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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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First total synthesis,antitumor evaluation and target identification of mornaphthoate E:A new tubulin inhibitor template acting on PI3K/Akt signaling pathway

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2177-2193页

作者： Peipei Shan Tao Ye Ying-De tang Hui Song chao Wang Kongkai Zhu Feifei Yang Shi-Lei Zhang Pei-Wen Su Shuanhu Gao Hua Zhang Institute of Translational Medicine the Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdao 266021China School of Biological Science and Technology University of JinanJinan 250022China Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinan 250012China College of Pharmaceutical Sciences Soochow UniversitySuzhou 215127China School of Chemistry and Molecular Engineering East China Normal UniversityShanghai 200062China

Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell lines.In the current project,the first total synthesis of(±)-MPE was achieved in seven steps and 5.6%overall yield.Then the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells,with the levoisomer exerting slightly better potency.The in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse model.Notably,MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic dosage.Mechanistic investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt signaling.In conclusion,our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

关键词： Mornaphthoate E Tubulin inhibitor Antitumor Anti-metastasis Breast cancer PI3K/Akt

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Markovian Quadratic BSDEs with an Unbounded Sub-quadratic Growth

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Chinese Annals of Mathematics,Series B 2024年第3期45卷 441-462页

作者： Jingnan JU Shanjian tang Shanghai Center for Mathematical Sciences Fudan UniversityShanghai 200433China Department of Finance and Control Sciences School of Mathematical SciencesFudan UniversityShanghai 200433China

This paper is devoted to the solvability of Markovian quadratic backward stochastic differential equations(BSDEs for short)with bounded terminal conditions.The generator is allowed to have an unbounded sub-quadratic growth in the second unknown variable z.The existence and uniqueness results are given to these BSDEs.As an application,an existence result is given to a system of coupled forward-backward stochastic differential equations with measurable coefficients.

关键词： Markovian BSDE Quadratic growth Unbounded sub-quadratic term coeficients Coupled FBSDE

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SARS-CoV-2 immunity in animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： Zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan chao Lv Tian tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian Zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory Disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its transmissibility.SARS-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected individuals.These complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ failure.Animal models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against SARS-CoV-2.Currently,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been developed.Each model possesses distinctive features and applications.In this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 patients.Finally,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 animal models immune response

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An economic way to achieve all-weather CO2 reduction

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National Science Review 2024年第3期11卷 46-47页

作者： Junwang tang Department of Chemical Engineering University College London

Utilising solar power to convert carbon dioxide（CO2） into hydrocarbon fuels presents an eco-friendly method to address dependence on fossil fuels and contribute to a net-zero CO2emission goal[1,2].

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High-precision modeling of tide-induced 3-D magnetic field and analysis of geomagnetic satellite orbit requirements

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Science China Earth Sciences 2024年第1期67卷 165-178页

作者： Zhengyong REN Cong YANG Hongbo YAO Xu tang Jingtian tang Keke ZHANG Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of Education Central South UniversityChangsha 410083China Hunan Key Laboratory of Nonferrous Resources and Geological Hazards Exploration Changsha 410083China School of Geosciences and Info-Physics Central South UniversityChangsha 410083China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China

Ground-based magnetic observatories and geomagnetic satellites can observe the induced magnetic field generated by the motion of seawater containing sodium and chlorine ions.Calculating the three-dimensional(3-D)spatial distribution of tide-induced magnetic fields(TIMF)is crucial for inverting the electrical conductivity structure of the oceanic lithosphere.It also serves as an essential basis for designing optimal geomagnetic observatories and satellite orbits.However,existing methods for simulating TIMF suffer from limitations in inaccurately modeling realistic coastlines,heterogeneous land and sea surface properties,and complex deep Earth structures,thereby the interpretational level of TIMF data is reduced.To overcome this issue,we developed a tetrahedral-based finite element method for simulating TIMF,which can efficiently approximate realistic coastlines,heterogeneous land and sea surface properties,and complex deep Earth structures.Firstly,we derived the boundary value problem for the seawater motion-induced electromagnetic field,which was solved using the vector finite element method based on tetrahedral elements.Secondly,using the latest ocean depth and seafloor sediment layer models,we constructed a 3-D conductivity model of the Earth,which includes realistic coastlines,heterogeneous land and sea conductivity distributions.We then computed the TIMF using the M_(2)tidal source as an example and validated our method by comparing it with results obtained from spherical harmonic finite element and integral equation methods.Finally,utilizing the computed high-precision M_(2),N_(2),and O1 TIMF signals,we marked global observatories capable of observing strong M_(2),N_(2),and O1 TIMF signals and predicted alternative stations suitable for tide signal observations.Additionally,we calculated TIMF at heights of 450 and 200 km for the Macao Science Satellite 1 and its subsequent satellites.The results indicate that the amplitude of the tidal-induced magnetic field at 200 km is approximately twice that at 450 km.Th

