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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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Chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei Deng Wenqing Xu Feiya Xu qian gao Wanmu Xie Rongguo Zhang Min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China National Center for Respiratory Medicine 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 HospitalBeijing 100029China Institute of Advanced Research Infervision Medical Technology Co.Ltd.Beijing 100025China Department of Radiology China-Japan Friendship HospitalBeijing 100029China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China Department of Radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise diagnosis.In population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying biomarkers.This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods:This is a single-center retrospective study.Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose APE.Thereafter,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years algorithm.Eventually,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)analysis.Results:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart failure.Among eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment strategy.The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726.Conclusions:Based on RF algorithm,a novel prediction model was finally constructed for APE diagnosis.When compared to the current clinica

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and Experimental Medicine 2024年第3期7卷 324-336页

作者： Bowen Niu Lingling Liu qian gao Meng-Min Zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of Laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

Characterisation of IL-21 and IL-21Rαin grass carp:IL-21-producing cells are upregulated during Flavobacterium columnare infection

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Aquaculture and Fisheries 2024年第2期9卷 126-135页

作者： Jiawen Xu Junya Wang Qingyu Min Wei Wang Yuting Qin Lina Lei qian gao Jun Zou Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources Ministry of EducationShanghai Ocean UniversityShanghai201306China International Research Center for Marine Biosciences at Shanghai Ocean University Ministry of Science and TechnologyShanghai201306China National Demonstration Center for Experimental Fisheries Science Education Shanghai Ocean UniversityShanghai201306China Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao266200China

Interleukin-21(IL-21)is produced mainly by activated CD4^(+)T cells and promotes the proliferation,survival and differentiation of immune cells.This study characterised a high affinity binding receptor of IL-21(IL-21 Rα)from grass carp(Ctenopharyngodon idella,Ci)and analyzed the expression of CiIL-21 and CiIL-21 Rα.It has been shown that they were modulated by PAMPs and during infection with bacterial and viral pathogens.Recombinant CiIL-21 protein produced in bacteria was active in inducing the expression of genes involved in Th responses.A monoclonal CiIL-21 antibody was generated against the rCiIL-21 and showed good reactive specificity with the rCiIL-21 proteins expressed in E.coli cells,and HEK293 T cells and the native protein from PHA-stimulated kidney leukocytes.In addition,the IL-21-producing cells detected by the CiIL-21 monoclonal antibody were found to be increased to in the kidney,spleen and hindgut after infection with Flavobacterium columnare.Our data indicate that IL-21 is involved in the regulation of immune response to bacterial and viral infection.

关键词： IL-21 IL-21Rα Gene expression IL-21-Producing cell Bacterial and viral infection Fish

HSH-carbon: A novel sp^(2)–sp^(3) carbon allotrope with an ultrawide energy gap

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Frontiers of physics 2022年第6期17卷 79-84页

作者： Jia-Qi Liu qian gao Zhen-Peng Hu School of Physics Nankai UniversityTianjin 300071China

An sp^(2)-sp^(3) hybrid carbon allotrope named HSH-carbon is proposed by the first-principles calculations.The structure of HSH-carbon can be regarded as a template polymerization of[1.1.1]propellane molecules in a hexagonal lattice,as well as,an AA stacking of recently reported HSH-C10 consisting of carbon trigonal bipyramids.Based on calculations,the stability of this structure is demonstrated in terms of the cohesive energy,phonon dispersion,Born–Huang stability criteria,and ab initio molecular dynamics.HSHcarbon is predicted to be a semiconductor with an indirect energy gap of 3.56 eV at the PBE level or 4.80 eV at the HSE06 level.It is larger than the gap of Si and close to the gap of c-diamond,which indicates HSH-carbon is potentially an ultrawide bandgap semiconductor.The effective masses of carriers in the VB and CB edge are comparable with wide bandgap semiconductors such as GaN and ZnO.The elastic behavior of HSH-carbon such as bulk modulus,Young’s modulus and shear modulus is comparable with that of T-carbon and much smaller than that of c-diamond,which suggests that HSH-carbon would be much easier to be processed than c-diamond in practice.

关键词： first-principles calculation novel carbon allotropes pentagonal ring

Establishment of a humanized ST6GAL1 mouse model for influenza research

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Animal Models and Experimental Medicine 2024年第3期7卷 337-346页

作者： Lyu Chao Han Feng gao qian Lv Limin Lu Ziwei Lu Shuangshuang Li Xiaoyan Hu Yuechao Yang Mengjie Zhao Yingze Liu Jun Lu Xuancheng Duo Shuguang National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina NHC Key Laboratory of Biosafety National Key Laboratory of Intelligent Tracking and Forecasting for Infectious DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouChina

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

关键词： hST6GAL1 humanized mice influenza animal model

Coupling physics in machine learning to investigate the solution behavior of binary Mg alloys

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Journal of Magnesium and Alloys 2022年第10期10卷 2817-2832页

作者： Tao Chen qian gao Yuan Yuan Tingyu Li qian Xi Tingting Liu Aitao Tang Andy Watson Fusheng Pan National Engineering Research Center for Magnesium Alloys College of Materials Science and EngineeringChongqing UniversityChongqing 400000PR China State Key Laboratory of Mechanical Transmissions College of Materials Science and EngineeringChongqing UniversityChongqing 400000PR China Faculty of Materials and Energy Southwest UniversityChongqing 400715PR China Hampton Thermodynamics Hampton TW121NLUnited Kingdom

The solution behavior of a second element in the primary phase(α(Mg))is important in the design of high-performance alloys.In this work,three sets of features have been collected:a)interaction features of solutes and Mg obtained from first-principles calculation,b)intrinsic physical properties of the pure elements and c)structural features.Based on the maximum solid solubility values,the solution behavior of elements inα(Mg)are classified into four types,e.g.,miscible,soluble,sparingly-soluble and slightly-soluble.The machine learning approach,including random forest and decision tree algorithm methods,is performed and it has been found that four features,e.g.,formation energy,electronegativity,non-bonded atomic radius,and work function,can together determine the classification of the solution behavior of an element inα(Mg).The mathematical correlations,as well as the physical relationships among the selected features have been analyzed.This model can also be applied to other systems following minor modifications of the defined features,if required.

