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Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

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Neural Regeneration Research 2024年第9期19卷 2081-2088页

作者： Xiaoli Fang Sha Liu Bilal Muhammad Mingxuan Zheng xing Ge Yan Xu Shu Kan Yang Zhang Yinghua Yu Kuiyang Zheng Deqin Geng chun-Feng Liu Department of Neurology and Clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Department of Neurology Xuzhou Central HospitalXuzhouJiangsu ProvinceChina Jiangsu Key Laboratory of Neuropsychiatric Disease and Institute of Neuroscience Soochow UniversitySuzhouJiangsu ProvinceChina

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal *** dysfunction can precede the onset of motor symptoms by several *** microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain ***/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease *** this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota *** found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor ***,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with ***,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and *** of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier *** results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s ***,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that c

关键词： C/EBP/AEP signaling pathway endotoxemia fecal microbiota transplantation intestinal barrier intestinal inflammation microbiota-gut-brain axis Parkinson’s disease

An optimization-oriented modeling approach using input convex neural networks and its application on optimal chiller loading

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Building Simulation 2024年第4期17卷 639-655页

作者： Shanshuo xing Jili Zhang Song Mu Dalian University of Technology Dalian116024China Guangdong Airport Baiyun Information Technology Co. Ltd.Guangzhou510000China

Optimization for the multi-chiller system is an indispensable approach for the operation of highly efficient chiller *** optima obtained by model-based optimization algorithms are dependent on precise and solvable objective *** classical neural networks cannot provide convex input-output mappings despite capturing impressive nonlinear fitting capabilities,resulting in a reduction in the robustness of model-based *** this paper,we leverage the input convex neural networks(ICNN)to identify the chiller model to construct a convex mapping between control variables and the objective function,which enables the NN-based OCL as a convex optimization problem and apply it to multi-chiller optimization for optimal chiller loading(OCL).Approximation performances are evaluated through a four-model comparison based on an experimental data set,and the statistical results show that,on the premise of retaining prior convexities,the proposed model depicts excellent approximation power for the data set,especially the unseen ***,the ICNN model is applied to a typical OCL problem for a multi-chiller system and combined with three types of optimization *** with conventional and meta-heuristic methods,the numerical results suggest that the gradient-based BFGS algorithm provides better energy-saving ratios facing consecutive cooling load inputs and an impressive convergence speed.

关键词： chiller plant input convex neural network optimal load distribution convex optimization

Numerical simulation study on the hygrothermal performance of building exterior walls under dynamic wind-driven rain condition

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Building Simulation 2024年第2期17卷 207-221页

作者： xing Hu Huibo Zhang Hui Yu School of Design Shanghai Jiao Tong UniversityShanghai200240China

Wind-driven rain(WDR)has a significant influence on the hygrothermal performance,durability,and energy consumption of building *** calculation of WDR loads using semi-empirical models has been incorporated into the boundary conditions of coupled heat and moisture transfer ***,prior research often relied on fixed WDR absorption ratio,which fail to accurately capture the water absorption characteristics of porous building materials under rainfall ***,this study aims to investigate the coupled heat and moisture transfer of exterior walls under dynamic WDR boundary conditions,utilizing an empirically obtained WDR absorption ratio model based on field *** developed coupled heat and moisture transfer model is validated against the HAMSTAD *** findings reveal that the total WDR flux calculated with the dynamic WDR boundary is lower than that obtained with the fixed WDR boundary,with greater disparities observed in orientations experiencing higher WDR *** variations in moisture flow significantly impact the surface temperature and relative humidity of the walls,influencing the calculation of cooling and heating loads by different *** to the transient heat transfer model,the coupled heat and moisture transfer model incorporating dynamic WDR boundary exhibits maximum increases of 17.6%and 16.2%in cooling and heating loads,*** dynamic WDR boundary conditions provide more precise numerical values for surface moisture flux,offering valuable insights for the thermal design of building enclosures and load calculations for HVAC systems.

