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Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells

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Journal of Integrative Medicine 2024年第3期22卷 286-294页

作者： Jia-jia Liu Xue Zhang bang-lan cai Man-man Qi Yong-bin Chi Bin Peng Deng-hai Zhang School of Medicine Shanghai UniversityShanghai 200444China Shanghai Health Commission Key Lab of Artificial Intelligence-Based Management of Inflammation and Chronic Diseases Shanghai Pudong Gongli HospitalSecondary Military Medical UniversityShanghai 200135China School of Basic Medicine Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina

Objective:Research has shown that celastrol can effectively treat a variety of diseases,yet when passing a certain dosage threshold,celastrol becomes toxic,causing complications such as liver and kidney damage and erythrocytopenia,among *** this dichotomy in mind,it is extremely important to find ways to preserve celastrol’s efficacy while reducing or preventing its ***:In this study,insulin-resistant Hep G2(IR-Hep G2)cells were prepared using palmitic acid and used for in vitro ***-Hep G2 cells were treated with celastrol alone or in combination with Nacetylcysteine(NAC)or ferrostatin-1(Fer-1)for 12,24 or 48 h,at a range of *** counting kit-8assay,Western blotting,quantitative reverse transcription-polymerase chain reaction,glucose consumption assessment,and flow cytometry were performed to measure celastrol’s cytotoxicity and whether the cell death was linked to ***:Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-Hep G2 *** downregulated glutathione peroxidase 4(GPX4)m *** docking models predicted that solute carrier family 7 member 11(SLC7A11)and GPX4 were covalently bound by ***,we found for the first time that the application of ferroptosis inhibitors(especially NAC)was able to reduce celastrol’s toxicity while preserving its ability to improve insulin sensitivity in IR-Hep G2 ***:One potential mechanism of celastrol’s cytotoxicity is the induction of ferroptosis,which can be alleviated by treatment with ferroptosis *** findings provide a new strategy to block celastrol’s toxicity while preserving its therapeutic effects.

关键词： Celastrol Insulin resistance Ferroptosis N-Acetylcysteine Palmitic acid Molecular docking

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Key genes and regulatory networks for diabetic retinopathy based on hypoxia-related genes:a bioinformatics analysis

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1411-1417页

作者： cai-Han Yu cai-Xia Wu Dai Li lan-lan Gong Xu-Dong Lyu Jie Yang Department of Ophthalmology Xianning Central HospitalThe First Affiliated Hospital of Hubei University of Science and TechnologyXianning 437100Hubei ProvinceChina School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning 437100Hubei ProvinceChina School of Optometry Hubei University of Science and TechnologyXianning 430071Hubei ProvinceChina

AIM:To prevent neovascularization in diabetic retinopathy(DR)patients and partially control disease ***:Hypoxia-related differentially expressed genes(DEGs)were identified from the GSE60436 and GSE102485 datasets,followed by gene ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment *** candidate drugs were screened using the CMap ***,a protein-protein interaction(PPI)network was constructed to identify hypoxia-related hub genes.A nomogram was generated using the rms R package,and the correlation of hub genes was analyzed using the Hmisc R *** clinical significance of hub genes was validated by comparing their expression levels between disease and normal groups and constructing receiver operating characteristic curve(ROC)***,a hypoxia-related miRNA-transcription factor(TF)-Hub gene network was constructed using the NetworkAnalyst online ***:Totally 48 hypoxia-related DEGs and screened 10 potential candidate drugs with interaction relationships to upregulated hypoxia-related genes were identified,such as ruxolitinib,meprylcaine,and *** addition,8 hub genes were also identified:glycogen phosphorylase muscle associated(PYGM),glyceraldehyde-3-phosphate dehydrogenase spermatogenic(GAPDHS),enolase 3(ENO3),aldolase fructose-bisphosphate C(ALDOC),phosphoglucomutase 2(PGM2),enolase 2(ENO2),phosphoglycerate mutase 2(PGAM2),and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3).Based on hub gene predictions,the miRNA-TF-Hub gene network revealed complex interactions between 163 miRNAs,77 TFs,and hub *** results of ROC showed that the except for GAPDHS,the area under curve(AUC)values of the other 7 hub genes were greater than 0.758,indicating their favorable diagnostic ***:PYGM,GAPDHS,ENO3,ALDOC,PGM2,ENO2,PGAM2,and PFKFB3 are hub genes in DR,and hypoxia-related hub genes exhibited favorable diagnostic perform

