Journal articles on the topic 'Tong xin zhong xue'

Abstract 4-1BB (CD137) is a key costimulatory immunoreceptor and a promising therapeutic target in cancer. CEACAM5 (CEA) is a well-established tumor associated antigen overexpressed in many cancers, including colorectal, gastric, lung, pancreatic cancer, liver, breast and thyroid cancers. BGB-B167 is a novel immunoglobulin G (IgG)-based bispecific antibody targeting 4-1BB and CEA and is under clinical development for the treatment of advanced or metastatic solid tumors in humans. BGB-B167 binds to its target proteins with high specificity and affinity. Potent and CEA-dependent functional activities were demonstrated using peripheral blood mononuclear cell (PBMC)-based immune cell activation and cytotoxicity assays. In humanized 4-1BB knock-in mice bearing human CEA-expressing tumors, BGB-B167 exhibited potent, dose-associated single-agent efficacy as well as synergistic antitumor activity in combination with anti-PD-1 antibody. BGB-B167 was well tolerated in 1-month repeat-dose toxicology study in cynomolgus monkeys. Here, we describe the characterization of BGB-B167 with regard to preclinical proof-of-concept and basic drug-like properties. The combined dataset provides an overview on the design, mode of action, preclinical pharmacology and safety profile of BGB-B167. Citation Format: Zhuo Li, Liang Qu, Xin Chen, Liu Xue, Jie Li, Qi Liu, Jian Sun, Hanzi Sun, Yun Chen, Yuanyuan Xie, Wanyi Wang, Lin Zhu, Penghao Wang, Xiaosui Zhou, Hongjia Hou, Jie Chen, Xinyi Liu, Yilu Zhang, Ning Liu, Xinyi Liang, Shuo Zhang, Xiaoyan Tang, Jing Song, Tong Zhang, Xiaomin Song, Xuesong Liu, Kang Li, Chichi Huang. BGB-B167, a first-in-class 4-1BB/CEACAM5 bispecific antibody, exhibits potent in vitro and < for vivo antitumor activity and < for superior safety profile in preclinical models [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 2371.

Abstract Background: The standard approach of using one-size-fits-all endocrine therapy for hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancers has faced significant challenges due to variations in treatment response among individuals. Consequently, there is still an urgent need to understand the molecular biology of HR+/HER2- breast cancer and explore precision treatment strategy. Methods: We established a multiomics cohort (n = 351), multicenter real-world clinical cohorts (n = 643), a prospective clinical cohort (MULAN trial), and a drug-testing platform containing patient-derived organoids (n = 126) and patient-derived tumor fragments (n = 49) of HR+/HER2- breast cancers. Integrating "bench" and “bedside” data, we conducted comprehensive preclinical and clinical translational research on precision strategies in HR+/HER2- breast cancer. Results: We implemented a comprehensive classification system for HR+/HER2- breast cancer, comprising four distinct subtypes. We further demonstrated the efficacy and mechanisms of subtyping-directed precision treatment strategies through clinical cohort studies, omics analysis and functional assays: endocrine therapy alone for the canonical luminal subtype; the addition of CDK4/6 inhibitor and PARP inhibitor for the proliferative subtype; the immunotherapy for the immunogenic subtype; and tyrosine kinase inhibitors for the receptor tyrosine kinase-driven subtype. Using clinically applicable subtyping methods, we validated that matched precision treatment strategies outperformed unmatched approaches in a real-world cohort, almost doubling the median progression-free survival time for patients with refractory advanced HR+/HER2- breast cancer (9.83 months [95% CI, 5.74-13.93] vs 4.77 months [95% CI, 3.35-6.18]; hazard ratio 0.64 [95% CI, 0.41-0.99]). Importantly, the first-stage analysis of the MULAN phase II umbrella clinical trial (NCT04355858) verified the higher objective response rate (88.9%, 95%CI: 51.7%-99.7%) of the subtyping-directed precision treatment. Conclusion: Our study emphasizes the superiority of subtyping-directed precision treatment strategies for HR+/HER2- breast cancer, refines traditional “one-size-fits-all” therapy, and facilitates the translation of precision treatment strategies from bench to bedside. Overall study design Part 1 Subtype Molecular Characteristics: Molecular features of the four subtypes of HR+/HER2- breast cancer. Part 2 Multidimensional Efficacy Validation: Integrating data from a multiomics cohort, real-world study, drug testing platform and prospective clinical research to validate the subtyping-directed precision treatment strategy in HR+/HER2- breast cancer. Part 3 Subtyping-directed Precision Treatment Strategy: Integrating clinical cohort studies, omics analysis and functional assays revealed the heterogeneity of treatment response in HR+/HER2- breast cancer, and proposed a subtyping-directed precision treatment strategy. CIN, chromosomal instability; RTK, receptor tyrosine kinase; CNA, copy-number alteration; ER, estrogen receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2. Citation Format: Xiu-Zhi Zhu, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, Ming-Liang Jin, Ya-Xin Zhao, Yi-Fan Xie, Ruo-Xi Wang, Zhong-Hua Wang, Lei Fan, Yi-Zhou Jiang, Zhi-Ming Shao. Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-07.

Background: Acute ischemic stroke (AIS) is characterized by high morbidity, disability, mortality, recurrence, and economic burden. Clinical trials have demonstrated that the clinical efficacy of combining oral Chinese patent medicines (CPMs) with chemical drugs (CDs) is better than that of CDs alone. In this study, we performed a network meta-analysis (NMA) of RCTs to assess the efficacy of different CPMs in combination with CDs in the treatment of AIS. Methods: Search 6 databases from the beginning to January 10, 2023. The Cochrane Risk of Bias tool assessed the methodological quality of the included studies. The NMA was then performed using the STATA 13.0 program. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the studied treatments, and cluster analysis was used to compare the effects of CPMs between 2 different outcomes. Results: A total of 94 eligible RCTs, involving 9581 participants, were included in this analysis. Nine CPMs, including Nao-mai-li granule (NML), Nao-mai-tai granule (NMT), Qi-long granule (QL), Long-sheng-zhi capsule (LSZ), Nao-xin-tong capsule (NXT), Nao-xue-shu oral liquid (NXS), Tong-xin-luo capsule (TXL), Xiao-shuan-chang-rong capsule (XSCR), and Xue-shuan-xin-mai-ning capsule (XSXMN) were included. Regarding the clinical effective rate, all types of CPMs + CDs treatments were significantly better than CDs treatments alone, with significant differences among the 9 selected CPMs. Compared with CDs, results showed that NXS + CDs performed best in improving clinical effective rate [OR = 4.73; 95% CI: 1.26–17.78; (SUCRA: 76.1%)]. TXL + CDs showed the most effective effect in alleviating National Institutes of Health Stroke Scale (NIHSS) [MD = −3.84; 95% CI: −5.23, −2.45; (SUCRA: 81.6%)]; NXT + CDs were most effective in improving Barthel index [MD = 13.05; 95% CI: 3.98–22.12; (SUCRA: 63.5%)]. Combined with other outcome indicators and the results of cluster analysis, NXS + CDs may assist in the potential optimal treatment regimen for AIS. Conclusion: In conclusion, CPMs were found to be beneficial as adjuvant therapy in patients with AIS. Taking into account the clinical effective rate and other outcomes, NXS + CDs may be the most effective option to improve the condition of AIS patients.

