Auswahl der wissenschaftlichen Literatur zum Thema „Pei xun zhong xin“

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.

BTK inhibitors induce ABC-DLBCL cell apoptosis by inhibiting CYLD phosphorylation Xin Xu1, Zhigang Zhu1, Feng Liu1 , Weijie Zhong1,Huabao Xiong2, Tiefeng Feng3, and Qingshan Li3 1Geriatrics Department, GuangZhou First People's Hospital, GuangDong, 510180, People's Republic of China. 2Precision Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, U.S.A. 3Hemotology Department, GuangZhou First People's Hospital, GuangDong, 510180, People's Republic of China. Activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL) is a common aggressive diffuse large B cell lymphoma (DLBCL). Even though CD20 antibody (Rituximab) combination therapy improved the total prognosis of DLBCL, there are still many relapsed and refractory ABC-DLBCL cases. The new treatment options are urgently needed. Pathogenesis of ABC-DLBCL is different from germinal center B cell-like diffuse large B cell lymphoma (GCB-DLBCL), which is related to activation of B cell antigen receptor(BCR) signaling. The Bruton tyrosine kinase(BTK) plays a central role in BCR signaling. Inhibition of BTK function will affect BCR signaling activity, which is involved in maintaining the malignant phenotype in B-cell lymphoma. Now in clinic, BTK inhibitors like Ibrutinib or Acalabrutinib are used extensively in chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL), mantle cell lymphoma(MCL) as first line therapy or second line therapy. But in DLBCL its role is unclear now.Some DLBCL clinic trials got the better PFS and OS in BTK inhibitor combination therapy group(combined with Rituximab or RCHOP) but some got the negative results. Whether BTK inhibitors can definitely improve ABC-DLBCL survival and the mechanism how BTK inhibitors inducing cell death are needed further investigations. CYLD (cylindromatosis) is a tumor suppressor, its activity is inhibited by phosphorylation, which is related to apoptosis regulation pathway NF-kB in many kinds of tumors.In this study, we found that CYLD to be constitutively phosphorylated in ABC-DLBCL cell line models (HBL-1 and OCI-Ly10) as well as primary samples from patients with non-GCB DLBCL. We subsequently examined the effect of BTK inhibitors Ibrutinib (PCI-32765) and Acalabrutinib (ACP-196) on CYLD phosphorylation. We found that BTK inhibitors Ibrutinib and Acalabrutinib both induced ABC-DLBCL apoptosis by down-regulating CYLD phosphorylation in vivo and in vitro, even in the Rituximab resistant ABC-DLBCL cell line.Combination of BTK inhibitors and Rituximab would enhance this effect. Knockdown of CYLD in ABC-DLBCL cells reduced the level of cell death induced by BTK inhibitors, which showed that this cell death induced by BTK inhibitors was CYLD dependent. Through this study, we conclude that BTK inhibitors induce CYLD inactivation by regulating CYLD phosphorylation is clinical beneficial in ABC-DLBCL therapy, especially the relapsed or refractory ABC-DLBCL cases after Rituximab therapy. