 2.82 (1.16-6.85); p-trend=0.011). The combined effect of both a higher Alu/Alb ratio and longer LTL was 6.07 (1.75, 21.04; p=4.5x10-3) for LUAD compared with lower/shorter levels of both. Higher Alu copy number and longer LTL were associated with increased risk of lung cancer, especially LUAD. Our findings require replication. If confirmed, evaluation of Alu copy number and LTL in risk stratification and prediction analyses is warranted. Citation Format: Jason Yat-Yang Wong, Richard Cawthon, Wei Hu, Somayina Ezennia, Shahinaz Gadalla, Charles Breeze, Batel Blechter, Neal Freedman, Wen-Yi Huang, H. Dean Hosgood, Wei Jie Seow, Bryan Bassig, Mohammad Rahman, Richard Hayes, Nathaniel Rothman, Qing Lan. Alu retroelement copy number, leukocyte telomere length, and lung cancer risk in the prospective Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2251.

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Yadav, Siddhartha, Chunling Hu, Nicholas J. Boddicker, Eric Polley, Steven Hart, Rohan Gnanaolivu, Jie Na et al. « Abstract P2-09-01 : Population-based risk estimates of clinical subtypes of breast cancer among carriers of germline pathogenic variants in cancer predisposition genes ». Cancer Research 82, n^o 4_Supplement (15 février 2022) : P2–09–01—P2–09–01. http://dx.doi.org/10.1158/1538-7445.sabcs21-p2-09-01.

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Abstract Introduction: The risk of specific clinical subtype of breast cancer (defined by ER and HER2 status) among women in the general population who are carriers of germline pathogenic variants (PVs) in cancer predisposition genes is not well-defined. Methods: A total of 13,153 women with breast cancer (ER+/HER2-: 9381; ER+/HER2+: 1462; ER-/HER2+: 690; and ER-/HER2-: 1620) and 25,005 unaffected women (controls) from nine studies within the CAnceR RIsk Estimates Related to Susceptibility (CARRIERS) consortium that were not enriched for family history or early onset disease were included in the present analysis. A multiplex amplicon-based panel was used to perform germline sequencing for cancer predisposition genes. Case-control associations for each of the four clinical subtype of breast cancer was performed for PVs in 5 common breast cancer predisposition genes (ATM, BRCA1, BRCA2, CHEK2 and PALB2) utilizing a logistic regression model adjusting for study, age at diagnosis, race/ethnicity and family history of breast cancer. Results: The frequency of PVs in 5 genes was 3.8% for ER+/HER2-, 6.2% for ER+/HER2+, 4.2% for ER-/HER2+ and 9.3% for ER-/HER2- subtypes. PVs in BRCA1 and BRCA2 were associated with high risk (Odds Ratio (OR) >4) for all clinical subtypes of breast cancer, but the risk was highest (OR>8) for ER-/HER2- breast cancer. PVs in PALB2 were associated with high risk (OR>4) of ER-/HER2- and ER+/HER2+ subtypes and moderate risk (OR: 2-4) of ER+/HER2- breast cancer. Irrespective of the HER2 status, PVs in ATM were associated with a moderately increased risk (OR: 2-4) of ER+ breast cancer but the risk of ER- breast cancer was not elevated. In contrast, PVs in CHEK2 were associated with high risk (OR>4) of ER+/HER2+ breast cancer and moderate risk (OR: 2-4) of ER+/HER2- and ER-/HER2+ breast cancer, but the risk of ER-/HER2- breast cancer was not elevated. Conclusions: This study provides population-based estimates of risk of specific clinical subtypes of breast cancer which will be useful for genetic counseling and targeting appropriate screening strategies in PV carriers based on subtype specific risks of breast cancer. Citation Format: Siddhartha Yadav, Chunling Hu, Nicholas J. Boddicker, Eric Polley, Steven Hart, Rohan Gnanaolivu, Jie Na, Hongyan Huang, Song Yao, Celine M. Vachon, Lauren Teras, Jack A. Taylor, Dale P. Sandler, Julie R. Palmer, Janet E. Olson, Susan Neuhausen, Elena Martinez, Sara Lindstroem, Loic Le Marchand, Charles Kooperberg, Christopher Haiman, Mia M. Gaudet, James V. Lacey, Kimberly A. Bertrand, Leslie Bernstein, Paul W. Auer, Christine Ambrosone, Jeffrey N. Weitzel, Peter Kraft, David E. Goldgar, Katherine L. Nathanson, Susan M. Domchek, Fergus J. Couch, CARRIERS Consortium. Population-based risk estimates of clinical subtypes of breast cancer among carriers of germline pathogenic variants in cancer predisposition genes [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-09-01.

