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Undescribed Meroterpenoids from Hypericum japonicum with Neuroprotective Effects on H_(2)O_(2) Insult SH-SY5Y Cells Targeting Keap1-Nrf2

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Chinese Journal of Chemistry 2022年第11期40卷 1321-1330页

作者： Linzhen hu Zhenzhen Wang Zhou Tong ping hu Luqi Kong Mengying Luo Xiao-Nian Li Yuexing Zhang Zhiyong huang Yonghui zhang State Key Laboratory of Biocatalysis and Enzyme Engineering National&Local Joint Engineering Research Centre of High-throughput Drug Screening TechnologyHubei Key Laboratory of Biotechnology of Traditional Chinese MedicineSchool of Life SciencesHubei UniversityWuhanHubei 430062China School of Pharmacy Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Kunming Institute of Botany Chinese Academy of SciencesKunmingYunnan 650204China College of Chemistry and Chemical Engineering Hubei UniversityWuhanHubei 430062China Tianjin Institute of Industrial Biotechnology Chinese Academy of Sciences.Tianjin 300308China

Unreported tautomeric/enantiomeric meroterpenoids,(±)-hyperjaponols I—K(1-3),were discovered from Hypericum japonicum.Comprehensive chemical investigations established the absolute characteristics of these stereoisomers.The TS calculation demon-strated that 1a and 2a easily occur enol-keto tautomerism with steady configurations individually.Amongst isolates,1b showed the strongest neuroprotective activity with the concentration at 25μmol/L on H_(2)O_(2) insult SH-SY5Y cells.In vitro molecular biological ex-periments manifested that 1b activated the Keap1-Nrf2-ARE pathway,leading to the promotion of Nrf2 nuclear translocation,down-regulation of the expression level of Keap1,and upregulation of the levels of Nrf2,NQO-1,and HO-1.The results of in silico simulation showed that 1b possessed good binding features with Keap1(5FNQ)via forming multiple typical hydrogen and hydrophobic bonds as well as less fluctuation of RMSD and RMSF during a natural physiological condition.

关键词： Hypericum japonicum Natural products Tautomerism Neuroprotective activity Keap1-Nrf2-ARE pathway

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Using non-destructive sampling to evaluate the population genomic status of captive Brown Eared Pheasants

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Avian Research 2023年第2期14卷 291-297页

作者： Pengcheng Wang ping hu Jinping Zhang Lixia Zhang Jing Zhang Zhengwang Zhang Jiangsu Key Laboratory for Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjing210023China Taiyuan Zoo Taiyuan030009China Beijing Zoo Management Office Beijing Key Laboratory of Captive Wildlife Technologies of Beijing ZooBeijing100044China Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering College of Life SciencesBeijing Normal UniversityBeijing100875China

Evaluating the genetic status of threatened species is an essential task in conservation genetics.However,the genetic status of threatened species has been mostly evaluated through techniques that fail to estimate genetic diversity at the whole genomic level.Next generation sequencing can meet this demand,but high quality samples such as blood or muscle tissues are required.However,it is difficult to collect such samples from threatened species because sampling work may impact their health.Therefore,it is essential to design a workflow to evaluate the whole genomic status of threatened species using non-destructive sampling.Even though non-destructive sampling has been used in traditional barcoding technique,the barcoding technique cannot evaluate the whole genomic status.Brown Eared Pheasant(Crossoptilon mantchuricum)is an endangered species,with captive populations maintained in Taiyuan Zoo,China,and Europe.However,the genetic diversity,inbreeding pattern,and mutation load of these two populations are unclear.To uncover the genetic status of these two captive populations,we applied 2b-RAD technology to evaluate the genomic status of these populations using feathers as samples.The feathers could be collected by non-destructive sampling.The results indicate that the Taiyuan Zoo population has a lower genetic diversity and higher inbreeding coefficient than the European population.The Taiyuan Zoo population has lethal mutations when homozygous.The current project uses a non-destructive sampling technique to evaluate the whole genomic status of the two captive populations,providing a paradigm for conservation genetics,which will facilitate the development of conservation biology.

