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Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 802-814页

作者： ye hu Chao {2. {3. Chen Yu-Dong Liu Jian-Gao Fan department of Gastroenterology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina department of Geriatrics Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina department of Gastroenterology Changxing branch of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease(MASLD),the absence of licensed medications is striking.A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available *** therapies center on four major *** the close relationship between MASLD and type 2.diabetes,the first approach involves antidiabetic medications,including incretins,thiazolidinedione insulin sensitizers,and sodium-glucose cotransporter 2.*** second approach targets hepatic lipid accumulation and the resultant metabolic *** in this group include peroxisome proliferatoractivated receptor agonists(e.g.,pioglitazone,elafibranor,saroglitazar),bile acid-farnesoid X receptor axis regulators(obeticholic acid),de novo lipogenesis inhibitors(aramchol,NDI-010976),and fibroblast growth factor 2./19 *** third approach focuses on targeting oxidative stress,inflammation,and *** in this group include antioxi-dants(vitamin E),tumor necrosis factor a pathway regulators(emricasan,pentoxifylline,ZSP1601),and immune modulators(cenicriviroc,belapectin).The final group targets the gut(IMM-12.e,solithromycin).Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side *** review aimed to provide an update on these medications.

关键词： NAFLD MASLD Clinical trial Medication Hypoglycemic agents Intermediary metabolism

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Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang hu Li sun Hao Lin Yuheng Liao hui Yang {3. Mao department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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Reconsidering gas as clean energy:Switching to electricity for household cooking to reduce NO_(2.-attributed disease burden

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Eco-Environment & Health 2024年第2期3卷 174-182页

作者： ying hu {2. Wang Zhuohui Zhao Bin Zhao department of Building Science School of ArchitectureTsinghua UniversityBeijing 100084China School of Public Health Fudan UniversityShanghai 200433China Key Laboratory of Public Health Safety of the Ministry of Education NHC Key Laboratory of Health Technology AssessmentFudan UniversityShanghai 200433China Shanghai Typhoon Institute/CMA Shanghai Key Laboratory of Meteorology and HealthIRDR International Center of Excellence on Risk Interconnectivity and Governance on Weather/Climate Extremes Impact and Public HealthWMO/IGAC MAP-AQ Asian Office ShanghaiFudan UniversityShanghai 200433China Beijing Key Laboratory of Indoor Air Quality Evaluation and Control Tsinghua UniversityBeijing 100084China

Nitrogen dioxide(NO_(2.)is a prevalent air pollutant in urban areas,originating from outdoor sources,household gas consumption,and secondhand *** limited evaluation of the disease burden attributable to NO_(2.,encompassing different health effects and contributions from various sources,impedes our understanding from a public health *** on modeled NO2.exposure concentrations,their exposure–response relationships with lung cancer,chronic obstructive pulmonary disease,and diabetes mellitus,and baseline disability-adjusted life years(DALYs),we estimated that 1,675(655–2.62.)thousand DALYs were attributable to NO2.in urban china in {2.[13.(54–2.6)billion Chinese yuan(CNY)economic losses].The transition from gas to electricity for household cooking was estimated to reduce the attributable economic losses by 3.%.This reduction falls within the range of reductions achieved when outdoor air meets the World Health Organization interim target 3.and air quality guidelines for annual NO_(2.,highlighting the significance of raising awareness of gas as a polluting household energy for *** findings align with global sustainable development initiatives,providing a sustainable solution to promote public health while potentially mitigating climate change.

