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p.p.R14A is Associated with Immunotherap. Resistance in Head and Neck Squamous Cell Carcinoma Identified by Single-Cell and Bulk RNA-Sequencing

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Chinese Medical Sciences Journal 2024年第2期39卷 111-121页

作者： Jun-Jie ma Lei Zhang Jin Lu Hao-Xuan Zhang Dep.rtment of Clinical Medicine Bengbu Medical UniversityBengbu 233030AnhuiChina Dep.rtment of General Surgery The Second Affiliated Hospital of Bengbu Medical UniversityBengbu 233030AnhuiChina Dep.rtment of Human Anatomy Bengbu Medical UniversityBengbu 233030AnhuiChina Anhui Key Laboratory of Comp.tational Medicine and Intelligent Health Bengbu Medical UniversityBengbu 233030AnhuiChina

Objective To identify nivolumab resistance-related genes in p.tients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing *** The single-cell and bulk RNA-sequencing data downloaded from the Gene Exp.ession Omnibus database were analyzed to screen out differentially exp.essed genes(DEGs)between nivolumab resistant and nivolumab sensitive p.tients using R *** Least Absolute Shrinkage Selection Op.rator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were p.rformed to identify key genes associated with nivolumab *** enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclop.dia of Genes and Genomes *** relationship. of key genes with immune cell infiltration,differentation trajectory,dynamic gene exp.ession p.ofiles,and ligand-recep.or interaction were *** We found 83 *** were mainly enriched in T-cell differentiation,p.-1 and p.-L1 checkp.int,and T-cell recep.or *** six key genes identified using machine learning algorithms,only p.p.R14A gene was differentially exp.essed between the nivolumab resistant and nivolumab sensitive group. both before and after immunotherap.(p.0.05).The high p.p.R14A gene exp.ession group.had lower immune score(p.0.01),higher exp.ession of immunosup.ressive factors(such as p.CD1,CTLA4,and p.CD1LG2)(r>0,p.0.05),lower differentiation of infiltrated immune cells(p.0.05),and a higher degree of interaction between HLA and CD4(p.0.05).Conclusions p.p.R14A gene is closely associated with resistance to nivolumab in HNSCC ***,p.p.R14A may be a target to ameliorate nivolumab resistance of HNSCC p.tients.

关键词： p.p.R14A head and neck squamous cell carcinoma immunotherap. drug resistance

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A Dynamic Covalent Bonding-based Nanop.atform for Intracellular Co-Delivery of p.otein Drugs and Chemotherap.utics with Enhanced Anti-Cancer Effect

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Chinese Journal of p.lymer Science 2024年第5期42卷 559-569,I0005页

作者： sai-Nan Liu Jia-Hui Meng Li-Yun Cui Hua Chen Lin-Qi Shi Ru-Jiang ma Key Laboratory of Functional p.lymer materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of p.otein drugs is critical for p.otein *** combination of p.otein drugs with chemotherap.utics rep.esents a p.omising strategy in enhancing anti-cancer ***,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different ***,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two p.lymers,p.G-b-p.Asp.co-Asp.A)and p.E-b-p.Asp.co-Asp.BA),and two 2-acetylp.enylboronic acid(2-Ap.A)-functionalized drugs,2-Ap.A-RNase A and 2-Ap.A-DOX,self-assemble into mixed-shell nanop.rticles(RNase A/DOX@MNp.)via dynamic p.enylboronic acid(p.A)-catechol bond between p.A and dop.mine(DA)*** p.A-catechol bond endows the nanop.rticles with high stability and excellent stimulus-resp.nsive drug release *** the slight acidic environment at tumor tissue,RNase A/DOX@MNp. are p.sitively charged,p.omoting their *** cellular up.ake into endosome,further p.otonation of p.E chains leads to the rup.ure of endosomes because of the p.oton sp.nge effect and the cleavage of p.A-catechol bond p.omotes the release of two *** cytop.asm,the high level of GSH removed the modification of 2-Ap.A on *** restored RNase A and DOX show a synergistic and enhanced antic-cancer *** system may be a p.omising p.atform for intracellular co-delivery of p.otein drugs and chemotherap.utics.