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Hu, Yingying, Yayuan Fu, Lei Liu, Wenjing Li, Liting Xue, Zhiyong Yu, Yun Zhang et al. « Abstract 6357 : Generation of a mutant SIRPa fusion protein with highly-improved affinity and favorable safety profile ». Cancer Research 83, n^o 7_Supplement (4 avril 2023) : 6357. http://dx.doi.org/10.1158/1538-7445.am2023-6357.

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Abstract Background/Purpose: CD47 has been validated to be expressed on various tumor types including acute myeloid leukemia, myelodysplastic syndrome and other hematologic or solid tumors. As primary ‘don’t eat me’ signal, high expression of CD47 on tumor cells interacts with SIRPα negatively regulating the phagocytosis level. However, poor safety profile as well as insufficient combinatory effect remain to be the issues limiting the clinical outcomes of CD47-targeting molecules. Herein, we used rational design strategies to generate SCR9168 with potent affinity improvement, and maintained favorable safety profiles in different animal species, including cynomolgus monkeys. Procedures: Mutagenesis was introduced to the residues critical for CD47/SIRPα binding interface. Affinity was measured by SPR analysis. In vitro activities were determined by biochemical- or cell-based binding, blocking and antibody-dependent cellular phagocytosis (ADCP) assays. The efficacy in vivo was assessed with the OE19 xenograft model. Pharmacokinetics (PK) and safety were monitored in both mice and cynomolgus monkeys. Results: The affinity of SCR9168 achieves 178 pM for human CD47 which is nearly 50-fold increase in comparison with wild-type SIRPα. Enhanced affinity has also been confirmed in binding to OE19 or DLD1 cell lines, as well as in blocking human SIRPα binding to Raji cells. SCR9168 remains strong binding potency to monkey, mouse or rat CD47 which allows the PK and safety assessment using these animal species. The combined effects of SCR9168 and multiple therapeutic antibodies targeting tumor-associated antigens (TAAs) have been evaluated with ADCP assays using human monocyte-derived macrophages. SCR9168 markedly increases the ratio of phagocytic cells combining with antibodies, such as cetuximab. However, due to the inert function of Fc fragment, no phagocytosis of red blood cells or platelets was caused after the incubation in vitro. In addition, SCR9168 treatment in combination with trastuzumab leads to significantly improved suppression of tumor growth in a dose-dependent manner. Moreover, administration of two doses at day 1 and day 11 in cynomolgus monkeys results in no toxicity events related to SCR9168 based on the data from hematological analysis. Conclusion: SCR9168 demonstrates the best-in-class potential among SIRPα mutein molecules. It elicits improved and dose-dependent efficacy in phagocytosis or tumor suppression combining with therapeutic antibodies, such as trastuzumab or cetuximab. Favorable safety profile with no phagocytosis of RBC or platelets in vitro as well as no hematological toxicity observation in cynomolgus monkeys allows broader dose range exploration in early clinical phase. SCR9168 is currently in development stage and IND enabling will be expected in the end of 2023. Citation Format: Yingying Hu, Yayuan Fu, Lei Liu, Wenjing Li, Liting Xue, Zhiyong Yu, Yun Zhang, Meijuan Gao, Yixin Tan, Fudong Wang, Yadan Wu, Jie Li, Zhenzhen Li, Feng Zhou, Wenqing Yang, Zhuoxiao Cao, Renhong Tang. Generation of a mutant SIRPa fusion protein with highly-improved affinity and favorable safety profile [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6357.