关键词： diabetic retinopathy hypoxia-related genes hub genes miRNA-TF-Hub gene drug prediction

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Study on preparation,characterization and application of mixed-colorants thermochromic microcapsules

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Particuology 2024年第5期88卷 89-97页

作者： lan Zhou Jingpeng Ye Qinze cai Guojin Liu Mehran Dadgar Guocheng Zhu Guoqing Zhang College of Textile Science and Engineering (International Institute of Silk) Zhejiang Sci-Tech UniversityHangzhou310018China School of Materials Science& Engineering Zhejiang Sci-Tech UniversityHangzhou310018China Department of Textile University of NeyshaburAdib BoulevardKhorasan Razavi ProvinceIran Zhejiang Charming Dyeing and Finishing Co. LtdJiaxing314500China Zhejiang Provincial Innovation Center of Advanced Textile Technology Shaoxing312000China

In order to expand the color-change range and make the discoloration temperature suitable for the daily textiles,a new formulation of mixed-colorants thermochromic core material is designed,in which crystal violet lactone(CVL)is the basic color former,bisphenol A(BPA)is the developer,especially the solvent-based dye and dodecyl dedecanoate are used as the extended dye and the solvent,*** electron microscope(SEM),differential scanning calorimeter(DSC)and thermogravimetric analyzer(TGA)were applied to study the morphology,encapsulation rate,non-isothermal crystallization behavior and thermal stability of the mixed-colorant thermochromic microcapsules(MCTMs)prepared by in-situ *** results show that MCTMs have good sphericity,uniform particle size,good thermal stability and the encapsulation rate can reach 86.73%.Under the non-isothermal conditions,the encapsulation of formaldehyde-melamine resin wall material can slightly reduce the crystallization rate of the solvent,but does not affect the relative crystallinity,thermal properties and discoloration sensitivity of the core *** the variety of ambient temperatures in the range of 20–35℃,the printed cotton fabrics with MCTMs could change color reversibly between different tones with good reliability and durability,and exhibit more gorgeous colors than the common thermochromic materials.

关键词： Thermochromic microcapsule Color-change range Phase-change material Crystallization behavior

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Pulmonary rehabilitation protocols in urgent lung transplantation patients

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World Journal of Emergency Medicine 2024年第1期15卷 47-51页

作者： Fei Zeng Lingyun cai Luyao Guo Meijuan lan Jiangshuyuan Liang Peipei Gu Nursing Department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex *** aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant ***:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January *** were retrieved from electronic medical records at our lung transplant ***:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and *** mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±*** Nutritional Risk Screening 2002(NRS 2002)scores were≥*** was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,*** total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 *** patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

关键词： Urgent lung transplantation End-stage lung disease Extracorporeal membrane oxygenation Invasive respiratory support Pulmonary rehabilitation.

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High-resolution neutronics model for ^(238)Pu production in high-flux reactors

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Nuclear Science and Techniques 2024年第5期35卷 226-236页

作者： Qing-Quan Pan Qing-Fei Zhao Lian-Jie Wang bang-Yang Xia Yun cai Jin-Biao Xiong Xiao-Jing Liu School of Nuclear Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China Science and Technology on Reactor System Design Technology Laboratory Nuclear Power Institute of ChinaChengdu 610200China

We proposed and compared three methods(filter burnup,single energy burnup,and burnup extremum analysis)to build a high-resolution neutronics model for 238Pu production in high-flux *** filter burnup and single energy burnup methods have no theoretical approximation and can achieve a spectrum resolution of up to~1 eV,thereby constructing the importance curve and yield curve of the full energy *** burnup extreme analysis method combines the importance and yield curves to consider the influence of irradiation time on production efficiency,thereby constructing extreme *** three curves,which quantify the transmutation rate of the nuclei in each energy region,are of physical significance because they have similar distributions.A high-resolution neutronics model for ^(238)Pu production was established based on these three curves,and its universality and feasibility were *** neutronics model can guide the neutron spectrum optimization and improve the yield of ^(238)Pu by up to 18.81%.The neutronics model revealed the law of nuclei transmutation in all energy regions with high spectrum resolution,thus providing theoretical support for high-flux reactor design and irradiation production of ^(238)Pu.

