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

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 COVID-19.Our research,along with others',has demonstrated that mast cells(MCs)play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2.In previous study,we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice.Additionally,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 injury.The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation,and inflammation in these regions could promote viral spread.MCs are widely distributed throughout the respiratory tract.Thus,in this study,we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium.Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2.MC degranulation caused lesions in trachea,and the formation of papillary hyperplasia was observed.Through transcriptome analysis in bronchial epithelial cells,we found that MC degranulation significantly altered multiple cellular signaling,particularly,leading to upregulated immune responses and inflammation.The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice.Taken together,our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions.Furthermore,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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Biomimetic nanomedicines for precise atherosclerosis theranostics

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4442-4460页

作者： Ying Tao Xinmiao Lan Yang Zhang Chenxing Fu Lu Liu feng cao Weisheng Guo Department of Minimally Invasive Interventional Radiology Key Laboratory of Molecular Target&Clinical PharmacologySchool of Biomedical Engineering&the Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China School of Pharmaceutical Sciences Capital Medical UniversityBeijing 100069China Department of Cardiology the Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Cardiology and Laboratory of Heart Center Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicinethe University of Hong KongHong Kong SAR 999077China

Atherosclerosis(AS)is a leading cause of the life-threatening cardiovascular disease(CVD),creating an urgent need for efficient,biocompatible therapeutics for diagnosis and treatment.Biomimetic nanomedicines(b NMs)are moving closer to fulfilling this need,pushing back the frontier of nano-based drug delivery systems design.This review seeks to outline how these nanomedicines(NMs)might work to diagnose and treat atherosclerosis,to trace the trajectory of their development to date and in the coming years,and to provide a foundation for further discussion about atherosclerotic theranostics.

关键词： Nanotheranostics Atherosclerosis Biomimetic nanomedicines Drug delivery Passive targeting Active targeting Plaques Diagnosis and treatment

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Establishment of a diagnostic model of coronary heart disease in elderly patients with diabetes mellitus based on machine learning algorithms

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Journal of Geriatric Cardiology 2022年第6期19卷 445-455页

作者： Hu XU Wen-Zhe cao Yong-Yi BAI Jing DONG He-Bin CHE Po BAI Jian-Dong WANG feng cao Li FAN Chinese PLA Medical School Chinese PLA General HospitalBeijingChina Department of Cardiology the Second Medical CenterNational Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijingChina Department of General Surgery the First Medical CenterChinese PLA General HospitalBeijingChina Institute of Geriatrics the Second Medical CenterChinese PLA General HospitalBeijingChina Medical Big Data Research Center&National Engineering Laboratory for Medical Big Data Application Technology Chinese PLA General HospitalBeijingChina Department of Respiratory Diseases Chinese PLA Rocket Force Characteristic Medical CenterBeijingChina

OBJECTIVE To establish a prediction model of coronary heart disease(CHD)in elderly patients with diabetes mellitus(DM)based on machine learning(ML)algorithms.METHODS Based on the Medical Big Data Research Centre of Chinese PLA General Hospital in Beijing,China,we identified a cohort of elderly inpatients(≥60 years),including 10,533 patients with DM complicated with CHD and 12,634 patients with DM without CHD,from January 2008 to December 2017.We collected demographic characteristics and clinical data.After selecting the important features,we established five ML models,including extreme gradient boosting(XGBoost),random forest(RF),decision tree(DT),adaptive boosting(Adaboost)and logistic regression(LR).We compared the receiver operating characteristic curves,area under the curve(AUC)and other relevant parameters of different models and determined the optimal classification model.The model was then applied to 7447 elderly patients with DM admitted from January 2018 to December 2019 to further validate the performance of the model.RESULTS Fifteen features were selected and included in the ML model.The classification precision in the test set of the XGBoost,RF,DT,Adaboost and LR models was 0.778,0.789,0.753,0.750 and 0.689,respectively;and the AUCs of the subjects were 0.851,0.845,0.823,0.833 and 0.731,respectively.Applying the XGBoost model with optimal performance to a newly recruited dataset for validation,the diagnostic sensitivity,specificity,precision,and AUC were 0.792,0.808,0.748 and 0.880,respectively.CONCLUSIONS The XGBoost model established in the present study had certain predictive value for elderly patients with DM complicated with CHD.

关键词： patients admitted coronary

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MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 119-134页

作者： Wenyi Chen Feiyan Lin Xudong feng Qigu Yao Yingduo Yu Feiqiong Gao Jiahang Zhou Qiaoling Pan Jian Wu Jinfeng Yang Jiong Yu Hongcui cao Lanjuan Li State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Key Laboratory of Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases of Zhejiang Province Hangzhou 310003China

Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.