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Xue, Jie, Keyu Li, Poonam Yakkundi, Palak Chadasama, Tina Mao, Zee Malik, Vidhya Rao et al. « Abstract 6726 : Costimulatory IgM T-cell engagers with enhanced and durable cytotoxicity ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 6726. http://dx.doi.org/10.1158/1538-7445.am2024-6726.

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Abstract T-cell engagers (TCEs) have established therapeutic effect in treatment of various cancers by harnessing the power of the immune system against tumors in a targeted manner. IgM-based TCEs may offer high avidity, specificity, and safety advantages over other modalities because of their multivalent architecture and unique positioning of the CD3 binding domain on the J-chain. We have built a costimulatory IgM TCE platform that engages both signal 1 and signal 2 on T-cells, with the goal of enabling their optimal activation and survival for more robust and durable cytotoxic activity. Multiple antigen targeting costimulatory IgM TCEs were generated and activity was evaluated both in vitro and in vivo to assess the role of CD28 co-stimulation. Costimulatory IgM TCEs engaged both CD3 and CD28 on the T-cell surface, enhancing in vitro cytotoxicity and T-cell activation. Levels of IL-2 increased significantly with dual signal engagement promoting proliferation and survival of T-cells. In long-term culture assays, costimulatory IgM TCEs promoted better T-cell proliferation and survival compared to IgM TCEs with only a CD3 binder, and was even more pronounced at low E:T ratios. In the absence of CD3 engagement, CD28 binding alone did not induce any T-cell activation, cytotoxicity, or cytokines. Activation of T-cells was also fully dependent on the presence of target cells, underscoring the safety profile of the platform. In Hu-PBMC xenograft tumor models, costimulatory IgM TCEs exhibited stronger in vivo anti-tumor activity compared to TCEs only engaging CD3. Tumor growth inhibition was maintained for longer after dosing was stopped with costimulatory IgM TCEs, indicating the durability of responses. Costimulatory IgM TCEs suppressed tumor growth in xenograft studies using cell lines that expressed both high and low target copy numbers suggestive of their broad utility against multiple tumor types. Enhanced in vivo anti-tumor activity of costimulatory IgM TCEs was associated with significant increases in intra-tumoral CD8/CD3+T-cells.Both peripheral and intra-tumoral T-cells exhibited enhanced anti-apoptotic and cytotoxic phenotypes indicative of the costimulatory activation. IgM-based costimulatory TCEs provide enhanced cytotoxicity through optimal T-cell activation and proliferation/survival. This dual engagement of T-cell activation signals, along with the high avidity target binding offered by IgM platform, could enable the creation of effective therapeutics targeting pathogenic cells in autoimmune diseases and solid tumors that will maintain activity even in conditions with low T-cell counts. Citation Format: Jie Xue, Keyu Li, Poonam Yakkundi, Palak Chadasama, Tina Mao, Zee Malik, Vidhya Rao, Madhura Joglekar, Kristene Mai, Gene Li, Deepal Pandya, Rodnie Rosete, Zhongde Ye, Leyla Tahrani, Jinqiu Wang, Nardeen Hanna, Elizabeth Perez, Yue Wang, Sachi Ahmed, Lusiana Widjaja, Paul Hinton, Krzysztof Bzymek, Bruce Keyt, Miho Oyasu, Liqin Liu, Angus Sinclair, Umesh S. Muchhal. Costimulatory IgM T-cell engagers with enhanced and durable cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6726.

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Blîndu, Emanuel, Imre Benedek, Ioana-Patricia Rodean, Vasile-Bogdan Halațiu, Nora Raț, Constantin Țolescu, Theofana Mihăilă et al. « Regional Differences in the Level of Inflammation Between the Right and Left Coronary Arteries – a Coronary Computed Tomography Angiography Study of Epicardial Fat Attenuation Index in Four Scenarios of Cardiovascular Emergencies ». Journal of Cardiovascular Emergencies 9, n^o 4 (1 décembre 2023) : 111–19. http://dx.doi.org/10.2478/jce-2023-0014.