关键词： wind-driven rain building component hygrothermal model transient simulation cooling and heating loads

Prevalence of Cannabis Use around the World:A Systematic Review and Meta-Analysis,2000-2024

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China CDC weekly 2024年第25期6卷 597-604,I0013,I0014页

作者： Qianning Wang Zhen Qin xing xing He Zhu Zhongwei Jia National Institute of Health Data Science Center for Drug Abuse Prevention and ControlPeking UniversityBeijingChina School of Public Health Peking UniversityBeijingChina

This study aims to perform a systematic review and meta-analysis on the global prevalence of cannabis use to inform drug prevention strategies,policy-making,and resource *** study initially screened 177,843 studies published between January 1,2000,and January 15,2024,using peer-reviewed databases including Web of Science,PubMed,Scopus,Embase,and Cochrane ***,595 studies were identified for data extraction,and 39 of these were selected as country-representative *** among the selected studies was assessed using the chi-squared test and I2 statistic,while sensitivity analysis was conducted to evaluate the robustness of the *** prevalence of cannabis use varied between 0.42%and 43.90%across 33 European countries,1.40%to 38.12%across 15 North and South American countries,0.30%to 19.10%across 16 Asian countries,and 1.30%to 48.70%across 18 Oceania and African *** pooled prevalence of cannabis use was 12.0%[95%confidence interval(CI):10.0,14.3]in countries where cannabis is legalized,compared to 5.4%(95%CI:4.3,6.9)in non-legalized *** findings indicate that the prevalence of cannabis use has disproportionately increased in most countries with the implementation of medical or recreational cannabis legalization policies and relevant geographic *** efforts are needed to monitor newly cannabis-legalized countries and prevent initial use.

关键词： prevention legal initially

An improved analysis method for assessing the nuclear-heating impact on the stability of toroidal field magnets in fusion reactors

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Nuclear Science and Techniques 2024年第6期35卷 163-176页

作者： Yu-Dong Lu jin-xing Zheng Xu-Feng Liu Huan Wu Jian Ge Kun Xu Ming Li Hai-Yang Liu Lei Zhu Fei Liu Institute of Plasma Physics Hefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China University of Science and Technology of China Hefei 230026China

The superconducting magnet system of a fusion reactor plays a vital role in plasma confinement,a process that can be dis-rupted by various operational factors.A critical parameter for evaluating the temperature margin of superconducting magnets during normal operation is the nuclear heating caused by D-T *** study investigates the impact of nuclear heat-ing on a superconducting magnet system by employing an improved analysis method that combines neutronics and thermal *** the magnet system,toroidal field(TF)magnets are positioned closest to the plasma and bear the highest nuclear-heat load,making them prime candidates for evaluating the influence of nuclear heating on *** enhance the modeling accuracy and facilitate design modifications,a parametric TF model that incorporates heterogeneity is established to expedite the optimization design process and enhance the accuracy of the computations.A comparative analysis with a homogeneous TF model reveals that the heterogeneous model improves accuracy by over 12%.Considering factors such as heat load,magnetic-field strength,and cooling conditions,the cooling circuit facing the most severe conditions is selected to calculate the temperature of the *** selection streamlines the workload associated with thermal-hydraulic *** approach enables a more efficient and precise evaluation of the temperature margin of TF ***,it offers insights that can guide the optimization of both the structure and cooling strategy of superconducting magnet systems.

关键词： Superconducting magnet Nuclear heating Neutronics Thermal hydraulics

Glutathione-depleted cyclodextrin pseudo-polyrotaxane nanoparticles for anti-inflammatory oxaliplatin(Ⅳ) prodrug delivery and enhanced colorectal cancer therapy

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Chinese Chemical Letters 2024年第4期35卷 280-286页

作者： Wenjia Wang xingyue He Xiaojie Wang Tiantian Zhao Osamu Muraoka Genzoh Tanabe Weijia Xie Tianjiao Zhou Lei xing Qingri jin Hulin Jiang State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China Faculty of Pharmacy Kinki University HigashiosakaOsaka 577-8502Japan State Key Laboratory of Natural Medicines(SKLNM)and Department of Medicinal Chemistry School of PharmacyChina Pharmaceutical UniversityNanjing 210009China School of Pharmacy Hangzhou Medical CollegeHangzhou 311399China College of Pharmacy Yanbian UniversityYanji 133002China

Oxaliplatin(Oxa) is the first-line chemotherapeutic drug for the treatment of colorectal cancer(CRC). However, long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2(COX-2) and prostaglandin E2(PGE2), which can promote tumor metastasis. Moreover,high glutathione(GSH) levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa. Herein, an Oxa(Ⅳ) prodrug with anti-inflammatory properties(desmethyl naproxe, DN) and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles(designated DNPt@PPRI). The relesae of DN from DNPt@PPRI can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein,and also synergize with Oxa to inhibit tumor. More importantly, GSH depletion can reduce the detoxification of Oxa and further enhance chemotherapy-induced apoptosis. DNPt@PPRI have a good GSH depletion ability to enhance the sensitivity of Oxa, indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.