In this paper, I have examined whether the three methods elucidated by Han Won-jin in the preface of Jujaeonrondongeego(朱子言論同異攷)—namely, the verification of the time of writings, mutual comparison of relevant remarks, and judgment based on theoretical consistency—successfully achieve the purpose of this book, which aims to confirm the final conclusion of Zhu Xi(朱熹), especially focused on the part of dealing with Ren Xin Dao Xin (人心道心) of Shujing(書經). Although it may sound somewhat conventional, it seems inevitable to acknowledge that this book also has both achievements and limitations. In ‘Ren Xin Dao Xin(人心道心)’, the distinction between the early theory and the final conclusion of Zhu Xi, the rejection of ｢Answer to Cai Ji-tong(答蔡季通)｣ in favor of ｢Answer to Zheng Zi-shang(答鄭子上)｣, and the demonstration that the ‘Xing Qi(形氣)’ mentioned in the preface of Zhong Yong Zhang Ju(中庸章句) refers to the body, based on ｢Answer to Chen An-qing(答陳安卿)｣ and others, undoubtedly represent the achievements of this book. On the other hand, it is also true that there were certain limitations in establishing Zhu Xi's final conclusion based on theoretical consistency. Han Won-jin seems to have been aware of these limitations himself. And he appears helpless when confronted with remarks expressing the early theory despite his later writings. Moreover, he might not have been able to effectively criticize those who used this as the basis for their arguments. In this regard, it is difficult to say that the purpose of this book, which was to distinguish between the early theory and the final conclusion and to demonstrate that his own and his school's doctrines are consistent with Zhu Xi's final conclusion, has also been successfully realized. As Han Won-jin mentioned, the decisions regarding what to accept and what to reject from this book will ultimately be left to the reader's judgment.

Abstract Lenvatinib is used as the first-line therapy for advanced hepatocellular carcinoma (HCC) patients. However, poor response and compromised therapeutic effect with prolonged treatment are frequently observed in HCC patients. To elucidate the underlying mechanisms, lenvatinib responsive and non-responsive stages were modeled in liver tumor-bearing immunocompetent mice which were divided into lenvatinib and vehicle control treatment groups. Tumor tissues after short and prolonged lenvatinib treatment were harvested for single-cell RNA sequencing. Results from single-cell RNA sequencing revealed heterogenous tumor cell sub-populations associated with tumor differentiation and identified an upregulated expression of class IIa histone acetylase HDAC9 in lenvatinib-treated tumor at the non-responsive stage. Upregulation of HDAC9 was similarly observed in lenvatinib-resistant human patient-derived xenograft (PDX). Functional studies suggested that suppressing HDAC9 could re-sensitize lenvatinib response in both in vitro and in vivo models. In sum, we identified a potential regulator of lenvatinib treatment response in HCC. Citation Format: Yunong Xie, Minghe Zhang, Yan Liu, Linglin Liu, Alfred Sze-Lok Cheng, Stephanie Ma, Man Tong. HDAC9 as a potential regulator of lenvatinib resistance in hepatocellular 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 4667.

Background: Exosomes have emerged as pivotal mediators in modulating physiological and pathological processes implicated in osteoporosis (OP) through their distinctive mode of intracellular communication. The use of exosomes has evoked considerable interest, catalyzing a surge in research endeavors on a global scale. This study endeavors to scrutinize contemporary landscapes and burgeoning trends in this realm. Methods: The Web of Science Core Collection was used to retrieve publications on exosomes therapy for OP within the time frame of January 1, 2004 to December 31, 2023. The bibliometric methodology was applied to study and index the collected data. VOSviewer and citespace software were used to conduct visualization, co-authorship, co-occurrence, and publication trend analyses of exosome therapy in OP. Results: A total of 610 publications (443 articles and 167 reviews) from 51 countries and 911 institutions were included in this study. Shanghai Jiao Tong University, Central South University, Sichuan University, and Zhejiang University are leading research institutions in this field. Stem Cell Research Therapy published the highest number of articles and has emerged as the most cited journal. Of the 4077 scholars who participated in the study, Xie, Hui, Zhang, Yan, Tan, and Yi-Juan had the largest number of articles. Furthermore, according to the cluster analysis of external keywords, future research hotspots can be categorized into 3 directions: research status of exosomes for the treatment of OP, treatment of OP through exosome-regulated signaling pathways, and exosomes as targeted drug delivery systems. Conclusion: This study suggests that the number of future publications on exosome therapy for OP will increase, with a focus on fundamental investigations into drug-loading capacities and molecular mechanisms. In summary, this study presents the first systematic bibliometric analysis of exosome therapy publications in OP, providing an objective and comprehensive overview of the field and a valuable reference for researchers in this domain.