关键词： Drug co-delivery Combination therap. Dynamic covalent bond

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Liquid-p.ase ep.taxial layer by layer brushing fabrication of metalorganic frameworks films

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Nano Research 2024年第6期17卷 5698-5704页

作者： Li-Mei Chang Rui Zhai Zhi-Zhou ma Jian-Dong Huang Zhi-Gang Gu Jian Zhang College of Chemistry Fuzhou UniversityFuzhou 350108China State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China University of Chinese Academy of Sciences Beijing 100049China

Develop.ent of metal-organic framework(MOF)films is of great imp.rtance to exp.nd their ***,we rep.rt a facile and universal method of liquid-p.ase ep.taxial(Lp.)layer by layer(LBL)brushing ap.roach for fabricating MOF films on various substrates in a high-throughp.t *** MOF films p.ep.ration method offers a great p.osp.ctive to cost-effectively construct films with short p.ep.ration time and little reagent ***,this LBL brushing ap.roach has been imp.emented successfully to assemble various MOF films,including HKUST-1,zeolitic imidazolate framework-8(ZIF-8),Cu(bdc),and Cu_(2)(L)_(2)p.L=bdc,ndc,and cam;p.dabco and bip.).Afterwards,the classic MOF HKUST-1 and ZIF-8 films were grown on sensor chip.electrode and p.rous fiber sup.ort for good volatile organic comp.unds(VOCs)selective sensing and water p.rification *** study demonstrates that this LBL brushing p.ep.ration method can be emp.oyed to synthesize various MOF films with a variety of characteristics to realize their sensing and sep.ration ap.lications.

关键词： metal-organic framework p.rous materials layer by layer fabrication film

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Stable carbon isotop. comp.sition and intrinsic water use efficiency in p.ants along an altitudinal gradient on the eastern slop. of Yulong Snow Mountain, China

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Ecological p.ocesses 2024年第2期13卷 218-230页

作者： Feng Jiang Tao p. Zi-Jing Xue Yan-Wei ma Xiao-Yi Shi Fu-Xi Shi College of Geograp.y and Environmental Sciences Zhejiang Normal University Yulong Snow Mountain Glacier and Environment Observation and Research Station/State Key Laboratory of Cryosp.eric Sciences Northwest Institute of Eco-Environment and ResourcesChinese Academy of Sciences Key Laboratory of National Forestry and Grassland Administration on Forest Ecosystem p.otection and Restoration of p.yang Lake Watershed College of Forestry Jiangxi Agricultural University

Background Stable carbon isotop. comp.sition(δ13Cp. can be used to estimate the changes in intrinsic water use efficiency（iWUE） in p.ants,which help. us to better understand p.ants' resp.nse strategies to climate *** study focused on the variations in δ13Cp.nd iWUE for the different life-form p.ants（i.e.,herbs,shrubs,and trees）along an altitudinal gradient（3300,3600,3900,4100,4300,and 4500 m） on the eastern slop. of Yulong Snow Mountain,southeastern margin of the Qinghai-Tibet *** resp.nse mechanisms of δ13Cp.nd iWUE for different life-form p.ants to altitude were thoroughly analyzed in this mountain *** The δ13Cp.alues of p.ants on the eastern slop.s of Yulong Snow Mountain ranged from-30.4‰to-26.55‰,with a mean of-28.02‰,indicating a dominance of *** δ13Cp.nd iWUE values varied among different life-form p.ants in the order of herbs> shrubs> trees,p.rticularly in 3600,3900,and 4300 ***δ13Cp.nd iWUE values for herbs and shrubs increased with altitude and were mainly controlled by air *** two p.rameters for trees exhibited a trend of initial decrease followed by an increase with *** 3900 m,the δ13Cp.nd iWUE values decreased with altitude,influenced by soil ***,above 3900 m,the two p.rameters increased with altitude,mainly regulated by air *** addition,iWUE was p.sitively correlated with leaf p.content but negatively correlated with leaf N:p.ratio,esp.cially for herbs and trees,suggesting that p.p.ays a key role in modulating iWUE in this *** The diffe rentiated resp.nses of water availability for different life-form p.ants to a higher altitudinal gradient are regulated by air temp.rature,soil moisture,and leaf p.content in the Yulong Snow *** results p.ovide valuable insights into understanding the wate r-carbon relationship. in high-altitude ecosystems.

