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DNA of neutrophil extracellular traps promote NF-κBdependent autoimmunity via cGAS/TLR9 in chronic obstructive pulmonary disease

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3040-3055页

作者： Jun Chen Tao Wang Xiaoou Li Lijuan Gao Ke Wang Mengxin Cheng Zijian Zeng Lei Chen Yongchun Shen Fuqiang Wen Department of respiratory and Critical Care Medicine West China HospitalWest China School of Medicineand Division of Pulmonary DiseasesState Key Laboratory of BiotherapySichuan UniversityChengduSichuan 610041China

Chronic obstructive pulmonary disease(COPD)is characterised by persistent airway inflammation even after cigarette smoking *** extracellular traps(NETs)have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke(CS).However,whether and how NETs contribute to sustained airway inflammation in COPD remain *** study aimed to elucidate the immunoregulatory mechanism of NETs in COPD,employing human neutrophils,airway epithelial cells(AECs),dendritic cells(DCs),and a long-term CS-induced COPD mouse model,alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice(cGAS-^(−/−)TLR9^(−/−));Additionally,bronchoalveolar lavage fluid(BALF)of COPD patients was *** from COPD patients released greater cigarette smoke extract(CSE)-induced NETs(CSE-NETs)due to mitochondrial respiratory chain *** CSE-NETs,containing oxidatively-damaged DNA(NETs-DNA),promoted AECs proliferation,nuclear factor kappa B(NF-κB)activation,NF-κB-dependent cytokines and type-I interferons production,and DC maturation,which were ameliorated/reversed by silencing/inhibition of cGAS/*** the COPD mouse model,blocking NETs-DNA-sensing via cGAS^(−/−)and TLR9^(−/−)mice,inhibiting NETosis using mitoTEMPO,and degrading NETs-DNA with DNase-I,respectively,reduced NETs infiltrations,airway inflammation,NF-κB activation and NF-κBdependent cytokines,but not type-I interferons due to IFN-α/βreceptor *** NETs components(myeloperoxidase and neutrophil elastase activity)in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels,but not type-I interferon *** conclusion,NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced ***,targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.

关键词： inflammation TLR9 neutrophil

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UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

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Experts’Consensus on the Management of respiratory Disease Syndemic

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China CDC weekly 2024年第8期6卷 131-138页

作者： Weizhong Yang Zhongjie Li Ting Yang Yanming Li Zhengde Xie Luzhao Feng Zhibin Peng Jue Liu School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina state key laboratory of respiratory Health and Multimorbidity BeijingChina key laboratory of Pathogen Infection Prevention and Control Peking Union Medical CollegeMinistry of EducationBeijingChina National Center for respiratory diseases State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijingChina Department of Pulmonary and Critical Care Medicine National Center of GerontologyBeijing HospitalInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina Beijing key laboratory of Pediatric respiratory Infection diseases Key Laboratory of Major Diseases in ChildrenMinistry of EducationNational Clinical Research Center for Respiratory DiseasesResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016National Key Discipline of Pediatrics(Capital Medical University)Beijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina Chinese Center for Disease Control and Prevention BeijingChina Department of Epidemiology and Biostatistics School of PublicHealthKey Laboratory of Epidemiology of Major DiseasesMinistry of EducationPeking University Health Science Center-Weifang Joint Research Center for Maternal and Child HealthPeking UniversityBeijingChina

The global burden of respiratory diseases is a significant and increasing threat to individuals *** 2017,there were 544.9 million cases of chronic respiratory diseases,a 39.8%increase since 1990(1).These diseases were the third leading cause of global mortality in 2017,accounting for 7.0%of all deaths,an 18.0%increase compared to 1990.

关键词： diseases respiratory mortality

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Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — China, September 2022–August 2023

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China CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen Qian Wang Tao Huang Si Chen Wei Wu Mengxuan Wang Lina Sun Mifang Liang Shiwen Wang Ling Chen Qun Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National key laboratory of Intelligent Tracking and Forecasting for Infectious diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of respiratory Health Xiamen CityFujian ProvinceChina Guangzhou laboratory Guangzhou CityGuangdong ProvinceChina state key laboratory of respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

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EGFR-mutant non-small cell lung cancer patients harboring CDK4 amplification show favorable response to afatinib:Two case reports

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Chinese Medical Journal 2024年第12期137卷 1465-1467页

