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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

Science China(Life Sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen wang Yangming Song Zhibo shan Xuyuan wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan chen chengjun Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Numerical investigation of hydro-morphodynamic characteristics of a cascading failure of landslide dams

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Journal of Mountain Science 2024年第6期21卷 1868-1885页

作者： ZHONG Qiming chen Lingchun MEI Shengyao shan Yibo WU Hao ZHAO Kunpeng Department of Geotechnical Engineering Nanjing Hydraulic Research InstituteNanjing 210024China National Key Laboratory of Water Disaster Prevention Nanjing 210098China Key Laboratory of Reservoir and Dam Safety of the Ministry of Water Resources Nanjing 210029China

A cascading failure of landslide dams caused by strong earthquakes or torrential rains in mountainous river valleys can pose great threats to people’s lives,properties,and *** this study,based on the three-dimensional Reynoldsaveraged Navier-Stokes equations(RANS),the renormalization group(RNG)k-εturbulence model,suspended and bed load transport equations,and the instability discriminant formula of dam breach side slope,and the explicit finite volume method(FVM),a detailed numerical simulation model for calculating the hydro-morphodynamic characteristics of cascading dam breach process has been *** developed numerical model can simulate the breach hydrograph and the dam breach morphology evolution during the cascading failure process of landslide dams.A model test of the breaches of two cascading landslide dams has been used as the validation *** comparison of the calculated and measured results indicates that the breach hydrograph and the breach morphology evolution process of the upstream and downstream dams are generally consistent with each other,and the relative errors of the key breaching parameters,i.e.,the peak breach flow and the time to peak of each dam,are less than±5%.Further,the comparison of the breach hydrographs of the upstream and downstream dams shows that there is an amplification effect of the breach flood on the cascading landslide dam *** key parameters,i.e.,the distance between the upstream and the downstream dams,the river channel slope,and the downstream dam height,have been used to study the flood amplification *** parameter sensitivity analyses show that the peak breach flow at the downstream dam decreases with increasing distance between the upstream and the downstream dams,and the downstream dam ***,the peak breach flow at the downstream dam first increases and then decreases with steepening of the river channel *** the flood caused by the upstream dam failure flows to the

关键词： Cascading landslide dams Cascading dam failure process Detailed numerical simulation model Flood amplification effect Parameter sensitivity analyses

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Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids

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Zoological Research 2024年第2期45卷 233-241页

作者： Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang Yan Zhuo shan-Gang Li Jiao-Jian wang Wen-Ting Guo Zheng-Bo wang Yong-Chang chen State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China Yunnan Key Laboratory of Primate Biomedical Research KunmingYunnan 650500China

Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube *** folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain *** SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains *** tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural *** determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate *** of SHROOM3 resulted in shorter neuroepithelial cells and smaller *** morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial ***,these defects were not rescued by folate *** sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ *** summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关键词： Neural tube defects SHROOM3 Neuroepithelial Organoids Cynomolgus monkey

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Wavelength-dependent nonlinear wavefront shaping in 3D nonlinear photonic crystal

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Chinese Optics Letters 2024年第7期22卷 66-70页

作者： Yunze wang Yan Sheng shan Liu Ruwei Zhao Tianxiang Xu Tiefeng Xu Feng chen Wieslaw Krolikowski Laboratory of Infrared Materials and Devices Research Institute of Advanced TechnologiesNingbo UniversityNingbo 315211China Engineering Research Center for Advanced Infrared Photoelectric Materials and Devices of Zhejiang Province Ningbo UniversityNingbo 315211China Quantum Science and Technology Research School of PhysicsAustralian National UniversityCanberraACT 2601Australia Ningbo Institute of Oceanography Ningbo 315832China State Key Laboratory of Crystal Materials and Key Laboratory of Particle Physics and Particle Irradiation of the Ministry of Education School of PhysicsShandong UniversityJinan 250100China

