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Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a responseguided therapy strategy

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World Journal of Hepatology 2024年第3期16卷 405-417页

作者： Pei-Xin Zhang Xiao-Wei Zheng Ya-Fei Zhang Jun ye Wei Li Qian-Qian Tang Jie Zhu Gui-Zhou zou Zhen-Hua Zhang Department of Infectious Diseases The Second Affiliated Hospital of Anhui Medical UniversityHefei 230601Anhui ProvinceChina Department of Infectious Diseases Anhui Provincial HospitalHefei 230000Anhui ProvinceChina Department of Hepatology The Second People’s Hospital of Fuyang CityFuyang 236000Anhui ProvinceChina

BACKGROUND Models for predicting hepatitis B e antigen(HBeAg)seroconversion in patients with HBeAg-positive chronic hepatitis B(CHB)after nucleos(t)ide analog treatment are rare.AIM To establish a simple scoring model based on a response-guided therapy(RGT)strategy for predicting HBeAg seroconversion and hepatitis B surface antigen(HBsAg)clearance.METHODS In this study,75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa(PEG-IFNα)treatment and a 24-wk follow-up.Logistic regression analysis was used to assess parameters at baseline,week 12,and week 24 to predict HBeAg seroconversion at 24 wk post-treatment.The two best predictors at each time point were used to establish a prediction model for PEG-IFNαtherapy efficacy.Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0.RESULTS The two most meaningful predictors were HBsAg≤1000 IU/mL and HBeAg≤3 S/CO at baseline,HBsAg≤600 IU/mL and HBeAg≤3 S/CO at week 12,and HBsAg≤300 IU/mL and HBeAg≤2 S/CO at week 24.With a total score of 0 vs 2 at baseline,week 12,and week 24,the response rates were 23.8%,15.2%,and 11.1%vs 81.8%,80.0%,and 82.4%,respectively,and the HBsAg clearance rates were 2.4%,3.0%,and 0.0%,vs 54.5%,40.0%,and 41.2%,respectively.CONCLUSION We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNαtherapy.

关键词： Chronic hepatitis B Hepatitis B e antigen-positive Peginterferon-alfa Prediction model Response-guided therapy strategy

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Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan zou Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and established.Despite this,the clinical approval of drugs targeting the cGAS-STING pathway has been limited.The Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our study.We found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)cells.This inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling pathways.In vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

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牛蒡子苷元对白血病K562/A02细胞耐药性的逆转作用及机制

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中国实验血液学杂志 2024年第2期32卷 409-415页

作者：邹琳方烨何威中国人民解放军中部战区总医院综合科湖北武汉430070

目的:研究牛蒡子苷元对白血病耐药细胞株K562/A02阿霉素耐药性的影响及其作用机制。方法:体外培养人白血病细胞株K562及阿霉素耐药细胞株K562/A02,使用2.5-50μmol/L阿霉素处理,CCK-8检测细胞生长情况并计算药物半数抑制浓度(IC_(50))... 详细信息

目的:研究牛蒡子苷元对白血病耐药细胞株K562/A02阿霉素耐药性的影响及其作用机制。方法:体外培养人白血病细胞株K562及阿霉素耐药细胞株K562/A02,使用2.5-50μmol/L阿霉素处理,CCK-8检测细胞生长情况并计算药物半数抑制浓度(IC_(50))。采用不同浓度的牛蒡子苷元(1、2、4、8、16 mmol/L)处理K562/A02细胞,检测牛蒡子苷元对K562/A02细胞的影响,筛选适用浓度用于后续实验。在2 mmol/L牛蒡子苷元处理的K562/A02细胞中加入5μmol/L阿霉素,流式细胞术检测细胞凋亡,Western blot检测P-gp、MRP、cleaved caspase-3、Bax、Bcl-2以及TLR4/NF-κB信号通路蛋白的表达。在牛蒡子苷元和阿霉素共处理的K562/A02细胞中转染TLR4过表达质粒,检测细胞的药物敏感性和凋亡水平。结果:阿霉素对K562/A02细胞的IC_(50)为36.57μmol/L,高于K562细胞(1.30μmol/L)。当牛蒡子苷元浓度≤2 mmol/L时,K562/A02的细胞生长不会受到明显抑制。经2 mmol/L的牛蒡子苷元处理后,阿霉素对K562/A02细胞的IC_(50)明显降低。与对照组相比,牛蒡子苷元组K562/A02细胞凋亡率明显上升,cleaved caspase-3、Bax蛋白的表达明显上调,P-gp、MRP、Bcl-2、TLR4、My D88和p-NF-κB蛋白的表达明显下调,差异均具有统计学意义(P<0.05)。在转染TLR4过表达质粒后,牛蒡子苷元处理的K562/A02细胞对阿霉素的敏感性明显降低(P<0.05),细胞凋亡下降,并显著提升了P-gp、MRP、Bcl-2和TLR4/NF-κB信号通路蛋白的表达(P<0.05),同时降低了cleaved caspase-3和Bax蛋白的表达(P<0.05)。结论:牛蒡子苷元可能通过抑制TLR4/NF-κB信号通路从而逆转人白血病耐药细胞株K562/A02对阿霉素的耐药性。

