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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-yun Zhou jie Sheng Lei Zhao yun-Xin Zhu Jing Sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Understanding the cooperative effects in the catalysis of homodimeric fluoroacetate dehalogenase

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Science China Chemistry 2024年第7期67卷 2382-2391页

作者： Ke-Wei Chen Jia-Nan Chen Jun Zhang Chao Wang Tian-Yu Sun yun-Dong wu Key Laboratory of Computational Chemistry and Drug Design State Key Laboratory of Chemical OncogenomicSchool of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China Institute of Chemical Biology Shenzhen Bay LaboratoryShenzhen 518132China College of Chemistry and Molecular Engineering Peking UniversityBeijing 100871China Changping Laboratory Beijing 102200China

Fluoroacetate dehalogenases(FAcD),a homodimeric enzyme,catalyzes the conversion of fluoroacetic acid to glycolic acid(GoA).It has been proved that the enzyme has a half-of-the-site ***,its catalytic(C)subunit converts the first substrate to a covalent intermediate;then,the non-catalytic(NC)subunit binds a second substrate and promotes the conversion of the intermediate in the C subunit into the final *** the release of the product,the C subunit becomes the NC subunit,and the previous NC subunit becomes the C *** elucidate the detailed mechanism behind this cooperative catalysis,we have conducted microsecond-scale MD simulations along the reaction *** simulations indicate that the substrate in the NC subunit induces W185 and Y141 adopting an open conformation in the C *** opening of W185(C)facilitates the entry of catalytic water,enhancing the catalytic activity for product formation,while the opening of Y141(C)creates an unfavorable environment for product binding,promoting its *** interaction network analysis reveals that the substrate in the NC subunit can induce conformational changes through a conserved water chain at the interface.

关键词： enzyme catalysis molecular dynamics cooperative effect pre-reaction state

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Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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Food Science and Human Wellness 2024年第4期13卷 2289-2309页

作者： jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua wu Kamil Kuca Tushuai Li Wenda wu School of Biology and Food Engineering Changshu Institute of TechnologySuzhou 215500China Center for Clinical Mass Spectrometry School of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary MedicineNanjing Agricultural UniversityNanjing 210095China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic College of Life Science Yangtze UniversityJingzhou 434025China wuxi Medical College Jiangnan UniversityWuxi 214122China wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute wuxi Branch Wuxi 214013China

Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to *** podocytes are terminally differentiated epithelial ***_(1)induces podocyte inflammation,proteinuria and renal *** the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse *** of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte *** also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway *** of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney *** findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte *** study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关键词： Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation

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Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng wu yun-Jia Li Hao Shi Wei-Chao Zhong Mu-Keng Hong Jun-jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-yun Zeng Wei-Min Zhang Ken Kin Lam yung Zhi-Ping Lv Lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional Chinese Medicine Hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron *** previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the *** study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in ***:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this ***-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in ***,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload ***,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and *** related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and ***:Significant disorder of lipid and iron metabolism occurred in *** expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism ***-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the ***,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in *** correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that reg

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

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Low Surface Brightness Galaxies Selected by Different Model Fitting

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Research in Astronomy and Astrophysics 2024年第1期24卷 223-236页

作者： Bing-Qing Zhang Hong wu Wei Du Pin-Song Zhao Min He Feng-jie Lei Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China School of Astronomy and Space Science University of Chinese Academy of SciencesBeijing 100049China

We present a study of low surface brightness galaxies(LSBGs) selected by fitting the images for all the galaxies inα.40 SDSS DR7 sample with two kinds of single-component models and two kinds of two-component models(disk+bulge):single exponential,single sersic,exponential+deVaucular(exp+deV),and exponential+sérsic(exp+ser).Under the criteria of the B band disk central surface brightness μ_(0,disk)(B)≥22.5 mag arcsec^(-2) and the axis ratio b/a> 0.3,we selected four none-edge-on LSBG samples from each of the models which contain 1105,1038,207,and 75 galaxies,*** are 756 galaxies in common between LSBGs selected by exponential and sersic models,corresponding to 68.42% of LSBGs selected by the exponential model and 72.83% of LSBGs selected by the sersic model,the rest of the discrepancy is due to the difference in obtaining μ_(0) between the exponential and sersic *** on the fitting,in the range of 0.5≤n≤1.5,the relation of μ_(0) from two models can be written as μ_(0,sérsic)-μ_(0,exp)=-1.34(n-1).The LSBGs selected by disk+bulge models(LSBG_(2)comps) are more massive than LSBGs selected by single-component models(LSBG_1comp),and also show a larger disk *** the bulges in the majority of our LSBG_(2)comps are not prominent,more than 60% of our LSBG_(2)comps will not be selected if we adopt a single-component model *** also identified 31 giant low surface brightness galaxies(gLSBGs) from LSBG_(2)*** are located at the same region in the color-magnitude diagram as other *** we compared different criteria of gLSBGs selection,we find that for gas-rich LSBGs,M_(*)> 10^(10)M_⊙ is the best to distinguish between gLSBGs and normal LSBGs with bulge.

