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Multifunctional nanoparticle-mediated combining therapy for human diseases

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Signal Transduction and Targeted Therapy 2024年第2期9卷 343-375页

作者： Xiaotong Li Xiuju Peng Makhloufi Zoulikha George Frimpong Boafo Kosheli Thapa Magar Yanmin ju wei He School of Pharmacy China Pharmaceutical UniversityNanjing 2111198PR China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013PR China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Combining existing drug therapy is essential in developing new therapeutic agents in disease prevention and treatment.In preclinical investigations,combined effect of certain known drugs has been well established in treating extensive human diseases.Attributed to synergistic effects by targeting various disease pathways and advantages,such as reduced administration dose,decreased toxicity,and alleviated drug resistance,combinatorial treatment is now being pursued by delivering therapeutic agents to combat major clinical illnesses,such as cancer,atherosclerosis,pulmonary hypertension,myocarditis,rheumatoid arthritis,inflammatory bowel disease,metabolic disorders and neurodegenerative diseases.Combinatorial therapy involves combining or co-delivering two or more drugs for treating a specific disease.Nanoparticle(NP)-mediated drug delivery systems,i.e.,liposomal NPs,polymeric NPs and nanocrystals,are of great interest in combinatorial therapy for a wide range of disorders due to targeted drug delivery,extended drug release,and higher drug stability to avoid rapid clearance at infected areas.This review summarizes various targets of diseases,preclinical or clinically approved drug combinations and the development of multifunctional NPs for combining therapy and emphasizes combinatorial therapeutic strategies based on drug delivery for treating severe clinical diseases.Ultimately,we discuss the challenging of developing NP-codelivery and translation and provide potential approaches to address the limitations.This review offers a comprehensive overview for recent cutting-edge and challenging in developing NP-mediated combination therapy for human diseases.

关键词： drugs diseases prevention

Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong Zhong wei Zhao Bing Yao Lin Ding Huangxian ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive Medical Center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China Center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

Protective Graphite Coating for Two-Dimensional Carbon/Carbon Composites

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Fluid Dynamics & Materials Processing 2024年第1期20卷 97-108页

作者： wei Shi Zhengyi Li Xiaobing Xu Yingshui Yu Xiaofei Ding Heng ju School of Mechanical and Power Engineering Dalian Ocean UniversityDalian116023China School of Mechanical and Electrical Engineering Gongqing Institute of Science and TechnologyJiujiang332020China

Two-dimensional carbon/carbon(2D C/C)composites are a special class of carbon/carbon composites,generally obtained by combining resin-impregnated carbon fiber clothes,which are then cured and carbonized.This study deals with the preparation of a protective coating for these materials.This coating,based on graphite,was prepared by the slurry method.The effect of graphite and phenolic resin powders with different weight ratios was examined.The results have shown that the coating slurry can fill the pores and cracks of the composite surface,thereby densifying the surface layer of the material.With the increase of the graphite powder/phenolic resin weight ratio,the coating density is enhanced while the coating surface flatness decreases;moreover,the protective ability of coating against erosion first increases(from 1:3 to 2:2)and then decreases(from 2:2 to 3:1).When the weight ratio is about 1:1,the coating for 2D C/C composites exhibits the best erosion resistance,which greatly aids these materials during gas quenching.In this case,the erosion rate is decreased by approximately 41.5%at the impact angle of 30°and 52.3%at normal impact,respectively.This can be attributed to the ability of the coating slurry to infiltrate into the substrate,thereby bonding the fibers together and increasing the compactness of the 2D C/C composites.

关键词： Carbon/carbon composites graphite coating microstructure erosion resistance

Ten- year follow- up investigation of stroke risk in systemic lupus erythematosus

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Stroke & Vascular Neurology 2024年第1期9卷 1-7页

作者： Jin-An Huang Ching-Heng Lin Ming-ju Wu Yi-Hsing Chen Kuo-Cheng Chang Chung-wei Hou Division of Neurology Neurological InstituteTaichung Veterans General HospitalTaichungTaiwan Department of Health Business Administration Hungkuang UniversityTaichungTaiwan Department of Medical Research Taichung Veterans General HospitalTaichungTaiwan Division of Nephrology Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine Chung Shan Medical UniversityTaichungTaiwan College of Medicine National Chung Hsing UniversityTaichungTaiwan Division of Allergy Immunology and RheumatologyDepartment of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan School of Medicine National Yang-Ming Chiao Tung UniversityTaichungTaiwan

