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Elucidating the cardioprotective mechanisms of sodium-glucose cotransporter-2 inhibitors beyond glycemic control

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World Journal of Diabetes 2024年第2期15卷 137-141页

作者： ke-Xin Zhang Cheng-Xia Kan Fang han Jing-Wen Zhang Xiao-Dong Sun Department of Endocrinology and Metabolism Affiliated Hospital of Weifang Medical UniversityWeifang 261031Shandong ProvinceChina

Sodium-glucose cotransporter-2(SGLT2)inhibitors have emerged as a pivotal intervention in diabetes management,offering significant cardiovascular ***,in particular,has demonstrated cardioprotective effects beyond its glucose-lowering action,reducing heart failure hospitalizations and improving cardiac *** note,the cardioprotective mechanisms appear to be independent of glucose lowering,possibly mediated through several mechanisms involving shifts in cardiac metabolism and anti-fibrotic,anti-inflammatory,and anti-oxidative *** editorial summarizes the multifaceted cardiovascular advantages of SGLT2 inhibitors,highlighting the need for further research to elucidate their full therapeutic potential in cardiac care.

关键词： Diabetes Sodium-glucose cotransporter-2 Cardiovascular diseases Empagliflozin

HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus

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Journal of Genetics and Genomics 2024年第3期51卷 313-325页

作者： Pengya Xue Ling Zhang Renchun Fan Yanan Li Xinyun han Ting Qi Lifang Zhao Deshui Yu Qian-hua Shen State key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions College of Advanced Agricultural SciencesUniversity of Chinese Academy of SciencesBeijing 100049China Department of Nutritional Sciences&Toxicology University of CaliforniaBerkeleyCA 94720USA Lushan Botanical Garden Chinese Academy of ScienceJiujiangJiangxi 332900China

Mitogen-activated protein kinase(MAPK)cascades play important roles in disease resistance in model plant ***,the functions of MAPK signaling pathways in crop disease resistance are largely *** we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune ***4 is identified to play a negative role in barley immune response against Bgh,as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh ***,the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4,and the activated HvMKK1^(DD) variant specifically phosphorylates HvMPK4 in ***,the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1^(DD).Phosphorylation assay coupled with mutagenesis analyses identifies S122,T284,and S347 in HvWRKY1 as the major residues phosphorylated by ***1 is phosphorylated in barley at the early stages of Bgh infection,which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression *** data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

关键词： Barley MPK4 WRKY1 Phosphorylation Disease resistance Powdery mildew

Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling

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Nano-Micro Letters 2024年第6期16卷 14-37页

作者： Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng Huize han Zhipu Fan Wenbing Dai hua Zhang Xueqing Wang Qiang Zhang Bing He Department of Pharmaceutics School of Pharmaceutical Sciences Peking University38 Xueyuan RdHaidian DistrictBeijing 100191People’s Republic of China

Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of *** the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular ***,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to ***,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular ***(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in *** adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with ***-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over *** on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation *** importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in *** summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines.

关键词： Enzyme-induced proximity labeling Intracellular delivery Nano-protein interaction Dynamic molecule profiling Macrophages

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome:A pilot study

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World Journal of Gastroenterology 2024年第21期30卷 2777-2792页

作者： Xiao-Tong Niu Xiang-Yao Wang Yan Wang ke han Nan Ru Jing-Yuan Xiang En-Qiang Linghu Medical School of Chinese PLA Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely *** To reveal the transcriptomic changes in the jejunum involved in *** In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological *** another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier *** The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which *** enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD *** DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(Pkers(DAO and D-LA)were significantly increased in all obese individuals(Phan in the SO group(P<0.001).CONCLUSION Compared with health

关键词： Obesity Chronic diarrhea Jejunum Transcriptome Intestinal barrier

Multiscale urban design based on the optimization of the wind and thermal environments:A case study of the core area of Suzhou Science and Technology City

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Frontiers of Architectural Research 2024年第4期13卷 822-841页

作者： hua Liu Xin Zhou Xin Ge Dongqing han Weiren Zhuang Ying Tang Xiaohan Shen Architects&Engineers CO. LTD of Southeast UniversityNanjing 210096China School of Architecture Southeast UniversityNanjing 210096China

