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Homer1a reduces inflammatory response after retinal ischemia/reperfusion injury

Neural Regeneration Research 2024年第7期19卷 1608-1617页

作者： Yanan Dou Xiaowei fei Xin He Yu Huan Jialiang Wei Xiuquan Wu Weihao Lyu zhou fei Xia Li fei fei Department of Neurosurgery Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing HospitalAir Force Military Medical UniversityXi’anShaanxi ProvinceChina

Elevated intraocular pressure(IOP)is one of the causes of retinal ischemia/reperfusion injury,which results in NRP3 inflammasome activation and leads to visual damage.Homerla is repo rted to play a protective role in neuroinflammation in the cerebrum.However,the effects of Homerla on NLRP3inflammasomes in retinal ischemia/reperfusion injury caused by elevated IOP remain unknown.In our study,animal models we re constructed using C57BL/6J and Homer1^(flox/-)/Homerla^(+/-)/Nestin-Cre^(+/-)mice with elevated IOP-induced retinal ischemia/repe rfusion injury.For in vitro expe riments,the oxygen-glucose deprivation/repe rfusion injury model was constructed with M uller cells.We found that Homerla ove rexpression amelio rated the decreases in retinal thickness and Muller cell viability after ischemia/reperfusion injury.Furthermore,Homerla knockdown promoted NF-κB P65^(Ser536)activation via caspase-8,NF-κB P65 nuclear translocation,NLRP3 inflammasome formation,and the production and processing of interleukin-1βand inte rleukin-18.The opposite results we re observed with Homerla ove rexpression.Finally,the combined administration of Homerla protein and JSH-23 significantly inhibited the reduction in retinal thickness in Homer1^(flox/-)Homer1a^(+/-)/Nestin-Cre^(+/-)mice and apoptosis in M uller cells after ischemia/reperfusion injury.Taken together,these studies demonstrate that Homer1a exerts protective effects on retinal tissue and M uller cells via the caspase-8/NF-KB P65/NLRP3 pathway after I/R injury.

关键词： caspase-8 Homer1a interleukin-18 interleukin-1β intraocular pressure ischemia/reperfusion injury JSH-23 Müller cells NLRP3 nuclear factor-kB p65 retina

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Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang fei fei zhou fei Xia Li Department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'an 710000China Department of Neurosurgery The Central Hospital of BaojiBaoji 721000China Department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness.Autophagy plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains unknown.Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain damage.The autophagic agonist rapamycin only promotes the initiation of autophagy.By proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic flux.Overexpression of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with rapamycin.Furthermore,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure.These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

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Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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Chinese Journal of Natural Medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu zhou fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs Cytoskeleton ECM deposition

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Southern Hemisphere Volcanism Triggered Multi-year La Niñas during the Last Millennium

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Advances in Atmospheric Sciences 2024年第4期41卷 587-592页

作者： Shangrong zhou fei LIU School of Atmospheric Sciences Sun Yat-Sen University Key Laboratory of Tropical Atmosphere-Ocean System Ministry of Educationand Southern Marine Science and Engineering Guangdong LaboratoryZhuhai 519082China Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD) Nanjing University of Information Science and TechnologyNanjing 210044China

To explain the recent three-year La Niña event from 2020 to 2022,which has caused catastrophic weather events worldwide,Fasullo et al.(2023)demonstrated that the increase in biomass aerosol resulting from the 2019-20 Australian wildfire season could have triggered this multi-year La Niña.Here,we present compelling evidence from paleo-proxies,utilizing a substantial sample size of 26 volcanic eruptions in the Southern Hemisphere(SH),to support the hypothesis that ocean cooling in the SH can lead to a multi-year La Niña event.This research highlights the importance of focusing on the Southern Ocean,as current climate models struggle to accurately simulate the Pacific response driven by the Southern Ocean.