关键词： Oxaliplatin Glutathione depletion Tetravalent platinum prodrug Synergistic therapy Colorectal cancer

An empirical model for high energy density lithium-(ion)batteries with ultra-thick electrodes

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Tungsten 2024年第1期6卷 230-237页

作者： Li-Ming jin Guang-Guang xing Nan Qin Yan-Yan Lu Jun-Sheng Zheng Cun-Man Zhang Jim P.Zheng School of Automotive Studies and Clean Energy Automotive Engineering Center Tongji UniversityShanghai 201804China Department of Electrical Engineering University at BuffaloThe State University of New YorkBuffaloNY 14260USA

Increasing the electrode thickness is a significant method to decrease the weight and volume ratio of the inactive components for high energy density of the *** this contribution,we extracted a repeating unit in the configurations and establish the empirical energy density model based on some *** this model,the effects of the electrode thickness on the energy density for lithium-ion batteries(LIBs),lithium metal batteries(LMBs),and anode-free lithium batteries(ALBs)are evaluated quantitively with the current parameters of the *** results demonstrate that the structure evolutions from LIBs,LMBs to ALBs with the reduction of the anode weight contribution,the energy density can be well improved *** the increase of the thickness of the electrode provide another route to furthe r enhance the energydensity by decreasing the weight contribution of inactive materials;meanwhile the effects for ALBs are higher than LMBs and LIBs due to the higher weight ratio of inactive *** empirical energy density model is also applied into the practical system and provide intuitional results to guide the battery design for higher energy density.

关键词： Empirical model High energy density Lithium batteries Ultra-thick electrodes

Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： chun-Yang Li xing-Chen Liu Yu-Zhuo Li Yan Wang Yan-Hong Nie Yu-Ting Xu Xiao-Tong Zhang Yong Lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe *** replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA *** pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously *** this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear *** individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during *** successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer

New dating indicates intermittent human occupation of the Nwya Devu Paleolithic site on the high-altitude central Tibetan Plateau during the past 45,000 years

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Science China Earth Sciences 2024年第2期67卷 531-551页

作者： Junyi GE Xiaoling ZHANG Shejiang WANG Linhui LI Wei HE Yingshuai jin Peiqi ZhANG Bing XU Chenglong DENG John WOLSEN Zhengtang GUO xing GAO Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of SciencesBeijing 100044China University of the Chinese Academy of Sciences Beijing 100049China Tibetan Cultural Relics Conservation Institute Lhasa 850000China Key Laboratory of Cenozoic Geology and Environment Institute of Geology and GeophysicsChinese Academy of Sciences.Beijing 100029China State Key Laboratory of Lithospheric Evolution Institute of Geology and GeophysicsChinese Academy of SciencesBeijing100029China School of Anthropology University of ArizonaTucson85721USA

The timing and mechanisms of the human occupation of the demanding high-altitude Tibetan Plateau environment are of great ***,we report on our reinvestigations and dating of the Nwya Devu site,located nearly 4600 meters above sea level on the central Tibetan Plateau.A new microblade techno-complex was identified on a lower lake shore at this site,distinct from the previously reported blade tool *** two lithic assemblages were dated to 45.6±2.6 and10.3±0.5 ka using optically stimulated luminescence and accelerator mass spectrometry^(14)C *** represent,respectively,the earliest known Paleolithic and microlithic sites on the interior Tibetan Plateau,indicating multiple occupation episodes of hunter-gatherers during the past 45 *** studies reveal that relatively stable depositional conditions and a paleoenvironment characterized by a comparatively warm climate facilitated these multiple occupations at Nwya *** contemporaneous occurrence of the Upper Paleolithic blade technology on the Tibetan Plateau and most of Eurasia between 50 and 40 ka indicates rapid,large-scale dispersals of humans that profoundly affected human demography on a large *** new archaeological evidence and previously reported genetic data,we conclude that the Tibetan Plateau provided a relatively stable habitat for Upper Paleolithic hunter-gatherers,which may have contributed to the complex and multiple-origin gene pool of present-day Tibetans.

关键词： Tibetan Plateau Paleolithic Nwya Devu High-altitude adaptation Microblade industry Early Upper Paleolithic OSLdating AMS^(14)C dating