关键词： Ocean motional induction Electromagnetic induction Ocean tides Geomagnetic satellite Macao Science Satellite 1

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Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity:Insight from recent research

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World Journal of Diabetes 2024年第4期15卷 586-590页

作者： Hui-Hong tang Dong Wang Cheng-Chun tang Department of Cardiology Zhongda HospitalSoutheast UniversityNanjing 210009Jiangsu ProvinceChina School of Medicine Southeast UniversityNanjing 210009Jiangsu ProvinceChina

Obesity is a prevalent cause of diabetes mellitus(DM)and is a serious danger to human health.Type 2 DM(T2DM)mostly occurs along with obesity.Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy.Bariatric surgery can improve the symptoms of T2DM in some obese patients.But different types of bariatric surgery may have different effects.There are some models built by researchers to discuss the surgical procedures’effects on me-tabolism in diabetes animal models and diabetes patients.It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

关键词： Bariatric surgery Obesity Diabetes Animal models Diabetes patients

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Bioinspired nanomaterials for the treatment of bacterial infections

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Nano Research 2024年第2期17卷 691-714页

作者： Xiaojing Ma Wenjing tang Rong Yang Robert F.Smith School of Chemical&Biomolecular Engineering Cornell UniversityIthacaNY 14853USA

Infectious diseases pose a serious threat to global health.Although immunizations can control most viral infections,bacterial infections,particularly those caused by drug-resistant strains,continue to cause high rates of illness and death.Unfortunately,the creation of new antibiotics has come to a grinding halt in the last ten years.In response to this crisis,nanotechnology has emerged as a hopeful solution to tackle drug resistance and enhance treatment results.A large variety of biomimetic nanomaterials,termed nanozymes,have demonstrated strong antimicrobial efficacy.While the inherent toxicity of nanomaterials is a concern,recent studies have harnessed the stimuli-responsiveness of nanomaterials to enable local and/or targeted delivery to reduce the treatment side effects.Indeed,the physicochemical versatility of nanomaterials affords many degrees of freedom that enable rational design of smart or autonomous therapeutics,which cannot be achieved using conventional antibiotics.The design straddles the fields of catalysis,nanoscience,microbiology,and translational medicine.To provide an overview of this interdisciplinary landscape,this review is organized based on composition into lipid,metal,metal oxide,and non-metallic nanomaterials.Liposomes as a delivery vehicle enhance bioavailability and reduce toxicity.Metal-and metal oxide-based nanomaterials inhibit bacterial growth by mimicking natural enzymatic activities such as peroxidase(POD)and oxidase.Furthermore,carbon-,polymer-,and cell membrane-based nanomaterials are combined into a discussion on non-metallic materials.At the end of this review,potentially fruitful directions for future bioinspired nanomaterials in infectious disease treatment are included.

