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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA laboratory Medicine and pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Molecular features of gastroenteropancreatic neuroendocrine carcinoma: A comparative analysis with lung neuroendocrine carcinoma and digestive adenocarcinomas

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Chinese Journal of Cancer Research 2024年第1期36卷 90-102页

作者： Jianwei Zhang Hanxiao Chen Junli Zhang Sha Wang Yanfang Guan Wenguang Gu Jie Li Xiaotian Zhang Jian Li Xicheng Wang Zhihao Lu Jun Zhou Zhi Peng Yu Sun Yang Shao Lin Shen Minglei Zhuo Ming Lu Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Radiation Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518172China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department I of Thoracic OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Medical Department Nanjing Geneseeq Technology Inc.Nanjing 210061China Geneplus-Beijing Beijing 102200China State Key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of PathologyPeking University Cancer Hospital&InstituteBeijing 100142China

Objective: There is an ongoing debate about whether the management of gastroenteropancreatic(GEP)neuroendocrine carcinoma(NEC) should follow the guidelines of small-cell lung cancer(SCLC). We aim to identify the genetic differences of GEPNEC and its ***: We recruited GEPNEC patients as the main cohort, with lung NEC and digestive adenocarcinomas as comparative cohorts. All patients undergone next-generation sequencing(NGS). Different gene alterations were compared and analyzed between GEPNEC and lung NEC(LNEC), GEPNEC and adenocarcinoma to yield the remarkable ***: We recruited 257 patients, including 99 GEPNEC, 57 LNEC, and 101 digestive *** the mutations, KRAS, RB1, TERT, IL7R, and CTNNB1 were found to have different gene alterations between GEPNEC and LNEC samples. Specific genes for each site were revealed: gastric NEC(TERT amplification),colorectal NEC(KRAS mutation), and bile tract NEC(ARID1A mutation). The gene disparities between small-cell NEC(SCNEC) and large-cell NEC(LCNEC) were KEAP1 and CDH1. Digestive adenocarcinoma was also compared with GEPNEC and suggested RB1, APC, and KRAS as significant genes. The TP53/RB1 mutation pattern was associated with first-line effectiveness. Putative targetable genes and biomarkers in GEPNEC were identified in22.2% of the patients, and they had longer progression-free survival(PFS) upon targetable treatment [12.5 months vs. 3.0 months, HR=0.40(0.21-0.75), P=0.006].Conclusions: This work demonstrated striking gene distinctions in GEPNEC compared with LNEC and adenocarcinoma and their clinical utility.

关键词： Neuroendocrine carcinoma gastroenteropancreatic lung genetic alterations molecular markers

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comparative analysis of primate and pig cells reveals primate-specific PINK1 expression and phosphorylation

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Zoological Research 2024年第2期45卷 242-252页

作者： Xiu-Sheng Chen Rui Han Yan-Ting Liu Wei Huang Qi Wang Xin Xiong Ying Zhang Jian-Guo Zhao Shi-Hua Li Xiao-Jiang Li Wei-Li Yang Guangdong Key laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State Key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China University of Chinese Academy of Sciences Beijing 100049China

PTEN-induced putative kinase 1(PINK1),a mitochondrial kinase that phosphorylates Parkin and other proteins,plays a crucial role in mitophagy and protection against *** in PINK1 and Parkin can lead to loss of function and early onset Parkinson's ***,there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces ***,PINK1 knockout pigs(Sus scrofa)do not appear to exhibit *** our recent work involving non-human primates,we found that PINK1 is selectively expressed in primate brains,while absent in rodent *** extend this to other species,we used multiple antibodies to examine the expression of PINK1 in pig *** contrast to tissues from cynomolgus monkeys(Macaca fascicularis),our data did not convincingly demonstrate detectable PINK1expression in pig *** of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation,as observed in cultured monkey cells.A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey ***,PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and *** findings provide new evidence that PINK1expression is specific to primates,underscoring the importance of non-human primates in investigating PINK1function and pathology related to PINK1 deficiency.

关键词： PINK1 Parkin Mitochondria Phosphorylation Non-human primates Pigs

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NHE7 upregulation potentiates the uptake of small extracellular vesicles by enhancing maturation of macropinosomes in hepatocellular carcinoma

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Cancer Communications 2024年第2期44卷 251-272页

作者： Yue Yao Yi Xu Liang Yu Ting-Mao Xue Zhi-Jie Xiao Pui-Chi Tin Hiu-Ling Fung Hoi-Tang Ma Jing-Ping Yun Judy Wai Ping Yam Department of pathology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongP.R.China Department of Endocrinology and Metabolism Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjingP.R.China State Key laboratory of Oncology in South China Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Hepatobiliary Surgery II Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Scientific Research Center The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdongP.R.China State Key laboratory of Liver Research The University of Hong KongHong KongP.R.China Department of pathology Cancer Center of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

