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Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway

Research 2024年第3期2023卷 499-511页

作者： Hongen Meng yingying Yu Enjun Xie Qian Wu Xiangju yin Bin Zhao Junxia min Fudi Wang The Second Afiliated Hospital The First Affiliated HospitalInstitute of Translational MedicineScho of Public HealthZhejiang University School of MedicineHangzhouChina institute of Emergency Management Henan Polytechnic UniversityJiaozuoChina MOE Key Laboratory of Biosystems Homeostasis and Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biologyand Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou 310058China.

Histone deacetylases(HDACs)are epigenetic regulators that play an important role in determining cell fate and maintaining cellular ***,whether and how HDACs regulate iron metabolism and ferroptosis(an iron-dependent form of cell death)remain ***,the putative role of hepatic HDACs in regulating iron metabolism and ferroptosis was investigated using genetic mouse *** lacking Hdac3 expression in the liver(Hdac3-LKO mice)have significantly reduced hepatic Hamp mRNA(encoding the peptide hormone hepcidin)and altered iron *** profiling of Hdac3-LKO mice suggests that the Hippo signaling pathway may be downstream of ***,using a Hippo pathway inhibitor and overexpressing the transcriptional regulator Yap(Yes-associated protein)significantly reduced Hamp mRNA *** a promoter reporter assay,we then identified 2 Yap-binding repressor sites within the human HAMP promoter *** also found that inhibiting Hdac3 led to increased translocation of Yap to the nucleus,suggesting activation of ***,knock-in mice expressing a constitutively active form of Yap(Yap K342M)phenocopied the altered hepcidin levels observed in Hdac3-LKO ***,we show that iron-overload-induced ferroptosis underlies the liver injury that develops in Hdac3-LKO mice,and knocking down Yap expression in Hdac3-LKO mice reduces both iron-overload-and ferroptosis-induced liver *** results provide compelling evidence supporting the notion that HDAC3 regulates iron homeostasis via the Hippo/Yap pathway and may serve as a target for reducing ferroptosis in iron-overload-related diseases.

关键词： homeostasis metabolism expressing

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Natural products inspired[3+2]cycloaddition enables efficient construction of hydroxylated tetrahydrofuran acetals and concise syntheses of lignans

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Science China Chemistry 2024年第7期67卷 2306-2313页

作者： Dong-Yue Cai Weiming Shi Zhao-Hui Jin zhi-Xiang Yu Jin-Xin Zhao Jian-min Yue State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Beijing National Laboratory for Molecular Sciences(BNLMS) Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of ChemistryPeking UniversityBeijing 100871China

Mimicking biosynthetic pathways of hongkonoids led to the development of a new Cu(Ⅰ)-catalyzed[3+2]cycloaddition ofα-hydroxyketone andβ-keto enol ethers,affording tetrahydrofuran acetals in a highly diastereoselective manner and 100%atom *** studies on the mechanism disclosed a concerted but asynchronous Michael addition/aldol *** the same importance,this methodology provides a practical biomimetic approach for one-step construction of the dibenzylbutyrolactol lignan backbone starting from two phenyl propane derivatives,opening up a powerful new approach for lignan synthesis,which is showcased by succinct total syntheses of two biologically important aryltetralin-type lignans,β-apopicropodophyllin and *** the mild and operationally simple conditions,the developed chemistry might have a promising prospect in potential industrial applications.

关键词： [3+2]cycloaddition transition-metal catalysis tetrahydrofuran lignans natural products

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The occurrence characteristics of oil in shales matrix from organic geochemical screening data and pore structure properties:An experimental study Author links open overlay panel

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Petroleum Science 2024年第1期21卷 1-13页

作者： Zi-zhi Lin Jun-Qian Li Shuang-Fang Lu Qin-Hong Hu Peng-Fei Zhang Jun-Jie Wang Qi zhi Hong-Sheng Huang Na yin Yue Wang Tian-Chen Ge National Key Laboratory of Deep Oil and Gas China University of Petroleum(East China)Qingdao 266580ShandongChina School of Geosciences China University of Petroleum(East China)Qingdao 266580ShandongChina Sanya Offshore Oil&Gas Research Institute Northeast Petroleum UniversitySanya 572025HainanChina College of Earth Science and Engineering Shandong University of Science and TechnologyQingdao 266590ShandongChina