关键词： Environmental risk Indoor air pollution Nitrogen dioxide Health effect Cooking

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Low temperature albitization in Caino-Mesozoic reservoir sandstones from North Tarim, and a discussion on the fluid origin

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Chinese Science Bulletin 1999年第S2期44卷 35-37页

作者： ye ying~1, hu {2.~{3. sun {3.~2.1. department of Earth Sciences, Zhejiang University, hangzhou 3.0027, china 2. department of Earth Sciences, Nanjing University, Nanjing 2.0008, china department of Earth Sciences Zhejiang University Hangzhou 310027 China department of Earth Sciences Nanjing University Nanjing 210008 China

CAJNOZOIC and Mesozoic in North Tarim are predominantly a set of terrestrial detrital formations. In thereservoir sandstones in the area, albite is one of the widely developed authigenic mineral. Micro-structural evidence shows that diagenetic albite occurs as euhedral crystals in the pore, and replaces feldsparand other detritus along cleavage and micro-crack. EPMA analyzing found that some of the alteration product has a chemical composition between purealbite and the replaced detrital feldspar. For example, composition of replaced alkali feldspar is betweenmicrocline and albite, and content of altered plagioclase decreases continuously. This has been regardedas direct evidence for fluid replacement, for feldspar crystallized from solution or magma is usually withfixed chemical composition. Taking alkali feldspar as an example, although Kf and Ab forming completeisomorphous admixture in high temperature, they exsolved out as two relative pure phases while temperature decreases.

关键词： low temperature albitization sandstones fluid origin North Tarim.

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Three-dimensional configurations of organic/inorganic hybrid nanostructural blocks (I).A quantum mechanical investigation for ladder-like structure of vinylsilsesquioxane

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Science china Chemistry 2004年第5期47卷 388-395页

作者： ZHANG Xingwen1,2. hu Lijiang1, huANG Yudong1, {2. Dezhi2.& {2. Yi3.1. department of Applied Chemistry,Harbin Institute of Technology, huANG Yudong, Harbin 150001, china 2. department of Environmental Engineering, Harbin Institute of Technology, Harbin 150001, china 3. department of Experimental Mechanics,Harbin Institute of Technology, Harbin 150001, china 1. department of Applied Chemistry Harbin Institute of Technology HUANG Yudong 150001 Harbin China 2. department of Environmental Engineering Harbin Institute of Technology 150001 Harbin China 3. department of Experimental Mechanics Harbin Institute of Technology 150001 Harbin China

The organic/inorganic hybrid nanostructural vinylsilsesquioxanes (VSSO) were prepared from the hydrolytic condensation of vinyltrimethoxysilane (VMS). The proposed formu- las of VSSO were assigned with standard spectroscopic techniques, FTIR, NMR (1H, C and 13.2.Si) and MALDI-TOF MS, and a generic formula of the SSO, Tn(OH)x(OR’)y(x, y = 0, 1, 2.; n = 1, 2.; T = RSiO1.5 ?(x+y)/2.). Geometric parameters (Si-O and Si-C bond lengths, Si-O-Si and O-Si-O bond angles) and total energies of the multi-structures of VSSO were calculated by a quantum mechanical investigation and molecular symmetries. According to the results of the calculation, most molecules had stabler ladder structures than the cage isomers, therefore, the most probably reasonable and optimum structure of the VSSO system was the ladder type.

关键词： vinyltrimethoxysilane (VMS), silsesquioxanes (SSO), sol-gel process, quantum mechanical calculation, MNDO.

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A land surface model incorporated with soil freeze/thaw and its application in GAME/Tibet

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Science china Earth Sciences 2006年第12期49卷 1311-1322页

作者： hu Heping1, ye Baisheng2. ZHOU Yuhua3.& TIAN Fuqiang1 1. {3. of Hydraulic Engineering, Tsinghua University, Beijing 100084, china 2. Cold and Arid Regions Environmental and Engineering Research Institute, Chinese Academy of Sciences, Lanzhou 73.000, china 3. {3. of Civil Engineering, Massachusetts Institute of Technology, USA 1. department of Hydraulic Engineering Tsinghua University Beijing 100084 China 2. Cold and Arid Regions Environmental and Engineering Research Institute Chinese Academy of Sciences Lanzhou 730000 China 3. department of Civil Engineering Massachusetts Institute of Technology USA