New methods are need to coordinate the conflicting spatial demands through urban design research and strategies from the perspective of multi-scale urban climate *** integrate windethermal environment with urban design,we propose three scale levels,namely the district-superblock,superblock-block,and block-building levels,and divide the urban design elements into voids and ***,we establish a multiscale methodological framework in which the urban design contents are clarified by each scale,and the information transmitted between scales is obtained to ensure consistent value propositions and strategic *** microclimate shaping of the urban open space is transformed into guiding strategies and quantitative indicators of the spatial form of the solid *** is transmitted between the scales through the windethermal indicators of windward side and the morphological indicators of solid ***,the methodology was applied to the project in the core area of Suzhou Science and Technology City,and the findings preliminarily verify the effectiveness and feasibility of the *** research influences urban climate studies and urban design practice in three ways:1)improving understanding of the correlation between scales;2)facilitating interaction between the two domains;and 3)providing tools for urban design practices.

关键词： Multiscale transmission Windethermal environment optimization Urban design strategy Urban form

Development and validation of a model integrating clinical and coronary lesion-based functional assessment for longterm risk prediction in PCI patients

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Journal of Geriatric Cardiology 2024年第1期21卷 44-63页

作者： Shao-Yu WU Rui ZhanG Sheng YUAN Zhong-Xing CAI Chang-Dong GUAN Tong-Qiang ZOU Li-hua XIE ke-Fei DOU State key Laboratory of Cardiovascular Disease BeijingChina Cardiometabolic Medicine Center Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Catheterization Laboratories Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Fu Wai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES To establish a scoring system combining the ACEF score and the quantitative blood flow ratio(QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention(PCI).METHODS In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263consecutive cases of CAD patients after PCI in PANDA Ⅲ trial database. The newly developed score was then validated on the other remaining 542 patients in the *** In both the Random Forest Model and the Deep Surv Model, age, renal function(creatinine), cardiac function(LVEF)and post-PCI coronary physiological index(QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age(years)/EF(%) + 1(if creatinine ≥ 2.0 mg/d L) + 1(if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination(C-statistic = 0.651;95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration(Hosmer–Lemeshow χ^(2)= 7.070;P = 0.529) for predicting 2-year patient-oriented composite endpoint(POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan–Meier analysis(adjusted HR = 1.89;95% CI: 1.18–3.04;log-rank P < 0.01) after stratified the patients into high-risk group and low-risk *** An improved scoring system combining clinical and coronary lesion-based functional variables(ACEF-QFR)was developed, and its ability for prognostic prediction in patients with PCI was further validated to be signi

关键词： patients coronary prediction

T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 819-832页

作者： Hui-Da Zheng Qiao-Yi huang Qi-Ming huang Xiao-Ting ke Kai Ye Shu Lin Jian-hua Xu Department of Gastrointestinal Surgery The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Gynaecology and Obstetrics The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Computed Tomography/Magnetic Resonance Imaging The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Centre of Neurological and Metabolic Research The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Group of Neuroendocrinology Garvan Institute of Medical ResearchSydneyNSW 2010Australia

BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported *** a non-invasive model to predict the differentiation grade of CRC is of great *** To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July *** were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 *** were delineated layer by layer on high-resolution *** absolute shrinkage and selection operator regression was applied to screen for radiomic *** and clinical models were constructed using the multilayer perceptron(MLP)*** radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical *** performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic *** different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic *** AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation *** AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation *** clinical model achieved an AUC of 0.7

关键词： Radiomics Colorectal cancer Differentiation grade Machine learning T2-weighted imaging

冲击片雷管多点同步起爆爆轰波压力的数值模拟和试验

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含能材料 2016年第1期24卷 38-44页

作者：韩克华任西李慧张玉若褚恩义陕西应用物理化学研究所应用物理化学国家级重点实验室陕西西安710061

采用有限元程序AUTODYN软件分别进行了冲击片雷管三点、四点、六点、八点同步起爆爆轰波压力值的数值模拟。分析了影响多点同步起爆爆轰波压力的因素。采用锰铜测压方法测试了多点冲击片雷管的同步起爆爆轰波压力。使用高速摄影系统拍... 详细信息