关键词：牛蒡子苷元白血病 K562/A02细胞耐药 TLR4/NF-κB信号通路

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Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2210-2227页

作者： Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang zou Jiali ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510378China Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles Guangzhou University of Chinese MedicineGuangzhou 510006China Department of Laboratory Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China The Fifth Affiliated Hospital Sun Yat-sen University Zhuhai 519000China Department of Blood Transfusion Guangdong Heyou International HospitalFoshan 528306China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关键词： Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling Naringin Bone morphogenetic protein 2 Runt-related transcription factor 2

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Mono-and dioleyl p-coumarate phenolipids and their antioxidant activity in a muscle food model system

Food Production, Processing and Nutrition

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Food Production, Processing and Nutrition 2022年第1期4卷 72-84页

作者： Jiankang Wang Xiaojia Hu Yan Huang ye zou Linxiao Han Daoying Wang Fereidoon Shahidi School of Food and Biological Engineering Shaanxi University of Science and TechnologyXi’an710021People’s Republic of China Institute of Agricultural Products Processing Jiangsu Academy of Agricultural SciencesNanjing210014People’s Republic of China Department of Biochemistry Memorial University of NewfoundlandSt.John’sNLA1C 5S7Canada

Response surface methodology (RSM) was used to optimize the degree of esterification of p-coumaric acid to triolein via lipase-catalyzed acidolysis, and enzyme load, reaction time and mole ratio of substrates were selected as variables in the experimental design. The results showed that the model employed was highly sufficient for determining the effectiveness and interaction of three selected variables, enzyme load, reaction time and the mole ratio of substrates, on the dependent variable, the degree of esterification. Although the optimization point was not found in the selected range of the three variables, the steepest ascent analysis suggested that an increase of these three variables might lead to a stationary point. However, based on the limitations on increasing the range of tested variables, including possible oxidation of synthesized lipids and increased cost, the degree of esterification so yielded in the designed central composite design should be the one closest to the possible ideal optimized degree. The p-coumarates so produced exhibited varying antioxidant performance in the tested muscle food model, which could be explained by their different lipophilicity. Moreover, the potential health benefits of synthesized phenolic lipids have been discussed.

关键词： Response surface methodology Acidolysis P-coumaric acid Monooleyl p-coumarates Dioleyl p-coumarates Antioxidant activity

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No generality in biodiversity-productivity relationships along elevation in temperate and subtropical forest landscapes

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Forest Ecosystems 2024年第3期11卷 255-265页

作者： Jiayun zou Yahuang Luo Rupert Seidl Dominik Thom Jie Liu Lisa Geres Tobias Richter Linjiang ye Wei Zheng Liangliang Ma Jie Song Kun Xu Dezhu Li Lianming Gao Sebastian Seibold Ecosystem Dynamics and Forest Management Research Group School of Life SciencesTechnical University of MunichHans-Carl-von-Carlowitz-Platz 285354FreisingGermany State Key Laboratory of Plant Diversity and Specialty Crops Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100China Berchtesgaden National Park Doktorberg 683471Germany Gund Institute for Environment University of Vermont617 Main StreetBurlingtonVT 1105405USA Faculty of Biological Sciences Institute for EcologyEvolution and DiversityConservation BiologyGoethe University FrankfurtFrankfurt am MainGermany University of Chinese Academy of Sciences Beijing10049China TUD Dresden University of Technology Forest ZoologyPienner Str.701737TharandtGermany