Background:Small extracellular vesicles(sEVs)mediate intercellular commu-nication that contributes to hepatocellular carcinoma(HCC)progression via multifaceted *** success of cell entry determines the effect of sEV on recipient ***,we aimed to delineate the mechanisms underlying the uptake of sEV in ***:AF,Alexa Fluor;ANOVA,analysis of variance;ATP9A,ATPase Phospholipid Transporting 9A;BCECF-AM,2’,7’-bis-(2-barboxyethyl)-5-(and-6)-carboxyfluorescein,acetoxymethyl ester;BSA,bovine serum albumin;CCMR,Centre for comparative Medicine Research;CRISPR,clustered regularly interspaced short palindromic repeats;CTL,ctrl;CXCR4,C-X-C Chemokine Receptor Type 4;DAPI,4′,6-diamidino-2-phenylindole;DFS,disease-free survival;DMEM,Dulbecco’s Modified Eagle Medium;DMSO,dimethyl sulfoxide;Dox,doxycycline;EEA1,early endosome antigen 1;EIPA,5-(N-ethyl-N-isopropyl)-amiloride;FBS,fetal bovine serum;FITC,fluorescein isothiocyanate;GAPDH,glyceraldehyde-3-phosphate dehydrogenase;GM130,Golgi matrix protein 130;HCC,hepatocellular carcinoma;HEPES,4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;HPRT1,hypoxanthine phosphoribosyltransferase 1;H-score,histoscore;IAA,indole-3-acetic acid;KD,knockdown;KO,knockout;mAID,mini-auxin-inducible degron;MTT,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide;NHE7,Na(+)/H(+)exchanger 7;ns,non-significant;OD,optical density;OS,overall survival;PBS,phosphate-buffered saline;PCR,polymerase chain reaction;pHe,endosomal pH;pHi,intracellular pH;PKH67,Paul Karl Horan 67;Rab21,Ras-associated binding protein 21;RIPA,radioimmunoprecipitation assay;SAM,synergistic activation mediator;SEMs,standard error of the means;sEVs,small extracellular vesicles;sgRNA,single-guide RNA;shRNA,short-hairpin RNA;SLC9,solute carrier gene 9;SLiCE,Seamless Ligation Cloning Extract;TCGA,The Cancer Genome Atlas;TCL,total cell lysates;TGN,trans-Golgi network;TMA,tissue microarray;TMR,tetramethyl rhodamine;TSG101,tumor susceptibility gene *** Yao an

关键词： hepatocellular carcinoma small extracellular vesicles macropinocytosis pH regulation sodium-hydrogen exchanger

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Antioxidants Enzymes Activities and NO Levels in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis—A comparative Study

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Journal of Biosciences and Medicines 2024年第2期12卷 50-59页

作者： Natalia Cristina Aparecida Ribeiro e Ribeiro Anderson Martins Tavares Jaslana Hainfellner da Silva João Paulo Lima Daher Salim Kanaan Luciene de Carvalho Cardoso-Weide laboratory of Neuroplasticity Neurobiology Department Biology Institute Federal Fluminense University Rio de Janeiro Brazil Postgraduate Program in Medical Sciences School of Medicine Federal Fluminense University Rio de Janeiro Brazil School of Biology UNIVERSO—Salgado de Oliveira University Rio de Janeiro Brazil Department of pathology Faculty of Medicine Federal Fluminense University Rio de Janeiro Brazil

It consists of a retrospective study with twenty-two individuals diagnosed with DRC: fourteen HD and eight CAPD, followed up in the dialysis center of Antonio Pedro University Hospital (HUAP) of Fluminense Federal University (UFF), between 2015 and 2017. Fifteen healthy control (HC) subjects were included, without diagnosed CKD. Patients with HIV positive, hepatitis A, B, and C, pregnant, cancer, smokers, alcoholics and those exposed to X-rays in the last 3 months, were excluded. Objectives: As oxidative stress and endothelial dysfunction may be linked to the higher prevalence of CVD in CKD patients, we measured the activities of the antioxidants enzymes: SOD and GPx and total NO levels in the plasma and serum of end-stage CKD patients undergoing dialysis therapy, comparing with the HC group. Methods: Quantification of NO levels was performed by fluorometric kit, while activities of SOD and GPx were determined using kinetic methods. Results: We found higher plasma SOD activity in HD (8.58 U/ml) and CAPD (10.14 U/ml), compared to C (3.73 U/ml) group, while GPx activity was decreased in HD (115.38 nmol/h/ml) and CAPD (122.76 nmol/h/ml) groups compared to HC group (275.83 nmol/h/ml). Total serum NO concentration was decreased in HD (14.09 pmol/μl) and CAPD (10.26 pmol/μl), compared to non-CKD patients (49.65 pmol/μl). Conclusion: Decreased total serum NO and GPx activities may lead to endothelial dysfunction and consequently a higher prevalence of CVD in CKD patients.

