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Supramolecular systems for bioapplications:recent research progress in China

Science China Chemistry 2024年第5期67卷 1397-1441页

作者： Yue-Yang Liu Xiao-Yong Yu Yu-Chen Pan Hang Yin Shuang Chao Yujie Li He Ma Minzan Zuo Kun-Xu Teng Jun-Li Hou Yong Chen Dong-Sheng Guo Ruibing Wang Yuxin Pei Zhichao Pei Jiang-Fei Xu Xiao-Yu Hu Chunju Li Qing-Zheng Yang Leyong Wang Yu Liu Zhan-Ting Li State key laboratory of Organometallic Chemistry Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional MoleculesShanghai Institute of Organic ChemistryChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200032China Department of Chemistry Fudan UniversityShanghai 200438China College of Chemistry State Key Laboratory of Elemento-Organic ChemistryCollaborative Innovation Center of Chemical Science and EngineeringNankai UniversityTianjin 300071China State key laboratory of Quality Research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China College of Chemistry&Pharmacy Northwest A&F UniversityYangling 712100China key Lab of Organic Optoelectronics&Molecular Engineering Department of ChemistryTsinghua UniversityBeijing 100084China College of Materials Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211106China key laboratory of Radiopharmaceuticals Ministry of EducationCollege of ChemistryBeijing Normal UniversityBeijing 100875China Tianjin key laboratory of Structure and Performance for Functional Molecules College of ChemistryTianjin Normal UniversityTianjin 300387China State key laboratory of Analytical Chemistry for Life Science Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Supramolecular systems feature dynamic,reversible and stimuli-responsive characteristics,which are not easily achieved by molecular entities.The last decade has witnessed tremendous advances in the investigations of supramolecular systems for various bioapplications,which include drug delivery,anticancer therapy,antibacterial therapy,photodynamic therapy,photothermal therapy,combination therapy,antidotes for residual drugs or toxins,and bioimaging and biosensing.Host-guest chemistry has played a key role in the development of such bioactive supramolecular systems,and natural macrocycles(such as cyclodextrins),synthetic macrocycles(such as calixarenes,cucurbit[n]urils,and pillararenes),and porous framework polymers(such as supramolecular organic frameworks and flexible organic frameworks)have been most successfully used as hosts to build different kinds of host-guest systems for attaining designed biofunctions.The self-assembly of rationally designed amphiphilic molecules,macromolecules and polymers represent another important approach for the construction of supramolecular architectures with advanced biofunctions.In this review,we summarize the important contributions made by chinese researchers in this field,with emphasis on those reported in the past five years.

关键词： host-guest chemistry drug delivery anticancer and antibacterial photodynamic therapy photothermal therapy antidote transmembrane channel bioimaging and biosensing

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Cellular atlases of ovarian microenvironment alterations by diet and genetically-induced obesity

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Science China(Life Sciences) 2024年第1期67卷 51-66页

作者： Yonghui Jiang Xueying Gao Yue Liu Xueqi Yan Huangcong Shi Rusong Zhao Zi-Jiang Chen Fei Gao Han Zhao Shigang Zhao Center for Reproductive medicine Shandong UniversityJinan 250012China Research Unit of Gametogenesis and Health of ART-Offspring Chinese Academy of Medical Sciences(No.2021RU001)Jinan 250012China key laboratory of Reproductive Endocrinology of ministry of education Shandong UniversityJinan 250012China Shandong key laboratory of Reproductive medicine Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250012China Shandong Provincial Clinical Research Center for Reproductive Health Jinan 250012China National Research Center of Assisted Reproductive Technology and Reproductive Genetics Shandong UniversityJinan 250012China The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215000China Center for reproductive medicine Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai key laboratory for Assisted Reproduction and Reproductive Genetics Shanghai 200127China State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of ScienceBeijing 100101China

Obesity,which can arise from genetic or environmental factors,has been shown to cause serious damages to the reproductive system.The ovary,as one of the primary regulators of female fertility,is a complex organ comprised of heterogeneous cell types that work together to maintain a normal ovarian microenvironment(OME).Despite its importance,the effect of obesity on the entire ovary remains poorly documented.In this study,we performed ovary single-cell and nanoscale spatial RNA sequencing to investigate how the OME changed under different kinds of obesity,including high-fat diet(HFD)induced obesity and Leptin ablation induced obesity(OB).Our results demonstrate that OB,but not HFD,dramatically altered the proportion of ovarian granulosa cells,theca-interstitial cells,luteal cells,and endothelial cells.Furthermore,based on the spatial dynamics of follicular development,we defined four subpopulations of granulosa cell and found that obesity drastically disrupted the differentiation of mural granulosa cells from small to large antral follicles.Functionally,HFD enhanced follicle-stimulating hormone(FSH)sensitivity and hormone conversion,while OB caused decreased sensitivity,inadequate steroid hormone conversion,and impaired follicular development.These differences can be explained by the differential expression pattern of the transcription factor Foxo1.Overall,our study provides a powerful and high-resolution resource for profiling obesity-induced OME and offers insights into the diverse effects of obesity on female reproductive disorders.

