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Increase of PCSK9 expression in diabetes promotes VEGFR2ubiquitination to inhibit endothelial function and skin wound healing

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Science China Life Sciences 2024年

作者： Jian-Jun Gao Fang-Yuan Wu Yu-Jia Liu Le Li Yi-Jun Lin Yue-Ting Kang Yue-Ming Peng Yi-Fang Liu Chen Wang zhen-sheng ma Yang Cao Hong-Yu Cao Zhi-Wei Mo Yan Li Jing-Song Ou Zhi-Jun Ou Division of Cardiac Surgery Cardiovascular Diseases Institute The First Affiliated Hospital Sun Yat-sen University National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases NHC key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University) Key Laboratory of Assisted Circulation and Vascular Diseases Chinese Academy of Medical Sciences Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases Division of Hypertension and Vascular Diseases Department of Cardiology Heart Center The First Affiliated Hospital Sun Yat-sen University Division of Vascular Surgery The First Affiliated Hospital Sun Yat-sen University Guangdong Provincial Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-sen University

Diabetic foot ulcers（DFUs） are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9（PCSK9） regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells（ECs） increased significantly under high glucose（HG）stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2（VEGFR2）, which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase（eNOS）, and ERK1/2, leading to decreased nitric oxide（NO） production and increased superoxide anion(O2·-) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O2·-production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/***, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.

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Causal role of immune cells in obstructive sleep apnea hypopnea syndrome:Mendelian randomization study

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World Journal of Clinical Cases 2024年第7期12卷 1227-1234页

作者： Huang-Hong Zhao zhen ma Dong-sheng Guan Department of Encephalopathy Henan Provincial Hospital of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Personnel The First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina Department of Neurology Henan Provincial Hospital of Traditional Chinese MedicineZhengzhou 450000Henan ProvinceChina

BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic *** immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to *** a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of *** To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical *** A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and *** statistics for each immune cell feature were obtained from the GWAS *** on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic *** results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity *** Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was ***,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.

关键词： Obstructive sleep apnea hypopnea syndrome Immunity Causal inference MR analysis Sensitivity

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Stimuli-evoked NOergic molecules and neuropeptides at acupuncture points and the gracile nucleus contribute to signal transduction of propagated sensation along the meridian through the dorsal medulla-thalamic pathways

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Journal of Integrative Medicine 2024年第5期22卷 515-522页

作者： sheng-xing ma Lundquist Institute for Biomedical Innovation Harbor-University of California at Los Angeles (UCLA) Medical Center Department of Obstetrics and Gynecology David Geffen School of Medicine at UCLA and Harbor-UCLA Medical Center

Numerous studies from different international groups have demonstrated that sensations can be propagated along acupuncture channel pathways. The propagated sensation along the channel pathway(PSCP)can be elicited by electroacupuncture(EA), transcutaneous electrical nerve stimulation(TENS), manual acupuncture(ma), and heat applied to distal acupuncture points(acupoints). Nitric oxide(NO) levels were reported to be elevated in the gracile nucleus and skin regions near to the EA sites, with higher levels at acupoints associated with an enhanced expression of NO synthase and transient receptor potential vanilloid type 1. The stimuli, EA, ma, TENS, and heat, have been used to elicit axonal reflexes, which increase local release of NO and neuropeptides such as calcitonin gene related peptide. Furthermore, the sensation of PSCP along the body surface occurs only ipsilaterally to the stimulated acupoints in various human studies, which does not support the involvement of the spinal-thalamic pathway, which would involve cross over transmission of the signals. The gracile nucleus receives ascending input from the sciatic nerve and responds to somatosensory stimulation mainly on the ipsilateral side via the dorsal column pathway. EA at Zusanli(ST36) increases NO release and expression of NO synthase mainly in the ipsilateral side of the gracile nucleus, while the cardiovascular effects and analgesic responses to EA at ST36 are changed by influences of L-arginine-derived NO synthesis in the ipsilateral gracile nucleus in rats. The stimuli-induced release of NOergic molecules and neuropeptides exist high levels in the acupoints, which contain rich neuronal components and blood vessels. Enhanced NOergic molecules at acupoints cause axon reflexes during the stimuli, which elevate cutaneous blood flow. Elevated NOergic molecules and local blood flow may spread over acupoints one after another along the meridian lines differing from nerve pathways following the stimuli to induce PSC

