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TRIM21-dependent ultrasmall chiral gold nanoparticles for preventing microglia senescence against Alzheimer's disease

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Science China Chemistry 2024年第4期67卷 1360-1372页

作者： Meiru Lu Changlong Hao Liguang Xu Feng yu Jiwei Jiang Yanli Wang Jun Xu Hua kuang Chuanlai Xu Maozhong Sun International Joint Research Laboratory for Biointerface and Biodetection State Key Laboratory of Food Science and ResourcesSchool of Food Science and TechnologyJiangnan UniversityWuxi 214122China Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China National Clinical Research Center for Neurological Diseases Beijing 100070China

Tripartite motif 21(TRIM21)is an E3 ubiquitin ligase that shows great promise for protein degradation through ubiquitination.Here,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were fabricated.After conjugated with an NLR family pyrin domain-containing protein 3(NLRP3)antibody(D-NP-a NLRP3 or L-NP-a NLRP3),DNP-a NLRP3 showed effective delivery efficiency of the antibody into microglia and prevented Aβ-mediated microglia senescence,and p16^(ink4a),a marker of senescence,in the microglia was reduced by 90.3%±7.8% while L-NP-a NLRP3 decreased by 48.01%±3.1%.Mechanistic investigations revealed that the D-NP-a NLRP3((1.5±0.3)×10^(7)M^(-1))exhibited sixteen-fold larger binding affinity to transmembrane glycoprotein SLC3A2 than L-type((9.5±2.7)×10^(5)M^(-1)),which led to a high efficiency of antibody delivery and TRIM21-dependent NLRP3 degradation.Notably,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in vivo.The APP/PS1 Alzheimer's disease(AD)model mice experiments exhibited a reduction of 89.7%±6.8% for the NLRP3 protein and 84.2±7.5% for p16^(ink4a)following the intravenous administration of D-NP-a NLRP3 once a week for 60 days.Furthermore,the levels of the AD markers Aβ and phosphorylatedTau in the brains were reduced by 86.2%±8.2% and 81.6%±9.1%;these were 2.1-fold and 1.9-fold higher than those treated with L-NP-a NLRP3,respectively.The studies provide a method to rescue AD-like pathologies and prevent senescence.

关键词： chiral gold nanoparticles amyloid-β NLRP3 TRIM21 senescence Alzheimer's disease

Efficacy and safety of perioperative therapy for locally resectable gastric cancer:A network meta-analysis of randomized clinical trials

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1046-1058页

作者： Zi-yu kuang Qian-Hui Sun Lu-Chang Cao Xin-Yi Ma Jia-Xi Wang Ke-Xin Liu Jie Li Graduate College Beijing University of Traditional Chinese MedicineBeijing 100029China Oncology Department Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China

BACKGROUND Gastric cancer(GC)is the fifth most commonly diagnosed malignancy worldwide,with over 1 million new cases per year,and the third leading cause of cancer-related death.AIM To determine the optimal perioperative treatment regimen for patients with locally resectable GC.METHODS A comprehensive literature search was conducted,focusing on phase II/III randomized controlled trials(RCTs)assessing perioperative chemotherapy and chemoradiotherapy in treating locally resectable GC.The R0 resection rate,overall survival(OS),disease-free survival(DFS),and incidence of grade 3 or higher nonsurgical severe adverse events(SAEs)associated with various perioperative regimens were analyzed.A Bayesian network meta-analysis was performed to compare treatment regimens and rank their efficacy.RESULTS Thirty RCTs involving 8346 patients were included in this study.Neoadjuvant XELOX plus neoadjuvant radiotherapy and neoadjuvant CF were found to significantly improve the R0 resection rate compared with surgery alone,and the former had the highest probability of being the most effective option in this context.Neoadjuvant plus adjuvant FLOT was associated with the highest probability of being the best regimen for improving OS.Owing to limited data,no definitive ranking could be determined for DFS.Considering nonsurgical SAEs,FLO has emerged as the safest treatment regimen.CONCLUSION This study provides valuable insights for clinicians when selecting perioperative treatment regimens for patients with locally resectable GC.Further studies are required to validate these findings.