关键词： obesity ovarian microenvironment snRNA-seq Stereo-seq Foxo1

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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

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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC key laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina key laboratory of Animal Models and Human Disease Mechanisms of the chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State key laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State key laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原位”肿瘤疫苗用于高效化学免疫治疗（英文）

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Science China Materials 2024年

作者：孙艳菊陈文强孙硕商洪才关秀文张维芬 College of Pharmacy Shandong Second Medical University School of Clinical medicine Shandong Second Medical University key laboratory of chinese internal medicine of ministry of education and beijing Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine

作为一种新兴的联合治疗策略,肿瘤化学免疫治疗拓展了传统化疗药物的潜在可能性,利用某些化疗药物诱发免疫原性细胞死亡(ICD)激活抗肿瘤免疫应答,提升肿瘤治疗效率.本文设计了一种ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原...

作为一种新兴的联合治疗策略,肿瘤化学免疫治疗拓展了传统化疗药物的潜在可能性,利用某些化疗药物诱发免疫原性细胞死亡(ICD)激活抗肿瘤免疫应答,提升肿瘤治疗效率.本文设计了一种ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原位”肿瘤疫苗用于高效的化学免疫治疗.利用树状高分子PAMAM担载ICD引发药物DOX以及免疫激动剂CpG,该DOX@PAMAM/CpG(简称DPC)纳米粒子物理性能适宜,通过便捷的瘤内注射可在肿瘤组织良好蓄积和内化,并最大限度地降低全身毒性.在CpG的协助下该纳米粒子可引发强劲的ICD并激活全面的抗肿瘤免疫反应,体内动物实验证实该DPC纳米粒子对侵袭性黑色素瘤具有显著的抑制.本研究为肿瘤化学免疫治疗纳米递药平台的构建提供了一种切实可行的策略.

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The cooperative migration dynamics of particles correlates to the nature of hexatic-isotropic phase transition in 2D systems of corner-rounded hexagons

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Fundamental Research 2024年第2期4卷 284-290页

作者： Zhanglin Hou Mingwei Liu Yiwu Zong Fangfu Ye Kun Zhao Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang 325001China Frontiers Science Center for Synthetic Biology and key laboratory of Systems Bioengineering(ministry of education) School of Chemical Engineering and TechnologyTianjin 300072China School of Physical Science University of Chinese Academy of SciencesBeijing 100049China beijing National laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China Oujiang laboratory(Zhejiang Lab for Regenerative medicine Vision and Brain Health)WenzhouZhejiang 325001China Sichuan Provincial People’s Hospital University of Electronic Science and Technology of ChinaChengduSichuan 610054China Institute of Fundamental and Frontier Sciences University of Electronic Science and Technology of ChinaChengduSichuan 610054China

In the two-dimensional(2D)melting transition of colloidal systems,the hexatic-isotropic(H-I)transition can be either first-order or continuous.However,how particle dynamics differs at the single-particle level during these two different melting transitions remains to be disclosed.In this work,by Brownian dynamics(BD)simulations,we have systematically studied the dynamic behavior of corner-rounded hexagons during the H-I transition,for a range of corner-roundness𝜁=0.40 to 0.99 that covers the crossover from the continuous to first-order nature of H-I transition.The results show that hexagons with𝜁≤0.5 display a continuous H-I transition,whereas those with𝜁≥0.6 demonstrate a first-order H-I transition.Dynamic analysis shows different evolution pathways of the dominant cluster formed by migrating particles,which results in a droplet-like cluster structure for𝜁=0.40 hexagons and a tree-like cluster structure for𝜁=0.99 hexagons.Further investigations on the hopping activities of particles suggest a cooperative origin of migrating clusters.Our work provides a new aspect to understand the dependence of the nature of H-I transition on the roundness of hexagons through particle dynamic behavior.

关键词： Melting transition Colloids Hexatic phase Cooperative migration Hexagons

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Microbial interactions within chinese traditional medicinal plants

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chinese Herbal medicines 2024年第2期16卷 169-171页

作者： Juan Chen Luping Qin key laboratory of Bioactive Substances and Resource Utilization of chinese Herbal medicine Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China

Plants harbor diverse microbes(including bacteria,fungi,archaea,protists,and viruses)both inside and outside their tissues,so called the plant-associated microbiome.Decades of research have demonstrated the importance of plant microbiome in promoting the productivity and health of the plant in natural environment because of their essential functions in improving plant nutrition and plant resistance to biotic and abiotic stresses(Trivedi,Leach,Tringe,Sa,&Singh,2020).Thus,a plant can be regarded as a holobiont comprising the host plant and the associated microbiota(Hassani,Durán,&Hacquard,2018).Within the plant microbiota,mutualistic fungal and bacterial symbionts(e.***.mycorrhizal fungi and Rhizobia)are striking examples of microorganisms playing crucial roles in nutrient acquisition(Martin&van der Heijden,2024)and non-symbitic plant growth-promoting rhizobacteria or fungi(PGPR or PGPF)also have drawn interest due to their ability to improve soil properties and confer stress tolerance in plants(Upadhyay et al.,2023).