An improved understanding of biodiversity-productivity relationships(BPRs)along environmental gradients is crucial for effective ecosystem management and biodiversity conservation.The stress-gradient hypothesis suggests that BPRs are stronger in stressful environments compared to more favorable conditions.However,there is limited knowledge regarding the variation of BPRs along elevational gradients and their generality across different landscapes.To study how BPRs change with elevation,we harnessed inventory data on 6,431 trees from152 plots surveyed twice in eight to ten year intervals in mountain forests of temperate Europe and subtropical Asia.We quantified the relationship between aboveground productivity and different biodiversity measures,including taxonomic,functional,and phylogenetic diversity.To elucidate the processes underlying BPRs,we studied the variation of different functional traits along elevation across landscapes.We found no general pattern of BPRs across landscapes and elevations.Relationships were neutral for all biodiversity measures in temperate forests,and negative for taxonomic and functional diversity in subtropical forests.BPRs were largely congruent between taxonomic,functional and phylogenetic diversity.We found only weak support for the stress-gradient hypothesis,with BPRs turning from negative to positive(effect not significant)close to the tree line in subtropical forests.In temperate forests,however,elevation patterns were strongly modulated by species identity effects as influenced by specific traits.The effect of traits such as community-weighted mean of maximum plant height and wood density on productivity was congruent across landscapes.Our study highlights the context-dependence of BPRs across elevation gradients and landscapes.Species traits are key modulating factors of BPRs and should be considered more explicitly in studies of the functional role of biodiversity.Furthermore,our findings highlight that potential trade-offs between conserving biodiversity and fostering ecos

关键词： Biodiversity-ecosystem functioning Climate mitigation Elevation gradients Forest management Forest productivity Functional traits Nature conservation Phylogenetic diversity

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Theoretical analysis of the double-differential cross-sections of neutron,proton,deuteron,^(3)He,andαfor the p+^(6) Li reaction

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Nuclear Science and Techniques 2024年第3期35卷 181-197页

作者： Fang-Lei zou Xiao-Jun Sun Jing-Shang Zhang Hai-Rui Guo Yin-Lu Han Rui-Rui Xu Xi Tao Ji-Min Wang Xiao-Dong Sun Yuan Tian Tao ye Yong-Li Xu Chun-Tian Liang College of Physics Guangxi Normal University541004 GuilinChina Guangxi Key Laboratory of Nuclear Physics and Nuclear Technology 541004 GuilinChina China Institute of Atomic Energy P.O.Box 275(41)102413 BeijingChina Institute of Applied Physics and Computational Mathematics 10094 BeijingChina College of Physics and Electronic Shanxi Datong University037009 DatongChina School of Science Tianjin Chengjian University300384 TianjinChina

Based on the unified Hauser–Feshbach and exciton model,which can describe the particle emission processes between discrete energy levels with energy,angular momentum,and parity conservations,a statistical theory of light nucleus reaction(STLN)is developed to calculate the double-differential cross-sections of the outgoing neutron and light charged particles for the proton-induced^(6) Li reaction.A significant difference is observed between the p+^(6) Li and p+^(7) Li reactions owing to the discrepancies in the energy-level structures of the targets.The reaction channels,including sequential and simultaneous emission processes,are analyzed in detail.Taking the double-differential cross-sections of the outgoing proton as an example,the influence of contaminations(such as^(1) H,^(7)Li,^(12)C,and^(16)O)on the target is identified in terms of the kinetic energy of the first emitted particles.The optical potential parameters of the proton are obtained by fitting the elastic scattering differential cross-sections.The calculated total double-differential cross-sections of the outgoing proton and deuteron at E_(p)=14 MeV agree well with the experimental data for different outgoing angles.Simultaneously,the mixed double differential cross-sections of^(3) He andαare in good agreement with the measurements.The agreement between the measured data and calculated results indicates that the two-body and three-body breakup reactions need to be considered,and the pre-equilibrium reaction mechanism dominates the reaction processes.Based on the STLN model,a PLUNF code for the p+^(6) Li reaction is developed to obtain an ENDF-6-formatted file of the double-differential cross-sections of the nucleon and light composite charged particles.