Hydrogen gas is a type of alternative fuel for transportation that can serve a number of other potential needs. Water electrolysis is one way to get hydrogen gas. This study aims to determine the results of water electrolysis with three catalysts and mixed metal electrodes which are then applied to generator motor engines. The research method used was an experimental method with variations in electrolysis using KOH and NaOH base catalysts, H2SO4 acid catalysts, and stainless steel 316 electrodes. The best results for H2 gas production in this study were obtained with a 2M H2SO4 catalyst with a gas yield of 244.9mL H2 gas, while The lowest yield in this study was the 1M concentration of 1M NaOH catalyst of 12.5mL. The best results for H2 gas production were varied with pertalite fuel and then tested with a generator engine. Testing the generator motor engine is measured arm length and mass with a machine dynamometer. After testing, the data is obtained which is then analyzed to obtain the value of torque (Nm) and electric motor power (kW), and driving motor power (HP). The maximum energy produced pertalite + H2 gas has increased by 2.27kW on the electric motor and power of 4.13HP on the driving motor, while for pertalite fuel alone the power generated is 1.44kW on the electric motor and power of 2.62HP on the driving motor.[1] S. A. Grigoriev, V. N. Fateev, D. G. Bessarabov, and P. Millet, “Current status, research trends, and challenges in water electrolysis science and technology,” Int. J. Hydrogen Energy, vol. 45, no. 49, pp. 26036–26058, 2020, doi: 10.1016/j.ijhydene.2020.03.109.[2] Y. Song, X. Zhang, K. Xie, G. Wang, and X. Bao, “High-Temperature CO2 Electrolysis in Solid Oxide Electrolysis Cells: Developments, Challenges, and Prospects,” Adv. Mater., vol. 31, no. 50, pp. 1–18, 2019, doi: 10.1002/adma.201902033.[3] A. Nechache and S. Hody, “Alternative and innovative solid oxide electrolysis cell materials: A short review,” Renew. Sustain. Energy Rev., vol. 149, 2021, doi: 10.1016/j.rser.2021.111322.[4] O. Schmidt, A. Gambhir, I. Staffell, A. Hawkes, J. Nelson, and S. Few, “Future cost and performance of water electrolysis: An expert elicitation study,” Int. J. Hydrogen Energy, vol. 42, no. 52, pp. 30470–30492, 2017, doi: 10.1016/j.ijhydene.2017.10.045.[5] S. Wang, A. Lu, and C. J. Zhong, “Hydrogen production from water electrolysis: role of catalysts,” Nano Converg., vol. 8, no. 1, 2021, doi: 10.1186/s40580-021-00254-x.[6] N. A. Burton, R. V. Padilla, A. Rose, and H. Habibullah, “Increasing the efficiency of hydrogen production from solar powered water electrolysis,” Renew. Sustain. Energy Rev., vol. 135, no. July 2020, p. 110255, 2021, doi: 10.1016/j.rser.2020.110255.[7] J. Brauns and T. Turek, “Alkaline water electrolysis powered by renewable energy: A review,” Processes, vol. 8, no. 2, 2020, doi: 10.3390/pr8020248.[8] S. Anwar, F. Khan, Y. Zhang, and A. Djire, “Recent development in electrocatalysts for hydrogen production through water electrolysis,” Int. J. Hydrogen Energy, vol. 46, no. 63, pp. 32284–32317, 2021, doi: 10.1016/j.ijhydene.2021.06.191.[9] W. Tong et al., “Electrolysis of low-grade and saline surface water,” Nat. Energy, vol. 5, no. 5, pp. 367–377, 2020, doi: 10.1038/s41560-020-0550-8.[10] T. Nguyen, Z. Abdin, T. Holm, and W. Mérida, “Grid-connected hydrogen production via large-scale water electrolysis,” Energy Convers. Manag., vol. 200, no. September, p. 112108, 2019, doi: 10.1016/j.enconman.2019.112108.[11] A. Buttler and H. Spliethoff, “Current status of water electrolysis for energy storage, grid balancing and sector coupling via power-to-gas and power-to-liquids: A review,” Renew. Sustain. Energy Rev., vol. 82, no. February, pp. 2440–2454, 2018, doi: 10.1016/j.rser.2017.09.003.[12] I. V. Pushkareva, A. S. Pushkarev, S. A. Grigoriev, P. Modisha, and D. G. Bessarabov, “Comparative study of anion exchange membranes for low-cost water electrolysis,” Int. J. Hydrogen Energy, vol. 45, no. 49, pp. 26070–26079, 2020, doi: 10.1016/j.ijhydene.2019.11.011.[13] L. Peng and Z. Wei, “Catalyst Engineering for Electrochemical Energy Conversion from Water to Water: Water Electrolysis and the Hydrogen Fuel Cell,” Engineering, vol. 6, no. 6, pp. 653–679, 2020, doi: 10.1016/j.eng.2019.07.028.[14] S. Klemenz, A. Stegmüller, S. Yoon, C. Felser, H. Tüysüz, and A. Weidenkaff, “Holistic View on Materials Development: Water Electrolysis as a Case Study,” Angew. Chemie - Int. Ed., vol. 60, no. 37, pp. 20094–20100, 2021, doi: 10.1002/anie.202105324.[15] H. K. Ju, S. Badwal, and S. Giddey, “A comprehensive review of carbon and hydrocarbon assisted water electrolysis for hydrogen production,” Appl. Energy, vol. 231, no. May, pp. 502–533, 2018, doi: 10.1016/j.apenergy.2018.09.125.[16] F. ezzahra Chakik, M. Kaddami, and M. Mikou, “Effect of operating parameters on hydrogen production by electrolysis of water,” Int. J. Hydrogen Energy, vol. 42, no. 40, pp. 25550–25557, 2017, doi: 10.1016/j.ijhydene.2017.07.015.[17] F. Gutiérrez-Martín, L. Amodio, and M. Pagano, “Hydrogen production by water electrolysis and off-grid solar PV,” Int. J. Hydrogen Energy, vol. 46, no. 57, pp. 29038–29048, 2021, doi: 10.1016/j.ijhydene.2020.09.098.

Abstract Introduction: MEK inhibition combined with PD-1 axis inhibition may achieve a greater clinical response than either inhibitor alone due to increased T-cell infiltration of tumours. We combined binimetinib with pembrolizumab in patients with stage IV advanced non-small cell lung cancer (NSCLC) and PD-L1 tumor proportion score>=50%. Methods: A 3 + 3 dose escalation design was used. Binimetinib at a dose level 1 (DL1; 45 mg) or dose level -1 (DL-1; 30 mg) twice daily orally continuously was given with pembrolizumab 200 mg IV q 21 days. The primary objective was to define the recommended phase II dose (RP2D) of the combination. Secondary outcomes included safety of the combination and response (RECIST 1.1) with a planned Phase Ib expansion in patients with RAS/RAF/MEK dysregulated tumours via next generation gene sequencing. Genomic markers are being explored in tissue and plasma. Results: Eleven patients (3 DL1, 8 DL-1) were enrolled with the following mutations: 7 with KRAS (3 G12C, 2 G12D, 1 G12V, 1 G12A), 2 BRAF (1 G409A, 1 V600E) and 1 STK11 which acts as a tumor suppressor gene encoding for LKB1. Two of 3 patients at DL1 experienced dose limiting toxicity (DLT) including grade 3 elevated amylase, grade 3 diarrhea, grade 4 elevated lipase and severe grade 2 rash requiring dose reduction. Of 8 patients treated at DL-1, 1 progressed in cycle 1, another was noncompliant with treatment. Of the remaining 6 patients, 1 experienced DLT with grade 3 rash with inability to administer binimetinib for >75% of cycle 1. The most common toxicities across all cycles (n=11 patients) were: rash (82%), diarrhea (36%) and pruritis (36%). Nine patients were evaluated for response with partial response in 3 (33%), stable disease in 4 (44%) and progressive disease in 2 (22%). All 3 responding patients had RAS or RAF alterations (KRASG12C, KRASG12V, BRAFV600E) while the patient with STK11 mutant disease had early disease progression. Conclusion: The RP2D of the combination in patients with advanced NSCLC is binimetinib 30 mg BID plus pembrolizumab 200 mg IV q21 days. Updated data from cohort expansion including response and molecular correlates of treatment response and resistance will be presented. Citation Format: Christopher F. Theriau, Jamie Feng, Lawson Eng, Frances A. Shepherd, Mary DeCarolis, Vivian Glenns, Swati Kulkarni, Rachel VanderMeer, Urszula Zurawska-Fortin, Desiree Hao, Lisa Le, Isabel Wozniczka, Aida Al-Kindy, Danny Xie, Tong Zhang, Vasanth Subramanian, Tracy Stockley, Penelope A. Bradbury, Geoffrey Liu, Natasha B. Leighl. A phase I study of binimetinib, a MEK inhibitor, in combination with pembrolizumab in patients with advanced non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT206.