关键词： ^(238)Pu Neutronics model High-flux reactor Spectrum resolution Spectrum optimization

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Performance of water-coupled charge blasting under different in-situ stresses

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Journal of Central South University 2024年第7期31卷 2300-2320页

作者： ZHOU Zi-long WANG Zhen CHENG Rui-shan cai Xin lan Ri-yan School of Resources and Safety Engineering Central South UniversityChangsha 410083China Center for Infrastructural Monitoring and Protection School of Civil and Mechanical EngineeringCurtin UniversityBentleyAustralia Guangxi Xinfazhan Communication Group Co. Ltd.Nanning 530000China

Water-coupled charge blasting is a promising technique to efficiently break rock *** this study,numerical models of double boreholes with water-coupled charge are established using LS-DYNA and are calibrated by the tests of rock masses subjected to explosion loads to examine its *** crack levels of rock mass induced by water-coupled charge blasting and air-coupled charge blasting are first *** is found that water-coupled charge blasting is more appropriate to fracture deep rock mass than air-coupled charge *** addition,the effects of rock properties,water-coupled charge coefficients,and borehole connection angles on the performance of water-coupled charge blasting are *** results show that rock properties and water-coupled charge coefficients can greatly influence the crack and fragmentation levels of rock mass induced by water-coupled charge blasting under uniform and non-uniform in-situ ***,changing borehole-connection angles can only affect crack and fragmentation levels of rock mass under non-uniform in-situ stresses but barely affect those under uniform in-situ stresses.A formula is finally proposed by considering the above-mentioned factors to provide the design suggestion of water-coupled charge blasting to fracture rock mass with different in-situ stresses.

关键词： water-coupled blasting in-situ stress water-coupled charge coefficient rock type borehole-connection angle

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Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 214-233页

作者： Mao-Xiu Yuan Qi-Gui cai Zhen-Yang Zhang Jian-Zhong Zhou cai-Yun lan Jiang-Bo Lin The Graduate School Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina Department of Thoracic Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina Department of Thoracic Surgery Fujian Medical University Union HospitalFuzhou 350000Fujian ProvinceChina

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of *** To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database *** up to December 2022 comparing nCRT and nCT in patients with EC were *** The analysis revealed significant differences between nCRT and nCT in terms of disease-free *** results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than ***,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for ***,nCT exhibited better performance in terms of postoperative complications.

关键词： Esophageal cancer Neoadjuvant chemoradiotherapy Radical resection for esophageal cancer Neoadjuvant chemotherapy Meta-analysis

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Challenges and countermeasures for developing countries in addressing loss and damage caused by climate change

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Advances in Climate Change Research 2024年第2期15卷 353-363页

作者： Shuo LIU Yu-E LI Bin WANG An-Dong cai Chao FENG Hua lan Ruo-Chen ZHAO Institute of Environment and Sustainable Development in Agriculture Chinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Agricultural Environment Ministry of Agriculture and Rural AffairsBeijing 100081China China Clean Development Mechanism Fund Management Center Beijing 100045China School of International Law China University of Political Science and LawBeijing 100088China

Loss and damage caused by extreme climate events have attracted increasing *** 28th Conference of the Parties to the United Nations Framework Convention on Climate Change(hereinafter referred to as the Convention)has agreed to adopt Loss and Damage Fund agreement,which identified the source of funding and the funds to be entrusted to the World ***,there is still ambiguous that how to allocate the funds could accelerate the effectiveness of meeting the needs for developing ***-disaster prevention and preparedness is one of the most effective measures to deal with loss and damage,which closely related to *** studies rarely analyzed quantitatively the financial needs of pre-disaster prevention and preparedness relating to adaptation to reduce loss and *** on the official reports submitted by countries under the Convention,this study analyzes the annual change in the total financial support provided by developed countries to developing countries,the proportion of pre-disaster prevention and preparedness in the adaptation needs of developing countries,and the progress in raising the current annual funding target of 100 billion USD for developed countries,to reveal the financial and technical challenges facing by developing countries on addressing loss and *** results show that by 2030,the total adaptation financial needs of developing countries are estimated to be about 3.8 trillion USD,of which pre-disaster prevention matters account for about 9%.Therefore,by 2030,developing countries will need about 342 billion USD in pre-disaster prevention and preparedness finance to withstand loss and *** addition,developing countries face a lack of technical methods to quantify information about their *** on the above analysis,this study puts forward countermeasures and suggestions,including strengthening the allocation amount of loss and damage fund on pre-disaster warning,prevention and control actions,and