关键词： Statistical theory of light nucleus reaction p+^(6)Li reaction Light composite charged particle Double-differential cross-sections Two-body breakup Three-body breakup

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低纹波空间可调高压电源设计

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北京大学学报（自然科学版） 2024年第2期60卷 195-202页

作者：陈佳黎邹鸿叶雨光北京大学空间物理与应用技术研究所北京100871

为了满足空间探测载荷(如质谱仪和能量粒子探测器等)对高压电源输出纹波的要求,设计一款小功率、低纹波、最大输出电压为10 kV的可调高压直流电源。设计中使用罗耶架构的逆变器和倍压整流电路,利用反馈回路,使纹波电压峰峰值小于2 V;使... 详细信息

为了满足空间探测载荷(如质谱仪和能量粒子探测器等)对高压电源输出纹波的要求,设计一款小功率、低纹波、最大输出电压为10 kV的可调高压直流电源。设计中使用罗耶架构的逆变器和倍压整流电路,利用反馈回路,使纹波电压峰峰值小于2 V;使用51系列单片机控制电源输出电压,监测电源的工作状态。除在原理设计方面降低输出电压纹波外,还提出其他降低输出电压纹波的措施。测试结果表明,所设计的高压电源具有输出电压稳定可调、纹波低的特点,可以满足空间探测载荷对高压电源的基本性能要求。

关键词：高压电源倍压整流低纹波可变输出单片机

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Clions accelerating interface charge transfer in a Si/InSFaradaic junction photocathode for solar seawater splitting

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Science China Chemistry 2024年

作者： Jun Luo Ruotong Bao Hongzheng Dong ye Fu Dongjian Jiang Bo Wang Yuzhan Zheng Qiong Wang Wenjun Luo Zhigang zou Eco-materials and Renewable Energy Research Center (ERERC) Jiangsu Key Laboratory for Nano Technology National Laboratory of Solid State Microstructures College of Engineering and Applied Sciences Nanjing University National Laboratory of Solid State Microstructures and Department of Physics Nanjing University

Photoelectrocatalytic seawater splitting is a promising low-cost method to produce green hydrogen in a large scale.The effects of Cl-ions in seawater on the performance of a photoanode have been reported in previous studies.However,few researches have been done on the roles of Cl-ions in a photocathode.Herein,for the first time,we find that Cl-ions in the electrolyte improve the photocurrent of a Si/In2S3photocathode by 50%at-0.6 VRHE.An in-situ X-ray photoelectron spectroscopy （XPS） characterization combined with the time-of-flight secondary-ion mass spectrometry by simulating photoelectrochemical conditions was used to investigate the interface charge transfer mechanism.The results suggest that there is an In+32S3–x（OH）2xlayer on the surface of In2S3in the phosphate buffer solution （PBS） electrolyte,which plays a role as an interface charge transfer mediator in the Si/In2S3photocathode.The In+32S3–x（OH）2xsurface layer becomes In+32S3–x（Cl）2xin the PBS electrolyte with NaCl and accelerates the charge transfer rate at the In2S3/electrolyte interface.These results offer a new concept of regulating interface charge transfer mediator to enhance the performance of photoelectrocatalytic seawater splitting for hydrogen production.

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Experimental observation of the significant difference between surface and bulk Kondo processes in Kondo lattice YbCu_(2)Si_(2)

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Science China(Physics,Mechanics & Astronomy) 2024年第4期67卷 154-160页

作者： Yin-zou Zhao Jiao-Jiao Song Qi-Yi Wu Hao Liu Chen Zhang Bo Chen Hong-Yi Zhang Zhen-Hua Chen Yao-Bo Huang Xue-Qing ye Ya-Hua Yuan Yu-Xia Duan Jun He Jian-Qiao Meng School of Physics Central South UniversityChangsha 410083China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201204China

Synchrotron-based angle-resolved photoemission spectroscopy was employed to investigate the temperature evolution of the Yb 4 f spectral for surface and bulk in the Kondo lattice YbCu_(2)Si_(2).Our study quantitatively distinguishes between the surface and bulk hybridization processes,revealing that the onset temperatures for both surface and bulk hybridization processes are significantly higher than the Kondo temperature.Additionally,we found that the effective surface Kondo temperature is much lower than that of the bulk.These findings offer valuable insights into the understanding of heavy fermion physics.

关键词： Kondo lattice angle-resolved photoemission spectroscopy electronic structure hybridization surface state

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