关键词： volcanic eruptions multi-year La Niñas Australian wildfire southern ocean cooling

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Deep-reinforcement-learning-based UAV autonomous navigation and collision avoidance in unknown environments

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Chinese Journal of Aeronautics 2024年第3期37卷 237-257页

作者： fei WANG Xiaoping ZHU zhou zhou Yang TANG School of Astronautics Northwestern Polytechnical UniversityXi’an 710072China School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China

In some military application scenarios,Unmanned Aerial Vehicles(UAVs)need to perform missions with the assistance of on-board cameras when radar is not available and communication is interrupted,which brings challenges for UAV autonomous navigation and collision avoidance.In this paper,an improved deep-reinforcement-learning algorithm,Deep Q-Network with a Faster R-CNN model and a Data Deposit Mechanism(FRDDM-DQN),is proposed.A Faster R-CNN model(FR)is introduced and optimized to obtain the ability to extract obstacle information from images,and a new replay memory Data Deposit Mechanism(DDM)is designed to train an agent with a better performance.During training,a two-part training approach is used to reduce the time spent on training as well as retraining when the scenario changes.In order to verify the performance of the proposed method,a series of experiments,including training experiments,test experiments,and typical episodes experiments,is conducted in a 3D simulation environment.Experimental results show that the agent trained by the proposed FRDDM-DQN has the ability to navigate autonomously and avoid collisions,and performs better compared to the FRDQN,FR-DDQN,FR-Dueling DQN,YOLO-based YDDM-DQN,and original FR outputbased FR-ODQN.

关键词： Faster R-CNN model Replay memory Data Deposit Mechanism(DDM) Two-part training approach Image-based Autonomous Navigation and Collision Avoidance(ANCA) Unmanned Aerial Vehicle(UAV)

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Programmable synthetic receptors:the next-generation of cell and gene therapies

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Signal Transduction and Targeted Therapy 2024年第2期9卷 376-400页

作者： fei Teng Tongtong Cui Li zhou Qingqin Gao Qi zhou Wei Li University of Chinese Academy of Sciences Beijing 101408China State Key Laboratory of Stem Cell and Regenerative Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China

Cell and gene therapies hold tremendous promise for treating a range of difficult-to-treat diseases.However,concerns over the safety and efficacy require to be further addressed in order to realize their full potential.Synthetic receptors,a synthetic biology tool that can precisely control the function of therapeutic cells and genetic modules,have been rapidly developed and applied as a powerful solution.Delicately designed and engineered,they can be applied to finetune the therapeutic activities,i.e.,to regulate production of dosed,bioactive payloads by sensing and processing user-defined signals or biomarkers.This review provides an overview of diverse synthetic receptor systems being used to reprogram therapeutic cells and their wide applications in biomedical research.With a special focus on four synthetic receptor systems at the forefront,including chimeric antigen receptors(CARs)and synthetic Notch(synNotch)receptors,we address the generalized strategies to design,construct and improve synthetic receptors.Meanwhile,we also highlight the expanding landscape of therapeutic applications of the synthetic receptor systems as well as current challenges in their clinical translation.

关键词： synthetic landscape payload

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Construction of a nomogram model to predict technical difficulty in performing laparoscopic sphincter-preserving radical resection for rectal cancer

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World Journal of Gastroenterology 2024年第18期30卷 2418-2439页

作者： Xiao-Cong zhou Shi-Wei Guan fei-Yue Ke Gaurav Dhamija Qiang Wang Bang-fei Chen Medical University(Wenzhou Central Hospital) Wenzhou 325000Zhejiang ProvinceChina Department of Hepatobiliary Surgery The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Postgraduate Training Base Alliance of Wenzhou Medical University Wenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina School of International Studies Wenzhou Medical UniversityWenzhou Central HospitalWenzhou 325000Zhejiang ProvinceChina Department of Radiology The Dingli Clinical Institute of Wenzhou Medical University(Wenzhou Central Hospital)Wenzhou 325000Zhejiang ProvinceChina Department of Colorectal Surgery The Affiliated Zhejiang HospitalZhejiang University School of Medicine(Zhejiang Hospital)Hangzhou 310000Zhejiang ProvinceChina