关键词： Axon reflex Biophysical approaches Calcitonin related polypeptide Dorsal funiculus tract Meridian system Nitric oxide

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In silico optimization of actuation performance in dielectric elastomercomposites via integrated finite element modeling and deep learning

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Theoretical & Applied Mechanics Letters 2024年第1期14卷 48-56页

作者： Jiaxuan ma sheng Sun materials Genome Institute Shanghai UniversityShanghai 200444China Zhejiang Laboratory Hangzhou 311100China Shanghai Frontier Science Center of Mechanoinformatics Shanghai UniversityShanghai 200444China

Dielectric elastomers(DEs)require balanced electric actuation performance and mechanical integrity under applied *** high dielectric particles as fillers provides extensive design space to optimize concentration,morphology,and distribution for improved actuation performance and material *** study presents an integrated framework combining finite element modeling(FEM)and deep learning to optimize the microstructure of DE *** first calculates actuation performance and the effective modulus across varied filler combinations,with these data used to train a convolutional neural network(CNN).Integrating the CNN into a multi-objective genetic algorithm generates designs with enhanced actuation performance and material modulus compared to the conventional optimization approach based on FEM approach within the same *** framework harnesses artificial intelligence to navigate vast design possibilities,enabling optimized microstructures for high-performance DE composites.

关键词： Dielectric elastomer composites Multi-objective optimization Finite element modeling Convolutional neural network

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Amino acids TORC(talk)to anabolism through uncharged tRNA

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Science China(Life Sciences) 2024年第8期67卷 1775-1776页

作者： zhen-zhen ma Shi-Min Zhao The Obstetrics&Gynecology Hospital of Fudan University State Key Laboratory of Genetic EngineeringShanghai Key Laboratory of Metabolic Remodelling and HealthFudan UniversityShanghai 200090China

Anabolism is essential for proliferation as well as to replenish dysfunctional macromolecules in *** to that both substantial building blocks and energy are required for anabolism,cells must double check whether these prerequisites are met before deciding to start *** acids are building blocks of protein synthesis,their sufficiency in cells is closely monitored by several mechanisms,which all are linked to protein synthesis.

关键词： synthesis. synthesis deciding

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Further Results on Stability Analysis for Sampled-Data Systems via Refined Semi-Looped-Functional

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Journal of Systems Science & Complexity 2024年第1期37卷 318-328页

作者： sheng Zhaoliang XU shengyuan ma Qian ZHANG Baoyong School of Automation Nanjing University of Science and TechnologyNanjing 210094China

This paper investigates the stability problem for sampled-data systems by adopting a refined semi-looped-functional,which is with the following two ***,the new functional term is with a new integral vectorη0,which contains sampling information of the systems and associates two commonly used ***,the vectorη0 is combined into various zero equations for processing the functional,especially where a new equation is derived fromη*** on the refined functional,further stability results for sampled-data systems are *** the effectiveness of the results is numerically verified through two examples at the end.

关键词： Integral vector sampled-data systems semi-looped-functional stability analysis.

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Molecular Chaperone-Dependent Polymer Translocation through Nanopores: The Effects of Chaperone Concentration and Chaperone-Polymer Interaction

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Chinese Journal of Polymer Science 2024年第1期42卷 125-132,I0011页

作者： Chang-sheng Zuo Kang Wang Li-zhen Sun Ting-Ting Sun Department of Physics Zhejiang University of Science and TechnologyHangzhou 310023China Department of Applied Physics Zhejiang University of TechnologyHangzhou 310014China

The polymer translocation through a nanopore from a donor space(or named cis side) to a receiver space(trans side) in the chaperone-induced crowded environment has attracted increasing attention in recent years due to its significance in biological systems and technological applications. In this work, we mainly focus on the effects of chaperone concentration and chaperone-polymer interaction on the polymer translocation. By assuming the polymer translocation to be a quasi-equilibrium process, the free energy F of the polymer can be estimated by Rosenbluth-Rosenbluth method and then the translocation time τ can be calculated by Fokker-Plank equation based on the obtained free energy landscape. Our calculation results show that the translocation time can be controlled by independently tuning the chaperone concentration and chaperone-polymer interaction at the cis side or the trans side. There exists a critical chaperone-polymer attraction ε~*=-0.2 at which the volume exclusion and interaction effects of the chaperone can balance each other. Additionally, we also find that at large chaperone-polymer attraction, the translocation time is mainly governed by the diffusion coefficient of the polymer.