Land surface process is of great importance in global climate change, moisture and heat exchange in the interface of the earth and atmosphere, human impacts on the environment and eco- system, etc. Soil freeze/thaw plays an important role in cold land surface processes. In this work the diurnal freeze/thaw effects on energy partition in the context of GAME/Tibet are studied. A sophisti- cated land surface model is developed, the particular aspect of which is its physical consideration of soil freeze/thaw and vapor flux. The simultaneous water and heat transfer soil sub-model not only reflects the water flow from unfrozen zone to frozen fringe in freezing/thawing soil, but also demon- strates the change of moisture and temperature field induced by vapor flux from high temperature zone to low temperature zone, which makes the model applicable for various circumstances. The modified Picard numerical method is employed to help with the water balance and convergence of the numerical scheme. Finally, the model is applied to analyze the diurnal energy and water cycle char- acteristics over the Tibetan Plateau using the Game/Tibet datasets observed in May and July of 1998. Heat and energy transfer simulation shows that: (i) There exists a negative feedback mechanism between soil freeze/thaw and soil temperature/ground heat flux; (ii) during freezing period all three heat fluxes do not vary apparently, in spite of the fact that the negative soil temperature is higher than that not considering soil freeze; (iii) during thawing period, ground heat flux increases, and sensible heat flux decreases, but latent heat flux does not change much; and (iv) during freezing period, soil temperature decreases, though ground heat flux increases.

关键词： land surface model,soil freeze/thaw,GAME/Tibet,simultaneous liquid,vapor and heat transfer.

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Numerical simulation of inlet placement on sewage characteristics in the rounded square aquaculture tank with single inlet

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Journal of Oceanology and Limnology 2024年第4期42卷 1359-1382页

作者： Xiaozhong REN Yixuan hu Yinxin ZHOU Shupeng DU Wei {2. Hangfei LIU Chenxu ZHAO {3. LIU Key Laboratory of Environment Controlled Aquaculture(Dalian Ocean University)Ministry of Education Dalian 116023China College of Marine Science and Environment Dalian Ocean UniversityDalian 116023China College of Ocean and Civil Engineering Dalian Ocean UniversityDalian 116023China Zhejiang University Hangzhou 310058China

To improve the self-cleaning ability of aquaculture tank and the efficiency of circulating water,physical and numerical experiments were conducted on the influence of inlet structure on sewage discharge in a rounded square aquaculture tank with a single *** on the physical model of the tank,analysis of how inlet structure adjustment affects sewage discharge efficiency and flow field characteristics was conducted to provide suitable flow field conditions for sinkable solid particle *** addition,an internal flow field simulation was conducted using the RNG k-εturbulence model in hydraulic drive *** a solid-fluid multiphase model was created to investigate how the inlet structure affects sewage collection in the rounded square aquaculture tank with single inlet and *** finding revealed that the impact of inlet structure is considerably affecting sewage *** conditions of C/B=0.07-0.11(the ratio of horizontal distance between the center of the inlet pipe and the tank wall(C)to length of the tank(B))andα=2.°(αis the angle between the direction of the jet and the tangential direction of the arc angle)resulted in optimal sewage collection,which is similar to the flow field experiment in the rounded square aquaculture tank with single inlet and *** excellent correlation was revealed between sewage collection and fluid circulation stability in the aquaculture *** present study provided a reference for design and optimization of circulating aquaculture tanks in aquaculture industry.