关键词： bioinspired nanomaterial bacteria infectious disease antimicrobial liposome nanozyme

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A new 3D plastoelastohydrodynamic lubrication model for rough surfaces

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Friction 2024年第6期12卷 1176-1193页

作者： Shengyu YOU Jinyuan tang Qiang WANG State Key Laboratory of Precision Manufacturing for Extreme Service Performance Central South UniversityChangsha 410083China

Plastoelastohydrodynamic lubrication of rough surfaces(R-PEHL)is a cutting-edge area of research in interface fluid-structure coupling analysis.The existing R-PEHL model calculates the elastic-plastic deformation of rough surface by the Love equation in a semi-infinite space smooth surface,which deviates from the actual surface.Therefore,it is an innovative work to study the exact solution of elastic-plastic deformation of rough surface and its influence on the solution results of R-PEHL model.In this paper,a new contact calculation model of plastoelastohydrodynamic lubrication(PEHL)with three-dimensional(3D)rough surface is proposed by integrating numerical method of EHL and finite element method.The new model eliminates an original error introduced by the assumption of semi-infinite space in contact calculation,providing wide applicability and high accuracy.Under the given rough surfaces and working conditions,the study reveals that:(1)the oil film pressure calculated by the new model is lower than that of the smooth surface in semi-infinite space by 200–800 MPa;(2)the Mises stress of the new model is 2.5%–26.6%higher than that of the smooth surface in semi-infinite space;(3)compared with the semi-infinite space assumption,the rough surface plastic deformation of the new model is increased by 71%–173%,and the local plastic deformation singularity may appear under the semi-infinite space assumption;(4)the plastic deformation caused by the first contact cycle on the rough surface of the new model accounts for 66.7%–92.9%of the total plastic deformation,and the plastic deformation of the semi-infinite space accounts for 50%–83.3%.This study resolves the contradiction between the smooth surface assumption and the rough surface in the existing R-PEHL model,establishing a solid logic foundation for the accurate solution of R-PEHL model.

关键词： rough surface plastoelastohydrodynamic lubrication(PEHL) asperity plastic deformation semi-infinite space

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Experimental study on reactions between alkaline basaltic melt and orthopyroxenes: constraints on the evolution of lithospheric mantle in the North China Craton

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Acta Geochimica 2024年第2期43卷 354-365页

作者： Hanqi He Mingliang Wang Hongfeng tang Key Laboratory for High Temperature and High Pressure Study of the Earth’s Interior Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China University of Chinese Academy of Sciences Beijing 100049China School of Resource and Civil Engineering Suzhou UniversitySuzhou 234000AnhuiChina

The experimental results of the reactions between an alkaline basaltic melt and mantle orthopyroxenes under high-temperature and high-pressure conditions of 1300–1400℃ and 2.0–3.0 GPa using a six-anvil apparatus are reported in this paper.The reactions are proposed to simulate the interactions between melts from the asthenospheric mantle and the lithospheric mantle.The starting melt in the experiments was made from the alkaline basalt occurring in Fuxin,Liaoning Province,and the orthopyroxenes were separated from the mantle xenoliths in Damaping,Hebei Province.The results show that clinopyroxenes were formed in all the reactions between the alkaline basaltic melt and orthopyroxenes under the studied P–T conditions.The formation of clinopyroxene in the reaction zone is mainly controlled by dissolution–crystallization,and the chemical compositions of the reacted melt are primarily infl uenced by the diff usion eff ect.Temperature is the most important parameter controlling the reactions between the melt and orthopyroxenes,which has a direct impact on the melting of orthopyroxenes and the diff usion of chemical components in the melt.Temperature also directly controls the chemical compositions of the newly formed clinopyroxenes in the reaction zone and the reacted melt.The formation of clinopyroxenes from the reactions between the alkaline basaltic melt and orthopyroxenes can result in an increase of CaO and Al_(2)O_(3) contents in the rocks containing this mineral.Therefore,the reactions between the alkaline basaltic melt from the asthenospheric mantle and orthopyroxenes from the lithospheric mantle can lead to the evolution of lithospheric mantle in the North China Craton from refractory to fertile with relatively high CaO and Al 2 O 3 contents.In addition,the reacted melts in some runs were transformed from the starting alkaline basaltic into tholeiitic after reactions,indicating that tholeiitic magma could be generated from alkaline basaltic one via reactions between the latter and orthopyroxene.

关键词： Alkaline basaltic melt Orthopyroxene Melt–mineral reaction High-temperature and high-pressure experiment Genesis of basalt Evolution of lithospheric mantle in the North China Craton

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