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The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 139-158页

作者： Fengjuan Jiao Lingyan Meng Kang du Xuezhi Li school of Mental Health Jining Medical UniversityJiningShandong ProvinceChina shandong Collaborative Innovation Center for Diagnosis Treatment and Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandong ProvinceChina

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in *** one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these *** evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s ***,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome ***,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s *** this review,we briefly introduce the machinery of ***,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome ***,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

关键词： autophagy chemical therapy gene therapy Parkinson’s disease α-synuclein

Enantio-divergent C–H borylation with two different ligands from a single chiral source

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science China Chemistry 2025年第1期68卷 226-232页

作者： Rongrong du senmiao Xu state Key Laboratory for Oxo synthesis and selective Oxidation Lanzhou Institute of Chemical Physics Chinese Academy of Sciences College of Material Chemistry and Chemical Engineering Key Laboratory of Organosilicon Chemistry and Material TechnologyMinistry of Education Hangzhou Normal University University of Chinese Academy of sciences

Reported here is an iridium-catalyzed enantio-divergent C（sp3）–H borylation of α-gem-dimethyl groups of trifluoromethyl ketone-derived hydrazones to construct a series of acyclic all-carbon quaternary stereocenters with a high level of chiral induction. Two different chiral bidentate boryl ligands from a common chiral source not only can switch the enantioselectivity but also are complementary in terms of the substrate scope.

关键词： asymmetric catalysis C–H borylation all-carbon quaternary stereocenters synthetic methods

Preparation of Co/s co-doped carbon catalysts for excellent methylene blue degradation

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 169-181页

作者： Haixu Li Haobo He Tiannan Jiang yunfei du Zhichen Wu Liang Xu Xinjie Wang Xiaoguang Liu Wanhua yu Wendong Xue school of Materials science and Engineering University of Science and Technology BeijingBeijing 100083China Beijing Jinyu Tongda Refractory Technologies Co. Ltd.Beijing 100085China

s and Co co-doped carbon catalysts were prepared via pyrolysis of MOF-71 and thiourea mixtures at 800℃at a mass ratio of MOF-71 to thiourea of 1:0.1 to effectively activate peroxymonosulfate(PMs)for methylene blue(MB)*** effects of two different mixing routes were identified on the MB degradation ***,the catalyst obtained by the alcohol solvent evaporation(MOF-AEP)mixing route could degrade 95.60%MB(50 mg/L)within 4 min(degradation rate:K=0.78 min^(-1)),which was faster than that derived from the direct grinding method(MOF-DGP,80.97%,K=0.39 min^(-1)).X-ray photoelectron spectroscopy revealed that the Co-s content of MOF-AEP(43.39at%)was less than that of MOF-DGP(54.73at%),and the proportion of C-s-C in MOF-AEP(13.56at%)was higher than that of MOF-DGP(10.67at%).Density functional theory calculations revealed that the adsorption energy of Co for PMs was -2.94 eV when sulfur was doped as C-s-C on the carbon skeleton,which was higher than that when sulfur was doped next to cobalt in the form of Co-s bond(-2.86 eV).Thus,the C-s-C sites might provide more contributions to activate PMs compared with ***,the degradation parameters,including pH and MOF-AEP dosage,were ***,radical quenching experiments and electron paramagnetic resonance(EPR)measurements revealed that ^(1)O_(2)might be the primary catalytic species,whereas·O~(2-)might be the secondary one in degrading MB.

关键词： advanced oxidation process alcohol solvent evaporation hydrogen bond s and Co co-doped carbon catalysts wastewater remediation

Cobalamin-dependent radical s-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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science China Chemistry 2025年第1期68卷 308-316页

作者： sili Wang Jiancheng Huang yanan du Wei Huang yufeng Xue Xiaokun Xu Guannan Zhong yuanyuan shi Bin Hong Xiaoying Bian Wen Liu state Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences state Key Laboratory of Microbial Technology Shandong University National Health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical s-adenosyl-L-methionine(sAM) proteins constitute the largest collection of the radical sAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical sAM protein, with Cxm9, a duF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-s-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the duF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical sAM activity.

关键词： cbl-dependent radical sAM protein biosynthesis chuangxinmycin stereoselective methylation

Effect of a Carbon Fibre-steel Fibre-graphite Conductive Filler on the Electrothermal Properties of Cementitious Materials

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Journal of Wuhan University of Technology(Materials science) 2025年第1期40卷 141-151页

作者： FAN yanan WEI Hong ZHENG Hongyong du Hongxiu Department of Architecture and Environmental Engineering Taiyuan UniversityTaiyuan 030032China College of Civil Engineering Taiyuan University of TechnologyTaiyuan 030032China

Carbon fibre,steel fibre and graphite were used as conductive fillers to prepare cementitious materials with excellent electrothermal *** electrically conductive cementitious materials with different volume dosages were analysed through compressive and flexural strength,electrochemical impedance spectroscopy and temperature rise *** equivalent circuit model was established to study the electrically conductive heat generation mechanism in the electrically conductive cementitious *** results indicate that the mechanical properties of cementitious composite materials with a ternary conductive phase are better than those of pristine cementitious materials because the fibrous filler improves their mechanical ***,the incorporation of graphite in the material reduces its *** fibrous and point-like conductive phase materials into the cementitious material enhances the overall conductive pathway and considerably reduces the electrical resistance of the cementitious material,enhancing its conductive *** volume ratios of carbon fibre,steel fibre and graphite that achieve an optimal complex doping in the cementitious material were 0.35%,0.6%and 6%,*** was determined using the mutation point of each circuit element parameter as the percolation *** addition,at a certain safety voltage,there is a uniform change between the internal and surface temperatures of the conductive cementitious material,and the heating effect in this materialis is considerably better than that in the pristine cementitious material.