作者： Shuting Zhan Bo Cheng Xiwen Liu Jianfu Li Ge Bai Qi Cai Huiting Wang Yang Xiang Chunyan Li Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology The First Affiliated Hospital of Guangzhou Medical University&Guangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory Disease&National Clinical Research Center for Respiratory DiseaseGuangzhouGuangdong 510120China National Center for respiratory Medicine State Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseasesGuangzhou Institute of Respiratory Health&The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510120China Southern Medical University GuangzhouGuangdong 510120China Department of respiratory and Critical Care Medicine The Tenth Affiliated Hospital of Southern Medical UniversityDongguanGuangdong 523108China

To the Editor:Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)show significant efficacy in patients with advanced-stage non-small cell lung cancer(NSCLC)with sensitive EGFR mutations and significantly prolong the survival of these ***,drug resistance emerges in most *** studies indicated that cyclin-dependent kinase 4/6(CDK4/6)gene amplification was one of the resistance mechanisms of the EGFR-TKI osimertinib,weakening its *** options for EGFR-mutant NSCLC patients with CDK4 amplification are limited to add CDK4 inhibitors.

关键词： CDK4 NSCLC EGFR

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Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in Guangzhou, China, winter 2022

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Biosafety and Health 2024年第2期6卷 92-97页

作者： Qinghong Fan Mengling Jiang Jun Zhang Guofang Tang Ming Gao Yingfen Wen Xizi Deng Jun Dai Honghao Lai Peng Qian Yaqing Lin Ruiying He Liya Li Yueping Li Zhengtu Li Xuesong Liu Yimin Li Na Yu Yun Lan Fengyu Hu Feng Li Institute of Infectious diseases Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhou 510440China state key laboratory of respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of GuangzhouMedicalUniversityGuangzhou510120China Guangzhou laboratory Guangzhou 510700China

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be *** analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic *** found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(***)(24.2%),Staphylococcus aureus(***)(14.0%),andKlebsiella pneumoniae(***)(13.4%)ranked as the top three coinfected *** fumigatus(***)(39.5%),Pneumocystis jirovecii(***)(24.4%)andCanidia albicans(***)(22.1%)were the top three coinfected ***-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected *** note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease *** study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

关键词： SARS-CoV-2 Omicron BA.5.2 Omicron BF.7 Coinfection Severeinfection

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Intratumoural microbiota:a new frontier in cancer development and therapy

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Signal Transduction and Targeted Therapy 2024年第2期9卷 597-620页

作者： Yaqi Cao Hui Xia Xueyun Tan Chunwei Shi Yanling Ma Daquan Meng Mengmeng Zhou Zhilei Lv Sufei Wang Yang Jin Department of respiratory and Critical Care Medicine Hubei Province Clinical Research Center for Major Respiratory DiseasesKey Laboratory of Respiratory Diseases of National Health CommissionState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious DiseasesUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy MOE Key Laboratory of Biological Targeted TherapyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Hubei Province key laboratory of Biological Targeted Therapy Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Pathogen Biology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

Human microorganisms,including bacteria,fungi,and viruses,play key roles in several physiological and pathological *** studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms,which have been confirmed to be closely related to *** concept of intratumoural microbiota was subsequently *** could colonise tumour tissues through mucosal destruction,adjacent tissue migration,and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour *** studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations,affecting epigenetic modifications,promoting inflammation response,avoiding immune destruction,regulating metabolism,and activating invasion and *** more comprehensive and profound insights about intratumoral microbiota are continuously emerging,new methods for the early diagnosis and prognostic assessment of cancer patients have been under *** addition,interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy,especially immunotherapy,although there are some inevitable ***,we aim to provide an extensive review of the concept,development history,potential sources,heterogeneity,and carcinogenic mechanisms of intratumoural microorganisms,explore the potential role of microorganisms in tumour prognosis,and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

关键词： tumour invasion metabolism

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Endothelial phosphodiesterase 4B inactivation ameliorates endothelial-to-mesenchymal transition and pulmonary hypertension

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1726-1741页

作者： Yanjiang Xing Yangfeng Hou Tianfei Fan Ran Gao Xiaohang Feng Bolun Li Junling Pang Wenjun Guo Ting Shu Jinqiu Li Jie Yang Qilong Mao Ya Luo Xianmei Qi Peiran Yang Chaoyang Liang Hongmei Zhao Wenhui Chen Jing Wang Chen Wang state key laboratory of respiratory Health and Multimorbidity Institute of Basic Medical SciencesChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100005China Department of Lung Transplantation National Center for Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina–Japan Friendship HospitalInstitute of Respiratory MedicineChinese Academy of Medical SciencesBeijing 100029China Haihe laboratory of Cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300051China The state key laboratory of Complex Severeand Rare DiseasesInstitute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100005China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610044China

