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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 ***,ultrasmall chiral gold nanoparticles(D-or L-NPs)modified by D-or L-glutathione ligands were *** 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 ***,the blood-brain barrier(BBB)-crossing ability of chiral NP-a NLRP3 as well as NLRP3 degradation was demonstrated in *** 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 ***,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,*** 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

Danhongqing formula alleviates cholestatic liver fibrosis by downregulating long non-coding RNA H19 derived from cholangiocytes and inhibiting hepatic stellate cell activation

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Journal of Integrative Medicine 2024年第2期22卷 188-198页

作者： Meng Li Yang Zhou Hui Zhu Lie-ming xu Jian ping Institute of Liver Diseases Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Preventive Treatment Center Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437 China Department of Gastroenterology Suzhou Traditional Chinese Medicine HospitalSuzhou 215000Jiangsu ProvinceChina Shanghai Key Laboratory of Traditional Chinese Medicine Shanghai 201203China Key Laboratory of Liver and Kidney Diseases(Ministry of Education) Shanghai 201203China

Objective:This study explores the mechanism of action of Danhongqing formula(DHQ),a compoundbased Chinese medicine formula,in the treatment of cholestatic liver ***:In vivo experiments were conducted using 8-week-old multidrug resistance protein 2 knockout(Mdr2-/-)mice as an animal model of cholestatic liver *** was administered orally for 8 weeks,and its impact on cholestatic liver fibrosis was evaluated by assessing liver function,liver histopathology,and the expression of liver fibrosis-related ***-time polymerase chain reaction,Western blot,immunohistochemistry and other methods were used to observe the effects of DHQ on long non-coding RNA H19(H19)and signal transducer and activator of transcription 3(STAT3)phosphorylation in the liver tissue of Mdr2-/-*** addition,cholangiocytes and hepatic stellate cells(HSCs)were cultured in vitro to measure the effects of bile acids on cholangiocyte injury and H19 *** overexpressing H19 were constructed,and a conditioned medium containing H19 was collected to measure its effects on STAT3 protein expression and cell *** intervention effect of DHQ on these processes was also *** overexpressing H19 were constructed to measure the impact of H19 on cell activation and assess the intervention effect of ***:DHQ alleviated liver injury,ductular reaction,and fibrosis in Mdr2-/-mice,and inhibited H19expression,STAT3 expression and STAT3 *** formula also reduced hydrophobic bile acid-induced cholangiocyte injury and the upregulation of H19,inhibited the activation of HSCs induced by cholangiocyte-derived conditioned medium,and decreased the expression of activation markers in *** overexpression of H19 in a human HSC line confirmed that H19 promoted STAT3 phosphorylation and HSC activation,and DHQ was able to successfully inhibit these ***:DHQ effectively alleviated spontaneous cholestatic liver fibrosis in Md

关键词： Liver cirrhosis biliary Long non-coding RNA H19 Danhongqing formula Cholangiocyte Hepatic stellate cells STAT3 transcription factor

OSMR is a potential driver of inflammation in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第11期19卷 2513-2521页

作者： Wenzhi Chen Shishi jiang Shu Li Cheng Li Renshi xu Department of Neurology Jiangxi Provincial People’s HospitalXiangya Hospital Jiangxi Hospital of Central South UniversityThe Clinical College of Nanchang Medical CollegeThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis is a neurodegenerative disease,and the molecular mechanism underlying its pathology remains poorly ***,inflammation is known to play an important role in the development of this *** identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis,as well as potential treatment targets,it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral ***,in this study we used a network-driven gene analysis tool,NetBID2.0,which is based on SJARACNe,a scalable algorithm for the reconstruction of accurate cellular networks,to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral *** results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory ***,there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral *** findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis driver neuroinflammation OSMR C9ORF72 neurodegenerative disease pathogenesis oxidative stress protein misfolding mitochondrial dysfunction

A disk I/O optimized system for concurrent graph processing jobs

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Frontiers of Computer Science 2024年第3期18卷 13-29页

作者： Xianghao xu Fang WANG Hong jiang Yongli CHENG Dan FENG Peng FANG School of Computer Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China Department of Computer Science&Engineering University of Texas at ArlingtonArlingtonTX 76019USA College of Computer and Data Science Fuzhou UniversityFuzhou 350108China Zhejiang Lab Hangzhou 311121China