Background and purpose To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus(SLE).Methods A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database.Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date,age,gender and Charlson Comorbidity Index(CCI).These subjects were followed until either stroke event or 31 December 2013.Adjusted HRs(aHRs)for strokes were estimated with Cox regression models,and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis.Results In total,8310 patients with SLE and 16620 patients without SLE were included.In general,patients with SLE had higher rates of ischaemic stroke(5.4%vs 3.3%)and haemorrhagic stroke(1.5%vs 0.6%)than in controls.In multivariate analysis adjusted to age,gender,CCI,urbanisation level and antithrombotics uses,aHRs of all strokes,ischaemic stroke and haemorrhagic stroke were 1.73(95%CI:1.54 to 1.94),1.65(95%CI:1.45 to 1.87)and 2.24(95%CI:1.71 to 2.95),respectively,in patients with SLE.Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE,even 10 years after SLE diagnosis(6.12%vs 3.50%,p<0.001).Antiplatelet use increased the risk of haemorrhagic stroke in SLE group(aHR=1.74,95%CI:1.18 to 2.57).Conclusions Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years.Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.

关键词： erythematosus diagnosis likely

Machine learning-based comparison of factors influencing estimated glomerular filtration rate in Chinese women with or without nonalcoholic fatty liver

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World Journal of Clinical Cases 2024年第15期12卷 2506-2521页

作者： I-Chien Chen Lin-ju Chou Shih-Chen Huang Ta-wei Chu Shang-Sen Lee Department of Nursing Kaohsiung Armed Forces General HospitalKaohsiung 802Taiwan Department of Obstetrics and Gynecology Tri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan Chief Executive Officer's Office MJ Health Research FoundationTaipei 114Taiwan Department of Urology Taichung Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationTaichung 427Taiwan School of Medicine Tzu Chi UniversityHualian 970Taiwan Department of Urology Tri-Service General HospitalNational Defense Medical CenterTaipei 114Taiwan

BACKGROUND The prevalence of non-alcoholic fatty liver(NAFLD)has increased recently.Subjects with NAFLD are known to have higher chance for renal function impairment.Many past studies used traditional multiple linear regression(MLR)to identify risk factors for decreased estimated glomerular filtration rate(eGFR).However,medical research is increasingly relying on emerging machine learning(Mach-L)methods.The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD(NAFLD+,NAFLD-)and to rank their importance.AIM To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD.METHODS A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort,accounting for 32 independent variables including demographic,biochemistry and lifestyle parameters(independent variables),while eGFR was used as the dependent variable.Aside from MLR,three Mach-L methods were applied,including stochastic gradient boosting,eXtreme gradient boosting and elastic net.Errors of estimation were used to define method accuracy,where smaller degree of error indicated better model performance.RESULTS Income,albumin,eGFR,High density lipoprotein-Cholesterol,phosphorus,forced expiratory volume in one second(FEV1),and sleep time were all lower in the NAFLD+group,while other factors were all significantly higher except for smoking area.Mach-L had lower estimation errors,thus outperforming MLR.In Model 1,age,uric acid(UA),FEV1,plasma calcium level(Ca),plasma albumin level(Alb)and T-bilirubin were the most important factors in the NAFLD+group,as opposed to age,UA,FEV1,Alb,lactic dehydrogenase(LDH)and Ca for the NAFLD-group.Given the importance percentage was much higher than the 2nd important factor,we built Model 2 by removing age.CONCLUSION The eGFR were lower in the NAFLD+group compared to the NAFLD-group,with age being was the most important impact factor in both groups of healthy Chinese women,followed by LDH,UA,FEV1 and

关键词： Non-alcoholic fatty liver Estimated glomerular filtration rate Machine learning Chinese women

Epicardial adipose tissue in obesity with heart failure with preserved ejection fraction: Cardiovascular magnetic resonance biomarker study

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World Journal of Cardiology 2024年第3期16卷 149-160页

作者： ju-wei Shao Bing-Hua Chen Kamil Abu-Shaban Ahmad Baiyasi Lian-Ming Wu Jing Ma Department of Radiology The Affiliated Hospital of Yunnan UniversityKunming 650021Yunnan ProvinceChina Department of Radiology Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of Radiology University of Toledo College of MedicineToledoOH 43623United States Department of Radiology Wayne State University School of MedicineDetroitMI 48201United States Department of Endocrinology Ren Ji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.