关键词： Stable carbon isotop. Water use efficiency Altitude Life form Yulong Snow Mountain

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Artemisia vulgaris Induces Tumor-Selective Ferrop.0}is and Necrop.0}is via Lysosomal Ca^(2+) Signaling

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Chinese Journal of Integrative Medicine 2024年第6期30卷 525-533页

作者： Lucas dos sa.tos Zamarioli Michele Rosana maia sa.tos Adolfo Garcia Erustes Vanessa marques Meccatti Thais Cristine p.reira Soraya S Smaili maria Cristina marcucci Carlos Rocha Oliveira Gustavo JS p.reira Claudia Bincoletto Dep.rtment of p.armacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group.on p.ytocomp.exes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Dep.rtment of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical comp.sition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** p.ytochemical analysis of HEAV was done by high-p.rformance liquid chromatograp.y-mass(Hp.C)*** and cell death studies were p.rformed using tryp.n blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAp.A-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(p.0.05).The viability of HEAV-treated K562 cells was reduced comp.red to HEAV-exp.sed fibroblasts(p.0.05).Treatment of K562 cells with HEAV induced cell death p.imarily by late ap.p.3}is and necrosis in assays using annexin V-FITC/7-AAD(p.0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exp.sed to HEAV alone(p.0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(p.0.01).Furthermore,BAp.A-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(p.0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are p.rtially dep.ndent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main comp.unds identified in HEAV.

关键词： Artemisia vulgaris necrop.0}is ferrop.0}is late ap.p.0}is Ca^(2+)signaling

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Cytochrome p.5026A1 Contributes to the maintenance of Neurop.thic p.in

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Neuroscience Bulletin 2024年第3期40卷 293-309页

作者： De-Li Cao Ling-Jie ma Bao-Chun Jiang Qiang Gu Yong-Jing Gao Institute of p.in Medicine and Sp.cial Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong226019China Nantong University Medical School Nantong226001China Dep.rtment of p.in management The Affiliated Hospital of Nantong UniversityNantong226001China

The cytochrome p.50 p.oteins(CYp.50s)have been imp.icated in catalyzing numerous imp.rtant biological reactions and contribute to a variety of ***26A1,a member of the CYp.50 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin *** we rep.rt that CYp.6A1 was dramatically up.egulated in the sp.nal cord after sp.nal nerve ligation(SNL).CYp.6A1 was mainly exp.essed in sp.nal neurons and *** analysis disp.ayed that the content of all-trans-RA(at-RA),the substrate of CYp.6A1,was reduced in the sp.nal cord on day 7 after *** of CYp.6A1 by siRNA or inhibition of CYp.6A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance p.ase of neurop.thic *** also reduced SNL-induced glial activation and p.oinflammatory cytokine p.oduction but increased anti-inflammatory cytokine(IL-10)*** RA recep.ors RARα,RXRβ,and RXRγwere exp.essed in sp.nal neurons and glial *** p.omoter of Il-10 has several binding sites for RA recep.ors,and at-RA directly increased Il-10 mRNA exp.ession in ***,intrathecal IL-10 attenuated SNL-induced neurop.thic p.in and reduced the activation of astrocytes and ***,the inhibition of CYp.6A1-mediated at-RA catabolism alleviates SNL-induced neurop.thic p.in by p.omoting the exp.ession of IL-10 and sup.ressing glial ***26A1 may be a p.tential therap.utic target for the treatment of neurop.thic p.in.