The occurrence characteristics of shale oil are of great significance to the movability of shale *** this study,the occurrence characteristics of oil in the shale matrix at Funing Formation shale in Subei Basin were quantitatively evaluated by organic geochemistry and microscopic pore structure characterization *** Multiple Isothermal Stages Pyrolysis(MIS)experiment results show that the content of total oil,adsorbed oil,and free oil in the shales are 3.15-11.25 mg/g,1.41-4.95 mg/g,and 1.74-6.51 mg/g,*** which the silicon-rich shale has the best *** relative content of free oil shows an increasing trend in pores with pore diameters greater than 3 *** the relative content of free oil reaches 100%,the pore size of silicon-rich shale is about 200 nm,while that of calcium-rich shale,clay-rich shale,and siliceous mixed shale is about 10 *** occurrence law of adsorbed oil is opposite to that of free oil,which indicates that shale oil will occur in the pores and fractures in a free state in a more extensive pore size range(>200 nm).This study also enables us to further understand the occurrence characteristics of shale oil under the interaction of occurrence state and occurrence space.

关键词： Shale oil Occurrence characteristics Sequential solvent extraction Low-temperature nitrogen adsorption Funing Formation Dongtai Depression

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Stereospecific Assembly of Trisubstituted Alkenes via Photoinduced Nitrogen-Centered Radical-Triggered C—C Bond Cleavage/Functionalization of Oxime Esters

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Chinese Journal of Chemistry 2024年第12期42卷 1399-1406页

作者： Yu Bao zhi-Jie Song Jin-Long Dai Shenghu Yan Yue Zhang Jia-yin Wang Guigen Li School of Pharmacy Changzhou UniversityChangzhouJiangsu 213164China Department of Chemistry and Biochemistry Texas Tech University79409USA

Comprehensive Summary A general and convenient photoredox-catalyzed acylation and alkylcyanation of MBH acetates has been established,enabling the assembly of the C(sp2)–C(sp3)bond by a nitrogen-centered radical strategy for the synthesis of trisubstituted alkenes in moderate to excellent chemical yields(48 examples in total).The reaction of MBH acetates with acyl(indanone)oxime esters afforded trisubstituted alkenes containing 1,4-dicarbonyl ***,the use of Eosin Y as a photocatalyst in the catalytic system resulted in the formation of distal cyano group-anchored trisubstituted alkenes via deconstructive functionalization of cycloketone oxime ***,these resulting 1,4-dicarbonyl compounds could be applied to late-stage transformations,providing important methods for the synthesis of dihydropyridazin-3(2H)-one.

关键词： Photocatalysis Radical reactions MBH acetates Oxime esters Stereoselectivity Acylation Alkylation Green chemistry

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Chemical biology investigation of a triple-action,smart-decomposition antimicrobial booster based-combination therapy against“ESKAPE”pathogens

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Science China Chemistry 2024年第9期67卷 3071-3082页

作者： min Wang Huangsheng Pu Yangfan Xu Chenxuan Wu Yuanxin Gu Qingyun Cai Guoxing yin Peng yin Chunhui Zhang Wing-Leung Wong Muyang Wan Yugang Bai Xinxin Feng State Key Laboratory of Chem-/Bio-Sensing and Chemometrics Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biologyand School of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China College of Biology Hunan UniversityChangsha 410082China College of Advanced Interdisciplinary Studies&Hunan Provincial Key Laboratory of Novel Nano Optoelectronic Information Materials and Devices National University of Defense TechnologyChangsha 410073China Nanhu Laser Laboratory National University of Defense TechnologyChangsha 410073China Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research(ministry of Education) College of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081China State Key Laboratory of Chemical Biology and Drug Discovery Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs The Third Hospital of Changsha(The Affiliated Changsha Hospital of Hunan University)Changsha 410015China

The global antibiotic resistance crisis necessitates urgent *** innovative approach involves potentiating antibiotics and non-antibiotic drugs with adjuvants or boosters.A major drawback of these membrane-active boosters is their limited biocompatibility,as they struggle to differentiate between prokaryotic and eukaryotic *** study reports the chemical biology investigation of a dual-action oligoamidine(OA1)booster with a glutathione-triggered decomposition ***1,when combined with other antimicrobial molecules,exhibits a triple-targeting mechanism including cell membrane disruption,DNA targeting,and intracellular enzyme *** multi-targeting mechanism not only enhances the in vitro and in vivo eradication of antibiotic-resistant“ESKAPE”pathogens,but also suppresses the development of bacterial ***,OA1 maintains its activity in bacterial cells by creating an oxidative environment,while it quickly decomposes in mammalian cells due to high glutathione *** mechanistic insights and design principles may provide a feasible approach to develop novel antimicrobial agents and effective anti-resistance combination therapies.