关键词： Hemodialysis CAPD SOD GPx NO

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Stem cell therapy for Alzheimer’s disease:An overview of experimental models and reality

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Animal Models and Experimental Medicine 2022年第1期5卷 15-26页

作者： Chuan Qin Kewei Wang Ling Zhang Lin Bai Institute of laboratory Animal Sciences Chinese Academy of Medical Sciences(CAMS)Comparative Medicine CenterPeking Union Medical College(PUMC)NHC Key Laboratory of Human Disease Comparative MedicineKey Laboratory of Human Diseases Animal ModelBeijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases BeijingBeijingChina

Alzheimer's disease(AD)is a neurodegenerative *** pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain *** therapies have been tested to improve or at least effectively modify the course of *** data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's *** stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be *** review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these *** cell therapy provides perspective and chal-lenges for its clinical application in the future.

关键词： Alzheimer's disease animal model cognitive deficits memory loss stem cell therapy

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Comparison of resistive index and shear-wave elastography in the evaluation of chronic kidney allograft dysfunction

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World Journal of Transplantation 2024年第1期14卷 154-163页

作者： Ameet Kumar Jesrani Syed M Faiq Rahma Rashid Tariq Ali Kalwar Rehan Mohsin Tahir Aziz Nida Amin Khan Muhammed Mubarak Department of Radiology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of pathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of Transplantation Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of Urology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan

BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term *** and novel ultrasound-based investigations are being increasingly used for this purpose with variable *** To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological *** This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February *** consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this *** and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic *** The mean age of all patients was 35.32±11.08 *** these,126(81.8%)were males and 28(18.2%)were *** mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 *** allograft biopsy results showed chronic changes in 55(37.66%)*** sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft *** can be of great help during the routine follow-up of kidney transplant recipients for screening a

关键词： Shear wave Sonoelastography Resistive index Chronic allograft changes Biopsy Histopathology

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SARS-CoV-2 treatment effects induced by ACE2-expressing microparticles are explained by the oxidized cholesterolincreased endosomal pH of alveolar macrophages

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Cellular & Molecular Immunology 2022年第2期19卷 210-221页

作者： Zhenfeng Wang Jiadi Lv Pin Yu Yajin Qu Yabo Zhou Li Zhou Qiangqiang Zhu Shunshun Li Jiangping Song Wei Deng Ran Gao Yuying Liu Jiangning Liu Wei-Min Tong Chuan Qin Bo Huang Department of Immunology&National Key laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical CollegeBeijing 100005China NHC Key laboratory of Human Disease comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina State Key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesCAMS and Peking Union Medical CollegeBeijingChina Department of pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&TechnologyWuhan 430030China

Exploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising ***,we show that ACE2-overexpressing A549 cell-derived microparticles(AO-MPs)are a potential therapeutic agent against SARS-CoV-2 *** administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages(AMs).Then,AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs,thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for *** pH regulation is attributable to oxidized cholesterol,which is enriched in AO-MPs and translocated to endosomal membranes,thus interfering with proton pumps and impairing endosomal *** addition to promoting viral degradation,AO-MPs also inhibit the proinflammatory phenotype of AMs,leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side *** findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.

关键词： SARS-CoV-2 microparticles Alveolar macrophages Endosomes Lysosomes

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Therapeutic regulation of autophagy in hepatic metabolism

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Acta Pharmaceutica Sinica B 2022年第1期12卷 33-49页

作者： Katherine Byrnes Sophia Blessinger Niani Tiaye Bailey Russell Scaife Gang Liu Bilon Khambu Department of pathology and laboratory Medicine Tulane University School of MedicineNew OrleansLA 70112USA

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ thatgoverns body energy metabolism. Autophagy’s role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders.

关键词： Autophagy Liver metabolism Signaling proteins Lysosome Nutrient regeneration Quality control Farnesoid X receptor Cryptochrome 1

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Airway administration of bisphosphate and dexamethasone inhibits SARS-CoV-2 variant infection by targeting alveolar macrophages

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1375-1378页

作者： Zhenfeng Wang Yabo Zhou Linlin Bao Dan Li Jiadi Lv Dianheng Wang Shunshun Li Jiangning Liu Chuan Qin Wei-Min Tong Bo Huang Department of Immunology&National Key laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College100005 BeijingChina NHC Key laboratory of Human Disease comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceCAMS and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Department of pathology Institute of Basic Medical SciencesCAMS and Peking Union Medical CollegeBeijingChina Department of Biochemistry&Molecular Biology Tongji Medical CollegeHuazhong University of Science&Technology430030 WuhanChina

Dear Editor,Alveolar macrophages(AMs)are among the first immune cells to encounter SARS-CoV-2 during an infection due to their abundant numbers and physical location in the ***,the reaction of AMs to SARS-CoV-2 has a profound impact on the outcome of the *** most cases,AMs can release cytokines and prime adaptive T-and B-cell immune responses to resolve the infection.

关键词： infection alveolar release

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