BACKGROUND Colorectal surgeons are well aware that performing surgery for rectal cancer becomes more challenging in obese patients with narrow and deep pelvic cavities.Therefore,it is essential for colorectal surgeons to have a comprehensive understanding of pelvic structure prior to surgery and anticipate potential surgical difficulties.AIM To evaluate predictive parameters for technical challenges encountered during laparoscopic radical sphincter-preserving surgery for rectal cancer.METHODS We retrospectively gathered data from 162 consecutive patients who underwent laparoscopic radical sphincterpreserving surgery for rectal cancer.Three-dimensional reconstruction of pelvic bone and soft tissue parameters was conducted using computed tomography(CT)scans.Operative difficulty was categorized as either high or low,and multivariate logistic regression analysis was employed to identify predictors of operative difficulty,ultimately creating a nomogram.RESULTS Out of 162 patients,21(13.0%)were classified in the high surgical difficulty group,while 141(87.0%)were in the low surgical difficulty group.Multivariate logistic regression analysis showed that the surgical approach using laparoscopic intersphincteric dissection,intraoperative preventive ostomy,and the sacrococcygeal distance were independent risk factors for highly difficult laparoscopic radical sphincter-sparing surgery for rectal cancer(P<0.05).Conversely,the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance was identified as a protective factor(P<0.05).A nomogram was subsequently constructed,demonstrating good predictive accuracy(C-index=0.834).CONCLUSION The surgical approach,intraoperative preventive ostomy,the sacrococcygeal distance,and the anterior-posterior diameter of pelvic inlet/sacrococcygeal distance could help to predict the difficulty of laparoscopic radical sphincter-preserving surgery.

关键词： Nomogram Rectal cancer Laparoscopic operation Sphincter-preserving surgery Technical difficulty

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Efficient Preparation and Electrochemical Properties of BiOCl/Graphite by One-step Solvothermal Method

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Journal of Wuhan University of Technology(Materials Science) 2024年第3期39卷 651-657页

作者：门丽娟 fei Chi LIU An 陈春钰 zhou Jiankang JU Dianchun School of Metallurgy Engineering Jiangsu University of Science and TechnologyZhangjiagang 215600China

We used the surface-pretreated graphite paper(Gp)as a carrier and loaded BiOCl with high selectivity to Cl^(-)on its surface by solvothermal method to form BiOCl@Gp electrode.The morphology,structure,and composition of the materials were characterized by scanning electron microscopy and nitrogen adsorption/desorption,and the results showed that the spherical BiOCl particles were uniformly dispersed on the surface of the Gp,forming a mesoporous BiOCl@Gp composite with a specific surface area of 22.82 m^(2)/g and a pore volume of 0.043 cm3/g.Furthermore,cyclic voltammetry and electrochemical impedance spectroscopy were used to test the electrochemical properties of the composites,and the stability of BiOCl and the high conductivity of Gp were synergistic,the BiOCl@Gp exhibited a specific capacitance of 30.2 F·g^(-1) at a current density of 0.5 A·g^(-1),and the selectivity of the BiOCl@Gp materials for Cl^(-)was significantly higher than that of SO_(4)^(2-),NO_(2)^(-),and HCO_(3)^(-).Therefore,BiOCl@Gp composite electrode materials can be used for the selective adsorption of Cl^(-)in wastewater,in order to achieve efficient wastewater recycling.