In order to analyze and process the large graphs with high cost efficiency,researchers have developed a number of out-of-core graph processing systems in recent years based on just one commodity *** the other hand,with the rapidly growing need of analyzing graphs in the real-world,graph processing systems have to efficiently handle massive concurrent graph processing(CGP)***,due to the inherent design for single graph processing job,existing out-of-core graph processing systems usually incur unnecessary data accesses and severe competition of I/O bandwidth when handling the CGP *** this paper,we propose GraphCP,a disk I/O optimized out-of-core graph processing system that efficiently supports the processing of CGP *** proposes a benefit-aware sharing execution model to share the I/O access and processing of graph data among the CGP jobs and adaptively schedule the graph data loading based on the states of vertices,which efficiently overcomes above challenges faced by existing out-of-core graph processing ***,GraphCP adopts a dependency-based future-vertex updating model so as to reduce disk I/Os in the future *** addition,GraphCP organizes the graph data with a Source-Sorted Sub-Block graph representation for better processing capacity and I/O access *** evaluation results show that GraphCP is 20.5×and 8.9×faster than two out-of-core graph processing systems GridGraph and GraphZ,and 3.5×and 1.7×faster than two state-of-art concurrent graph processing systems Seraph and GraphSO.

关键词： graph processing disk I/O concurrent jobs

Transition-metal-catalyzed remote meta-C-H alkylation and alkynylation of aryl sulfonic acids enabled by an indolyl template

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Chinese Chemical Letters 2024年第8期35卷 254-259页

作者： Pengfei Zhang Qingxue Ma Zhiwei jiang Xiaohua xu Zhong Jin College of Chemistry State Key Laboratory of Elemento-organic ChemistryNankai UniversityTianjin 300071China Key Laboratory of Xinjiang Native Medicinal and Edible Plant Resource Chemistry College of Chemistry and Environmental SciencesKashi UniversityKashgar 844007China

Transition-metal-catalyzed remote sp^(2)C-H functionalization of aryl sulfonic acids was hardly ever real-ized owing to competitive ortho-C-H functionalization of aryl sulfonates and electron-deficient nature of phenyl ***,with the assistance of a practical biaryl indolyl directing template,palladium-catalyzed remote sp^(2)C-H alkylation of aryl sulfonic acids have been achieved in moderate to good yields with exclusive meta ***,remote meta-selective C-H alkynylation of aryl sulfonic acids was also accomplished with a rhodium *** meta-C-H functionalized products proved to be the superior synthetic precursors,which are difficult to access using the conventional strategy.

关键词： C-H functionalization Aryl sulfonic acid Site-selectivity Transition-metal catalysis Alkylation Alkynylation

Decoding the Molecular Mechanisms of BRAFV600E-Induced Nevi Formation

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Biomedical and Environmental Sciences 2024年第7期37卷 774-784页

作者： Weizheng Liang Yuxuan Liu Dandan xu Wenjie jiang Rensen Ran Central Laboratory The First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000HebeiChina Institute of Molecular Immunology School of Laboratory Medicine and BiotechnologySouthern Medical UniversityGuangzhou 510515GuangdongChina Department of Artificial Intelligence and Data Science Hebei University of TechnologyTianjin 300401China Department of Chemical Biology School of Life SciencesSouthern University of Science and TechnologyShenzhen 518055GuangdongChina

Melanocytes derived from neural crest cells harbor the BRAFV600E mutation,which is the predominant driver of nevus formation in *** mutation leads to malignant cell proliferation and subsequent cell cycle arrest,culminating in oncogene-induced senescence and nevus ***,emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAFV600E-induced senescent ***,the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAFV600E,via the mitogen-activated protein kinase signaling pathway,triggers nevus *** study provides an overview and discussion of the molecular mechanisms underpinning BRAFV600E-induced melanocyte nevus formation and the relevant animal models employed for their *** also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAFV600E animal models created through gene editing technologies.

