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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao key laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal key laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina key laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Nanocarrier-mediated siRNA delivery:a new approach for the treatment of traumatic brain injury-related Alzheimer's disease

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Neural Regeneration Research 2025年第9期20卷 2538-2555页

作者： Jie Jin Huajing Zhang Qianying Lu Linqiang Tian Sanqiao Yao Feng Lai Yangfan Liang Chuanchuan Liu Yujia Lu Sijia Tian Yanmei Zhao Wenjie Ren Institute of disaster and Emergency Medicine Tianjin UniversityTianjinChina key laboratory for disaster Medicine Technology TianjinChina Henan Medical key laboratory for Research of Trauma and Orthopedics The Third Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenan ProvinceChina Clinical Medical Center of Tissue Engineering and Regeneration Xinxiang Medical UniversityXinxiangHenan ProvinceChina Institutes of Health Central Plain Xinxiang Medical UniversityXinxiangHenan ProvinceChina School of Public Health Xinxiang Medical UniversityXinxiangHenan ProvinceChina

Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ***,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's *** offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug *** review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future *** principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various *** the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain *** have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain *** are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional *** use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective *** this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular tar

关键词： blood-brain barrier cognitive dysfunction exosomes gene silencing immunotherapy inorganic nanomaterials liposome nanoparticles neuroinflammation polymer nanoparticles stem cells

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Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases

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Science China Life Sciences 2025年第01期 303-305页

作者： Ziqian Xu Lianpan Dai Jun Liu national key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases (NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention CAS key laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences

Vector-borne viruses, transmitted among humans and animal hosts through bites of vectors such as mosquitoes and ticks,pose a great and ongoing threat to public health and biosafety(Yang et al., 2022).Among them, dengue virus-induced epidemics, have dramatically increased worldwide in recent decades. The report released by the World Health Organization(WHO) at the end of 2023 showed that dengue epidemic globally surged in2023, with the number of reported cases nearing a historical peak.

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Numerical Analyses of Ice Jamming in Jacket Platform Conductor Array in Bohai Sea

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China Ocean Engineering 2023年第6期37卷 885-896页

作者： ZHAI Bi-yao YANG Fan PAN Jun-ning XIE Dong-mei River and Harbour Engineering Department Nanjing Hydraulic Research InstituteNanjing 210029China the national key laboratory of water disaster prevention Nanjing 210098China

Serious ice accumulating,pile-up and ice jamming occur around the conductor array of offshore jacket platforms during the winter every year in Bohai Sea,which could cause grave threats to the stability of platform structure,the safety of people and equipment,and even severer ***,the process of ice accumulation and ice jamming in the jacket platform area needs more *** study focuses on ice accumulation and jamming behaviors in the jacket platform conductor area by using a coupled two-dimensional hydro-ice dynamics model.A series of cases are conducted with different flow conditions,such as flow velocity,drifting direction and oscillatory *** the simulation,the ice pile-up process is described and changes in ice-jamming thickness,ice pile-up location and ice pile-up volume are *** differences in ice pile-up in the steady flow and oscillatory flow are *** study proposes a new approach to simulate the ice jamming process in the jacket platform conductor area,providing a reference for ice management on the platform.

关键词： sea ice ice jamming conductor array numerical modeling hydro-ice dynamics

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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo key laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina key laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Effect of Wave Nonlinearity on the Instantaneous Seabed Liquefaction

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China Ocean Engineering 2024年第1期38卷 93-103页

作者： WANG Zhao-jun SUI Ti-ti ZHANG Chi PAN Jun-ning key laboratory of Port Waterway and Sedimentation Engineering of the Ministry of TransportNanjing Hydraulic Research InstituteNanjing 210024China key laboratory of Coastal disaster and Protection(Hohai University) Ministry of EducationNanjing 210098China the national key laboratory of water disaster prevention Nanjing 210098China

The nonlinear variation of wave is commonly seen in nearshore area,and the resulting seabed response and liquefaction are of high concern to coastal *** this study,an analytical formula considering the nonlinear wave skewness and asymmetry is adopted to provide wave pressure on the seabed *** liquefaction depth attenuation coefficient and width growth coefficient are defined to quantitatively characterize the nonlinear effect of wave on seabed *** on the 2D full dynamic model of wave-induced seabed response,a detailed parametric study is carried out in order to evaluate the influence of the nonlinear variation of wave loadings on seabed ***,new empirical prediction formulas are proposed to fast predict the maximum liquefaction under nonlinear *** indicate that(1)Due to the influence of wave nonlinearity,the vertical transmission of negative pore water pressure in the seabed is hindered,and therefore,the amplitude decreases significantly.(2)In general,with the increase of wave nonlinearity,the liquefaction depth of seabed decreases *** under asymmetric and skewed wave loading,the attenuation of maximum seabed liquefaction depth is the most significant among all the nonlinear wave ***,highly skewed wave can cause the liquefaction depth of seabed greater than that under linear wave.(3)The asymmetry of wave pressure leads to the increase of liquefaction width,whereas the influence of skewedness is not significant.(4)Compared with the nonlinear waveform,seabed liquefaction is more sensitive to the variation of nonlinear degree of wave loading.