关键词： CYp.6A1 Microglia Astrocytes ERK p.8 IL-10 Neurop.thic p.in

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Integrated transcrip.omics and metabolomics analysis reveal the molecular mechanism of unsap.nifiable matter in delaying aging

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Food Science and Human Wellness 2024年

作者： Dan Hong Aijin ma Xiao Xiao Mengge ma Zhou Chen Siting Li Yingmin Jia School of Food and Health， Beijing Technology and Business University

Aging is one of the causes of cognitive dysfunction， which seriously affects p.op.e's quality of life. Unsap.nifiable matter (USM) has antioxidant p.tential， but the molecular mechanisms that ameliorate aging and cognitive dysfunction are unknown. In this study， we used a galactose-induced brain aging mouse model and systematically analyzed the mechanism of USM in delaying aging in mice by detecting changes in serum and brain by metabolomics and *** was comp.red with the model group. and non-targeted metabolomics identified 68 (15 up. regulated，53down-regulated) differentially metabolites，andtranscrip.omics identified 303 differentially exp.essed genes (228 up.regulated， 75 down-regulated). Combined multi-omics analyses showed that USM maintains normal brain function by regulating glycolytic p.ocesses， the tricarboxylic acid cycle (TCA)， tryp.op.an metabolism， p.rimidine metabolism， the alanine， asp.rtate， and glutamate metabolism， and p.8map. p.thway. Meanwhile， USM increased neurotransmitter release from GABAergic synap.es and cholinergic synap.es by regulating synap.ic vesicle cycling. In summary， USM increased energy metabolism and enhanced brain nerve signaling in the mouse brain， thereby delaying brain aging. This investigation offers novel p.rsp.ctives into the molecular mechanism of USM to mitigate brain aging.

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Op.imization design and exp.riment of the variable differential gear train p.anting mechanism

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International Journal of Agricultural and Biological Engineering 2024年第2期17卷 85-93页

作者： Xiong Zhao Ziwei Liu Yuanwu Jia Xingxiao ma p.ngfei Zhang Jianneng Chen School of Mechanical Engineering Zhejiang Sci-Tech UniversityHangzhou 310018China Xi’an International University Engineering College Xi’an 710077China Hangzhou Vocational&Technical College Hangzhou 310018China

In order to imp.ove the adap.ability of the p.anting mechanism for different p.ant sp.cings,a variable differential gear train p.anting mechanism based on p.ecise p.se and trajectory control was p.op.sed by combining the op.n chain 2R rod group.and the variable differential gear *** to the p.se requirements of receiving seedling p.int,transp.rting seedling p.int and p.anting p.int,three p.ecise p.se p.ints of constrained p.anting trajectory were *** the three-p.sition motion generation structural synthesis method,combined with comp.ter-aided op.imization design software,a set of mechanism p.rameters that meet the p.anting requirements were *** on the op.imized mechanism p.rameters,by only changing the coordinates of two trajectory shap. control p.ints,three p.anting trajectories with key p.int p.sition information adap.ed to 300 mm,400 mm and 500 mm p.ant sp.cing were obtained by interp.lation,and three p.irs of total transmission ratio of three group. of variable differential gear trains were *** distributing the total transmission ratio of the mechanism,the fixed axis gear train and the differential gear train are *** fixed axis gear train included a p.ir of non-circular gear p.irs and a p.ir of p.sitive gear p.irs,which were convenient for disassembly and *** former drives the sun gear at variable sp.ed,and the latter drives the p.anet carrier at uniform *** on this structure,the transmission ratio of the p.sitive gear p.ir is-1,and the transmission ratio of the differential gear train is *** sub-transmission ratio of the single-stage non-circular gear p.ir was calculated and the p.tch curves of three p.irs of noncircular gears were *** p.irs of non-circular gear p.irs with different transmission ratios were rep.aced in turn and three sets of p.anting mechanisms were modeled in three *** virtual p.ototyp. motion simulation was comp.eted by ADAMS software,and the p

关键词： p.ant sp.cing p.anting mechanism variable differential gear train p.ecise p.se trajectory control p.rameter op.imization

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Changes of the p.rip.p.llary vascular p.rameters inp.emature infants without retinop.thy of p.ematurityusing U-net segmentation

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International Journal of Op.thalmology(English edition) 2024年第8期17卷 1453-1461页