关键词： rounded square aquaculture tank sewage collection characteristic inlet structure computational fluid dynamic

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Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory

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Neuroscience Bulletin 2024年第2期40卷 147-156页

作者： Minghong Su Kejia hu Wei Liu Yunhao Wu Tao Wang Chunyan Cao Bomin {2. Shikun Zhan Zheng {3. Institute of Psychology Chinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China department of Neurosurgery Center for Functional NeurosurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial *** stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential *** patients with epilepsy(eight women,age 2..6±8.2.years)completed a line ordering task with SEEG recordings over the DLPFC and the *** showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular ***,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3.10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line ***,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized ***,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized *** study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

关键词： Sequential working memory Hippocampus Dorsolateral prefrontal cortex Theta oscillations Stereoelectroencephalography(SEEG) Phase coherence Granger causality

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Endogenous biosynthesis of docosahexaenoic acid(DHA)regulates fish oocyte maturation by promoting pregnenolone production

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Zoological Research 2024年第1期45卷 176-188页

作者： Yi Li Xuehui Li Ding ye Ru Zhang Chengjie Liu Mudan He Houpeng Wang Wei hu Yonghua sun State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyInnovation Academy for Seed DesignChinese Academy of SciencesWuhanHubei 430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China hubei Hongshan Laboratory WuhanHubei 430070China

Omega-3.polyunsaturated fatty acids(n-3.PUFAs),particularly docosahexaenoic acid(2.:6n-3.DHA),play crucial roles in the reproductive health of vertebrates,including ***,the underlying mechanism related to this phenomenon remains largely *** this study,we employed two zebrafish genetic models,i.e.,elovl2.(-/-)mutant as an endogenous DHAdeficient model and fat1(omega-3.desaturase encoding gene)transgenic zebrafish as an endogenous DHA-rich model,to investigate the effects of DHA on oocyte maturation and *** show that the elovl2.(-/-)mutants had much lower fecundity and poorer oocyte quality than the wild-type controls,while the fat1 zebrafish had higher fecundity and better oocyte quality than wildtype *** deficiency in elovl2.(-/-)embryos led to defects in egg activation,poor microtubule stability,and reduced pregnenolone *** study revealed that DHA promoted pregnenolone synthesis by enhancing transcription of cyp11a1,which encodes the cholesterol side-chain cleavage enzyme,thereby stabilizing microtubule assembly during *** turn,the hypothalamic-pituitary-gonadal axis was enhanced by *** conclusion,using two unique genetic models,our findings demonstrate that endogenously synthesized DHA promotes oocyte maturation and quality by promoting pregnenolone production via transcriptional regulation of cyp11a1.

关键词： Docosahexaenoic acid Oocyte maturation Oocyte quality Pregnenolone Microtubule

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Enhancement in the Hg^(0) oxidation efficiency and sulfur resistance of CuCl_(2.-modified MnO_(x)-CeO_(x) nanorod catalysts

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第8期25卷 680-686页

作者： Shujie GAO Yongjin hu Zhichang JIANG Xiaoxiang WANG Dong {2. Changxing hu College of Quality&Safety Engineering China Jiliang UniversityHangzhou 310018China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Institute of Industrial Ecology and EnvironmentCollege of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310027China School of Mechatronics and Energy Engineering Ningbo Tech UniversityNingbo 315100China

In this study,a series of CuCl_(2.-modified MnO_(x)-CeO_(x)nanorods were synthesized for the oxidation of Hg^(0).The addition of CuCl_(2.resulted in an enhancement in the catalyst’s Hg^(0)oxidation ability,and Hg^(0)oxidation efficiency reached>97%from 150 to 2.0°*** the MnO_(x)-CeO_(x)catalysts,Mn^(4+)played the role of the active species for Hg^(0)oxidization,but in the CuCl_(2.-doped catalysts Cl−also contributed to Hg^(0)oxidation,conferring the superior performance of these *** introduction of SO_(2. led to a decrease in the availability of Mn^(4+),and the Hg^(0)oxidation efficiency of MnO_(x)-CeO_(x)decreased from about 100%to about 78%.By contrast,CuCl_(2.-promoted samples maintained a Hg^(0)oxidation efficiency of about 100%during the SO_(2. deactivation cycle due to the high reactivity of Cl−.

关键词： Hg^(0)oxidation CuCl_(2.modification MnO_(x)-CeO_(x)nanorods Sulfur resistance O_(x)idation activity

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