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Abstract Introduction The pericoronary fat attenuation index (FAI) is an emerging computed tomography-derived marker for measuring vascular inflammation at coronary vessels. It holds prognostic significance for major cardiovascular events and enhances cardiac risk assessment, complementing traditional risk factors and coronary artery calcium scores. However, the impact of local coronary circulation factors on pericoronary inflammation development in right versus left coronary arteries has not been clearly understood. Objective This study aimed to investigate the regional differences in inflammation levels between the right and left coronary arteries in four clinical scenarios: acute coronary event in the follow-up period, post-COVID patients, recent percutaneous intervention, and unstable angina with significant lesions on native coronary arteries. Methods The study included 153 patients (mean age 62 years, 70.5% male) who underwent clinically indicated coronary computed tomography angiography (CCTA). Vulnerable plaque features were analyzed to identify high-risk plaques. FAI and the FAI score, a score integrating risk factors and age, were calculated for each case at the left anterior descending artery (LAD), circumflex artery (LCX), and right coronary artery (RCA). Results A total of 459 coronary arteries were analyzed. Both FAI and FAI scores were higher in the RCA (15.23 ± 11.97) compared to the LAD (10.55 ± 6.78) and (11.48 ± 6.5) LCX (p = 0.02). FAI values showed a significantly higher level at the RCA (−71.25 ± 7.47 HU) compared to the LCX (−76 ± 7.68 HU) and the LAD (−73.04 ± 8.9 HU, p <0.0001). This trend persisted across all subgroups, including post-COVID CT scans (−75.49 ± 7.62 HU for RCA vs. −72.89 ± 9.40 HU for the LCX vs. −71.28 ± 7.82 HU for the LAD, p = 0.01) and patients with high-risk plaques (20.98 ± 16.29 for the RCA vs. 11.77 ± 7.68 for the LCX vs. 12.83 ± 6.47 for the LAD, p = 0.03). Conclusion Plaques in different coronary areas show varied vulnerability and inflammation levels. The RCA, in particular, demonstrates greater inflammation susceptibility, with higher inflammation scores in areas surrounding the coronary plaques.

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Cheng, Ying, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen et al. « Abstract CT038 : Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC : A phase 3 trial ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : CT038. http://dx.doi.org/10.1158/1538-7445.am2022-ct038.