关键词： Mesenchymal stem cell Exosomes Primary sclerosing cholangitis Fibrosis Organoids Th17

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan cao Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Research Progress on the Preparation of Inorganic/Natural Materials Composite Microspheres

Expert Review of Chinese Chemical

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Expert Review of Chinese Chemical 2024年第1期2卷 15-20页

作者： Jing cao Chaojie feng Wen Duan College of Mathematics and Science Southwest University of Science and Technology

Microspheres are a new type of drug carrier with great potential for development and application.Natural polymers have good biocompatibility,biodegradability,and are easily dispersed in living organisms,making them suitable for preparing microspheres.Inorganic materials(mainly inorganic minerals)have excellent mechanical properties and are inexpensive and easy to obtain.Through the coupling and hybridization of natural polymers and inorganic materials,they can complement each other's advantages and synergistically enhance efficiency,resulting in many excellent physical and chemical properties.Inorganic materials/natural polymer composite microspheres can be prepared by modifying natural polymers with inorganic materials through various methods such as emulsification crosslinking,solution mixing,in-situ synthesis,extrusion,etc.The application of inorganic materials/natural polymer composite microspheres in drug delivery systems has significant sustained-release effects,is safe and non-toxic,and the cost of carrier materials is relatively low,which has certain significance for the development of new drug carriers.This article reviews the recent research on the preparation,drug loading and release properties of inorganic material/natural polymer composite microspheres,analyzes the advantages and disadvantages of commonly used preparation methods,and looks forward to the development direction of composite microspheres.

关键词： natural polymer materials composite microspheres preparation research progress

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Cocktail nano-adjuvant enhanced cancer immunotherapy based on NIR-Ⅱ-triggered in-situ tumor vaccination

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Chinese Chemical Letters 2024年第3期35卷 346-351页

作者： Lilin Fan Yanwen feng Jiang Bian Anhong Chen Donglin Xie Zheng cao Jun Yue Jiangsu Key Laboratory of Environmentally Friendly Polymeric Materials School of Materials Science and EngineeringJiangsu Collaborative Innovation Center of Photovoltaic Science and EngineeringChangzhou UniversityChangzhou 213164China School of Biomedical Engineering Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China

Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.

关键词： Nano-adjuvant Cocktail formulation In-situ tumor vaccination NIR-Ⅱphotothermal effect Anticancer immune response

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A Post-Quantum Cross-Domain Authentication Scheme Based on Multi-Chain Architecture

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Computers, Materials & Continua 2024年第2期78卷 2813-2827页

作者： Yi-Bo cao Xiu-Bo Chen Yun-feng He Lu-Xi Liu Yin-Mei Che Xiao Wang Ke Xiao Gang Xu Si-Yi Chen Information Security Center State Key Laboratory ofNetworking and Switching TechnologyBeijing University of Posts and TelecommunicationsBeijing100876China Information Center of China North Industries Group Corporation Beijing100089China School of Information Science and Technology North China University of TechnologyBeijing100144China

Due to the rapid advancements in network technology,blockchain is being employed for distributed data storage.In the Internet of Things(IoT)scenario,different participants manage multiple blockchains located in different trust domains,which has resulted in the extensive development of cross-domain authentication techniques.However,the emergence of many attackers equipped with quantum computers has the potential to launch quantum computing attacks against cross-domain authentication schemes based on traditional cryptography,posing a significant security threat.In response to the aforementioned challenges,our paper demonstrates a post-quantum cross-domain identity authentication scheme to negotiate the session key used in the cross-chain asset exchange process.Firstly,our paper designs the hiding and recovery process of user identity index based on lattice cryptography and introduces the identity-based signature from lattice to construct a post-quantum cross-domain authentication scheme.Secondly,our paper utilizes the hashed time-locked contract to achieves the cross-chain asset exchange of blockchain nodes in different trust domains.Furthermore,the security analysis reduces the security of the identity index and signature to Learning With Errors(LWE)and Short Integer Solution(SIS)assumption,respectively,indicating that our scheme has post-quantum security.Last but not least,through comparison analysis,we display that our scheme is efficient compared with the cross-domain authentication scheme based on traditional cryptography.

关键词： Cross-domain identity authentication lattice-based cryptography blockchain hashed time-locked contract

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Cardiovascular risk burden,dementia risk and brain structural imaging markers:a study from UK Biobank

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General Psychiatry 2024年第1期37卷 94-102页