采用有限元程序AUTODYN软件分别进行了冲击片雷管三点、四点、六点、八点同步起爆爆轰波压力值的数值模拟。分析了影响多点同步起爆爆轰波压力的因素。采用锰铜测压方法测试了多点冲击片雷管的同步起爆爆轰波压力。使用高速摄影系统拍摄了四点冲击片雷管的作用过程。结果表明,四点冲击片雷管的爆轰波压力平均值相比三点、六点、八点高。在中心距为4 mm并且装药量均为180 mg时,四个起爆点产生的爆轰波发生相互碰撞,爆轰波叠加形成超压爆轰,并能可靠起爆钝感炸药TATB。在中心距为8 mm并且装药量均为180 mg时,由于中心距较远,爆轰波衰减较快,相邻两点爆轰波发生的碰撞较少,产生的超压值也随之降低。

关键词：钝感弹药冲击片雷管多点同步起爆超压起爆数值模拟

MXene@c-MWCNT Adhesive Silica Nanofiber Membranes Enhancing Electromagnetic Interference Shielding and Thermal Insulation Performance in Extreme Environments

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Nano-Micro Letters 2024年第10期16卷 82-98页

作者： Ziyuan han Yutao Niu Xuetao Shi Duo Pan Hu Liu hua Qiu Weihua Chen Ben Bin Xu Zeinhom MEl-Bahy hua Hou Eman Ramadan Elsharkawy Mohammed AAmin Chuntai Liu Zhanhu Guo key Laboratory of Materials Processing and Mold(Zhengzhou University) Ministry of EducationNational Engineering Research Center for Advanced Polymer Processing TechnologyZhengzhou UniversityZhengzhou 450002People's Republic of China School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaHefei 230026People's Republic of China key Laboratory of Multifunctional Nanomaterials and Smart Systems Advanced Materials DivisionSuzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhou 215123People's Republic of China Shaanxi key Laboratory of Macromolecular Science and Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi'an 710072People's Republic of China College of Chemistry&Green Catalysis Center Zhengzhou UniversityZhengzhou 450001People's Republic of China Mechanical and Construction Engineering Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle Upon Tyne NE18UK Department of Chemistry Faculty of ScienceAl-Azhar UniversityNasr City 11884CairoEgypt Department of Chemistry Faculty of ScienceNorthern Border UniversityArarSaudi Arabia Department of Chemistry College of ScienceTaif UniversityP.O.Box 1109921944 TaifSaudi Arabia

A lightweight flexible thermally stable composite is fabricated by com-bining silica nanofiber membranes(SNM)with MXene@c-MWCNT hybrid *** flexible SNM with outstanding thermal insulation are prepared from tetraethyl orthosilicate hydrolysis and condensation by electrospinning and high-temperature calcination;the MXene@c-MWCNT_(x:y)films are prepared by vacuum filtration *** particular,the SNM and MXene@c-MWCNT_(6:4)as one unit layer(SMC_(1))are bonded together with 5 wt%polyvinyl alcohol(PVA)solution,which exhibits low thermal conductivity(0.066 W m^(-1)K^(-1))and good electromagnetic interference(EMI)shielding performance(average EMI SE_(T),37.8 dB).With the increase in func-tional unit layer,the overall thermal insulation performance of the whole composite film(SMC_(x))remains stable,and EMI shielding performance is greatly improved,especially for SMC_(3)with three unit layers,the average EMI SET is as high as 55.4 *** addition,the organic combination of rigid SNM and tough MXene@c-MWCNT_(6:4)makes SMC_(x)exhibit good mechanical tensile ***,SMC_(x)exhibit stable EMI shielding and excellent thermal insulation even in extreme heat and cold ***,this work provides a novel design idea and important reference value for EMI shielding and thermal insulation components used in extreme environmental protection equipment in the future.

关键词： SiO_(2)nanofiber membranes MXene@c-MWCNT Composite film Thermal insulation Electromagnetic interference shielding