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Most pancreatic cancers (PC) are resistant to immunotherapy and have a poor prognosis with advanced stage (III/IV, 80%). However, recent cancer vaccine trials have demonstrated that long-term host anti-cancer immunity can improve outcomes of patients (pts) with resectable PC (stage I/II, 20%), harboring high-quality neoantigens or select KRAS alterations. It has been proposed that immunogenic PC is a genetically defined subgroup (5-10%), enriched by hypermutated PC with DNA-damage repair deficiencies including homologous repair (HRD) and mismatch repair (dMMR). Until now, comprehensive molecular studies have been mostly conducted in resected PC. Methods: All tissues were collected following an Institutional Review Board (IRB 21-275) protocol at the Memorial Sloan Kettering. Whole-exome from N=78, exome-captured bulk RNA from N=61, and single-nucleus RNA from N=23 biopsy samples of advanced PC were analyzed. Gene set enrichment and digital cytometry, singe base substitution (SBS) mutational signature, neoantigen, and genomic instability score (GIS) for HRD and immunogenicity were evaluated. Demographics, treatment history, and overall survival (OS) for pts with PC with or without HRD and dMMR were abstracted from the medical record. Results: A total of N=77 WES samples included N=21 core HRD (cHRm: 3 BRCA1, 17 BRCA2, 1 both), N=7 non-core HRD (ncHRm: 3 ATM, 2 CHEK2, 1 RAD50, 1 BARD1), and N=7 dMMR, and N=42 No DDR. N=46 males. Median age 65 years. Median OS (95% confidence interval): 26 months (m) (17-NR) for cHRm, 90m (14-NR) for dMMR, 7.4m (6.8-NR) for ncHRm, and 19m (15-27) for No DDR group. N=49 (63%) pts received first-line platinum chemotherapy. Median tumor mutation burden (TMB-WES): 2 (IQR: 2-3), 35 (30-47), 1 (1-2), and 1, respectively for cHRm, dMMR, ncHRm, and No DDR. TMB-WES significantly higher for dMMR vs. No DDR (95%CI: 35 [30-47] vs 1 [1-2], p=0.001). GIS higher for cHRm vs. No DDR (95%CI: 31 [18-38) vs 14 [9-18], p=0.008). Only two BRCA1m tumors had significant SBS3. N=61 exome captured RNAseq analysis showed cHRm (N=17) vs. No DDR (N=39) had highly enriched gene programs for upregulated immune activity in adaptive immune response (odds ratio [OR]: 0.49, p=1.7e-10), humoral immune response, and T cell activation (OR: 0.44, p=2.7e-8). Digital cytometry showed higher infiltration of gamma delta T cells (p=0.039) and lower regulatory T cells (p=0.001) in cHRm vs. No DDR. 59,771 nuclei were profiled from 23 (16 baseline and 7 follow-ups [5 matched]) biopsy samples from pts with HRD [gBRCA1 (N=3), gBRCA2 (N=14)] and No DDR (N=6). HRD tumors vs. No DDR had higher level of infiltrating CD8+ cytotoxic T cells (p&lt;0.01). Tumors of long-term survivors (&gt; 18m) vs. short-term survivors had significantly lower-level infiltration of macrophages (p&lt;0.01) and Tregs (p=0.05). Conclusions: Our deep genomic and single-cell resolution transcriptomic analyses successfully profiled advanced PC enriched with DDR. HRD and dMMR render PC immunogenic. Further investigations for targeted immunotherapy is warranted. Citation Format: Wungki Park, Shigeaki Umeda, Catherine O'Connor, Haochen Zhang, Roshan Sharma, Allison Richards, Yingjie Zhu, Elias-Ramzey Karnoub, Xin Pei, Anna M. Varghese, Kevin Soares, Alejandro Jimenez Sanchez, Hulya Ozkan Sahin, Kenneth Yu, Vinod P. Balachandran, Joanne Chou, Fergus Keane, David Kelsen, Olca Basturk, Chaitanya Bandlamudi, Marinela Capanu, Tal Nawy, Michael Berger, Ronan Chaligne, Ghassan Abou-Alfa, Jorge S. Reis-Filho, Nadeem Riaz, Dana Pe'er, Christine A. Iacobuzio-Donahue, Eileen M. O'Reilly. Deep genomic and single cell molecular profiles define immunogenic pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B045.