关键词： Mg alloys Solid solubility Machine learning First-principles calculation Diagrammatic method

Nicotinamide mononucleotide supplementation improves the quality of porcine oocytes under heat stress

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Journal of Animal Science and Biotechnology 2022年第5期13卷 1326-1339页

作者： Meijie Song Yu Li Yihang Zhou Jiner Yan Xiaohua Zhou qian gao Yilong Miao Bo Xiong College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China College of Veterinary Medicine Nanjing Agricultural UniversityNanjing 210095China

Background:Elevated ambient temperature-caused heat stress is a major concern for livestock production due to its negative impact on animal feed intake,growth,reproduction,and health.Particularly,the germ cells are extremely sensitive to the heat stress.However,the effective approach and strategy regarding how to protect mammalian oocytes from heat stress-induced defects have not been determined.Methods:Germinal vesicle(GV)porcine oocytes were cultured at 41.5℃ for 24 h to induce heat stress,and then cultured at 38.5℃ to the specific developmental stage for subsequent analysis.Nicotinamide mononucleotide(NMN)was dissolved in water to 1 mol/L for a stock solution and further diluted with the maturation medium to the final concentrations of 10μmol/L,20μmol/L,50μmol/L or 100μmol/L,respectively,during heat stress.Immunostaining and fluorescence intensity quantification were applied to assess the effects of heat stress and NMN supplementation on the key processes during the oocyte meiotic maturation.Results:Here,we report that NMN supplementation improves the quality of porcine oocytes under heat stress.Specifically,we found that heat stress resulted in oocyte maturation failure by disturbing the dynamics of meiotic organelles,including the cytoskeleton assembly,cortical granule distribution and mitochondrial function.In addition,heat stress induced the production of excessive reactive oxygen species(ROS)and DNA damage,leading to the occurrence of apoptosis in oocytes and subsequent embryonic development arrest.More importantly,we validated that supplementation of NMN during heat stress restored the meiotic defects during porcine oocyte maturation.Conclusions:Taken together,our study documents that NMN supplementation is an effective approach to improve the quality of oocytes under heat stress by promoting both nuclear and cytoplasmic maturation.

关键词： Heat stress Meiotic defects Nicotinamide mononucleotide Oocyte quality Porcine oocytes

HSH-C_(10):A new quasi-2D carbon allotrope with a honeycomb-star-honeycomb lattice

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Chinese Chemical Letters 2022年第8期33卷 3941-3946页

作者： qian gao Lifu Zhang Caiyan Zheng Shulai Lei Shujuan Li Zhenpeng Hu School of Physics Nankai UniversityTianjin 300071China Hubei Key Laboratory of Low Dimensional Optoelectronic Materials and Devices Hubei University of Arts and ScienceXiangyang 441053China Institute of Mathematics Free University of BerlinArnimallee 6Berlin D-14195Germany

Two-dimensional(2 D)materials with honeycomb,kagome or star lattice have been intensively studied because electrons in such lattices could give rise to exotic quantum effects.In order to improve structural diversity of 2 D materials to achieve unique properties,here we propose a new quasi-2 D honeycombstar-honeycomb(HSH)lattice based on first-principles calculations.A carbon allotrope named HSH-C_(10) is designed with the HSH lattice,and its mechanical properties have been intensively investigated through total energy,phonon dispersion,ab initio molecular dynamic simulations,as well as elastic constants calculations.Besides the classical covalent bonds,there is an interesting charge-shift bond in this material from the chemical bonding analysis.Additionally,through the analysis of electronic structure,HSH-C_(10) is predicted to be a semiconductor with a direct band gap of 2.89 e V,which could combine the desirable characteristics of honeycomb and star lattice.Importantly,by modulating coupling strength,a flat band near the Fermi level can be obtained in compounds HSH-C_(6)Si_(4) and HSH-C_(6)Ge_(4),which have potential applications in superconductivity.Insight into such mixed lattice would inspire new materials with properties we have yet to imagine.

关键词： Carbon allotrope Two-dimensional lattice Charge-shift bond Flat band First-principles

结核病控制的新挑战:出人意料的气溶胶检测新发现

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中国防痨杂志 2024年第7期46卷 739-742页

作者：李蒙高谦复旦大学基础医学院教育部、卫健委、医科院医学分子病毒学重点实验室/上海市重大传染病和生物安全研究院上海200032

气溶胶是结核分枝杆菌传播的重要媒介,存在于气溶胶和痰液中的结核分枝杆菌的特性是否相同?近期在美国科学院院刊上发表了一篇气溶胶中结核分枝杆菌特征的论文,其研究结果颠覆了已有的认知。笔者将对此研究进行介绍,并提出基于此研究的... 详细信息

气溶胶是结核分枝杆菌传播的重要媒介,存在于气溶胶和痰液中的结核分枝杆菌的特性是否相同?近期在美国科学院院刊上发表了一篇气溶胶中结核分枝杆菌特征的论文,其研究结果颠覆了已有的认知。笔者将对此研究进行介绍,并提出基于此研究的一些思考。

关键词：结核传染病控制气溶胶

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