关键词： Genetic diversity Inbreeding coefficient Kinship Mutation load Threatened species

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Artificial Intelligence and Network Pharmacology Reveal the Medication Rules of Professor Wang Yu-Ying in the Treatment of Climacteric Syndrome

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 180-190页

作者： Meng-Yuan hu Tian-Xing Yi Qi-Rui Liu Xin-Yu Zhang Ai-ping Chen Yu-Ying Wang Yi Lu School of Traditional Chinese Medicine Beijing University of Chinese Medicine

Objective: The objective of this study was to explore the medication rules and academic ideas of Professor Wang Yu-Ying in the treatment of climacteric syndrome(CLS) and to predict new prescriptions. Materials and Methods: The characteristics of frequency, clustering, four properties, and five flavors were analyzed, and new prescriptions were predicted through an artificial intelligence(AI)-based method. The potential pathways of new prescriptions were explored through network pharmacology-based analysis. Results: The top 16 medicinals used by Professor Wang Yu-Ying in the treatment of CLS included Danggui, Longgu, Muli, Fuling, Chuanxiong, Gancao, Xiangfu, and Tusizi. The AI method was applied to predict the basic prescription for treating CLS: Danggui 15 g, Duanlonggu 30 g, Duanmuli 30 g, Fuling 28 g, Chuanxiong 10 g, Gancao 6 g, Xiangfu 12 g, Tusizi 14 g, etc., Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the pathogenesis of CLS might be related to the estrogen pathway, involving typical steroid responses. Conclusions: This study summarized Professor Wang's medication experience in the treatment of CLS based on the data mining of clinical diagnoses and treatment cases. The AI method was used to predict the new prescription of CLS treatment, which was found to be reasonable by network pharmacology studies on its multi-target and multi-pathway mechanisms.

关键词： Artificial intelligence climacteric syndrome medication rules network pharmacology Professor Wang Yu‑Ying

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Association between MTHFR c.677C>T variant and erectile dysfunction among males attending fertility clinic

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Asian Journal of Andrology 2024年第1期26卷 41-45页

作者： Shun Bai Ming-Zhen Li Yang-Yang Wan Xue-Chun hu Yi-Xun Liu Xian-Hong Tong Tong-Hang Guo Lu Zong Ran Liu Yuan-Qi Zhao ping Xiang Bo Xu Xiao-hua Jiang Department of Gynecology and Obstetrics Reproductive and Genetic HospitalThe First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China NHC Key Laboratory of Male Reproduction and Genetics Guangdong Provincial Reproductive Science Institute(Guangdong Provincial Fertility Hospital)Guangzhou 510600China Department of Urology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Wannan Medical College Wuhu 241002China

Genetic risk factors have been shown to contribute to the development of sexual dysfunction.However,the role of methylenetetrahydrofolate reductase(MTHFR)gene variants in the risk of erectile dysfunction(ED)remains unclear.In this study,we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5.The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction(PCR).No significant difference in the genotypic frequency of the MTHFR C677T polymorphism(CC,CT,and TT)was observed between men from the ED and non-ED groups.In addition,on binary logistic regression analysis,both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism.Interestingly,a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED(P=O.02).The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis,even after adjusting for potential confounders(odds ratio[OR]=2.46,95%confidence interval[CI]:1.15-5.50,P=0.02).These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED.Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routineclinicaldiagnosis.