关键词： solvothermal method bismuth oxychloride electrochemistry electrode materials

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Water-soluble brown carbon in atmospheric aerosols from the resource-dependent cities:Optical properties,chemical compositions and sources

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Journal of Environmental Sciences 2024年第4期138卷 74-87页

作者： Haoji Wang Yue Su Yangzheng Liu fei Xie Xingjun zhou Ruihong Yu Changwei Lü Jiang He School of Ecology and Environment Inner Mongolia UniversityHohhot 010021China Institute of Environmental Geology Inner Mongolia UniversityHohhot 010021China Environmental Monitoring Center of Inner Mongolia Hohhot 010011China

As a vital type of light-absorbing aerosol,brown carbon(BrC)presents inherent associations with atmospheric photochemistry and climate change.However,the understanding of the chemical and optical properties of BrC is limited,especially in some resource-dependent cities with long heating periods in northwest China.This study showed that the annual average abundances of Water-soluble BrC(WS-BrC)were 9.33±7.42 and 8.69±6.29μg/m^(3)in Baotou and Wuhai and the concentrations,absorption coefficient(Abs_(365)),and mass absorption efficiency(MAE365)of WS-BrC presented significant seasonal patterns,with high values in the heating season and low values in the non-heating season;while showing opposite seasonal trends for the Absorption Angstr?m exponent(AAE_(300-400)).Comparatively,the levels of WS-BrC in developing regions(such as cities in Asia)were higher than those in developed regions(such as cities in Europe and Australia),indicating the significant differences in energy consumption in these regions.By combining fluorescence excitation-emission matrix(EEM)spectra with the parallel factor(PARAFAC)model,humic-like(C1 and C2)and proteinlike(C3)substances were identified,and accounted for 61.40%±4.66%and 38.6%±3.78%at Baotou,and 60.33%±6.29%and 39.67%±4.17%at Wuhai,respectively.The results of source apportionment suggested that the potential source regions of WS-BrC varied in heating vs.non-heating seasons and that the properties of WS-BrC significantly depended on primary emissions(e.g.,combustion emissions)and secondary formation.

关键词： Water-soluble brown carbon Atmospheric aerosols Optical properties PARAFAC Source apportionment

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Homer signaling pathways as effective therapeutic targets for ischemic and traumatic brain injuries and retinal lesions

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Neural Regeneration Research 2022年第7期17卷 1454-1461页

作者： Xiu-Quan Wu Ning Su zhou fei fei fei Department of Neurosurgery Xijing Hospitalthe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Radiation Oncology Xijing Hospitalthe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of Ophthalmology Xijing Hospitalthe Fourth Military Medical UniversityXi’anShaanxi ProvinceChina

Ischemic and traumatic insults to the central nervous system account for most serious acute and fatal brain injuries and are usually characterized by primary and secondary damage.Secondary damage presents the greatest challenge for medical staff;however,there are currently few effective therapeutic targets for secondary damage.Homer proteins are postsynaptic scaffolding proteins that have been implicated in ischemic and traumatic insults to the central nervous system.Homer signaling can exert either positive or negative effects during such insults,depending on the specific subtype of Homer protein.Homer 1b/c couples with other proteins to form postsynaptic densities,which form the basis of synaptic transmission,while Homer 1a expression can be induced by harmful external factors.Homer 1c is used as a unique biomarker to reveal alterations in synaptic connectivity before and during the early stages of apoptosis in retinal ganglion cells,mediated or affected by extracellular or intracellular signaling or cytoskeletal processes.This review summarizes the structural features,related signaling pathways,and diverse roles of Homer proteins in physiological and pathological processes.Upregulating Homer 1a or downregulating Homer 1b/c may play a neuroprotective role in secondary brain injuries.Homer also plays an important role in the formation of photoreceptor synapses.These findings confirm the neuroprotective effects of Homer,and support the future design of therapeutic drug targets or gene therapies for ischemic and traumatic brain injuries and retinal disorders based on Homer proteins.

关键词： brain injury calcium signaling cerebral ischemia dendritic spine glutamate receptor Homer scaffolding protein neuron neuroprotection retinal ganglion cell review traumatic brain injury

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