关键词： nonlinear wave seabed response seabed liquefaction numerical simulation liquefaction prediction

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Exploration of the Mechanisms for the Low Sensitivity of Deposition Flux to Upstream Sediment Reduction in the North Passage, Yangtze Estuary

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China Ocean Engineering 2023年第4期37卷 533-546页

作者： WANG Xiao-guang ZHANG Wei TONG Chao-feng LEI Zhi-yi QIN Jie JI Xiao-mei HUANG Rui the national key laboratory of water disaster prevention Hohai UniversityNanjing 210098China College of Harbor Coastal and Offshore EngineeringHohai UniversityNanjing 210098China

Deltas are densely populated industrialized regions,and home to important ports and navigation *** to human interferences,the Yangtze Estuary has experienced a significant reduction in sediment load caused by the Three Gorges Dam(TGD),as well as adjustment to local morphodynamics by the Deep-water Navigation Channel(DNC).While the dramatic reduction in sediment triggers the increased channel erosion,the deposition flux of the DNC located at the estuary mouth has little *** explore the physical mechanism of this phenomenon,a two-dimensional model is used to establish the relationship between sediment load and the sediment budget of channels based on the bathymetry in *** results show that the tidal reach and the inner estuary have a negative sediment *** the seasonal characteristics of water and sediment fluxes become less obvious *** analysis shows that the influence of upstream sediment load on deposition flux decreases along the channel,with a transition from deposition to erosion occurring in the tidal *** the last-level bifurcation,the annual siltation of sediment in the North Passage(NP)decreases by 4.5%with low *** is attributed to the reduction of sediment load partially mitigated by riverbed erosion and cascade *** addition,the lateral sediment supply,which accounts for 68%of the sediment input in the NP,is ***,this study strengthens the understanding of the relationship between sediment load and artificially deepened systems,thus allowing for better management of estuarine sediment and navigation channel.

关键词： delta navigation channel sediment load erosion and deposition sediment budget Yangtze Estuary

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Experimental study on the effect of hydrodynamic conditions on flocculation and settling properties of fine-grain sediment

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International Journal of Sediment Research 2023年第6期38卷 821-833页

作者： Bismark Odum Chunyang Xu Yongping Chen Yinpeng Yao Yan Zhou the national key laboratory of water disaster prevention Hohai University College of Harbor Coastal and Offshore Engineering Hohai University School of Engineering University of Liverpool

The flocculation of cohesive sediment particles is a function of the collision efficiency of sediment particles,which is mainly influenced by local flow hydrodynamics.A detailed study on local hydrodynamic characteristics in a novel stirred tank was done to measure the flow field of a turbulent *** flow velocity fields were obtained and processed,and the average flow field was *** image velocimetry(PIV) results measuring the hydrodynamic characteristics(expressed as turbulent kinetic energy(TKE),local dissipation rate of TKE,velocity gradient or shear rate,turbulent shear stress,etc.) were analyzed and *** tracking and automated image processing techniques were utilized to analyze the impact of the hydrodynamic conditions on the floc and settling *** differences in floc properties under the two turbulent shear states(i.e.,steady-state(SS)and unsteady-state(US)) hydrodynamic conditions were *** results show that floc size and floc size distribution(FSD) of pure kaolin clay flocs are significantly influenced by the local dissipation rate of TKE and the turbulent intensity *** floc size,df,84,at local dissipation rate of TKE of11×10-4,29 × 10-4,44 × 10-4,83 × 10-4,and 142 × 10-4m2/s3is 97,108,107,124,and 150 μ*** was found that by increasing the local dissipation rate of TKE,the FSD was skewed *** US shear condition generated larger flocs(and in higher proportions) relative to the SS *** settling velocity and flux settling velocities of flocs formed under SS conditions are higher than those formed under US *** fractal dimension of SS flocs also is higher than the fractal dimension of US *** results highlight a significant impact of the states of hydrodynamics on floc properties such as floc size and FSD as well as the settling and morphological properties of flocs.

关键词： Turbulent kinetic energy Turbulent shear rate Flocculation Floc size Settling velocity

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Trinuclear gold-catalyzed site-selective alkylation of peptides

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Science China Chemistry 2025年第01期 249-256页

作者： Qing-Yun Fang Chengyihan Gu Yinghan Chen Wencheng Yan Yong Liang Weipeng Li Chengjian Zhu Jie Han Jin Xie State key laboratory of Coordination Chemistry Jiangsu Key Laboratory of Advanced Organic Materials Chemistry and Biomedicine Innovation Center (Chem BIC) School of Chemistry and Chemical Engineering Nanjing University Green Catalysis Center College of Chemistry Zhengzhou University State key laboratory of Natural Medicines China Pharmaceutical University

Selective modification of peptides has always been a challenging issue. The selective alkylation of peptides can alter the biological activity and physical properties of molecules, and it has gained significant research interest. We herein disclose an intriguing gold-catalyzed alkylation of peptides using bench-stable unactivated alkyl bromides under photoredox catalysis. A wide range of structurally diverse primary, secondary and tertiary alkyl bromides serve as effective coupling partners to precisely connect with the α-C(sp3)–H in glycine residue of peptides. This protocol demonstrates an exceptionally broad scope for alkyl halides and excellent tolerance for a wide range of useful functional groups. A series of relay transformations to construct cyclic peptides, to proceed click reaction and to realize peptide fluorescence labeling further enhance its synthetic practicality. In addition, mechanistic studies and density functional theory(DFT) calculations reveal an inner-sphere and subsequent outersphere single electron transfer(SET) mechanism.

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