A 3D nonlinear photonic crystal containing four parallel segments of periodicχ^((2))grating structure is fabricated employing the femtosecond laser poling of ferroelectric Ca_(0.28)Ba_(0.72)Nb_(2)O_(6) *** second harmonic generation from this foursegment structure is studied with a fundamental Gaussian *** tuning the wavelength of the fundamental wave,the second harmonic varies from the Laguerre-Gaussian beam(topological charge l_(c)=1)to the higher-order Hermite-Gaussian beam and Laguerre-Gaussian again(l_(c)=−1).This effect is caused by the wavelength-dependent phase delays introduced by the four-grating *** study contributes to a deeper understanding of nonlinear wave interactions in 3D nonlinear photonic *** also offers new possibilities for special beam generation at new frequencies and their control.

关键词： quasi-phase matching nonlinear photonic crystal second harmonic generation nonlinear beam shaping

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Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance

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Cancer Communications 2024年第2期44卷 205-225页

作者： chen Ming-Kun chen Zi-Xian Cai Mao-Ping chen Hong chen Zhuang-Fei Zhao shan-Chao Department of Urology The Third Affiliated Hospital of Southern Medical UniversityGuangzhouGuangdongP.R.China The Third Clinical College Southern Medical UniversityGuangzhouGuangdongP.R.China Luoyang Key Laboratory of Organic Functional Molecules College of Food and DrugLuoyang Normal UniversityLuoyangHenanP.R.China Department of Urology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malig-nant tumor cells remain significant clinical ***,there are only few effective methods to address these *** vesicles(EVs),actively secreted by cells,play a crucial role in intercellular information transmis-sion and cargo *** studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application ***,there is an urgent need for further improvements in the isolation and purification of EVs,surface modification techniques,drug assem-bly processes,and precise recognition of tumor cells for targeted drug delivery *** this review,we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance,and current challenges asso-ciated with engineered EVs are also *** review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

关键词： drug delivery drug resistance extracellular vesicles nanoparticles

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Persistent greening against drying in northeast Asian semiarid grasslands:Asymmetrical responses of direct and legacy effects to intensified drought

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Advances in Climate Change Research 2024年第1期15卷 9-20页

作者： Yu-Tong MA Hai-shan chen Yao-Ming SONG Bo-Tao ZHOU shan-Lei SUN Xin-Guan DU Yue SUN Key Laboratory of Meteorological Disaster Ministry of Education/Joint International Research Laboratory of Climate and Environment Change/Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science and TechnologyNanjing 210044China School of Atmospheric Sciences Nanjing University of Information Science and TechnologyNanjing 210044China

Despite experiencing a decadal shift towards drought conditions at the end of the 2Oth century,semiarid grasslands in northeast Asia(NEA)exhibited an evident greening trend from 1982 to ***,the mechanism behind this phenomenon remains ***,we analysed the interdecadal changes in vegetation response to drought on the basis of the standardised precipitation evapotranspiration index(SPEI)and Global Inventory Modelling and Mapping Studies LAI4g datasets,with an emphasis on the differences between direct and legacy effects(as measured by resilience),to explore the mechanism of persistent grassland *** revealed that during the post-drought shift period(2000-2020),the sudden decrease in the water content of the intermediate soil layer triggered an intensified vegetation response to ***,although direct effects and resilience were amplified,they exhibited asymmetric *** was stronger than direct effects,and this difference increased with increasing drought(drought recovery)*** combined effects may account for persistent greening against intensified drying in the semiarid grasslands in *** the projected exacerbation of future droughts,this study holds notable importance for comprehending the long-term change dynamics of dryland ecosystems.