Методом цитратной золь-гель технологии получен новый двойной борат рубидия–гольмия состава Rb3HoB6O12. Соединение кристаллизуется в тригональной сингонии (пр. гр. R32, a = 13.4038(7), с = 30.315(2) Å, V = 4716.76 Å3) и плавится инконгруэнтно при 818 °С. Попытки получить в однофазном состоянии Rb3HoB6O12 методом твердофазных реакций не привели к положительному результату REFERENCES Wu C., Yang G., Humphrey M.G., Zhang C. Recent advances in ultraviolet and deep-ultraviolet secondorder nonlinear optical crystals // Chem. Rev., 2018, v. 375, pp. 1–30. https://doi.org/10.1016/j.ccr.2018.02.017 Bubnova R., Volkov S., Albert B., Filatov S. Borates – crystal structures of prospective nonlinear optical materials: high anisotropy of the thermal expansion caused by anharmonic atomic vibrations // Crystals, 2017, v. 7, pp.1–32. DOI: 10.3390/cryst7030093 Becker P. Borate materials in nonlinear optics // Mater., 1998, v. 10, pp. 979–992. https://doi.org/10.1002/(SICI)1521-4095(199809)10:13<979::AIDADMA979>3.0.CO;2-N Chen C., Li R. The anionic group theory of the nonlinear optical effect and its applications in the development of new high-quality NLO crystals in the borate series // Rev. Phys. Chem., 1988, v. 8, pp. 65–91. https://doi.org/10.1080/01442358909353223 Chen C., Wu Y., Jiang A., Wu B., You G., Li R., Lin S. New nonlinear-optical crystal: LiB3O5 // Opt. Soc. Am. B: Opt. Phys., 1989, v. 6, pp. 616–621. https://doi.org/10.1364/JOSAB.6.000616 French R. H., Ling J. W., Ohuchi F. S., Chen C. T. Electronic structure of b-BaB2O4 and LiB3O5 nonlinear optical crystals // Rev. B: Condens. Matter, 1991, v. 44, pp. 8496–8502. https://doi.org/10.1103/Phys-RevB.44.8496 Yusuke Mori, Ikio Kuroda, Satoshi Nakajima, Takamoto Sasaki, Sadao Nakai. New nonlinear optical crystal: Cesium lithium borate // Phys. Lett., 1995, v. 67, pp. 1818–1820. https://doi.org/10.1063/1.115413 Haohai Yu, Zhongben Pan, Huaijin Zhang, Jiyang Wang. Recent advances in self-frequency-doubling crystals // Materiomics, 2016, v. 2, pp. 55–65. https://doi.org/10.1016/j.jmat.2015.12.001 Bajor A.L., Kisielewski J., Klos A., Kopzyński K., Lukasiewicz T., Mierczyk J., Mlyńczak J. Assessment of gadolinium calcium oxoborate (GdCOB) for laser applications // Opto-electronics Review, 2011, v. 19, pp. 439–448. https://doi.org/10.2478/s11772-011-0042-2 Dan Zhao, Cong-Kui Nie, Ye Tian, Bao-Zhong Liu, Yun-Chang Fan, Ji Zhao. A new luminescent host material K3GdB6O12: synthesis, crystal structure and luminescent properties activated by Sm3+ // Kristallogr., 2018, v. 233, pp. 411–419. https://doi.org/10.1515/zkri-2017-2101 Dan Zhao, Fa-Xue Ma, Rui-Juan Zhang, Wei Wei, Juan Yang, Ying-Jie Li. A new rare-earth borate K3LuB6O12: crystal and electronic structure, and luminescent properties activated by Eu3+ // Mater Sci: Mater Electron., 2017, pp. 1–9. https://doi.org/10.1007/s10854-016-5501-6 Atuchin V. V., Subanakov A. K., Aleksandrovsky A. S., Bazarov B. G., Bazarova J. G., Dorzhieva S. G., Gavrilova T. A., Krylov A. S., Molokeev M. S., Oreshonkov A. S., Pugachev A. M., Tushinova Yu. L., Yelisseyev A. P. Exploration of structural, thermal, vibrational and spectroscopic properties of new noncentrosymmetric double borate Rb3NdB6O12 // Powder Technol., 2017, v. 28, pp. 1309–1315. https://doi.org/10.1016/j.apt.2017.02.019 Atuchin V. V., Subanakov A. K., Aleksandrovsky A. S., Bazarov B. G., Bazarova J. G., Gavrilova T. A., Krylov A. S., Molokeev M. S., Oreshonkov A. S., Stefanovich S. Yu. Structural and spectroscopic properties of new noncentrosymmetric selfactivated borate Rb3EuB6O12 with B5O10 units // Des., 2018, v. 140, pp. 488–494. https://doi.org/10.1016/j.matdes.2017.12.004 Sangen Zhao, Guochun Zhang, Jiyong Yao, Yicheng Wu. K3YB6O12: A new nonlinear optical crystal with a short UV cutoff edge // Res. Bull., 2012, v. 47, pp. 3810–3813. https://doi.org/10.1016/j.materresbull.2012.05.062 Miriding Mutailipu, Zhiqing Xie, Xin Su, Min Zhang, Ying Wang, Zhihua Yang, Muhammad Ramzan Saeed Ashraf Janjua, Shilie Pan. Chemical cosubstitution- oriented design of rare-earth borates as potential ultraviolet nonlinear optical materials // Am. Chem. Soc., 2017, v. 139, pp. 18397–18405. https://doi.org/10.1021/jacs.7b11263 Li Yang, Yingpeng Wan, Honggen Weng, Yanlin Huang, Cuili Chen, Hyo Jin Seo. Luminescence and color center distributions in K3YB6O12 : Ce3+ phosphor // Phys. D: Appl. Phys., 2016, v. 49 (325303), pp. 1–12. https://doi.org/10.1088/0022-3727/49/32/325303

Abstract Background: Breast cancer is one of the most common malignant tumors in women worldwide. In China, the incidence of breast cancer has been steadily increasing. Approximately 30% of human breast cancers exhibit human epidermal growth factor receptor 2 (HER2) positivity, which is closely associated with tumor aggressiveness, high recurrence rate and high mortality. This study aimed to evaluate the efficacy, safety, and immunogenicity of TQ-B211 (a trastuzumab biosimilar) compared to the reference trastuzumab in combination with docetaxel as first-line treatment for patients with HER2-positive metastatic breast cancer. Methods: This randomized, multicenter, double-blind phase III equivalence study enrolled HER2+ metastatic breast cancer patients aged 18-75, ECOG PS ≤1, no prior systemic chemotherapy, biologic, or targeted therapy for recurrent or metastatic disease, and at least one measurable lesion (RECIST 1.1). The patients were randomly assigned to two groups: the experimental group received TQ-B211 (8 mg/kg iv on day 1, cycle 1, followed by 6 mg/kg q3w for cycles 2-8) in combination with docetaxel (75 mg/m2 on day 2, cycle1, followed by 75 mg/m2 on day 1 for cycles 2-8), while the control group received Herceptin® in combination with docetaxel. For subjects who completed 8 cycles of treatment without disease progression and demonstrated tolerability, they were subsequently administered TQ-B211 as monotherapy until disease progression or unsuitable for further treatment. The primary efficacy endpoint was ORR up to week 24 (ORR24w). Equivalence was declared if the 90% confidence interval (CI) of relative ratio (RR) value was within the range of 0.8 to 1.25. Secondary efficacy endpoints included duration of response (DoR); progression-free survival (PFS); disease control rate (DCR); overall survival (OS), safety and immunogenicity. Results: Between December 6, 2018 and July 31, 2021, a total of 386 patients (pts) were enrolled (192 pts in the TQ-B211 group and 194 pts in the Herceptin® group). In the intention-to-treat (ITT) population, the ORR24w of the TQ-B211 group was 67.19% (95% CI: 60.55, 73.83), while the ORR24w of the Herceptin® group was 65.98% (95% CI: 59.31, 72.65). The RR of the confirmed ORR24w between the two groups was 1.02 (90%CI, 0.90, 1.15), which fell entirely in the predefined equivalence margins (0.8, 1.25), indicating comparable efficacy of the two drugs. In the ITT population, the DCR of the TQ-B211 group and the Herceptin® group were 83.85% (78.65, 89.06) and 78.35% (72.56, 84.15) respectively, with no statistically significant difference between the two groups (P=0.1940). By the data cutoff date of October 31, 2021, the median PFS was not statistically different (P=0.6834); the median OS was not reached in both groups (P=0.9246). Additionally, the data results of the per-protocol (PP) population were similar to those of the ITT population. In total, similar rates of treatment-related grade ≥3 adverse events (41.05% vs. 46.39%) occurred in the TQ-B211 and Herceptin® groups, respectively. The incidence and magnitude of immunogenicity were low in both of the two groups (ADA: 0.53% vs. 0%, Nab: both negative). Conclusion: Equivalence for efficacy was demonstrated between TQ-B211 and Herceptin® on the basis of ORR24w. Safety and immunogenicity were comparable. Citation Format: Xichun Hu, Qingyuan Zhang, Shusen Wang, Tao Sun, Xiaohua Zeng, Weimin Xie, Zhongsheng Tong, Hui Cao, Huihua Xiong, Xiuwen Wang, Jin Yang, Shuqun Zhang, Ying Wang, Chunhong Hu, Kaijian Lei, Binlin Ma, Wei Liu, Zhiyong Yu, PeiJian Peng, Hongwei Yang, Zhijun Yuan, Xiaojia Wang, Xujuan Wang, Hong Wang, Yongqian Shu, Nanlin Li, Wenbin Yue, Jingfen Wang, Daqing Wang, Zhiguo Luo, Junyang Mo, Yarong Li, Lili Sheng. Efficacy, Safety, and Immunogenicity of TQ-B211 (a Trastuzumab Biosimilar) Plus Docetaxel versus Herceptin® Plus Docetaxel for HER2-positive Metastatic Breast Cancer: a Double-blind, Randomised, Multicenter, Phase 3 Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-03.