关键词： erectile dysfunction gene variant genetic risk factors methylenetetrahydrofolate reductase sexual function

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Probing the Gamma-Ray Emission Region of Five TeV Flat Spectrum Radio Quasars

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Research in Astronomy and Astrophysics 2024年第6期24卷 158-171页

作者： hu-Bing Xiao Hai-Tao Cao Rui Xue Jin-Ting Cai Ge-Ge Wang Marina Manganaro Shao-hua Zhang Zhi-Hao Ouyang Li-ping Fu Jun-hui Fan Shanghai Key Lab for Astrophysics Shanghai Normal University School of Information Engineering Department of Physics Zhejiang Normal University College of Mathematics and Physics Guangxi Minzu University Key Laboratory of Cosmology and Astrophysics (Liaoning) College of Sciences Northeastern University Department of Physics University of Rijeka Center for Astrophysics Guangzhou University Key Laboratory for Astronomical Observation and Technology of Guangzhou Astronomy Science and Technology Research Laboratory of Department of Education of Guangdong Province

The location of γ-ray emission of blazars remains a contested topic, inspiring the development of numerous investigative techniques to address this issue. In this work, we analyzed Fermi γ-ray light curves in the GeV and MeV bands, employing the discrete cross-correlation function method to discern time lags between the two bands.For 4C +21.35, Ton 599, B2 1420+32, and PKS 1510-089, we identified a time lag spanning several days, while for PKS 1441+25, the time lag was not statistically found. The results imply that the soft photons necessary for inverse Compton scattering predominantly originate from the dusty torus in the first four sources, whereas for PKS1441+25, they seem to be sourced mainly from the broad-line region. Further analysis of the opacity(τγγ) and the GeV spectra study supports the conclusion that the location of the dissipation region must be beyond the BLR to avoid significant absorption. Notably, for PKS 1441+25, the emission region is also posited to lie outside yet proximate to the BLR. The parameters of describing the emission region were obtained by fitting broadband spectral energy distribution with contemporaneous observation data. Our findings suggest that for the five TeV FSRQs, during Te V flaring events, the jet appears to maintain an equilibrium between the energy density of the magnetic field and that of the particles for all investigated sources, with the exceptions of 4C +21.35 and PKS1441+25. In terms of the overall jet power, particle energy is the dominant contributor, and the observed blazar radiation cannot be solely attributed to the magnetic field, except in the case of 4C +21.35. Consequently,magnetic reconnection is unlikely to be the primary mechanism behind particle acceleration in these systems.

关键词： galaxies: active galaxies: jets gamma-rays: galaxies

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铁路路基动力响应的2.5D有限元方法研究现状及展望

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岩土力学 2024年第1期45卷 284-301页

作者：王瑞胡志平长安大学建筑工程学院陕西西安710061

作为一种频域计算方法,2.5D有限元具备计算效率高、内存占用小等优势,同时也存在诸多局限。经过20余年的发展,2.5D有限元方法已经具备了描述复杂土体本构关系和复杂路基几何特征条件下铁路路基动力响应的能力。荷载输入方法、建模策略... 详细信息

作为一种频域计算方法,2.5D有限元具备计算效率高、内存占用小等优势,同时也存在诸多局限。经过20余年的发展,2.5D有限元方法已经具备了描述复杂土体本构关系和复杂路基几何特征条件下铁路路基动力响应的能力。荷载输入方法、建模策略和波动吸收边界的持续优化使得2.5D有限元方法的精度不断提高,二维插值方法则为进一步提升计算效率提供了思路。目前,2.5D有限元已经成为铁路路基动力响应研究中的常用方法。为了理清铁路路基动力响应2.5D有限元方法的发展脉络,分别从荷载输入、路基系统、响应输出和计算精度及效率的提升方面总结了其发展现状,介绍了2.5D有限元在发展过程中遇到的瓶颈问题及解决对策。在此基础上,针对算法的精度和效率、研究的对象和内容进行了进一步的讨论和展望。

关键词： 2.5D有限元方法铁路路基动力响应建模吸收边界二维插值

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The RNA-binding protein Musashi2 governs osteoblast-adipocyte lineage commitment by suppressing PPARγsignaling

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Bone Research 2022年第3期10卷 536-547页