关键词： Semiarid grassland Drought decadal shift Direct effect Legacy effect(resilience) Northeast Asia

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Convolution-Transformer for Image Feature Extraction

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Computer Modeling in Engineering & Sciences 2024年第10期141卷 87-106页

作者： Lirong Yin Lei wang Siyu Lu Ruiyang wang Youshuai Yang Bo Yang shan Liu Ahmed AlSanad Salman A.AlQahtani Zhengtong Yin Xiaolu Li Xiaobing chen Wenfeng Zheng Department of Geography and Anthropology Louisiana State UniversityBaton RougeLA70803USA School of Automation University of Electronic Science and Technology of ChinaChengdu610054China College of Computer and Information Sciences King Saud UniversityRiyadh11574Saudi Arabia College of Resources and Environmental Engineering Key Laboratory of Karst Georesources and Environment(Guizhou University)Ministry of EducationGuiyang550025China School of Geographical Sciences Southwest UniversityChongqing400715China School of Electrical and Computer Engineering Louisiana State UniversityBaton RougeLA70803USA

This study addresses the limitations of Transformer models in image feature extraction,particularly their lack of inductive bias for visual *** to Convolutional Neural Networks(CNNs),the Transformers are more sensitive to different hyperparameters of optimizers,which leads to a lack of stability and slow *** tackle these challenges,we propose the Convolution-based Efficient Transformer Image Feature Extraction Network(CEFormer)as an enhancement of the Transformer *** model incorporates E-Attention,depthwise separable convolution,and dilated convolution to introduce crucial inductive biases,such as translation invariance,locality,and scale invariance,into the Transformer ***,we implement a lightweight convolution module to process the input images,resulting in faster convergence and improved *** results in an efficient convolution combined Transformer image feature extraction *** results on the ImageNet1k Top-1 dataset demonstrate that the proposed network achieves better accuracy while maintaining high computational *** achieves up to 85.0%accuracy across various model sizes on image classification,outperforming various baseline *** integrated into the Mask Region-ConvolutionalNeuralNetwork(R-CNN)framework as a backbone network,CEFormer outperforms other models and achieves the highest mean Average Precision(mAP)*** research presents a significant advancement in Transformer-based image feature extraction,balancing performance and computational efficiency.

关键词： Transformer E-Attention depth convolution dilated convolution CEFormer

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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li shan Sun Nana wang Yang chen Chunsheng Dong Kin Yip Tam Jochen H.M.Prehn Hongfeng wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

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BIOCELL 2024年第8期48卷 1265-1273页

作者： shan JIANG XIUFENG LIN YANFEI chen XINNING LI JIALI KANG Department of Gynecology and Obstetrics The First Affiliated Hospital of Jinan UniversityGuangzhou510180China Reproductive Medical Center Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou510180China

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor *** has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and ***,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still ***:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian *** assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer *** pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer ***:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian *** experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this ***,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

关键词： Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer

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Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury

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Virologica Sinica 2024年第2期39卷 309-318页

作者： Jian-Bo Cao Shu-Tong Zhu Xiao-shan Huang Xing-Yuan wang Meng-Li Wu Xin Li Feng-Liang Liu Ling chen Yong-Tang Zheng Jian-Hua wang Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China School of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026China Key Laboratory of Bioactive Peptides of Yunnan Province Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of SciencesKIZCUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesCenter for Biosafety Mega-ScienceKunming Institute of ZoologyChinese Academy of SciencesKunming 650223China University of Chinese Academy of Sciences Beijing 101408China

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of *** research,along with others',has demonstrated that mast cells(MCs)play a vital role in the initiation of hyper-inflammation caused by *** previous study,we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized ***,we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells,leading to subsequent lung *** trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation,and inflammation in these regions could promote viral *** are widely distributed throughout the respiratory ***,in this study,we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial *** analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with *** degranulation caused lesions in trachea,and the formation of papillary hyperplasia was *** transcriptome analysis in bronchial epithelial cells,we found that MC degranulation significantly altered multiple cellular signaling,particularly,leading to upregulated immune responses and *** administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in *** together,our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue ***,our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation,thereby preventing tissue damage caused by hyper-inflammation.

关键词： SARS-CoV-2 Mast cell(MC) Bronchial epithelial cell Inflammation Tracheal injury

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