关键词： Polymer translocation Rosenbluth-Rosenbluth method Fokker-Plank equation Free energy landscapes

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Theoretical study of aromaticity reversal in dimethyldihydropyrene derivatives

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Chinese Journal of Structural Chemistry 2024年第5期43卷 8-10页

作者： Fangwen Peng zhen Luo Yingjin ma Haibo ma School of Chemistry and Chemical Engineering Nanjing UniversityNanjing210023China Computer Network Information Center Chinese Academy of SciencesBeijing100190China Qingdao Institute for Theoretical and Computational Sciences School of Chemistry and Chemical EngineeringShandong UniversityQingdaoShandong266237China

Aromaticity has always been an intriguing chemistry topic,which is considered to have close relations with materials'stability and chemical reactivity due to special energy *** conjugated cycles,Hückel's rule,proposed in 1931,suggests that annulenes having[4n+2]and[4n]πelectrons present aromatic and antiaromatic characters with closed and open electronic configurations,respectively[1].

关键词： Hückel aromatic reactivity

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Solvent-free carbon sphere nanofluids towards intelligent lubrication regulation

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Friction 2024年第1期12卷 95-109页

作者： sheng ZHANG Wen LI Xiaoliang ma Xiaoqiang FAN Minhao ZHU Tribology Research Institute School of Mechanical EngineeringSouthwest Jiaotong UniversityChengdu 610031China Key Laboratory of Advanced Technologies of materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

By simply switching the electrical circuit installed on steel/steel contact,the tribological behaviors of nanofluids(NFs)can be regulated in real time,thereby achieving the desired performance of friction reduction and wear ***,solvent-free carbon spherical nanofluids(C-NFs)were successfully prepared for intelligent lubrication regulation.C-NFs with excellent lubrication performance can immediately reduce the coefficient of friction(COF)despite applying a weak electric potential(1.5 V).Moreover,polyethylene glycol 400(PEG400)containing 5.0 wt%C-NFs remained responsive to electrical stimulation under the intermittent voltage application with an average coefficient of friction(ACOF)reduction of 20.8%over *** intelligent lubrication regulation of C-NFs under an external electric field(EEF)mainly depends on the orderly arranged double-electric adsorption film of ion canopy-adsorbed carbon spheres(CSs).The intermittent electrical application can continuously reinforce the adsorption film and its durability for real-time controlling the sliding ***-stimulation-responsive intelligent lubricants provide a new technical support for realizing intelligent stepless control of devices.

关键词： solvent-free carbon spherical nanofluids(C-NFs) intelligent lubrication regulation lubrication performance adsorption film

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SDCC: software-defined collective communication for distributed training

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Science China(Information Sciences) 2024年第9期67卷 105-125页

作者： Xin JIN zhen ZHANG Yunshan JIA Yun ma Xuanzhe LIU School of Computer Science Peking University Department of Computer Science and Technology Johns Hopkins University

Communication is crucial to the performance of distributed training. Today's solutions tightly couple the control and data planes and lack flexibility, generality, and performance. In this study, we present SDCC, a software-defined collective communication framework for distributed training. SDCC is based on the principle of modern systems design to effectively decouple the control plane from the data *** abstracts the operations for collective communication in distributed training with dataflow operations and unifies computing and communication with a single dataflow graph. The abstraction, together with the unification, is powerful: it enables users to easily express new and existing collective communication algorithms and optimizations, simplifies the integration with different computing engines(e.g., Py Torch and Tensor Flow) and network transports(e.g., Linux TCP and kernel bypass), and allows the system to improve performance by exploiting parallelism exposed by the dataflow graph. We further demonstrate the benefits of SDCC in four use cases.

关键词： machine learning systems distributed training deep learning collective communication software-defined networking

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