作者： Jinlong Suo Sihai Zou Jinghui Wang Yujiao Han Lingli Zhang Chenchen Lv Bo Jiang Qian Ren Long Chen Lele Yang ping Ji Xianyou Zheng ping hu Weiguo Zou Department of Orthopedic Surgery and Institute of Microsurgery on Extremities Shanghai Jiaotong University Affiliated Sixth People’s Hospital200233 ShanghaiChina Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationStomatological Hospital of Chongqing Medical University401147 ChongqingChina State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell SciencesChinese Academy of SciencesUniversity of Chinese Academy of Sciences200031 ShanghaiChina Guangzhou Laboratory No.9 XingDaoHuan RoadGuanghzou International Bio lsland510005 GuangzhouChina Colorectal Cancer Center/Department of Gastrointestinal Surgery Shanghai Tenth People’s Hospital Affiliated to Tongji UniversityShanghaiChina Institute for Stem Cell and Regeneration Chinese Academy of Sciences100101 BeijingChina Bio-Research Innovation Center Shanghai Institute of Biochemistry and Cell BiologySuzhouChina

Osteoporosis caused by aging is characterized by reduced bone mass and accumulated adipocytes in the bone marrow cavity. How the balance between osteoblastogenesis and adipogenesis from bone marrow mesenchymal stem cells(BMSCs) is lost upon aging is still unclear. Here, we found that the RNA-binding protein Musashi2(Msi2) regulates BMSC lineage commitment. Msi2 is commonly enriched in stem cells and tumor cells. We found that its expression was downregulated during adipogenic differentiation and upregulated during osteogenic differentiation of BMSCs. Msi2 knockout mice exhibited decreased bone mass with substantial accumulation of marrow adipocytes, similar to aging-induced osteoporosis. Depletion of Msi2 in BMSCs led to increased adipocyte commitment. Transcriptional profiling analysis revealed that Msi2 deficiency led to increased PPARγ signaling.RNA-interacting protein immunoprecipitation assays demonstrated that Msi2 could inhibit the translation of the key adipogenic factor Cebpα, thereby inhibiting PPAR signaling. Furthermore, the expression of Msi2 decreased significantly during the aging process of mice, indicating that decreased Msi2 function during aging contributes to abnormal accumulation of adipocytes in bone marrow and osteoporosis. Thus, our results provide a putative biochemical mechanism for aging-related osteoporosis, suggesting that modulating Msi2 function may benefit the treatment of bone aging.

关键词： adipocyte osteoporosis inhibiting

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制药废水中抗生素抗性的污染特征、检测手段和控制方法

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环境科学 2024年第2期45卷 844-853页

作者：彭安萍高虎张新波天津城建大学环境与市政工程学院天津300384

制药行业废水中含有大量的抗生素、抗生素抗性细菌(ARBs)及抗性基因(ARGs)等新污染物,现今的生物处理工艺尚不能有效地对其进行去除.最终以上新污染物随出水进入各类水体或渗入土壤,造成环境污染,影响人类健康.因此,探明制药废水中抗生... 详细信息

制药行业废水中含有大量的抗生素、抗生素抗性细菌(ARBs)及抗性基因(ARGs)等新污染物,现今的生物处理工艺尚不能有效地对其进行去除.最终以上新污染物随出水进入各类水体或渗入土壤,造成环境污染,影响人类健康.因此,探明制药废水中抗生素、ARBs和ARGs的污染特征,知晓检测和控制废水中抗生素抗性污染的方法,对于削减环境中的抗生素和ARGs,评估抗生素抗性的生态风险至关重要.针对制药废水处理厂(PWWTPs)环境中的抗生素抗性污染问题,讨论了制药废水中的抗生素、ARBs和ARGs的污染现状;概述了制药废水环境中抗生素抗性的不同评估方法;最后对PWWTPs中常用去除抗生素及ARGs的废水处理技术进行了概述,以期为环境中抗生素及抗性基因的生态风险评价及科学防治提供理论依据.