关键词： Gastric cancer Perioperative treatment Network meta-analysis Efficacy and safety

Network Pharmacology-Based Dissection of the Bioactive Compounds and Pharmacological Mechanisms of Yiqi Fumai Lyophilized Injection for the Treatment of Heart Failure

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 75-82页

作者： yu-Xi Huang Jing-Jing Fan Lu-Lu Xu Rong yu Yi kuang yue Chai Rui Zheng Xiao-yu Zhang Hong-Cai Shang Xue Qiao Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijingChina Key Laboratory of Chinese Internal Medicine of Ministry of Education Dongzhimen HospitalBeijing University of Chinese MedicineBeijingChina yunnan Baiyao International Medical Research Center Peking UniversityBeijingChina Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education Peking UniversityBeijingChina

Objective:Yiqi Fumai Lyophilized Injection(YQFM),a Chinese medicine injection,has been widely used for the treatment of cardiovascular diseases,especially heart failure(HF).However,bioactive compounds and underlying mechanisms of YQFM in treating HF remain poorly understood.Materials and Methods:Network pharmacology was employed to investigate the bioactive compounds and mechanisms of YQFM.A compound-target network was constructed to screen bioactive compounds based on contribution index calculation.Then,an adriamycin-induced HF rat model was established to evaluate the cardio-protective effects of YQFM by hematoxylin and eosin staining and enzyme-linked immunosorbent assays.Results:Network pharmacology indicated that YQFM may alleviate HF through 36 compounds and 109 targets.Particularly,ginsenosides Rb1,Rg1,Re,Rf,Rb2,Rh1,schisandrin,and ginsenoside Rc were indicated as the top contributors of YQFM in treating HF.YQFM was predicted to act on multiple targets such as vascular endothelial growth factor A,interleukin-2(IL-2),IL-6,and IL-1β,as well as to regulate signaling pathways such as hypoxia-inducible factor 1,tumor necrosis factor,VEGF,and PI3K-Akt.The pharmacological study suggested that YQFM could attenuate cardiac injury and up-regulate plasma concentrations of VEGFR-1 and NO in HF rats.Ginsenoside Rb1,as the major contributor from network pharmacology analysis,also showed a cardioprotective effect and up-regulation of VEGFR-1 in plasma.Conclusions:Ginsenosides and schisandrin were predicted as the most important contributors to the cardioprotective effect of YQMF.Ginsenoside Rb1 was proved to alleviate HF and increase the plasma concentration of VEGFR-1.

关键词： Contribution index heart failure network pharmacology traditional Chinese medicine yiqi fumai lyophilized injection

Robust leaderless time-varying formation control for unmanned aerial vehicle swarm system with Lipschitz nonlinear dynamics and directed switching topologies

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Chinese Journal of Aeronautics 2022年第1期35卷 124-136页

作者： yuhang KANG yu kuang Jun CHENG Bangchu ZHANG Yahui QI Shaolei ZHOU Kai MAO Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China School of Basic Science Naval Aviation UniversityYantai 264001China School of Aeronautics and Astronautics Sun Yat-Sen UniversityGuangzhou 510275China