关键词： mutual striking outside

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Impact of corticosteroids on initiation and half-year durability of humoral response in COVID-19 survivors

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chinese Medical Journal Pulmonary and Critical Care medicine 2024年第1期2卷 48-55页

作者： Yeming Wang Li Guo Guohui Fan Yang Han Qiao Zhang Lili Ren Hui Zhang Geng Wang Xueyang Zhang Tingxuan Huang Weiyang Wang Lan Chen Lixue Huang Xiaoying Gu Xinming Wang Jingchuan Zhong Ying Wang Hui Li Jiapei Yu Zhibo Liu Chaolin Huang Bin Cao Jianwei Wang 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 SciencesChina-Japan Friendship HospitalBeijing 100029China National Health Commission key laboratory of Systems Biology of Pathogens and Christophe Mérieux laboratory Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical SciencesBeijing 100029China School of Population medicine and Public Health Chinese Academy of Medical Sciences&Peking Union Medical CollegeState Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationBeijing 100730China 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 Clinical research and Data managementCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Jin Yin-tan Hospital WuhanHubei 430023China Department of Pulmonary and Critical Care medicine West China HospitalSichuan UniversityChengduSichuan 610041China Department of Rheumatology and Clinical Immunology Chinese Academy of Medical Sciences&Peking Union Medical CollegeNational Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID)Ministry of Science&TechnologyState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College Hospital(PUMCH)Key Laboratory of Rheumatology and Clinical ImmunologyMinistry of EducationBeijing 100730China Department of Pulmonary and Critical Care medicine Center of Respiratory MedicineChina-Japan Friendship HospsitalInstitute of Respiratory MedicineChinese

Background:The impact of corticosteroids on humoral responses in coronavirus disease 2019(COVID-19)sur-vivors during the acute phase and subsequent 6-month period remains unknown.This study aimed to determine how the use of corticosteroids influences the initiation and duration of humoral responses in COVID-19 survivors 6 months after infection onset.Methods:We used kinetic antibody data from the lopinavir-ritonavir trial conducted at Jin Yin-Tan Hospital in January 2020,which involved adults hospitalized with severe COVID-19(LOTUS,ChiCTR2000029308).Anti-body samples were collected from 192 patients during hospitalization,and kinetic antibodies were monitored at all available time points after recruitment.Additionally,plasma samples were collected from 101 COVID-19 survivors for comprehensive humoral immune measurement at the half-year follow-up visit.The main focus was comparing the humoral responses between patients treated with systemic corticosteroid therapy and the non-corticosteroid group.Results:From illness onset to day 30,the median antibody titre areas under the receiver operating characteristic curve(AUCs)of nucleoprotein(N),spike protein(S),and receptor-binding domain(RBD)immunoglobulin G(IgG)were significantly lower in the corticosteroids group.The AUCs of N-,S-,and RBD-IgM as well as neutralizing antibodies(NAbs)were numerically lower in the corticosteroids group compared with the non-corticosteroid group.However,peak titres of N,S,RBD-IgM and-IgG and NAbs were not influenced by corticosteroids.During 6-month follow-up,we observed a delayed decline for most binding antibodies,except N-IgM(𝛽−0.05,95%CI[−0.10,0.00])in the corticosteroids group,though not reaching statistical significance.No significant difference was observed for NAbs.However,for the half-year seropositive rate,corticosteroids significantly accelerated the decay of IgA and IgM but made no difference to N-,S-,and RBD-IgG or NAbs.Additionally,corticosteroids group showed a trend towards delayed viral clearance compared with the non-cort

关键词： COVID-19 Corticosteroid Immunity Antibody Humoral response

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Artemisia argyi extract subfraction exerts an antifungal effect against dermatophytes by disrupting mitochondrial morphology and function

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chinese Journal of Natural medicines 2024年第1期22卷 47-61页

作者： CHEN Le ZHU Yunyun GUO Chaowei GUO Yujie ZHAO Lu MIAO Yuhuan DU Hongzhi LIU Dahui College of Pharmacy Hubei University of Chinese MedicineWuhan 430065China National Resource Center for chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties.Despite its widespread use,scientific evidence validating the antifungal efficacy of A.argyi water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains limited.This study aimed to substantiate the scientific basis of the folkloric use of A.argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes.The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species.The subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent subfraction.The minimum inhibitory concentrations(MICs)of AAWE6 against T.rubrum,M.gypseum,and T.mentagrophytes were 312.5,312.5,and 625μg·mL−1,respectively.Transmission electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T.rubrum,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy metabolism.Additionally,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of AAWE6.In conclusion,the subfraction AAWE6 from A.argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function.This research validates the traditional use of A.argyi and provides scientific support for its antidermatophytic applicati

关键词： Artemisia argyi Dermatophyte Antifungal activity Mitochondrial structure Mitochondrial function Transcriptome analysis

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA ministry of education key laboratory of Diagnostic medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical laboratory medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling paths.Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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