关键词：制药废水抗生素抗性基因(ARGs) 抗性细菌(ARBs) 污染特征检测方法

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Characterization of the effects of hyaluronan oligosaccharides on human gut microbiota using a simulated batch fermentation system

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Food Science and human Wellness 2024年

作者： Xinwei Gao Hongkang Zhu Litao hu Jieyu Sun Wenjie Zuo ping Liu Yang Wang Guocheng Du Zhen Kang The Science Center for Future Foods Jiangnan University The Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University The Key Laboratory of Industrial Biotechnology Ministry of Education School of Biotechnology Jiangnan University School of Food Science and Technology Jiangnan University

The prebiotic effects of hyaluronan (HA) are widely recognized， contributing to improved gut health and immune modulation. Despite its extensive use as dietary supplement， the specific interactions between HA oligosaccharides (o-HAs) and the gut microbiome remain largely unexplored. To investigate its role and metabolic fate in gut homeostasis， 200 mg/day of o-HAs (average molecule weight 1k Da) were added to an automated computer-controlled SIMulator of the Gastrointestinal tract (SIMGI). The results revealed a significant reshaping of the intestinal flora composition by o-HAs， notably reducing the Firmicutes/Bacteroides ratio. Fermentation of o-HAs by gut microbiota significantly increased the abundance of Bifidobacteria， Prevotellaceae＿Prevotella， Dialister， Eubacterium， and Sutterella， but decreased that of Catenibacterium， Oscillospira， Klebsiella， and Citrobacter (P human diseases， particularly infectious ones (parasitic and bacterial). Potential inhibitions were observed in metabolic pathways associated with pentose and glucuronate interconversions as well as cationic antimicrobial peptide resistance. These findings underscore the in vitro prebiotic effects of o-HAs and their potential relevance in managing diverticular diseases or preventing metabolic disorders through the regulation of gut microbiota.

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AG8 Reduces Hypoxia-induced Triple Negative Breast Cancer Metastasis by Stemness Regulation

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Clinical Complementary Medicine and Pharmacology 2024年第1期4卷 54-61页

作者： Lihua Mu Yuan hu Hong Yan Rui Jing ping Liu Department of Pharmacy Medical Supplies Center of Chinese PLA General HospitalBeijing 100853China Department of Obstetrics and Gynecology the First Medical Centre of Chinese PLA General HospitalBeijing 100853China

Background:AG8,a triterpenoid saponin isolated from Ardisia gigantifolia Stapf.,our previous studies found that AG8 inhibited the proliferation of triple negative breast cancers(TNBCs)by including ROS generation and triggering mitochondrial apoptotic pathways.Cancer stem cells(CSCs)capable of maintain relatively low levels of ROS,are vulnerable to the interference of redox state.Compounds capable of generating ROS can affect the finely balanced redox state of CSCs and have potency to selectively kill them.Objective:We selected BT-549 which is most sensitive to AG8 to further study the effects of AG8 on hypoxia-induced proliferation,metastasis and CSCs.Methods:The hypoxia condition was simulated by CoCl2 and cell viability assay of BT-549 cells was performed us-ing MTT.Stemness phenotype were identified using breast CSCs marker(CD24^(−)/low/CD44^(+))and mammosphere formation assay.Cell motility was determined via the wound healing assay and transwell migration.Protein levels of HIF1-α,Oct-4,SOX-2,c-MYC were tested by western blotting.Results:In this study,AG8 showed significant cytotoxic effects on BT-549 triple negative breast cancer cells,but the effects were impaired by HIF1 activation.AG8 inhibited the hypoxia-induced migration and invasion of BT-549 cells.Further studies revealed that hypoxia-induced increases of CD44^(+)CD24^(−)/low and mammosphere population were significantly inhibited by AG8 dose-dependently.Moreover,AG8 decreased the Oct-4 and SOX-2 protein expression without affecting HIF1-αand c-MYC.AG8 significantly inhibited BT-549 xenograft tumors growth in BALB/c nude mice comparing with that of the control group.Conclusion:In summary,AG8 inhibited hypoxia-induced cell migration and invasion through stemness regula-tions,indicating novel mechanisms for the antitumor effects of AG8 against triple negative breast cancer.

关键词： Triterpenoid saponin TNBC hypoxia CSC Metastasis

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