关键词： antimicrobial booster oligoamidine membrane disruption DNA targeting triggered degradation anti-resistance

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Advanced modeling of the absorption enhancement of black carbon particles in chamber experiments by considering the morphology and coating thickness

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Frontiers of Environmental Science & Engineering 2024年第9期18卷 129-142页

作者： Xiaodong Wei Jianlin Hu Chao Liu Xiaodong Xie Junjie yin Song Guo min Hu Jianfei Peng Huijun Wang Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control Collaborative Innovation Center of Atmospheric Environment and Equipment TechnologySchool of Environmental Science and EngineeringNanjing University of Information Science&TechnologyNanjing 210044China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Key Laboratory of Meteorological Disaster(Ministry of Education)Nanjing University of Information Science and TechnologyNanjing 210044China Nansen−Zhu International Research Centre Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China East China Air Traffic Management Bureau CAAC Shanghai 200335China State Key Joint Laboratory of Environmental Simulation and Pollution Control International Joint Laboratory for Regional Pollution Control(IJRC)(Ministry of Education)College of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China Tianjin Key Laboratory of Urban Transport Emission Research&State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control College of Environmental Science and EngineeringNankai UniversityTianjin 300071China

Measurements studies have shown that the absorption of radiation by black carbon(BC)increases as the particles ***,there are significant discrepancies between the measured and modeled absorption enhancement(E_(abs)),largely due to the simplifications used in modeling the mixing states and shape *** took advantage of chamber experiments on BC aging and developed an efficient method to resolve the particle shape based on the relationship between the coating fraction(ΔD_(ve)/D_(ve),0)and fractal dimension(D_(f)),which can also reflect the variations of D_(f)during the whole BC aging *** with externally and partly mixed states(0≤ΔD_(ve)/D_(ve),0≤0.5)can be considered to be uniformly distributed with the D_(f)values of 1.8–2.1,whereas the Df values are constrained in the range 2.2–2.8 for fully mixed states(ΔD_(ve)/D_(ve),0>0.5).The morphological parameters(i.e.,the effective density and the dynamic shape factor)were compared with the measured values to verify the simulated *** simulated mean deviations of morphological parameters were smaller than 8%for the method resolving the particle *** applying a realistic shape and refractive index,the mass absorption cross for fully mixed states can be improved by 11%compared with a simplified core–shell *** on our understanding of the influence of D_(f)andΔD_(ve)/D_(ve),0 on E_(abs),we propose a two-stage calibration equation to correct the E_(abs)values estimated by the core–shell model,which reduces the simulation error in the Mie calculation by 6%–14%.

关键词： Black carbon Mixing states Fractal dimension Dynamic shape factor Absorption enhancement

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Effect of aging time on precipitation behavior, mechanical and corrosion properties of a novel Al-Zn-Mg-Sc-Zr alloy

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Transactions of Nonferrous Metals Society of China 2016年第9期26卷 2263-2275页

作者：李波潘清林陈从平尹志民三峡大学机械与动力学院宜昌443002 中南大学材料科学与工程学院长沙410083

The precipitation behavior, mechanical properties and corrosion resistance of a novel Al-Zn-Mg-Sc-Zr alloy aged at different time were studied by optical microscopy（OM）, scanning electron microscopy（SEM）, transmission electron microscopy（TEM）, tensile tests, potentiodynamic polarization and electrochemical impedance spectroscopy. The results revealed that with increasing aging time at 120 ℃, the hardness and tensile strength of the alloy increased rapidly at first and then slightly decreased. The resistance of exfoliation corrosion（EXCO） and intergranular corrosion（IGC） increased gradually with increasing aging time. The same trend of corrosion properties was demonstrated by electrochemical polarization curves and EIS test. The characteristics of grain boundary precipitates and precipitate free zone（PFZ） had a significant influence on the mechanical and corrosion behaviors of the studied alloy. On the basis of TEM observations, the size of grain boundary precipitates and the width of PFZ became larger, and the distributed spacing of grain boundary precipitates was enhanced with increasing aging time.