关键词： catalogs galaxies:spiral galaxies:bulges methods:data analysis methods:statistical

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Experimental and numerical study on atmospheric-pressure air dielectric barrier discharge via 50 Hz/5000 Hz dual-frequency excitation

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High Voltage 2024年第2期9卷 391-402页

作者： Junwen He Bangfa Peng Guanglin Yu Ronggang Wang Nan Jiang jie Li Yan wu School of Electrical Engineering Dalian University of TechnologyDalianChina Canmax Technologies Co. Ltd.SuzhouChina

A dual-frequency(DF)dielectric barrier discharge,excited by the superposition of a 50 Hz low frequency(LF)and a 5000 Hz intermediate frequency(IF),is proposed to enhance *** effect of the LF voltage component on the breakdown behaviour of the DF discharge during different periods has been studied both experimentally and *** number of high-current pulses rises as the LF voltage *** statistical analysis shows that the number of the current pulse amplitude above 80 mA in the DF discharge reaches nearly 6 times that in the IF ***,the total discharge energy in the DF discharge is significantly higher than that in the IF *** simulation re-produces the temporal variation of the breakdown behaviours in the DF *** simulated results reveal that the maximal electric field strength of the breakdown process is greater in the DF discharge compared to the IF discharge during a half-period of ***,the comparison between the IF and DF discharges exhibits that the LF voltage regulates the accumulation of residual charged species on the dielectric surface after the breakdown by modulating the residual voltage between the air gap.

关键词： dielectric excitation excited

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Dynamic emission characteristics and control strategies of air pollutants from motor vehicles in downtown Beijing,China

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Journal of Environmental Sciences 2024年第2期136卷 637-646页

作者： Yan Shen Tongran wu Aiping Lian jie Gao Fei Peng Guohua Song Xuefang wu Yangyang Cui Xinyu Liu yunfei Wan Jing Yan Yifeng Xue National Engineering Research Center of Urban Environmental Pollution Control Beijing Municipal Research Institute of Eco-Environmental ProtectionBeijing 100037China Beijing Municipal Ecology and Environment Bureau Beijing 100048China Beijing Jiaotong University Beijing 100091China

This study combined the real-time monitoring and investigation of traffic flows to comprehensively analyze the road traffic flow and vehicle structure in downtown Beijing.A dynamic emission inventory of motor vehicle air pollutants in downtown Beijing in 2021 was established,and the impact of these emissions on air quality was simulated and quantified,and different emission reduction control scenarios were proposed to evaluate their environmental improvement effects and explore measures to mitigate the impact of pollution *** results show that the high traffic flow and the structure of the motor vehicle emissions in downtown Beijing are the main causes of severe motor vehicle *** data shows that traffic flow in central Beijing is dominated by small passenger vehicles,while the vehicle mix is better than in other regions,with 72.0%of vehicles meeting"National V"or higher emission ***,to achieve higher air quality goals,further reducing vehicle emissions is *** on dynamic traffic flow,the average daily emissions of nitrogen oxides(NOX),particulate matters(PM_(2.5))and volatile organic compounds(VOC)from motor vehicles in central Beijing are 17.7 tons,0.6 tons and 14.0 tons,respectively,accounting for 23.0%of the city’s average daily motor vehicle *** a zero-emission zone for motor vehicles were implemented in central Beijing,the annual average emission level of pollutants will be reduced by 10.4%to 21.0%.The designation of ultra-low emission zones for motor vehicles could be effective in improving the air quality in the center of Beijing.

关键词： Motor vehicle Air pollutant Emission characteristics Control strategy Beijing

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Influence of Heat-setting Temperature on the Microporous Structure and Properties of PP/HDPE Bilayer Microporous Membranes

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Chinese Journal of Polymer Science 2024年第8期42卷 1243-1252页

作者： jie Xie Yong-Shi wu Jia-Yi Xie Rui-jie Xu Cai-Hong Lei Sai-Nan Song Guang-Quan Li An-Ping Huang School of Materials and Energy Guangdong University of TechnologyGuangzhou 510006China Lanzhou Petrochemical Research Center Petrochemical Research InsititutePetroChinaLanzhou 730060China School of Chemistry and Civil Engineering Shaoguan CollegeShaoguan 512005China