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Abstract Introduction: Extensive-stage small cell lung cancer (ES-SCLC) is associated with limited treatment options and poor prognosis. Immunotherapy has recently showed robust clinical activity in ES-SCLC. In this double-blind, phase 3 trial, we evaluated adebrelimab (SHR-1316), a novel anti-PD-L1 antibody, in combination with standard chemotherapy (chemo) as first-line treatment for ES-SCLC. Methods: Patients naïve to systemic treatment for ES-SCLC were randomized 1:1 to receive 4-6 cycles of adebrelimab (20 mg/kg, iv, d1, q3w) or placebo with carboplatin (AUC 5, d1, q3w) plus etoposide (100 mg/m2, d1, d2, d3, q3w), followed by maintenance therapy with adebrelimab or placebo. The primary endpoint was overall survival (OS). Results: 462 patients were randomized and treated (adebrelimab+chemo, n=230; placebo+chemo, n=232). As of Oct 08, 2021, with an median follow-up of 13.5 mo (all patients; 22.5 mo for patients alive), OS was significantly prolonged with adebrelimab+chemo vs placebo+chemo (median, 15.3 mo [95% CI 13.2-17.5] vs 12.8 mo [95% CI 11.3-13.7]; hazard ratio [HR], 0.72 [95% CI 0.58-0.90], 1-sided p=0.0017); OS rate was 62.9% vs 52.0% at 12 mo and 31.3% vs 17.2% at 24 mo. Progression-free survival (PFS) per independent review committee (IRC) was 5.8 mo (95% CI 5.6-6.9) with adebrelimab+chemo vs 5.6 mo (95% CI 5.5-5.7) with placebo+chemo (HR 0.67, 95% CI 0.54-0.83); PFS rate was 49.4% vs 37.3% at 6 mo and 19.7% vs 5.9% at 12 mo. Objective response rate (ORR) and duration of response (DoR) also favored the adebrelimab+chemo group (Table 1). Grade ≥3 treatment-related adverse events occurred in 85.7% vs 84.9% of patients with adebrelimab+chemo vs placebo+chemo, with the most common (frequency ≥5%) being hematological toxicities in both groups. Conclusions: The addition of adebrelimab to chemotherapy significantly improved OS with an acceptable safety profile, supporting this combination as a new first-line treatment option for ES-SCLC. Efficacy outcomes Adebrelimab+Chemo (n=230) Placebo+Chemo (n=232) Median OS (95% CI), mo 15.3 (13.2-17.5) 12.8 (11.3-13.7) HR (95% CI)*, 1-sided log-rank p 0.72 (0.58-0.90); p=0.0017 12-mo OS rate (95% CI), % 62.9 (56.3-68.8) 52.0 (45.4-58.2) 24-mo OS rate (95% CI), % 31.3 (24.9-37.9) 17.2 (12.1-23.0) Median PFS (95% CI), mo 5.8 (5.6-6.9) 5.6 (5.5-5.7) HR (95% CI)*, 1-sided log-rank p 0.67 (0.54-0.83); p <0.0001 6-mo PFS rate (95% CI), % 49.4 (42.4-56.0) 37.3 (30.7-43.9) 12-mo PFS rate (95% CI), % 19.7 (14.5-25.5) 5.9 (3.1-10.1) IRC-assessed ORR (95% CI), % 70.4 (64.1-76.3) 65.9 (59.5-72.0) Median DoR (95% CI), mo 5.6 (4.6-6.7) 4.6 (4.3-5.5) *Stratified Cox proportional-hazards model Citation Format: Ying Cheng, Jie Wang, Caicun Zhou, Wenxiu Yao, Qiming Wang, Xuhong Min, Gongyan Chen, Xingxiang Xu, Xingya Li, Fei Xu, Yong Fang, Runxiang Yang, Guohua Yu, Youling Gong, Jun Zhao, Yun Fan, Quan Liu, Lejie Cao, Yu Yao, Yunpeng Liu, Xiaoling Li, Jingxun Wu, Zhiyong He, Kaihua Lu, Liyan Jiang, Huiqing Yu, Chengping Hu, Wenhua Zhao, Jian Zhao, Gang Wu, Dingzhi Huang, Chengshui Chen, Cuimin Ding, Baihong Zhang, Xiuwen Wang, Hui Luo, Baolan Li, Ben Zhang, Haowen Li, Ke Ma. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage SCLC: A phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT038.

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Cheng, Ying, Lin Wu, Yong Fang, Yun Fan, Xingya Li, Mingjun Zhang, Yan Yu et al. « Abstract CT248 : Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2 mutant non-small cell lung cancer (NSCLC) : primary analysis from the Phase 2 DESTINY-Lung05 (DL-05) trial ». Cancer Research 84, n^o 7_Supplement (5 avril 2024) : CT248. http://dx.doi.org/10.1158/1538-7445.am2024-ct248.