关键词： Heart failure with preserved ejection fraction Epicardial adipose tissue Obesity Cardiac magnetic resonance

Styrax japonicus functional genomics:an efficient virus induced gene silencing(VIGS)system

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Horticultural Plant Journal 2024年第1期10卷 252-258页

作者： Gangyu Sun Yiqian ju Cuiping Zhang Lulu Li Xinqiang Jiang Xiaoman Xie Yizeng Lu Kuiling Wang wei Li College of Landscape Architecture and Forestry Qingdao Agricultural UniversityQingdaoShandong 266109China Shandong Provincial Center of Forest and Grass Germplasm Resources JinanShandong 250102China

VIGS(Virus-induced gene silencing),a method for posttranscriptional gene silencing,is an effective technique for investigating the activities of genes in plants.Since there is no report for available VIGS system in Styrax japonicus,the application of a VIGS approach that results in a gene knockdown to study gene function is limited.In this study,we compared the characteristics that could affect the viability of VIGS in S.japonicus,including the acetosyringone(AS)concentration,the Agrobacterium’s optical density and the inoculation method.The stable reference genes of S.japonicus were selected to validate the gene’s knockdown by quantitative PCR.As a result,we successfully constructed 2 VIGS systems based on TRV virus:vacuum with AS concentration of 200μmol·L^(-1)and OD600of 0.5,and friction-osmosis with AS concentration of 200μmol·L^(-1)and OD600of 1.0,which silencing efficiency was 83.33%and 74.19%,respectively.The successfully applied VIGS method provides a rapid and effective reverse gene functional analysis approach in S.japonicus to identify unknown gene functions.

关键词： Styrax japonicus VIGS Reference gene

A smart hybrid memory scheduling approach using neural models

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Science China(Information Sciences) 2024年第4期67卷 333-334页

作者： Yanjie ZHEN Huijun ZHANG Yongheng DENG weining CHEN wei GAO ju REN Yu CHEN Department of Computer Science and Technology Tsinghua University China Huaneng Clean Energy Research Institute

Traditional dynamic random access memory is limited by its low capacity and high cost because of the increasing demand for the memory capacity of applications. Hybrid memory architectures, including new memory hardwar... 详细信息

关键词： Cost reduction

Resistance development,cross-resistance,and fitness costs associated with Aphis gossypii resistance towards sulfoxaflor and acetamiprid in different geographical regions

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Journal of Integrative Agriculture 2024年第7期23卷 2332-2345页

作者： wei Wang Renfu Zhang Haiyang Liu Ruifeng Ding Qiushi Huang ju Yao Gemei Liang Key Laboratory of Integrated Pest Management on Crop in Northwestern Oasis of Ministry of Agriculture and Rural Affairs Institute of Plant ProtectionXinjiang Academy of Agricultural SciencesUrumqi 830091China State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China

Aphis gossypii has become increasingly difficult to manage due to its strong insecticide resistance.In the laboratory,we established sulfoxaflor-resistant and acetamiprid-resistant strains in two A.gossypii populations with different basal insecticide resistance levels,and evaluated the effects of basal insecticide resistance on the resistance development and cross-resistance,as well as differences in fitness.Under the same selection pressure,Yarkant A.gossypii(with low basal insecticide resistance)evolved resistance to sulfoxaflor and acetamiprid more quickly than Jinghe A.gossypii(with high basal insecticide resistance),and the evolution of A.gossypii resistance to sulfoxaflor developed faster than acetamiprid in both Yarkant and Jinghe,Xingjiang,China.The sulfoxaflor-resistant strains selected from Yarkant and Jinghe developed significant cross-resistance to acetamiprid,imidacloprid,thiamethoxam and pymetrozine;while the acetamiprid-resistant strains developed significant cross-resistance to sulfoxaflor,imidacloprid,thiamethoxam,pymetrozine,and chlorpyrifos.The relative fitness of A.gossypii decreased as the resistance to sulfoxaflor and acetamiprid developed.The relative fitness levels of the sulfoxaflor-resistant strains(Yarkant-SulR and Jinghe-SulR)were lower than those of the acetamipridresistant strains(Yarkant-AceR and Jinghe-AceR).In addition,the relative fitness levels of sulfoxaflor-and acetamiprid-resistant strains were lower in Jinghe than in Yarkant.In summary,basal insecticide resistance of A.gossypii and insecticide type affected the evolution of resistance to insecticides in A.gossypii,as well as cross-resistance to other insecticides.The sulfoxaflor-and acetamiprid-resistant A.gossypii strains had obvious fitness costs.The results of this work will contribute to the insecticide resistance management and integrated management of A.gossypii.

关键词： Aphis gossypii sulfoxaflor acetamiprid cross-resistance fitness costs different sensitivities