Due to the mechanical stability of PP layer,the PP/HDPE double-layer microporous mem brane could be prepared at a higher heat-setting temperatu re than that of PE monolayer *** this work,the effects of heat-setting temperature on the pore structure and properties of PP/HDPE dou ble-layer membrane were *** the increase of heat-setting temperature from 120℃to 130℃,the length of connecting bridge crystal and crystallinity in the PE layer increase due to the melting of thin lamellae and the stability of connecting bridge structure during *** corresponding air permeability,po rosity,wetta bility of liquid electrolyte and mechanical property of the heat-set microporous membrane increase,exhibiting better electrochemical ***,when the heat-setting temperature is further increased to 140℃,higher than the melting point of PE resin,some pores are closed since the lamellae and connecting bridges melt and shrink during heat-setting,resulting in a decrease of air permeability and *** contrast,there is negligible change in the PP layer within the above heat-setting temperature *** study successfully builds the relationship between the stable pore structure and property of microporous membrane during heat-setting,which is helpful to guide the production of high-pe rformance PP/PE/PP lithium batteries separator.

关键词： PP/HDPE bilayer microporous membranes Heat-setting temperature SAXS

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The role of anesthesia in peri-operative neurocognitive disorders:Molecular mechanisms and preventive strategies

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Fundamental Research 2024年第4期4卷 797-805页

作者： Ran Li yun Zhang Qinxin Zhu Yili wu Weihong Song The Second Affiliated Hospital and Yuying Children's Hospital Institute of AgingKey Laboratory of Alzheimer's Disease of Zhejiang ProvinceWenzhou Medical UniversityWenzhou325035China The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou 32500o0China

Peri-operative neurocognitive disorders(PNDs)include postoperative delirium(POD)and postoperative cognitive dysfunction(POCD).Children and the elderly are the two populations most vulnerable to the development of POD and POCD,which results in both high morbidity and *** are many factors,including neuroinflammation and oxidative stress,that are associated with POD and *** anesthesia is a major risk factor of ***,the molecular mechanisms of PNDs are poorly ***(DEX)is a useful sedative agent with analgesic properties,which significantly improves POCD in elderly *** this review,the current understanding of anesthesia in PNDs and the protective effects of DEX are summarized,and the underlying mechanisms are further discussed.

关键词： Peri-operative neurocognitive disorders General anesthesia Postoperative cognitive dysfunction Postoperative delirium Dexmedetomidine Alzheimer'sdisease

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Composition,function,and timing:exploring the early‑life gut microbiota in piglets for probiotic interventions

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Journal of Animal Science and Biotechnology 2024年第2期15卷 659-678页

作者： Jianping Quan Cineng Xu Donglin Ruan Yong Ye Yibin Qiu jie wu Shenping Zhou Menghao Luan Xiang Zhao Yue Chen Danyang Lin Ying Sun Jifei Yang Enqin Zheng Gengyuan Cai Zhenfang wu jie Yang College of Animal Science and National Engineering Research Center for Breeding Swine Industry South China Agricultural UniversityGuangzhouGuangdongPeople’s Republic of China Guangdong Provincial Key Laboratory of Agro‑Animal Genomics and Molecular Breeding South China Agricultural UniversityGuangzhouGuangdongChina yunfu Subcenter of Guangdong Laboratory for Lingnan Modern Agriculture YunfuGuangdongChina National Engineering Research Center for Breeding Swine Industry Wens Foodstuff Group Co.Ltd.YunfuGuangdongPeople’s Republic of China

Background The establishment of a robust gut microbiota in piglets during their early developmental stage holds the potential for long-term advantageous ***,the optimal timeframe for introducing probiotics to achieve this outcome remains *** In the context of this investigation,we conducted a longitudinal assessment of the fecal microbiota of 63 piglets at three distinct pre-weaning time ***,we gathered vaginal and fecal samples from 23 *** 16S rRNA gene and metagenomic sequencing methodologies,we conducted a comprehensive analysis of the fluctuation patterns in microbial composition,functional capacity,interaction networks,and colonization resistance within the gut microbiota of *** the piglets progressed in age,discernible modifications in intestinal microbial diversity,composition,and function were observed.A source-tracking analysis unveiled the pivotal role of fecal and vaginal microbiota derived from sows in populating the gut microbiota of neonatal *** D21,the microbial interaction network displayed a more concise and efficient configuration,accompanied by enhanced colonization resistance relative to the other two time ***,we identified three strains of Ruminococcus *** D10 as potential candidates for improving piglets’weight gain during the weaning *** The findings of this study propose that D10 represents the most opportune juncture for the introduction of external probiotic interventions during the early stages of piglet *** investigation augments our comprehension of the microbiota dynamics in early-life of piglets and offers valuable insights for guiding forthcoming probiotic interventions.

关键词： Colonization resistance Intestinal microbiota Piglet Weaning Weight gain

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