关键词： BRAFV600E Melanocytes Nevi Oncogene-induced senescence Animal models

A Dual Closed-Loop Digital Twin Construction Method for Optimizing the Copper Disc Casting Process

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IEEE/CAA Journal of Automatica Sinica 2024年第3期11卷 581-594页

作者： Zhaohui jiang Chuan xu Jinshi Liu Weichao Luo Zhiwen Chen Weihua Gui IEEE the School of Automation Central South UniversityChangsha 410083China the Peng Cheng Laboratory Shenzhen 518000China

The copper disc casting machine is core equipment for producing copper anode plates in the copper metallurgy *** copper disc casting machine casting package motion curve(CPMC) is significant for precise casting and efficient ***,the lack of exact casting modeling and real-time simulation information severely restricts dynamic CPMC *** this end,a liquid copper droplet model describes the casting package copper flow pattern in the casting ***,a CPMC optimization model is proposed for the first *** top of this,a digital twin dual closed-loop self-optimization application framework(DT-DCS) is constructed for optimizing the copper disc casting process to achieve self-optimization of the CPMC and closed-loop feedback of manufacturing information during the casting ***,a case study is carried out based on the proposed methods in the industrial field.

关键词： Copper disc casting machine digital twin(DT) mechanism modeling self-optimization

Collaborative positioning for swarms:A brief survey of vision,LiDAR and wireless sensors based methods

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Defence Technology（防务技术） 2024年第3期33卷 475-493页

作者： Zeyu Li Changhui jiang Xiaobo Gu Ying xu Feng zhou Jianhui Cui College of Geodesy and Geomatics Shandong University of Science and TechnologyQingdao266590China Geoloc Laboratory Universite Gustave EiffelParis77454France School of Automation Guangdong University of TechnologyGuangzhou510006China

As positioning sensors,edge computation power,and communication technologies continue to develop,a moving agent can now sense its surroundings and communicate with other *** receiving spatial information from both its environment and other agents,an agent can use various methods and sensor types to localize *** its high flexibility and robustness,collaborative positioning has become a widely used method in both military and civilian *** paper introduces the basic fundamental concepts and applications of collaborative positioning,and reviews recent progress in the field based on camera,LiDAR(Light Detection and Ranging),wireless sensor,and their *** paper compares the current methods with respect to their sensor type,summarizes their main paradigms,and analyzes their evaluation ***,the paper discusses the main challenges and open issues that require further research.

关键词： Collaborative positioning Vision LiDAR Wireless sensors Sensor fusion

Photoperiod Mediates the Effects of Temperature and Light Intensity on the Proliferation of Ulva prolifera

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Journal of Ocean University of China 2024年第1期23卷 255-263页

作者： jiang Jianan YU Yanyan CHEN Yili LI Yahe xu Nianjun Key Laboratory of Marine Biotechnology of Zhejiang Province School of Marine SciencesNingbo UniversityNingbo 315211China

In order to study the complex effects of photoperiod,temperature,and light intensity on the spore maturation and release number of Ulva prolifera,we cultured thalli segment(2–3 mm)under three different photoperiods(L:D=12:12,14:10 and 10:14),temperature(15℃(LT),25℃(MT)and 30℃(HT))and light intensity(100,200 and 400μmol m^(−2)s^(−1),noted as LL,ML and HL,respectively)*** the maturation time,spore release number and chlorophyll fluorescence were *** results suggested that:1)The spore maturation time was accelerated by higher temperature or higher light intensity from 62 h to 36 h,and changes in day length accelerated the spore maturation to a certain extent as compared with 12:12 light/dark cycle;2)Higher light intensity significantly decreased the chlorophyll fluorescence(Fv′/Fm′,NPQ,rETRmax andα)of the mature reproductive segment under 30℃with 12:12 light/dark *** when in the other photoperiods(10:14 and 14:10 conditions),the inhibitory effects of high light intensity were alleviated significantly;3)The optimum condition for the spore maturation and release was 12:12 light/dark cycle,25℃,400μmol m^(−2)s^(−1),with both shorter and longer photoperiod reducing the spore release number;4)Higher light intensity significantly increased the spore release number under 25℃,but these effects were alleviated by 30℃*** study is the first attempt to elucidate the coincidence effects of photoperiod,temperature and light intensity on the reproduction of Ulva,which would help to reveal the mechanism of the rapid proliferation of green tide.

关键词： light intensity maturation photoperiod reproduction temperature Ulva prolifera