作者： Shuai Liu Lei Liu Cui-Xia ma Liu-Hui Huang Bin Li School of Information Science and Technology University of Science and Technology of ChinaHefei 230022Anhui ProvinceChina Zhejiang Lab Hangzhou 311121Zhejiang ProvinceChina Eye Institute Affiliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226006Jiangsu ProvinceChina Anhui p.ovince maternity and Child Health Hosp.tal Maternity and Child Health Hospital Affiliated to Anhui Medical UniversityHefei 230001Anhui ProvinceChina Dep.rtment of Op.thalmology Tenth People’s Hospital Affiliated with Shanghai Tongji University School of MedicineShanghai 200072China

AIM:To quantitatively assess the changes in mean vascular tortuosity(mVT)and mean vascular width(mVW)around the op.ic disc and their correlation with gestational age(GA)and birth weight(BW)in p.emature infants without retinop.thy of p.ematurity(ROp..METHODS:A single-center retrosp.ctive study included a total of 133(133 eyes)p.emature infants[mean corrected gestational age(CGA)43.6wk]without ROp.as the p.emature group.and 130(130 eyes)CGA-matched fullterm infants as the control *** p.rip.p.llary mVT and mVW were quantitatively measured using comp.terassisted ***:p.emature infants had significantly higher mVT(p.0.0032)and lower mVW(p.0.0086)by 2.68(10^(4) cm^(-3))and 1.85μm,*** analysis with GA showed significant differences(p.0.0244)in mVT between the early p.eterm and middle to late p.eterm group.,but the differences between mVW were not significant(p.0.6652).The results of the multip.e linear regression model showed a significant negative correlation between GA and BW with mVT after adjusting sex and CGA(p.0.0211 and p.0.0006,resp.ctively).For each day increase in GA at birth,mVT decreased by 0.1281(10^(4) cm^(-3))and for each 1 g increase in BW,mVT decreased by 0.006(10^(4) cm^(-3)).However,GA(p.0.9402)and BW(p.0.7275)were not significantly correlated with ***:p.eterm birth significantly affects the p.rip.p.llary vascular p.rameters that indicate higher mVT and narrower mVW in p.emature infants without *** in these p.rameters may p.ovide new insights into the p.thogenesis of ocular vascular disease.

关键词： p.emature infants retinop.thy of p.ematurity retinal vessels p.rameter comp.ter-assisted techniques

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Electrostatic and hydrop.obic interaction coop.rative nanochap.rone regulates p.otein folding

Aggregate

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Aggregate 2024年第1期5卷 419-426页

作者： Xiaohui Wu Fei Deng Yujie Chen Mengchen Xu Feihe ma Linqi Shi Key Laboratory of Functional p.lymer materials of Ministry of Education State Key Laboratory of Medicinal Chemical BiologyInstitute of Polymer Chemistry and College of ChemistryNankai UniversityTianjinP.R.China School of materials Science and Engineering and State Key Laboratory of Sep.ration Membranes and Membrane p.ocesses Tiangong UniversityTianjinP.R.China

Natural molecular chap.rones utilize sp.tially ordered multip.e molecular forces to effectively regulate p.otein ***,synthesis of such molecules is a big *** concep. of“aggregate science”p.ovides insights to construct chemical entities(aggregates)beyond molecular levels to mimic both the structure and function of natural *** by this concep.,herein we fabricate a novel multi-interaction(i.e.,electrostatic and hydrop.obic interaction)coop.rative nanochap.rone(multi-co-nChap.to regulating p.otein *** multi-co-nChap.is fabricated by rationally introducing electrostatic interactions to the surface(corona)and confined hydrop.obic microdomains(shell)of traditional single-hydrop.obic interaction *** demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrop.obic microdomains,while the shell electrostatic interaction balances the cap.ure and release of *** finely synergizing corona electrostatic attraction with shell electrostatic rep.lsion and hydrop.obic interaction,the op.imized multi-co-nChap.effectively facilitated de novo folding of nascent ***,the synergy between corona electrostatic attraction,shell electrostatic attraction and shell hydrop.obic interaction significantly enhanced the cap.bility of multi-co-nChap.to p.otect native p.oteins from denaturation at harsh *** work p.ovides imp.rtant insights for understanding and design of nanochap.rone,which is a kind of ordered aggregate with chap.rone-like activity that beyond the level of single molecule.

关键词： chap.rone-like activity coop.rative effect nanochap.rones ordered aggregates p.otein folding

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