The achievement of children's quality of life is undoubtedly linked to the development of positive habits that will continue to be practiced in future lives. This can be done by developing awareness and behavior of a balanced clean and healthy lifestyle. The purpose of this study was to determine the increase in the PHBS ability of children. Various efforts have been made so that children with intellectual disabilities can maintain their cleanliness. The efforts made by the teacher are still not maximal so that the delivery of information about PHBS must be completed by another method, namely demonstration. This research was conducted at SDLB 127710 Pematangsiantar5 with an action research method that refers to the Kurt Lewin model. Data collection techniques used purposive sampling and data analysis with the Wilcoxon test. The results showed an increase in understanding of the PHBS of children with intellectual disabilities able to learn SDLB 127710 Pematangsiantar through the demonstration method. This is evidenced by the increase in the score, where the initial assessment was obtained (59%), while in the first cycle, the average score was good (69.9%). In short, the understanding of children with intellectual disabilities being able to learn about PHBS is increased by using the demonstration method. Keywords: Intellectual Disability Children, PHBS program, Demonstration methods References Agarwal, R. (2017). Importancia de la atención primaria de salud en la sociedad. International Journal of Health Sciences, 1(1), 5–9. Aiello, A. E., Coulborn, R. M., Perez, V., & Larson, E. L. (2008). Effect of hand hygiene on infectious disease risk in the community setting: A meta-analysis. American Journal of Public Health, 98(8), 1372–1381. https://doi.org/10.2105/AJPH.2007.124610 Arip, M. pdfo., & Emilyani, D. (2018). Strategy to improve knowledge, attitude, and skill toward clean and healthy life behaviour. International Journal of Social Sciences and Humanities, 2(3), 125–135. https://doi.org/10.29332/ijssh.v2n3.222 Basheer, A., Hugerat, M., Kortam, N., & Hofstein, A. (2017). The effectiveness of teachers’ use of demonstrations for enhancing students’ understanding of and attitudes to learning the oxidation-reduction concept. Eurasia Journal of Mathematics, Science and Technology Education, 13(3), 555–570. https://doi.org/10.12973/eurasia.2017.00632a Bloomfield, S. F., Aiello, A. E., Cookson, B., O’Boyle, C., & Larson, E. L. (2007). The effectiveness of hand hygiene procedures in reducing the risks of infections in home and community settings including handwashing and alcohol-based hand sanitizers. American Journal of Infection Control, 35(10 SUPPL. 1). https://doi.org/10.1016/j.ajic.2007.07.001 Cavanaugh, L. K. (n.d.). Intellectual Disabilities (D. L. Porretta (Ed.); 6 th). Human Kinetics. Chang, Y. J., Lee, M. Y., Chou, L. Der, Chen, S. F., & Chen, Y. C. (2011). A Mobile Wetness Detection System Enabling Teachers to Toilet Train Children with Intellectual Disabilities in a Public School Setting. Journal of Developmental and Physical Disabilities, 23(6), 527–533. https://doi.org/10.1007/s10882-011-9243-3 Cummings, S., Bridgman, T., & Brown, K. G. (2016). Unfreezing change as three steps: Rethinking Kurt Lewin’s legacy for change management. Human Relations, 69(1), 33–60. https://doi.org/10.1177/0018726715577707 Dirjen P2P Kemkes RI. (2019). Rencana Aksi Program Pencegahan Dan Pengendalian Penyakit 2015-2019 ( Revisi I - 2018 ). Rencana AKSI Program P2P 2015-2019, 2019, 86. Flanagan, D. P., Alfonso, V. C., & Hale, J. B. (2010). The Wechsler Intelligence Scale for Children - Fourth Edition in Neuropsychological Practice. Handbook of Pediatric Neuropsychology, January, 397–414. Giridharan, K., & Raju, R. (2017). Impact of Teaching Strategies: Demonstration and Lecture Strategies and Impact of Teacher Effect on Academic Achievement in Engineering Education. International Journal of Educational Sciences, 14(3), 174–186. https://doi.org/10.1080/09751122.2016.11890491 Hooman, N., Safaii, A., Valavi, E., & Amini-Alavijeh, Z. (2013). Toilet training in Iranian children: A cross-sectional study. Iranian Journal of Pediatrics, 23(2), 154–158. Hung, J.-W., Chang, Y.-J., & Han, W.-Y. (2016). Game technology to increase range of motion for adolescents with cerebral palsy: a feasibility study. International Journal on Disability and Human Development, 16(3). https://doi.org/10.1515/ijdhd-2016-0026 Kang, Y. S., & Chang, Y. J. (2019). Using a motion-controlled game to teach four elementary school children with intellectual disabilities to improve hand hygiene. Journal of Applied Research in Intellectual Disabilities, 32(4), 942–951. https://doi.org/10.1111/jar.12587 Kementerian, & Indonesia, R. (2011). Profil Kesehatan Indonesia. Kemenenterian Kesehatan RI. Kesehatan, K. (2011). PHBS di Sekolah. Kementerian Kesehatan Republik Indonesia. Ketut Sudiana, I., Adiputra, N., & Budi Adnyana, P. (2020). Integrative Health Thematic Strategy Increases Learning Outcomes and Students ’Clean and Healthy Living Behaviors. Journal of Physics: Conference Series, 1503(1). https://doi.org/10.1088/1742-6596/1503/1/012050 Koh, W. M., Bogich, T., Siegel, K., Jin, J., Chong, E. Y., Tan, C. Y., Chen, M. I. C., Horby, P., & Cook, A. R. (2016). The epidemiology of hand, foot and mouth disease in Asia: A systematic review and analysis. Pediatric Infectious Disease Journal, 35(10), e285–e300. https://doi.org/10.1097/INF.0000000000001242 Kroeger, K., & Sorensen, R. (2010). A parent training model for toilet training children with autism. Journal of Intellectual Disability Research, 54(6), 556–567. https://doi.org/10.1111/j.1365-2788.2010.01286.x Laporan Akuntabilitas Kinerja Kementerian Kesehatan tahun 2014. (n.d.). Lee, R. L. T., & Lee, P. H. (2014). To evaluate the effects of a simplified hand washing improvement program in schoolchildren with mild intellectual disability: A pilot study. Research in Developmental Disabilities, 35(11), 3014–3025. https://doi.org/10.1016/j.ridd.2014.07.016 Lee, R. L. T., Leung, C., Tong, W. K., Chen, H., & Lee, P. H. (2015). Comparative efficacy of a simplified handwashing program for improvement in hand hygiene and reduction of school absenteeism among children with intellectual disability. American Journal of Infection Control, 43(9), 907–912. https://doi.org/10.1016/j.ajic.2015.03.023 Levato, L. E., Aponte, C. A., Wilkins, J., Travis, R., Aiello, R., Zanibbi, K., Loring, W. A., Butter, E., Smith, T., & Mruzek, D. W. (2016). Use of urine alarms in toilet training children with intellectual and developmental disabilities: A review. Research in Developmental Disabilities, 53–54, 232–241. https://doi.org/10.1016/j.ridd.2016.02.007 Noah Ekeyi, D. (2013). Effect of Demonstration Method of Teaching on Students’ Achievement in Agricultural Science. World Journal of Education, 3(6), 1–7. https://doi.org/10.5430/wje.v3n6p1 Pedoman Umum Program Indonesia Sehat dengan Pendekatan Keluarga. (2015). Kementerian Kesehatan Republik Indonesia. Purba, N., Handini, M. C. H., & Yetti, E. (2018). Development of Media Vocabulary Cards to Improve the Speech Competence of Children with Intellectual Disabilities. 6. Puspita, W. A., Sulistyorini, M. P., & Wibowo, B. (2020). Learning Clean, Healthy and Safe Life Behavior in Inclusive Early Childhood Education. 454(Ecep 2019), 270–274. https://doi.org/10.2991/assehr.k.200808.053 Putri, R. M., Rosdiana, Y., & Nisa, A. C. (2019). Application of Clean and Healthy Living Behavior (PHBS) From The Household Knowledge and Attitude Study. Journal Of Nursing Practice, 3(1), 39–49. https://doi.org/10.30994/jnp.v3i1.64 Rosenberg, N. E., Schwartz, I. S., & Davis, C. A. (2010). Evaluating the utility of commercial videotapes for teaching hand washing to children with autism. Education and Treatment of Children, 33(3), 443–455. https://doi.org/10.1353/etc.0.0098 Ruan, F., Yang, T., Ma, H., Jin, Y., Song, S., Fontaine, R. E., & Zhu, B. P. (2011). Risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing. Pediatrics, 127(4). https://doi.org/10.1542/peds.2010-1497 Shen, K., Yang, Y., Wang, T., Zhao, D., Jiang, Y., Jin, R., Zheng, Y., Xu, B., Xie, Z., Lin, L., Shang, Y., Lu, X., Shu, S., Bai, Y., Deng, J., Lu, M., Ye, L., Wang, X., Wang, Y., & Gao, L. (2020). Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts’ consensus statement. World Journal of Pediatrics, 16(3), 223–231. https://doi.org/10.1007/s12519-020-00343-7 Steenkamp, L., Williams, M., Ronaasen, J., Feeley, A., Truter, I., & Melariri, P. (2020). Handwashing knowledge and practices among caregivers of pre-school children in underprivileged areas of Nelson Mandela Bay. South African Journal of Clinical Nutrition, 0(0), 1–5. https://doi.org/10.1080/16070658.2020.1769336 van Nunen, K., Kaerts, N., Wyndaele, J. J., Vermandel, A., & van Hal, G. V. (2015). Parents’ views on toilet training (TT): A quantitative study to identify the beliefs and attitudes of parents concerning TT. Journal of Child Health Care, 19(2), 265–274. https://doi.org/10.1177/1367493513508232 Walpole, R. E. (1955). Pengantar Statistika. Gramedia.