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Abstract Background: In China, non-approved therapies are used for pts with HER2 (ERBB2) mutant (HER2m) NSCLC. In DESTINY-Lung02 (DL-02), T-DXd 5.4 mg/kg showed clinical benefit with an acceptable and manageable safety profile in pts with pretreated HER2m metastatic NSCLC. DL-02 did not include any Chinese pts. We report the primary analysis of T-DXd in Chinese pts with pretreated HER2m metastatic NSCLC. Methods: In this open-label, single-arm, Phase 2 trial (NCT05246514), Chinese pts with HER2m (locally or centrally confirmed activating HER2 exon 19 or 20 mutation) metastatic non-squamous NSCLC with disease progression on or after ≥1 prior anticancer therapy (no prior HER2-directed) received T-DXd 5.4 mg/kg IV once every 3 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included investigator-assessed (INV) confirmed ORR; ICR and INV duration of response, disease control rate, progression-free survival, and safety. Results: At data cutoff (September 23, 2023), 72 pts with HER2m NSCLC received T-DXd 5.4 mg/kg (full analysis set). Median T-DXd exposure was 7.9 (0.7-13.5) months. Pt characteristics and efficacy data are in the table. 71 pts had drug-related adverse events (AEs), of which 51.4% were grade (G) ≥3. Most common G≥3 AEs by grouped term: neutropenia (26.4%), thrombocytopenia (18.1%), and leukopenia (11.1%). Drug-related AEs leading to discontinuations occurred in 2 (2.8%) pts. 17 (23.6%) pts had serious AEs, with no INV-adjudicated G5. Centrally adjudicated drug-related ILD/pneumonitis occurred in 7 (9.7%) pts (n=6 G2; n=1 G5). Conclusion: T-DXd 5.4 mg/kg demonstrated clinically meaningful and durable responses and a manageable safety profile in Chinese pts with HER2m metastatic NSCLC. Results were consistent with DL-02 and the known safety profile of T-DXd, supporting its use in this pt population. TABLE 1. NAND Pt characteristics and efficacy data Full analysis set* N=72 Median age, years (min, max) 57.0 (34, 76) Female, n (%) 41 (56.9) Former smoker, n (%) 22 (30.6) Prior lines of therapy, n (%) 1 30 (41.7) ≥2 42 (58.3) Most common prior treatment modalities, n (%) Cytotoxic chemotherapy 67 (93.1) Platinum chemotherapy 65 (90.3) Immunotherapy 49 (68.1) Antiangiogenic therapy 49 (68.1) Median duration of follow up, months (range) 9.8 (1.0–14.0) Efficacy ICR INV Confirmed ORR, % (95% CI) 58.3 (46.1, 69.8) 58.3 (46.1, 69.8) Median DOR, months (95% CI) NE (6.1, NE) 9.0 (7.2, NE) DCR, % (95% CI) 91.7 (82.7, 96.9) 93.1 (84.5, 97.7) Median PFS, months (95% CI) NE (7.2, NE) 10.8 (7.2, NE) 12-month PFS rate, % (95% CI) 55.1 (41.4, 66.8) 39.7 (19.5, 59.4) *Pts with HERm assessed by central testing. CI, confidence interval; DCR, disease control rate; DOR, duration of response; HER2m, HER2 mutant; ICR, independent central review; INV, investigator assessed; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; pts, patients Citation Format: Ying Cheng, Lin Wu, Yong Fang, Yun Fan, Xingya Li, Mingjun Zhang, Yan Yu, Yu Yao, Ruilian Xu, Jun Guo, Huaping Yang, Jian Fang, Feng Luo, Xuhong Min, Ke-jing Tang, Jie Hu, Yunru Chen, Rui Mao, Victor Zhang, Dairong Li. Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2 mutant non-small cell lung cancer (NSCLC): primary analysis from the Phase 2 DESTINY-Lung05 (DL-05) trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT248.

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Blechter, Batel, Chao Agnes Hsiung, Keitaro Matsuo, Kouya Shiraishi, Kevin Wang, Haoyu Zhang, Wei Jie Seow et al. « Abstract 6149 : Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status ». Cancer Research 84, n^o 6_Supplement (22 mars 2024) : 6149. http://dx.doi.org/10.1158/1538-7445.am2024-6149.