作者： Yaying cao Gaohong Zhu Chengwu feng Jing Chen Wei Gan Yuan Ma Yonghua Hu Klodian Dhana Trudy Voortman Jie Shen Ting Li Yan Zheng Changzheng Yuan Geng Zong Department of Food Nutrition and Health School of Medicine and HealthHarbin Institute of TechnologyHarbinHeilongjiangChina CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghaiChina Department of Nuclear Medicine First Affiliated Hospital of Kunming Medical UniversityKunmingYunnanChina Neurology Department Zhongshan Hospital Affliated with Fudan UniversityShanghaiChina Medical Research Council Population Health Research Unit University of OxfordOxfordUK Department of Genetics Novo Nordisk Research Centre OxfordOxfordUK Harvard University T H Chan School of Public Health BostonMassachusettsUSA Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Internal Medicine Rush University Medical CenterChicagolinoisUSA Department of Epidemiology rasmus MCUniversity Medical Center RotterdamRotterdamThe Netherlands Division of Human Nutrition and Health Wageningen University&ResearchWageningenThe Netherlands School of Public Health the Second Afliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina First Afiliated Hospital of Kunming Medical University KunmingYunnanChina State Key Laboratory of Genetic Engineering School f ife SCciencesFudan UniversityShanghaiChina Ministry of Education Key Laboratory of Public Health Safety School of Public HealthFudan UniversityShanghaiChina The Key Laboratory of Inteligent Preventive Medicine of Zhejang Province HangzhouZhejiangChina Shanghai Jiao Tong University Affiliated Sixth People's Hospital ShanghaiChina

Background Cardiovascular risk burden is associated with dementia risk and neurodegeneration-related brain structure,while the role of genetics and incident cardiovascular disease(CVD)remains unclear.Aims To examine the association of overall cardiovascular risk burden with the risk of major dementia subtypes and volumes of related brain regions in a large sample,and to explore the role of genetics and CVD onset.Methods A prospective study among 354 654 participants free of CVD and dementia(2006-2010,mean age 56.4 years)was conducted within the UK Biobank,with brain magnetic resonance imaging(MRl)measurement availablefor 15104participants since 2014.CVD risk burden was evaluated by the Framingham General Cardiovascular Risk Score(FGCRS).Dementia diagnosis was ascertained from inpatient and death register data.Results Overamedian 12.0-yearfollow-up,3998 all-cause dementia cases were identified.Higher FGCRS was associated with increasedall-cause dementia risk after adjusting for demographic,major lifestyle,clinical factors and the polygenic risk score(PRS)of Alzheimer's disease.Comparing the high versus low tertile of FGCRS,the odds ratios(ORs)and 95%confidence intervals(Cls)were 1.26(1.12 to 1.41)for all-cause dementia,1.67(1.33 to 2.09)for Alzheimer's disease and 1.53(1.07 to 2.16)for vascular dementia(all p_(treng)<0.05).Incident stroke and coronary heart disease accounted for 14%(95%Cl:9% to 21%)of the association between FGCRS and all-cause dementia.Interactions were not detected for FGCRS and PRS on the risk of any dementia subtype.We observed an 83%(95%Cl:47%to 128%)higher all-cause dementia risk comparing the high-high versus low-low FGCRS-PRS category.For brain volumes,higher FGCRS was associated with greater log-transformed white matter hyperintensities,smaller cortical volume and smaller grey matter volume.Conclusions Our findings suggest that the positive association of cardiovascular risk burden with dementia risk also applies to major dementia subtypes.The association of cardiovascular risk burden wit

关键词： Cardiovascular diagnosis burden

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Properties and microstructure of copper–titanium alloys with magnesium additions

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Rare Metals 2024年第5期43卷 2290-2299页

作者： Lue Huang Li-Jun Peng Jiang Li Xu-Jun Mi Gang Zhao Guo-Jie Huang Hao-feng Xie Yi-Cheng cao Wen-Jing Zhang Zhen Yang State Key Laboratory of Nonferrous Metals and Processes GRINM Group Co. Ltd. GRIMAT Engineering Institute Co. Ltd. School of Materials Science and Engineering Northeastern University General Research Institute for Nonferrous Metals China Academy of Space Technology China Nonferrous Metals Mining Group (Tianjin) Co.Ltd

The volume fractions and morphology of precipitates in precipitation-strengthened Cu-Ti alloys,which precipitate mainly as continuous and discontinuous precipitates,are important for the application of the alloy.This study employed hardness and electrical conductivity tests transmission electron microscopy （TEM）,atom probe tomography （APT）,and first-principles calculations to demonstrate that the addition of Mg is effective for accelerating nanosized continuous β'-Cu4Ti precipitation as well as for suppressing the precipitation of coarse lamellar discontinuous β-Cu4Ti precipitates along the grain boundaries,resulting in Cu-Ti alloys with high yield strength and good electrical conductivity.The results showed that the continuous precipitation of β'-Cu4Ti was accelerated by the Mg additions,which reduced the supersaturation of the matrix,thereby reducing the chemical driving force for the discontinuous precipitates.On the other hand,Mg additions increased the mismatch between the discontinuous β-Cu4Ti precipitates and matrix decreased the nucleation rate of the discontinuous precipitates,and increased the spacing of the discontinuous precipitation layer,resulting in a lower growth rate of the discontinuous precipitates.Therefore,the addition of Mg to Cu-Ti alloys enhances the strength and improves the resistance to over-ageing.

关键词： Cu-Ti-Mg alloy Precipitation hardening Discontinuous precipitation Continuous precipitation Microstructure formation mechanism

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