This paper tackles the robust leaderless Time-Varying Formation(TVF)control problem for the Unmanned Aerial Vehicle(UAV)swarm system with Lipschitz nonlinear dynamics,external disturbances and directed switching topologies.In comparison with the previous achievements on formation control problems,the UAV swarm system with Lipschitz nonlinear dynamics can accomplish the pre-designed TVF while tracking a pre-given trajectory which is produced by a virtual leader UAV in the presence of external disturbances.Firstly,by applying the consensus theory,a TVF controller is developed with the local neighborhood status information,the errors of real time status of all UAVs,the expected formation configuration and the pre-given trajectory under directed switching topologies.Secondly,through a certain matrix variable substitution,the UAV swarm system formation control issue is transformed into a lower dimensional asymptotically stable control issue.Thirdly,by introducing the minimum dwell time,the design steps of formation control algorithm are further acquired.In the meantime,the stability of the UAV swarm system is analyzed through the construction of a piecewise continuous Lyapunov functional and via the Linear Matrix Inequalities(LMIs)method.Finally,the comparison results of a numerical simulation are elaborated to verify the validity of the proposed approach.

关键词： Directed switching topologies Lipschitz nonlinear dynamics Lyapunov functional Swarm system Time-Varying Formation(TVF) Unmanned Aerial Vehicle(UAV)

Deep-large faults controlling on the distribution of the venting gas hydrate system in the middle of the Qiongdongnan Basin, South China Sea

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China Geology 2024年第1期7卷 36-50页

作者： Jin-feng Ren Hai-jun Qiu Zeng-gui kuang Ting-wei Li yu-lin He Meng-jie Xu Xiao-xue Wang Hong-fei Lai Jin Liang National Engineering Research Center of Gas Hydrate Exploration and Development Guangzhou 511458China Guangzhou Marine Geological Survey China Geological SurveyGuangzhou 511458China China Geological Survey Ministtry of Natural ResourcesBeijing 100037China

Many locations with concentrated hydrates at vents have confirmed the presence of abundant thermogenic gas in the middle of the Qiongdongnan Basin(QDNB).However,the impact of deep structures on gasbearing fluids migration and gas hydrates distribution in tectonically inactive regions is still unclear.In this study,the authors apply high-resolution 3D seismic and logging while drilling(LWD)data from the middle of the QDNB to investigate the influence of deep-large faults on gas chimneys and preferred gasescape pipes.The findings reveal the following:(1)Two significant deep-large faults,F1 and F2,developed on the edge of the Songnan Low Uplift,control the dominant migration of thermogenic hydrocarbons and determine the initial locations of gas chimneys.(2)The formation of gas chimneys is likely related to fault activation and reactivation.Gas chimney 1 is primarily arises from convergent fluid migration resulting from the intersection of the two faults,while the gas chimney 2 benefits from a steeper fault plane and shorter migration distance of fault F2.(3)Most gas-escape pipes are situated near the apex of the two faults.Their reactivations facilitate free gas flow into the GHSZ and contribute to the formation of fracture‐filling hydrates.

关键词： Venting gas hydrates Deep-large faults Gas chimney Gas-escape pipes High-resolution 3D seismic Logging while drilling Qiongdongnan Basin South China Sea

Reading of Qin Bamboo Slips

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China Book International 2024年第2期 88-91页

作者： Zhao Yan kuang yu Chen Dietrich Tschanz School of Liberal Arts Northeast Normal University Department of East Asian Studies at Rutgers University in New Jersey Confucius Institute at Rutgers University Rutgers University in New Jersey University Chinese of Zurich University of Pennsylvania Rutgers University

This book contains a total of 44 articles in 16 groups of Qin bamboo slips,through the interpretation of characters,words,sentence analysis,chapter identification,and interpretation of literary meaning,the original esoteric and difficult documents are dismantled layer by layer,and the relevant historical background is introduced,in an effort to enable readers to obtain a complete background of knowledge needed to understand Qin bamboo slips.