关键词： aluminum alloy heat treatment precipitation behavior Al3(Sc Zr) particles electrochemical impedance spectroscopy

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In-situ AFM and quasi-in-situ studies for localized corrosion in Mg-9Al-1Fe-(Gd) alloys under 3.5 wt.% NaCl environment

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Journal of Magnesium and Alloys 2024年第3期12卷 1170-1185页

作者： Junping Shen Tao Lai Zheng yin Yang Chen Kun Wang Hong Yan Honggun Song Ruiliang Liu Chao Luo zhi Hu School of Advanced Manufacturing Nanchang UniversityNanchang 330031China Institute for Advanced Study Nanchang UniversityNanchang 330031China Singapore Centre for Environmental Life Sciences Engineering Nanyang Technological University60 Nanyang Drive 637751Singapore

Revealing the localized corrosion process of Mg alloy is considered as one of the most significant ways for improving its corrosion *** reliable monitor should be high distinguishability and real-time in liquid ***,Mg-9Al-1Fe and Mg-9Al-1Fe-1Gd alloys were designed to highlight the impact of intermetallic on the corrosion ***-situ AFM with a special electrolyte circulation system and quasi-in-situ SEM observation were used to monitor the corrosion process of the designed ***-EDS and TEM-SAED were applied to identify the intermetallic in the designed alloys,and their volta potentials were measured by *** to the real-time and real-space in-situ AFM monitor,the corrosion process consisted of dissolution of anodicα-Mg phase,accumulation of corrosion products around cathodic phase and shedding of some fine cathodic ***,the localized corrosion process of Mg alloy was revealed combined with the results of the monitor of corrosion process and Volta potential difference.

关键词： Magnesium Localized corrosion In-situ AFM SKPFM Corrosion behaviour.

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A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2324-2340页

作者： Xin Wang Qian Liu Hai-tao Yu Jia-zhao Xie Jun-ning Zhao zhi-ting Fang min Qu Yao Zhang ying Yang Jian-zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Fundamental Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu 214122China Hubei Provincial Key Laboratory for Applied Toxicology Hubei Provincial Center for Disease Control and PreventionHubei Provincial Academy of Preventive MedicineWuhan 430000China Endocrine Department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease(AD);however,the fundamental mechanism is *** this study,we found a substantial decline in isocitrate dehydrogenase 3β(IDH3β)levels,a critical tricarboxylic acid cycle enzyme,in AD patients and AD-transgenic mice’s *** investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate *** resulting increased lactate,a source of lactyl,was found to promote histone lactylation,thereby enhancing the expression of paired-box gene 6(PAX6).As an inhibitory transcription factor of IDH3β,the elevated PAX6 in turn inhibited the expression of IDH3β,leading to tau hyperphosphorylation,synapse impairment,and learning and memory deficits resembling those seen in *** AD-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like ***,our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β.Breaking this loop by upregulating IDH3βor downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

关键词： metabolism Alzheimer impaired

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Effects of synthetic site water on bentonite-concrete system for a potential nuclear waste repository

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第9期16卷 3786-3797页

作者： Zhao Sun Yong-Gui Chen Wei-min Ye Qiong Wang Dong-Bei Wu Zhen-Yu yin Key Laboratory of Geotechnical and Underground Engineering of ministry of Education Department of Geotechnical EngineeringTongji UniversityShanghai200092China Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityHung HomKowloonHong KongChina School of Chemical Science and Engineering Tongji UniversityShanghai200092China

In high-level nuclear waste(HLW)repositories,concrete and compacted bentonite are designed to be employed as buffer materials,which may raise a problem of interactions between concrete and *** interactions would lead to mineralogy transformation and buffer performance decay of bentonite under the near field environment conditions in a repository.A small-scale experimental setup was established to simulate the concrete-bentonite-site water interaction system from a potential nuclear waste repository in *** types of mortars were prepared to correspond to the concrete at different degradation *** results permit the determination of the following:(1)The macroproperties of Gaomiaozi(GMZ)bentonite(*** pressure,permeability,the final dry density,and water content of reacted samples);(2)The composition evolution of fluids from the synthetic site water-concrete-bentonite interaction systems;(3)The sample characterization including Fourier transform infrared spectroscopy(FTIR)and X-ray powder diffraction(XRD).Under the infiltration of the synthesis Beishan site water(BSW),the swelling pressure of bentonite decreases slowly with time after reaching its second swelling *** flux decreases with time during the infiltrations,and it tends to be stable after more than 120 *** to the cation exchange reactions in the BSW-concrete-bentonite systems,the divalent cations(Ca and Mg)were consumed,and the monovalent cations(Na and K)were *** dissolution of minerals in the bentonite such as albite causes Si increasing in the pore *** was concluded that the hydro-mechanical property degradation of bentonite takes place when it comes into contact with concrete mortar,even under low-pH groundwater *** soil dispersion,the uneven water content,and the uneven dry density in bentonite samples may partly contribute to the swelling decay of ***,the direct contact with concrete has an obvious effect on the performance

关键词： Mock-up device GMZ bentonite Site water-concrete-bentonite system Geochemistry Buffer performance

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