In the last issue (Vol. 29, No.2), there was a mistake in Wai-Tong Lau's article, “Songs Tied onto the Chariot—Revolutionary Songs of the Cultural Revolution in China (1966–1976)” on page 106. JHRME regrets the inaccuracies. The corrected paragraph reads as follows: A number of revolutionary songs of the Cultural Revolution are written in the musical styles of the Chinese minorities. “The Great Beijing” (Wei Da De Beijing by Nu Er Mai Mai Ti), a song written by a Xinjiang composer, was very popular during the Cultural Revolution. This song is filled with syncopated rhythm typical of the Xinjiang minority dances. Another classic revolutionary song of the Cultural Revolution, “A Song within My Heart for the People's Liberation Army” (Wo Xin Zhong De Ge Xian Gei Jie Fang Jun by Chang Liuzhu), composed by a Han composer, is written with rhythmic patterns characteristic of the Tibetan dances. Other similar songs are one for the Bei Minority, “Never-Ending Singing of the Zhan Mountain” (Zhan Shan Ge Sheng Yong Bu Luo by Zhang Wen); one for the Korean minority, “Yanbian People Love Chairman Mao” (Yanbian Ren Ming Re Ai Mao Zhu Xi by Jin Fenghao); one for the Zhuang minority, “Zhuang People Sing for Chairman Mao” (Zhaung Zu Ren Ming Ge Chang Mao Zhu Xi by the Creation Group of the Department of Culture of Guangxi Zhaung Autonomous Region); and one for the Wa minority, “Ah Wa People Sing New Songs” (Ah Wa Ren Ming Chang in Ge by Yang Zhengren). These revolutionary songs of the minorities enriched the genre of revolutionary songs of the Cultural Revolution with a variety of rhythmic and tonal idioms different from those of the mainstream Han music.

Ethnopharmacology relevance: Yunnan Baiyao (YNBY), a traditional Chinese medicine formulae, has some significant properties including activating blood circulation to dissipate blood stasis (Huo-Xue-Hua-Yu), eliminating swelling and alleviating pain (Xiao-Zhong-Zhi-Tong), and eliminating necrotic tissues and promoting granulation (Qu-Fu-Sheng-Ji).Aim of this study: This paper intends to provide a comprehensive and critical analysis of studies on YNBY, proposing new possible therapeutic directions of this formula.Materials and methods: Relevant data on YNBY were retrieved from available databases and a hand-search by searching the keywords such as “Yunnan Baiyao,” “pharmacology,” “toxicity,” and “clinical applications.”Results: Traditionally, YNBY has been used to cure hemorrhage, bruises, swelling, and pain caused by injuries in the Chinese folk. Modern pharmacological studies show that YNBY possesses pharmacological activities including hemostasis, invigorating the circulation of blood, wound healing, anti-inflammation, analgesia, antibiosis, infection prevention, and other effects. Toxicological studies demonstrate that YNBY has a certain toxicology, which is mainly caused by Aconitum alkaloids from Cao-wu (CW, Aconiti Kusnezoffii Radix). The developmental non-toxic reaction dose (NOAEL) of YNBY for embryos and fetuses is 0.5 g/kg in rats. In addition, the NOAEL for fertility and early embryo development toxicity is 4.0 g/kg in rats. Clinical trials have confirmed the safety of YNBY in a large number of patients, and adverse drug reactions (ADRs) such as abdominal pain, diarrhea, allergy, and others in very few people. YNBY is routinely used in clinic to cure bleeding, pain, swelling, upper digestive tract ulcer, postoperative wound, arthritis, mouth ulcers, ulcerative colitis, etc.Conclusions: Hemostasis is a conspicuous effect of YNBY. Except for this effect, analgesia and anti-infection may be new research directions of this formula. In addition, the in vitro and in vivo pharmacology and mechanisms of action of YNBY are encouraged as well as the pharmacokinetics of this formulae. Furthermore, the material basis of the pharmacological effects of YNBY also needs clear identification.