关键词： meaning Bamboo enable

CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

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Research 2024年第1期2023卷 509-523页

作者： Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian yu Lei Li Jiaxiong Zhang Yehong kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology ChangshaHunanChina Furong Laboratory ChangshaHunanChina Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells.Although elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain unclear.We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse models.In mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation.We found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo.In CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of psoriasis.Using non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

关键词： CD147 pathogenesis markedly

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钢筋混凝土柱的易损性函数研究

工程力学 2024年第1期41卷 219-228页

作者：代旷宇于晓辉吕大刚郑州大学水利与土木工程学院郑州450001 哈尔滨工业大学土木工程学院哈尔滨150090 桂林理工大学土木建筑工程学院桂林541004

基于文献调研,建立了满足我国现行设计规范的钢筋混凝土(RC)框架柱的拟静力试验数据库。将RC柱的损伤状态分为六级,并给出了相应修复方法。基于FEMA P-58方法,以位移角为工程需求参数,建立了RC柱在各损伤状态下所对应的易损性函数。通过... 详细信息

基于文献调研,建立了满足我国现行设计规范的钢筋混凝土(RC)框架柱的拟静力试验数据库。将RC柱的损伤状态分为六级,并给出了相应修复方法。基于FEMA P-58方法,以位移角为工程需求参数,建立了RC柱在各损伤状态下所对应的易损性函数。通过与FEMA P-58的易损性函数对比,对所建立的易损性函数的质量进行了评定,并讨论了抗震设防等级和轴压比对易损性函数的影响。结果表明:该文所建立的易损性函数整体处于高质量水准。各极限状态下易损性函数中位值范围为0.764%~4.52%,对数标准差范围为0.339~0.425。三、四级框架柱与一级框架柱在各极限状态的易损性曲线的超越概率之差分别高达11.79%和15.39%。一级、二级及三、四级框架柱在高轴压比工况和低轴压比工况下各极限状态的易损性曲线的超越概率之差分别高达到42.61%、37.11%和43.37%。该文研究结果可辅助我国混凝土建筑结构的地震灾害损失评估及韧性分析。

关键词： RC柱易损性函数损伤状态修复方法抗震韧性

Efficient photocatalytic reduction of chromium(Ⅵ) using photoreduced graphene oxide as photocatalyst under visible light irradiation

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Journal of Materials Science & Technology 2021年第32期91卷 17-27页

作者： Mei yu Jing Shang yu kuang Department of Environment and Health State Key Joint Laboratory of Environmental Simulation and Pollution ControlCollege of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China

Graphene oxide(GO),a new and promising material,has been widely used as a co-catalyst in photocatalytic reactions;however,its capacity as a sole photocatalyst has rarely been investigated.In this study,ultraviolet(UV) light irradiation was used as a modification method to obtain reduced GO(rGO) samples.The samples were used as photocatalysts to examine their visible light photocatalytic activity toward hexavalent chromium(Cr(Ⅵ)) removal.Atomic force microscopy(AFM),X-ray diffraction(XRD),UV-vis spectrophotometry,Raman spectroscopy,X-ray photoelectron spectroscopy(XPS),and electron spin resonance(ESR) spectroscopy were applied to interpret the surface and structure changes with UV irradiation.The oxygen-containing functional groups(OFGs) on the GO surface were reduced to defective carbons andπ-conjugated C=C(sp^(2) domains) under UV light;this led to a decrease in the interlayer distance between GO sheets,GO fragmentation,and increased disorder on the GO surface.The restoration of sp^(2) domains led to a narrower band gap of GO,which favored the rGO excitation by visible light to generate electron-hole pairs.The rGO pre-irradiated with UV for 1 h(rGO-1),possessing the highest defect density and electron generation efficiency,exhibited the best Cr(Ⅵ) reduction efficiency,which was about three times that of the GO sample;moreover,it outperformed most of the reported GO-based nanomaterials.In addition,low pH and the addition of citric acid as a hole scavenger could further improve the photocatalytic activity.This study proves that GO or rGO can be used as a sole photocatalyst under visible light to remove environmental pollutants such as heavy-metal ions,and it paves the way for the development of this kind of material and its UV-irradiation modification for further applications.

关键词： Graphene oxide Chromium(Ⅵ) Defect density UV-irradiation modification Photocatalytic reduction