Pulmonary hypertension (PH) is a fatal disorder characterized by pulmonary vascular remodeling and obstruction. The phosphodiesterase 4 (PDE4) family hydrolyzes cyclic AMP (cAMP) and is comprised of four subtypes (PDE4A–D). Previous studies have shown the beneficial effects of pan-PDE4 inhibitors in rodent PH;however, this class of drugs is associated with side effects owing to the broad inhibition of all four PDE4 isozymes. Here, we demonstrate that PDE4B is the predominant PDE isozyme in lungs and that it was upregulated in rodent and human PH lung tissues. We also confirmed that PDE4B is mainly expressed in the lung endothelial cells (ECs). Evaluation of PH in Pde4b wild type and knockout mice confirmed that Pde4b is important for the vascular remodeling associated with PH. In vivo EC lineage tracing demonstrated that Pde4b induces PH development by driving endothelial-to-mesenchymal transition (EndMT), and mechanistic studies showed that Pde4b regulates EndMT by antagonizing the cAMP-dependent PKA–CREB–BMPRII axis. Finally, treating PH rats with a PDE4B-specific inhibitor validated that PDE4B inhibition has a significant pharmacological effect in the alleviation of PH. Collectively, our findings indicate a critical role for PDE4B in EndMT and PH, prompting further studies of PDE4B-specific inhibitors as a therapeutic strategy for PH.

关键词： Phosphodiesterase 4B Pulmonary hypertension Endothelial-to-mesenchymal transition

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A Large-Scale Online Survey on Clinical Severity and Associated Risk Factors for SARS-CoV-2 Omicron Infection — China, April–May 2023

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China CDC weekly 2024年第15期6卷 305-311,I0001-I0004页

作者： Yanxia Sun Yuping Duan Jie Qian Yimin Qu Ye Wang Guohui Fan Qiangru Huang Zhongjie Li Weizhong Yang Luzhao Feng state key laboratory of respiratory Health and Multimorbidity Key Laboratory of Pathogen Infection Prevention and ControlMinistry of EducationSchool of Population Medicine and Public HealthChinese Academy of Medical Science&Peking Union Medical CollegeBeijingChina

What is already known about this topic?Individuals who initially contract severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)lack significant mixed ***,it is crucial to monitor the clinical characteristics and associated factors of these individuals in order to inform *** is added by this report?The common symptoms reported were fever,cough,and sore *** and receiving four vaccination doses within a 6-month period were found to be associated with a shorter duration of virus shedding,decreased hospitalization rate,and reduced risk of *** aged 60 years and older,as well as those with underlying medical conditions,had a higher risk of developing *** are the implication for public health practices?Online surveys conducted through social media platforms have the potential to complement disease surveillance and data collection *** terms of vaccination prioritization,it is recommended to prioritize older individuals and those with underlying diseases.

关键词： doses Online initially

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PD-L1-driven efficient enrichment and elimination of circulating cancer cells by magnetic MoSe_(2) nanosheet

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Nano Research 2024年第5期17卷 4350-4358页

作者： Hongjie Huang Binhua Zou Shanlin Zhu Xingchen Zhang Jiale Huang Jinlin Wang Xiaoling Li Tianfeng Chen The Sixth Affiliated Hospital Jinan UniversityDongguan 523566China Department of Chemistry Institute of Food Safety and NutritionJinan UniversityGuangzhou 510632China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Pulmonary and Critical Care Medicine Guangzhou Institute of Respiratory HealthNational Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineState Key Laboratory of Respiratory DiseasesThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

Circulating tumor cells(CTCs)are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases,exacerbating lung cancer *** presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer ***,magnetic MoSe_(2) nanosheets loaded with programmed death-ligand 1(PD-L1),named PD-L1-MFP NS,were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy(PTT).In addition,by increasing the expression of cytomegalovirus UL16-binding protein(ULBP)ligands on tumor cells,the PD-L1-MFP NS further activated natural killer(NK)cells and triggered NK cell-induced cancer immunotherapy,thereby enhancing the overall tumor-killing *** summary,this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.

关键词： circulating tumor cells selenide photothermal therapy(PTT) natural killer(NK)cell immunotherapy

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