Article The Mechanism of Triacetyl Andrographolide in Inhibiting Proliferation of Pulmonary Artery Smooth Muscle Cells Zhe Wang 1,#, Yi-Xuan Zhang 2,#, Jun-Zhuo Shi 1,#, Chen-Chen Wang 1, Meng-Qi Zhang 1, Yi Yan 3, Yan-Ran Wang 1, Lu-Ling Zhao 1, Jie-Jian Kou 4, Qing-Hui Zhao 5, Xin-Mei Xie 1, Yang-Yang He 1,2, Jun-Ke Song 6,*, Guang Han 1,7,*, and Xiao-Bin Pang 1,2,* 1 School of Pharmacy, Henan University, Kaifeng 475004, China 2 Department of Anesthesiology, Huaihe Hospital of Henan University, Kaifeng 475004, China 3 Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, National Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200217, China 4 Department of Pharmacy, Huaihe Hospital of Henan University, Kaifeng 475004, China 5 Institute of Physical Culture, Huanghuai University, Zhumadian 463000, China 6 Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China 7 Henan Province Engineering Research Center of High Value Utilization to Natural Medical Resource in Yellow River Basin, Kaifeng 475004, China. * Correspondence: smilejunke@imm.ac.cn (Jun-Ke Song); hang@henu.edu.cn ( Guang Han); pxb@vip.henu.edu.cn ( Xiao-Bin Pang) Received: 17 April 2023 Accepted: 27 July 2023 Abstract: This study examines the impact of triacetyl-diacyllactone (ADA) on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and elucidates its underlying mechanism. PASMCs derived from SD rats were cultured in vitro and randomly divided into four groups: control group, administration group, model group, and model administration group. The appropriate concentration of ADA for intervention was determined using the MTT assay. The proliferation ability of PASMCs in each group was assessed using the EdU assay. The migration ability of PASMCs in each group was evaluated using the Scratch wound healing assay and Transwell assay. Western blot analysis was performed to determine the protein expression levels of BMPR2, PCNA, and TGF-β1, as well as the phosphorylation levels of SMAD1 and SMAD2/3 in PASMCs from each group. Results show that at a concentration of 5 µmol/L, ADA did not impact the cell activity of PASMCs and instead exerted inhibitory effects on both the proliferation and migration of PASMCs induced by PDGF-BB. PDGF-BB was found to upregulate the expression levels of PCNA and TGF-β1, while downregulating the expression of BMPR2. Furthermore, PDGF-BB led to enhanced protein phosphorylation of SMAD1 and SMAD2/3. However, following ADA intervention, the expression levels of PCNA and TGF-β1 decreased, while the expression of BMPR2 increased. Additionally, protein phosphorylation of SMAD1 and SMAD2/3 decreased. Therefore, ADA can hinder the proliferation and migration of PASMCs induced by PDGF-BB, as well as suppress the upregulation of PCNA and TGF-β1 caused by PDGF-BB. Furthermore, the downregulation of BMPR2 may be associated with the inhibition of SMAD1 and SMAD2/3 signaling pathways.

Graphene-based composites have received a great deal of attention in recent year because the presence of graphene can enhance the conductivity, strength of bulk materials and help create composites with superior qualities. Moreover, the incorporation of metal oxide nanoparticles such as Fe3O4 can improve the catalytic efficiency of composite material. In this work, we have synthesized a composite material with the combination of reduced graphene oxide (rGO), and Fe3O4 modified tissue-paper (mGO-PP) via a simple hydrothermal method, which improved the removal efficiency of the of methylene blue (MB) in water. MB blue is used as the model of contaminant to evaluate the catalytic efficiency of synthesized material by using a Fenton-like reaction. The obtained materials were characterized by SEM, XRD. The removal of materials with methylene blue is investigated by UV-VIS spectroscopy, and the result shows that mGO-PP composite is the potential composite for the color removed which has the removal efficiency reaching 65% in acetate buffer pH = 3 with the optimal time is 7 h. Keywords Graphene-based composite, methylene blue, Fenton-like reaction. References [1] Ma Joshi, Rue Bansal, Reng Purwar, Colour removal from textile effluents, Indian Journal of Fibre & Textile Research, 29 (2004) 239-259 http://nopr.niscair.res.in/handle/123456789/24631.[2] Kannan Nagar, Sundaram Mariappan, Kinetics and mechanism of removal of methylene blue by adsorption on various carbons-a comparative study, Dyes and pigments, 51 (2001) 25-40 https://doi.org/10.1016/S0143-7208(01)00056-0.[3] K Rastogi, J. N Sahu, B. C Meikap, M. N Biswas, Removal of methylene blue from wastewater using fly ash as an adsorbent by hydrocyclone, Journal of hazardous materials, 158 (2008) 531-540.https://doi.org/10.1016/j.jhazmat.2008.01. 105.[4] Qin Qingdong, Ma Jun, Liu Ke, Adsorption of anionic dyes on ammonium-functionalized MCM-41, Journal of Hazardous Materials, 162 (2009) 133-139 https://doi.org/10.1016/j.jhazmat. 2008.05.016.[5] Mui Muruganandham, Rps Suri, Sh Jafari, Mao Sillanpää, Lee Gang-Juan, Jaj Wu, Muo Swaminathan, Recent developments in homogeneous advanced oxidation processes for water and wastewater treatment, International Journal of Photoenergy, 2014 (2014). http://dx. doi.org/10.1155/2014/821674.[6] Herney Ramirez, Vicente Miguel , Madeira Luis Heterogeneous photo-Fenton oxidation with pillared clay-based catalysts for wastewater treatment: a review, Applied Catalysis B: Environmental, 98 (2010) 10-26 https://doi.org/ 10.1016/j.apcatb.2010.05.004.[7] Guo Rong, Jiao Tifeng, Li Ruifei, Chen Yan, Guo Wanchun, Zhang Lexin, Zhou Jingxin, Zhang Qingrui, Peng Qiuming, Sandwiched Fe3O4/carboxylate graphene oxide nanostructures constructed by layer-by-layer assembly for highly efficient and magnetically recyclable dye removal, ACS Sustainable Chemistry & Engineering, 6 (2017) 1279-1288 https://doi.org/10.1021/acssuschemeng.7b03635.[8] Sun Chao, Yang Sheng-Tao, Gao Zhenjie, Yang Shengnan, Yilihamu Ailimire, Ma Qiang, Zhao Ru-Song, Xue Fumin, Fe3O4/TiO2/reduced graphene oxide composites as highly efficient Fenton-like catalyst for the decoloration of methylene blue, Materials Chemistry and Physics, 223 (2019) 751-757 https://doi.org/ 10.1016/j.matchemphys.2018.11.056.[9] Guo Hui, Ma Xinfeng, Wang Chubei, Zhou Jianwei, Huang Jianxin, Wang Zijin, Sulfhydryl-Functionalized Reduced Graphene Oxide and Adsorption of Methylene Blue, Environmental Engineering Science, 36 (2019) 81-89 https://doi. org/10.1089/ees.2018.0157.[10] Zhao Lianqin, Yang Sheng-Tao, Feng Shicheng, Ma Qiang, Peng Xiaoling, Wu Deyi, Preparation and application of carboxylated graphene oxide sponge in dye removal, International journal of environmental research and public health, 14 (2017) 1301 https://doi.org/10.3390/ijerph14111301.[11] Yu Dandan, Wang Hua, Yang Jie, Niu Zhiqiang, Lu Huiting, Yang Yun, Cheng Liwei, Guo Lin, Dye wastewater cleanup by graphene composite paper for tailorable supercapacitors, ACS applied materials & interfaces, 9 (2017) 21298-21306 https://doi.org/10.1021/acsami.7b05318.[12] Wang Hou, Yuan Xingzhong, Wu Yan, Huang Huajun, Peng Xin, Zeng Guangming, Zhong Hua, Liang Jie, Ren MiaoMiao, Graphene-based materials: fabrication, characterization and application for the decontamination of wastewater and wastegas and hydrogen storage/generation, Advances in Colloid and Interface Science, 195 (2013) 19-40 https://doi. org/10.1016/j.cis.2013.03.009.[13] Marcano Daniela C, Kosynkin Dmitry V, Berlin Jacob M, Sinitskii Alexander, Sun Zhengzong, Slesarev Alexander, Alemany Lawrence B, Lu Wei, Tour James M, Improved synthesis of graphene oxide, ACS nano, 4 (2010) 4806-4814 https://doi.org/10.1021/nn1006368.[14] Zhang Jiali, Yang Haijun, Shen Guangxia, Cheng Ping, Zhang Jingyan, Guo Shouwu, Reduction of graphene oxide via L-ascorbic acid, Chemical Communications, 46 (2010) 1112-1114 http://doi. org/10.1039/B917705A [15] Gong Ming, Zhou Wu, Tsai Mon-Che, Zhou Jigang, Guan Mingyun, Lin Meng-Chang, Zhang Bo, Hu Yongfeng, Wang Di-Yan, Yang Jiang, Nanoscale nickel oxide/nickel heterostructures for active hydrogen evolution electrocatalysis, Nature communications, 5 (2014) 4695 https:// doi.org/10.1038/ncomms5695.[16] Wu Zhong-Shuai, Yang Shubin, Sun Yi, Parvez Khaled, Feng Xinliang, Müllen Klaus, 3D nitrogen-doped graphene aerogel-supported Fe3O4 nanoparticles as efficient electrocatalysts for the oxygen reduction reaction, Journal of the American Chemical Society, 134 (2012) 9082-9085 https://doi.org/10.1021/ja3030565.[17] Nguyen Son Truong, Nguyen Hoa Tien, Rinaldi Ali, Nguyen Nam Van, Fan Zeng, Duong Hai Minh, Morphology control and thermal stability of binderless-graphene aerogels from graphite for energy storage applications, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 414 (2012) 352-358 https://doi.org/ 10.1016/j.colsurfa.2012.08.048.[18] Deng Yang, Englehardt James D, Treatment of landfill leachate by the Fenton process, Water research, 40 (2006) 3683-3694 https://doi.org/ 10.1016/j.watres.2006.08.009.