关键词： cementitious composites conductive fillers electrothermal properties electrochemical impedance spectroscopy

Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

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Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng du Wang Rongjie Lin Weihong Xu Department of spinal surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis Clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

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Neural Regeneration Research 2025年第5期20卷 1445-1454页

作者： Meifeng Zheng Borui Zhang sonata s y yau Kwok-Fai so Li Zhang Haining Ou Department of Rehabilitation Medicine Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation Medicine The Fifth Clinical College of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Key Laboratory of CNs Regeneration(Ministry of Education) Guangdong-Hong Kong-Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina Department of Rehabilitation sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina state Key Laboratory of Brain and Cognitive science Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Center for Exercise and Brain science School of PsychologyShanghai University of SportShanghaiChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug *** exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after *** this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral *** also examined the role of exercise-induced circulating factors in these *** mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery *** found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory *** analysis showed that circulating adiponectin plays a critical role in these preventive effects of *** activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise *** summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

关键词： adiponectin cerebral ischemia exercise pre-conditioning hippocampus memory function middle cerebral artery occlusion prefrontal cortex synaptic proteins treadmill exercise

Investigation of bubbles escape behavior from low basicity mold flux for high-Mn high-Al steels using 3D X-ray microscope

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 102-110页

作者： Qiang Liu Xiang Li shen du Ming Gao yanbin yin Jiongming Zhang state Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing 100083China

during the continuous casting process of high-Mn high-Al steels,various types of gases such as Ar need to escape through the top of the *** which,the behavior of bubbles traversing the liquid slag serves as a restrictive link,closely associated with viscosity and the thickness of liquid *** contrast to two-dimensional surface observation,three-dimensional(3D)analysis method can offer a more intuitive,accurate,and comprehensive ***,this study employs a 3D X-ray microscope(3D-XRM)to obtained spatial distribution and 3D morphological characteristics of residual bubbles in mold flux under different basicity of liquid slag,different temperatures,and different holding *** results indicate that as basicity of slag increases from 0.52 to 1.03,temperature increases from 1423 to 1573 K,the viscosity of slag decreases,the floating rate of bubbles *** addition,when holding time increases from 10 to 30 s,the bubbles floating distance increases,and the volume fraction and average equivalent sphere diameter of the bubbles solidified in the mold flux gradually *** one word,increasing the basicity,temperature,and holding time leading to an increase in the removal rate of bubbles especially for the *** findings of bubbles escape behavior provide valuable insights into optimizing low basicity mold flux for high-Mn high-Al steels.

关键词： mold flux low basicity bubbles three-dimensional X-ray microscope viscosity

Effect of lamellarization on the microstructure and mechanical properties of marine 10Ni5CrMoV steel

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 402-413页

作者： Tao Zou yanwu Dong Zhouhua Jiang shuyang du yushuo Li school of Metallurgy Northeastern UniversityShenyang 110819China Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819China Key Laboratory for Ecological Metallurgy of Multimetallic Ores(Ministry of Education) Northeastern UniversityShenyang 110819China

Multistage heat treatment involving quenching(Q),lamellarizing(L),and tempering(T)is applied to marine 10Ni5CrMoV *** microstructure and mechanical properties were studied by multiscale characterizations,and the kinetics of reverse austenite transformation,strain hardening behavior,and toughening mechanism were further *** lamellarized specimens possess low yield strength but high toughness,especially cryogenic *** leads to the development of film-like reversed austenite at the martensite block and lath boundaries,refining the martensite structure and lowering the equivalent grain *** analysis of austenite reversion based on the JMAK model shows that the isothermal transformation is dominated by the growth of reversed austenite,and the maximum transformation of reversed austenite is reached at the peak temperature(750℃).The strain hardening behavior based on the modified Crussard-Jaoul analysis indicates that the reversed austenite obtained from lamellarization reduces the proportion of martensite,significantly hindering crack propagation via martensitic transformation during the *** a consequence,the QLT specimens exhibit high machinability and low yield *** with the QT specimen,the ductile-brittle transition temperature of the QLT specimens decreases from-116 to-130℃due to the low equivalent grain size and reversed austenite,which increases the cleavage force required for crack propagation and absorbs the energy of external load,*** work provides an idea to improve the cryogenic toughness of marine 10Ni5CrMoV steel and lays a theoretical foundation for its industrial application and comprehensive performance improvement.

关键词： 10Ni5CrMoV steel lamellarizing reversed austenite cryogenic toughness ductile-brittle transition temperature