Study of petrological and geochemical characteristics of mantle peridotite xenoliths in Pliocene alkaline basalt in Nghia Dan (West Nghe An) was carried out. Rock-forming clinopyroxenes, the major trace element containers, were separated from the xenoliths to analyze for major, trace element and Sr-Nd isotopic compositions. The data were interpreted for source geochemical characteristics and geodynamic processes of the lithospheric mantle beneath the region. The peridotite xenoliths being mostly spinel-lherzolites in composition, are residual entities having been produced following partial melting events of ultramafic rocks in the asthenosphere. They are depleted in trace element abundance and Sr-Nd isotopic composition. Some are even more depleted as compared to mid-ocean ridge mantle xenoliths. Modelled calculation based on trace element abundances and their corresponding solid/liquid distribution coefficients showed that the Nghia Dan mantle xenoliths may be produced of melting degrees from 8 to 12%. Applying various methods for two-pyroxene temperature- pressure estimates, the Nghia Dan mantle xenoliths show ranges of crystallization temperature and pressure, respectively, of 1010-1044°C and 13-14.2 kbar, roughly about 43km. A geotherm constructed for the mantle xenoliths showed a higher geothermal gradient as compared to that of in the western Highlands (Vietnam) and a conductive model, implying a thermal perturbation under the region. The calculated Sm-Nd model ages for the clinopyroxenes yielded 127 and 122 Ma. 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A doença mão-pé-boca é uma infecção viral, normalmente benigna que afeta comumente crianças até 10 anos, causada pelos enterovírus humano. O propósito deste estudo foi revisar os aspectos da doença que se faz presente nos dias atuais abordando a etiologia, epidemiologia, surtos, sintomatologia e comorbidades, diagnóstico, prevenção e tratamento. Foram selecionadas publicações em periódicos referenciados nas fontes de dados do Google Acadêmico, Pubmed e Periódicos Capes com as palavras chaves relacionadas ao tema desse trabalho como doença mão-pé-boca e crianças, sendo selecionados artigos produzidos até 2017. Apesar de diagnóstico clínico aparentemente simples, a doença pode ser confundida com outras enfermidades por suas características semelhantes, que podem induzir o colega odontólogo ao equívoco de diagnóstico.Descritores: Doença de Mão, Pé e Boca; Diagnóstico, Odontopediatria.ReferênciasSarkar PK, Sarker NK, Tayab A. Hand, foot and mouth disease (hfmd):an update. 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Vitamin E (VitE) is a potent antioxidant and contributes as an apoptosis inhibitor by preventing apoptotic death by suppressing cell membrane scrambling with phosphatidylserine translocation and caspase activites. Fas ligand (FasL) is well known to induce cell apoptosis. Activation of phosphoinositide 3 kinase (PI3K) signalling is stimulated by VitE. The present study addressed the effects of VitE on survival of mouse dendritic cells (DCs) and signalling molecules underlying. To this end, mouse bone marrow cells were isolated and cultured to attain bone marrow-derived DCs (BMDCs). The cells were treated with FasL in the presence or absence of VitE. Western blotting and FACS analysis were performed to determine expression of signalling molecules and their involvement in DC apoptosis. As a result, FasL treatment resulted in activation of caspase 8 and an increased number of Annexin V+ cells, the effects were significantly suppressed when VitE was present in the cell culture. Importantly, the anti-apoptotic effects of VitE were abolished by using pharmacological inhibition of PI3K signaling with LY294002. Our results showed that VitE inhibited FasL-mediated DC apoptosis through PI3K signalling, the effect is expected to facilitate the survival of DCs and promote the immune response against pathogens. Keywords Caspase, Dendritic cell; Fas ligand; PI3K and vitamin E. References [1] J. Banchereau, R.M. Steinman, Dendritic cells and the control of immunity, Nature 392 (1998) 245-52.[2] E. Ingulli, A. Mondino, A. Khoruts, M.K. Jenkins, In vivo detection of dendritic cell antigen presentation to CD4(+) T cells, J Exp Med 185 (1997) 2133-41.[3] C. Yang, H.Z. Liu, Z.X. Fu, PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via Fas/FasL and caspase-8, Cell Biol Int 36 (2012) 289-96.[4] Q.G. Yan, J.G. Shi, F. Zhang, Q.T. Zhao, X.W. Pang, R. Chen, P.Z. Hu, Q.L. Li, Z. Wang, G.S. 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