Scutellaria baicalensis Georgi. is a perennial herb in the Lamiaceae family, with a distribution in more than 10 provinces in China. At the current time, the cultivation area of S. baicalensis in China exceeds 58,000 hectares, with annual production approaching 28,000 tons. As a traditional Chinese herbal medicine, the root of S. baicalensis has many applications, such as anti-inflammatory, anti-neuroinflammatory and neuroprotective, anticancer, antiviral, antibacterial, and antioxidant activities, and is effective in treatment of colitis, hepatitis, pneumonia, respiratory infections, and allergic diseases. (Jang et al. 2023; Liu et al. 2023). From August to September 2022, septoria leaf spot symptoms were observed at the Institute of Medicinal Plant Development (40.04°N, 116.28°E), Beijing, China, and the incidence of this disease was up to 20% in the field through more than two weeks of continuous investigation. Initial symptoms on leaves were observed as small, dark-brown spots (0.5 to 2.0 mm), which then expanded to irregular lesions with a pale gray center surrounded by a black ring with a dark-brown edge and light brown halo (Fig. 1A1-A3). Plants were defoliated and withered in severe cases. Thirty-six symptomatic leaves of 12 diseased plants from three experimental sites were cut into 5 × 5 mm pieces, and surface sterilized with 75% ethanol for 30 s followed by 5% NaClO solution for 45 s, rinsed with sterile water three times, dried with sterile filter paper, and subsequently placed on potato dextrose agar (PDA) medium and incubated at 25°C in dark for two days. Isolates were purified by transferring hyphal tips to new PDA plates and incubated at 25°C in dark. Finally, eight isolates (A1, B3, D1, F2, E2, a4, e4 and f1) with similar colonial morphological characteristics were obtained. Colonies on PDA exhibited dense, downy, and white to grayish-green aerial mycelia and the reverse of colonies showed dark-brown in the center and grayish on the edge (Fig. 1D, E). Conidia were solitary or catenate, pale brown, obclavate to cylindrical, apex obtuse (Fig. 1B, C). The isolates were divided into two categories by examining 100 conidia (50 of each isolate), represented by isolates D1 and e4. Conidia of D1 measured 5.4 to 75.8 μm × 2.1 to 6.8 μm, mean 26.9 × 4.4 μm, had 0 to 6 pseudosepta, with 0 to 3 pseudosepta observed in 88% of conidia. Conidia of e4 measured 20.3 to 103.4 μm × 2.0 to 7.9 μm, mean 41.9 × 4.8 μm, had 0 to 6 pseudosepta, with 2 to 5 pseudosepta observed in 90% of conidia. These isolates were identified as Corynespora cassiicola based on morphology (Ellis 1971). DNA of the two isolates (D1 and e4) was extracted by the cetyltrimethylammonium bromide (CTAB) method, and internal transcribed spacer (ITS) region of rDNA, translation elongation factor 1 alpha (TEF1-α), and beta-tubulin (TUB2) gene were amplified, using the primers ITS1/ITS4 (Bandi et al. 2022), EF1-728F/EF-986R (Wang et al. 2021), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. Sequences of ITS OQ991339 (524 bp) and OR044050 (533 bp) shared 99.8% identity to C. cassiicola, with a 99% coverage to MT228951 (536 bp) and OQ991340 (546 bp) in GenBank. Sequences of TEF1-α OR047441 (304 bp) and OR047443 (306 bp) shared 99.3% identity to C. cassiicola, with a 98% and 99% coverage to ON381927 (300 bp) and ON381933 (301 bp) in GenBank, respectively. Sequences of TUB2 OR047449 (427 bp) and OR047451 (427 bp) shared 99.53% identity to C. cassiicola, with a 99% and 98% coverage to MN604075 (442 bp) in GenBank, respectively. Phylogenetic trees were computed with ITS, TEF1-α, and TUB2 sequences in MEGA 11 using the Neighbor-Joining (NJ) method (Fig. 2). The results showed that the two isolates were C. cassiicola with more than 90% bootstrap support (1000 replicates). Nine 2-year-old seedlings of S. baicalensis were used for the pathogenicity assay. Three leaves from each plant were punctured with flame-sterilized needles, and inoculated with mycelial plugs (5 mm in diameter) of D1 and e4. Plants inoculated with sterile PDA plugs were used as control. All the inoculated seedlings were incubated at 25 oC and 90% relative humidity. About 3 to 4 days after inoculation, similar symptoms to those observed in the field were present on leaves inoculated with D1 and e4, while no symptoms were observed in the uninoculated control seedlings (Supplementary Fig. 1). Isolates with vigorous, downy, and white to grayish-green aerial mycelia were reisolated from the diseased leaves inoculated with D1 and e4 and identified as C. cassiicola by DNA sequencing, fulfilling Koch’s postulates. Based on morphological and multilocus phylogenetic results, these isolates were identified as C. cassiicola, a pathogen that threatens several important crops (Dixon et al. 2009; Zhang et al. 2018; Xie et al. 2021). To our knowledge, this is the first report of C. cassiicola as the causal pathogen of septoria leaf spot on S. baicalensis in China, which poses a potential threat to the production of S. baicalensis.