关键词： Loss and damage Funding mechanism Pre-disaster warning and preparedness Convention negotiations Countermeasures

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Effects of heat treatment on microstructures and properties of a heterostructured alloy with dissimilar components fabricated by WAAM

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Rare Metals 2024年第9期43卷 4441-4461页

作者： Ming-cai Pan Jun-Qiang Xu Yong Peng Ning-Ning Liang Si lan Qi Zhou Ke-Hong Wang School of Materials Science and Engineering Nanjing University of Science and Technology Key Laboratory of Controlled Arc Intelligent Additive Manufacturing Technology

Heat treatment significantly influences homogeneous material microstructures and mechanical properties, which can be improved by an optimal heat treatment process. However, heat treatment application to heterogeneous materials presents significant challenges due to compositional and microstructural heterogeneities. Herein,a laminated heterostructured alloy comprising alternating316L stainless steel（SS） and 18Ni300 maraging steel（MS）layers fabricated using wire and arc additive manufacturing was investigated. A solution treatment was applied at900 °C for 0.5 h. Subsequently, the solution-treated and asfabricated（AF） samples were aged at 500 °C for 4 h; these samples were denoted SA and AT, respectively. The AT phase compositions and orientations were similar to those of AF. The SA 316L SS layer resembled that of AF, but the SA 18Ni300 MS layers exhibited a reduced austenite phase fraction and refined grain size, attributable to solid-state transformation. In the AT sample, aging induced the formation of nanoscale acicular ω phase and ellipsoidal Ni3Ti,Fe2Mo, and X precipitates in the 18Ni300 MS ***, the SA precipitates contained acicular Fe Ni2and ellipsoidal ω, Ni3Ti, and X precipitates, and their fractions were lower than those in AT precipitates. The18Ni300 MS layer microhardness in the heat-treated samples increased due to nanoprecipitation, but the 316L SS layer microhardness resembled that of AF. The AT and SA ultimate tensile strengths increased to（1360 ± 50） and（1473 ± 41） MPa, respectively, attributable to precipitation strengthening. The SA 316L SS layer exhibited a high stress-induced martensite fraction, enhancing the ductility of heated samples.

关键词： Heat treatment Laminated heterostructured alloy Mechanical property Microstructure Wire and arc additive manufacturing

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Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

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Traditional Medicine Research 2024年第9期9卷 1-13页

作者： Ting Li lan-Fang Tan Lin Shen Jie-Hui Kuang Si-Kai Zhan bang Liu Jia-Le cai Sheng-Wang Liang Ming-Hua Xian Shu-Mei Wang School of Chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China Engineering&Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province School of Chinese Materia MedicaGuangdong Pharmaceutical UniversityGuangzhou 510006China Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization Guangxi Institute of BotanyChinese Academy of SciencesGuilin 541006China Traditional Chinese Medicine Resource Germplasm Bank Management Center Yunfu 527300China

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum *** Balf.)with millet *** is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe *** study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in *** used integrated analysis of gut microbiota,metabolomics,and network ***:The compounds in CR were identified using LC-MS/*** impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE *** in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also *** microbiota composition was analyzed through 16S rRNA gene *** metabolites were examined using untargeted metabolomics and Spearman correlation *** pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut ***:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction *** also ameliorates brain and intestinal barrier damage caused by *** also decreased inflammation and oxidative stress in IS ***,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier ***,CR primarily influences the primary bile acid biosynthesis *** pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential *** relies on gut microbiota for its anti-inflammatory effects to improve ***:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid *** emerges as a potential therapeutic agent for

关键词： cooked rhubarb ischemic stroke gut microbiota metabolomics

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