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Abstract Background: Lung cancer is the leading cause of cancer mortality worldwide, and incidence rates for the disease in never-smokers is among the highest in East Asian (EAS) women. Epidermal growth factor receptor (EGFR) is a transmembrane protein that regulates cellular proliferation and apoptosis, and mutations in the EGFR gene have been found to be a defining hallmark of lung adenocarcinoma (LUAD). We investigated if overall genetic susceptibility to LUAD, defined as a polygenic risk score (PRS), is differentially associated with LUAD by EGFR mutation status. Methods: The study consists of 998 female never-smoking histologically confirmed LUAD cases with data on EGFR mutation status and 4,544 female never-smoking controls from the Female Lung Cancer Consortium in Asia. Germline DNA samples were genotyped using the 370K, 610Q, or 660W microarrays. Genomic DNA extracted from fresh, frozen or formalin-fixed paraffin-embedded tumor tissue samples of LUAD cases were genotyped for EGFR mutations on exons 19 and 21. We defined cases with EGFR mutation on either exon as EGFR+ (n=518) and cases without such EGFR mutation as EGFR- (n=480). Weights from 942,592 single nucleotide variants derived from a previously conducted genome-wide association study were used in a Bayesian-based approach, LDpred2, to derive a PRS for all participants. We estimated the odds ratios (OR) and 95% confidence intervals (CI) for the association between continuous PRS, PRS quartiles and tumor EGFR mutation status using logistic regression models in a case-case analysis, as well as using a multinomial logistic regression treating controls as the reference. All models were adjusted for age, study and the top 10 principal components. Results: In case-case comparisons, compared to EGFR- LUAD, we found a positive association between continuous PRS and risk of EGFR+ LUAD (OR=1.17, 95% CI: 1.02, 1.34), as well as a dose-response relationship between quartiles of the PRS and EGFR+ LUAD (p-trend=0.003). We further found that the association between the fourth quartile of the PRS with EGFR+ LUAD (OR=8.63, 95% CI: 5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR- LUAD (OR=3.50, 95% CI: 2.44, 5.00) compared to controls (p-heterogeneity=0.004). Conclusions: We found that the PRS developed for LUAD in EAS individuals was more strongly associated with EGFR+ LUAD compared to EGFR- LUAD, suggesting that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female EAS patients depending on the cancer’s mutation status. Given that patients with LUAD respond differently to treatments that are used as targeted therapy depending on their EGFR mutation status, our findings may have important public health and clinical implications, which may guide risk stratification, screening, and treatment. Citation Format: Batel Blechter, Chao Agnes Hsiung, Keitaro Matsuo, Kouya Shiraishi, Kevin Wang, Haoyu Zhang, Wei Jie Seow, Jianxin Shi, Nilanjan Chatterjee, Jason Y.Y. Wong, Juncheng Dai, H. Dean Hosgood, I-Shou Chang, Jiyeon Choi, Wei Hu, Wei Zheng, Young Tae Kim, Xiao-Ou Shu, Qiuyin Cai, Pan-Chyr Yang, Dongxin Lin, Kexin Chen, Yi-Long Wu, Hongbin Shen, Takashi Kohno, Stephen J. Chanock, Nathaniel Rothman, Qing Lan. Polygenic risk score and lung adenocarcinoma risk among never-smokers by EGFR mutation status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6149.

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Orzan, Marius, Roxana Hodas, Mihaela Dobra, Nora Rat, Monica Chitu et Imre Benedek. « Original Research. Transluminal Contrast Attenuation Gradient Is Associated with Coronary Plaque Vulnerability — a Computed Tomography Angiography-based Study ». Journal Of Cardiovascular Emergencies 3, n^o 3 (26 septembre 2017) : 121–27. http://dx.doi.org/10.1515/jce-2017-0016.

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Abstract The aim of this study was to demonstrate that the transluminal contrast attenuation gradient (TAG), a new CT imaging-derived marker of functional significance of a coronary stenosis, is directly associated with the vulnerability degree of atheromatous coronary plaques. Material and methods: This is a prospective study on 21 patients with 30 atheromatous plaques in the coronary arteries, who underwent cardiac computed tomography angiography (CCTA) for assessment of coronary plaques. Results: Twelve plaques were classified as vulnerable (40%) and 18 plaques (60%) as non-vulnerable. Plaques associated with a TAG value above 10 HU exhibited in a significantly higher proportion CCTA markers of plaque vulnerability, as compared to plaques in which the attenuation gradient was below 10 HU. TAG values >10 HU were associated with a higher amount of plaque volume (107.4 ± 91.2 mm3 vs. 56.0 ± 37.5 mm3, p = 0.009), necrotic core (32.5 ± 36.9 mm3 vs. 3.1 ± 3.2 mm3, p = 0.0003), and fibro-fatty tissue (17.7 ± 16.3 mm3 vs. 4.0 ± 2.6 mm3, p = 0.0002), as compared to those lesions with TAG values below 10 HU. Linear regression analysis revealed a significant correlation between TAG values and CCTA features of plaque instability: necrotic core (r = −0.73, p <0.0001), fibrofatty tissue (r = −0.63, p = 0.0002), and plaque volume (r = −0.48, p = 0.006). Conclusions: In patients with coronary artery disease, contrast attenuation gradient along the coronary plaques, determined by CCTA, correlates with CT markers of plaque vulnerability. Vulnerable coronary plaques are associated with a higher functional significance than the stable ones with a similar anatomic profile.

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Yadav, Madhuri, et Ravindra Kumar Purwar. « Hindi handwritten character recognition using oriented gradients and Hu-geometric moments ». Journal of Electronic Imaging 27, n^o 05 (12 avril 2018) : 1. http://dx.doi.org/10.1117/1.jei.27.5.051216.

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Su, Shiliang, Zhenlan Jiang, Qi Zhang et Yuan Zhang. « Transformation of agricultural landscapes under rapid urbanization : A threat to sustainability in Hang-Jia-Hu region, China ». Applied Geography 31, n^o 2 (avril 2011) : 439–49. http://dx.doi.org/10.1016/j.apgeog.2010.10.008.

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Pan, Baochao, Bin Yao, Meiling Hou, Chao Liu, Xiuhai Su, Shufang Zhang, YiMeng Li et al. « Alleviation of Type 2 Diabetes Mellitus by Bai-Hu-Jia-Ren-Shen Decoction Through Modulating Serum Metabolism ». Journal of Biobased Materials and Bioenergy 18, n^o 5 (1 octobre 2024) : 902–10. http://dx.doi.org/10.1166/jbmb.2024.2423.

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BHRS has been employed in clinical settings for the treatment of T2DM. However, the precise underlying mechanism of its action remains elusive. In this study, we elucidate the specific therapeutic effects of BHRS on T2DM and subsequently investigate its mechanism using untargeted metabolomics techniques. Our research demonstrates that BHRS modulates the levels of 22 metabolites, including alpha-ketoglutaric acid, L-ascorbate, and L-ornithine, among others. These metabolites primarily participate in metabolic pathways involving nicotinate and nicotinamide, arachidonic acid, and inositol phosphate. In conclusion, our findings establish that BHRS effectively lowers blood glucose levels, mitigates inflammatory responses, and attenuates oxidative stress in T2DM rats. Additionally, BHRS influences the metabolic pathways of nicotinate and nicotinamide, arachidonic acid, and inositol phosphate in the serum of T2DM rats.

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Zhang, Meng, Huaqiang Du, Fangjie Mao, Guomo Zhou, Xuejian Li, Luofan Dong, Junlong Zheng et al. « Spatiotemporal Evolution of Urban Expansion Using Landsat Time Series Data and Assessment of Its Influences on Forests ». ISPRS International Journal of Geo-Information 9, n^o 2 (21 janvier 2020) : 64. http://dx.doi.org/10.3390/ijgi9020064.

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Analysis of urban land use dynamics is essential for assessing ecosystem functionalities and climate change impacts. The focus of this study is on monitoring the characteristics of urban expansion in Hang-Jia-Hu and evaluating its influences on forests by applying 30-m multispectral Landsat data and a machine learning algorithm. Firstly, remote sensed images were preprocessed with radiation calibration, atmospheric correction and topographic correction. Then, the C5.0 decision tree was used to establish classification trees and then applied to make land use maps. Finally, spatiotemporal changes were analyzed through dynamic degree and land use transfer matrix. In addition, average land use transfer probability matrix (ATPM) was utilized for the prediction of land use area in the next 20 years. The results show that: (1) C5.0 decision tree performed with precise accuracy in land use classification, with an average total accuracy and kappa coefficient of more than 90.04% and 0.87. (2) During the last 20 years, land use in Hang-Jia-Hu has changed extensively. Urban area expanded from 5.84% in 1995 to 21.32% in 2015, which has brought about enormous impacts on cultivated land, with 198,854 hectares becoming urban, followed by forests with 19,823 hectares. (3) Land use area prediction based on the ATPM revealed that urbanization will continue to expand at the expense of cultivated land, but the impact on the forests will be greater than the past two decades. Rationality of urban land structure distribution is important for economic and social development. Therefore, remotely sensed technology combined with machine learning algorithms is of great significance to the dynamic detection of resources in the process of urbanization.

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