The influence of austenitizing temperature and austenite grain size on the crystallographic characteristics and mechanical properties of transformation products was investigated in a low-alloy steel.Annealing at a low...The influence of austenitizing temperature and austenite grain size on the crystallographic characteristics and mechanical properties of transformation products was investigated in a low-alloy steel.Annealing at a lower temperature after austenitization at 1050℃ can reduce the vacancy concentration and enhance the stability of austenite,thereby determining the martensite-start(Ms)temperature and density of twin-related V1/V2 variant pairs.V1/V2 variant pairs are predominately generated by autocatalytic nucleation,which can promote transformation by self-accommodation.Annealing at 800℃ after austenitization at 1050℃ generated the highest content of V1/V2 variant pairs,which contributed to high values of strength,Charpy impact energy,and elongation.In addition to refining the austenite grain size,niobium(Nb)microalloying increases the packet boundaries of the transformation products,mainly because the refined austenite grains provide more nucleation sites for the martensitic transformation.However,the density of block boundaries decreases after austenite refinement by Nb microalloying,owing to insufficient autocatalytic nucleation.展开更多
Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were deri...Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.POAG data were sourced from the largest FinnGen study,comprising 8,530 DR cases and 391,275 European controls.A two-sample MR analysis,supplemented by bidirectional MR,Bayesian co-localization analysis,and phenotype scanning,was conducted to examine the causal relationships between plasma proteins and POAG.The analysis was validated by identifying associations between plasma proteins and POAG-related traits,including intraocular pressure(IOP),retinal nerve fibre layer(RNFL),and ganglion cell and inner plexiform layer(GCIPL).By searching druggable gene lists,the ChEMBL database,and the ClinicalTrials.gov database,the druggability and clinical development activity of the identified proteins were systematically evaluated.Results:Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments.The ORs per standard deviation increase in protein levels ranged from 0.39(95%CI:0.24–0.62;P=7.70×10^(-5))for phospholipase C gamma 1(PLCG1)to 1.29(95%CI:1.16–1.44;P=6.72×10^(-6))for nidogen-1(NID1).Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses.Five proteins exhibited strong co-localization evidence(PH4≥0.8):protein sel-1 homolog 1(SEL1L),tyrosine-protein kinase receptor UFO(AXL),nidogen-1(NID1)and FAD-linked sulfhydryl oxidase ALR(GFER)were negatively associated with POAG risk,while roundabout homolog 1(ROBO1)showed a positive association.The phenotype scanning did not reveal any confounding factors between pQTLs and POAG.Further,validation analyses identified nine proteins causally related to POAG traits,with five proteins including interleukin-18 receptor 1(IL18R1),interleukin-1 receptor type 1(IL1R1),phospholipase C gamma 1(PLCG1),ribonuclease pancreatic(RNASE1),serine protease inhibitor Kazal-type 6(SPINK6)revealing consistent directional associations.In addition,18 causal proteins were highlighted for their druggability,of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets.Conclusions:This study identifies 18 plasma proteins as potential therapeutic targets for POAG,particularly emphasizing the role of genomic and proteomic integration in drug discovery.Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations,thus taking a significant leap toward innovative POAG treatments.展开更多
Background:Diabetic retinopathy(DR)urgently needs novel and effective therapeutic targets.Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel tar...Background:Diabetic retinopathy(DR)urgently needs novel and effective therapeutic targets.Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases,but no systematic screening for DR has been performed.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.DR data were sourced from the largest FinnGen study,comprising 10,413 DR cases and 308,633 European controls.Genetic instrumental variables were identified using multiple filters.In the two-sample MR analysis,Wald ratio and inverse variance-weighted(IVW)MR were utilized to investigate the causality of plasma proteins with DR.Bidirectional MR,Bayesian Co-localization,and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses.By systemically searching druggable gene lists,the ChEMBL database,DrugBank,and Gene Ontology database,the druggability and relevant functional pathways of the identified proteins were systematically evaluated.Results:Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate<0.05 including 11 with positive associations and 13 with negative associations.For each standard deviation increase in plasm protein levels,the odds ratios(ORs)for DR varied from 0.51(95%CI:0.36-0.73;P=2.22×10-5)for tubulin polymerization-promoting protein family member 3(TPPP3)to 2.02(95%CI:1.44-2.83;P=5.01×10-5)for olfactomedin like 3(OLFML3).Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses.Four proteins exhibited strong co-localization evidence(PH4≥0.8):cytoplasmic tRNA synthetase(WARS),acrosin binding protein(ACRBP),and intercellular adhesion molecule 1(ICAM1)were negatively associated with DR risk,while neurogenic locus notch homolog protein 2(NOTCH2)showed a positive association.No confounding factors were detected between pQTLs and DR according to the phenotypic scan.Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets,with metalloproteinase inhibitor 3(TIMP)currently in phase I clinical trials for DR.GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.Conclusions:Twenty-four promising drug targets for DR were identified,including four plasma proteins with particular co-localization evidence.These findings offer new insights into DR's etiology and therapeutic targeting,exemplifying the value of genomic and proteomic data in drug target discovery.展开更多
Organic polymer solar materials are shown to exhibit better solubility in mixed solvents than in pure ones,which affects the performance of their solar cells.In this article,poly[N-9-hepta-decanyl-2,7-carbazole-alt-5,...Organic polymer solar materials are shown to exhibit better solubility in mixed solvents than in pure ones,which affects the performance of their solar cells.In this article,poly[N-9-hepta-decanyl-2,7-carbazole-alt-5,5-(4.7-di-2-thienyI-2,l,3-benzothiadiazole)(PCDTBT0)and[6,6]-phenyl-C71-butyric acid methyl ester(PC_(71)BM)are used as active layer materials in solar cells.To optimize the performance of these active materials,the ratio of chloroform(CF)to chlorobenzene used as solvents to dissolve PCDTBT,and PC_(71)BM is varied,which is shown to affect power conversion efficiency(PCE).The solar cell that shows the best performance with a PCE as high as 6.82%is produced using a volume ratio of CF to chlorobenzene of1:1.展开更多
Transparent conductive films(TCFs)are crucial components of solar cells.In this study,F,Cl,and Ga codoped ZnO(FCGZO)TCFs were deposited onto a glass substrate using the sol-gel spin-coating method and rapid thermal an...Transparent conductive films(TCFs)are crucial components of solar cells.In this study,F,Cl,and Ga codoped ZnO(FCGZO)TCFs were deposited onto a glass substrate using the sol-gel spin-coating method and rapid thermal annealing.The effects of F-doping content on the structural,morphological,electrical,and optical properties of FCGZO films were examined by XRD,TEM,FE-SEM,PL spectroscopy,XPS,Hall effects testing,and UVeviseNIR spectroscopy.All prepared ZnO films exhibited a hexagonal wurtzite structure and preferentially grew along the c axis perpendicular to the substrate.Changes in the doping concentration of F changed the interplanar crystal spacing and O vacancies in the film.At a doping ratio of 2%(in mole),the F,Cl,and Ga co-doped ZnO film exhibited the best photoelectric performance,with a carrier concentration of 2.62×10^(20)cm^(-3),mobility of 14.56 cm^(2)/(V·s),and resistivity of 1.64×10^(-3)Ucm.The average transmittance(AT)in the 380-1600 nm region nearly 90%with air as the reference,and the optical band gap was 3.52 eV.展开更多
基金financially supported by the National Key Research and Development Program of China(Grant No.2020YFB0311000)the Research Center for Iron based New Materials(School of Materials Science and Engineering,Tsinghua University&Masteel Co.Ltd.).
文摘The influence of austenitizing temperature and austenite grain size on the crystallographic characteristics and mechanical properties of transformation products was investigated in a low-alloy steel.Annealing at a lower temperature after austenitization at 1050℃ can reduce the vacancy concentration and enhance the stability of austenite,thereby determining the martensite-start(Ms)temperature and density of twin-related V1/V2 variant pairs.V1/V2 variant pairs are predominately generated by autocatalytic nucleation,which can promote transformation by self-accommodation.Annealing at 800℃ after austenitization at 1050℃ generated the highest content of V1/V2 variant pairs,which contributed to high values of strength,Charpy impact energy,and elongation.In addition to refining the austenite grain size,niobium(Nb)microalloying increases the packet boundaries of the transformation products,mainly because the refined austenite grains provide more nucleation sites for the martensitic transformation.However,the density of block boundaries decreases after austenite refinement by Nb microalloying,owing to insufficient autocatalytic nucleation.
基金supported by the Hainan Province Clinical Medical Center,the National Natural Science Foundation of China(82171084,82371086).
文摘Purpose:To identify plasma proteins that are causally related to primary open-angle glaucoma(POAG)for potential therapeutic targeting.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.POAG data were sourced from the largest FinnGen study,comprising 8,530 DR cases and 391,275 European controls.A two-sample MR analysis,supplemented by bidirectional MR,Bayesian co-localization analysis,and phenotype scanning,was conducted to examine the causal relationships between plasma proteins and POAG.The analysis was validated by identifying associations between plasma proteins and POAG-related traits,including intraocular pressure(IOP),retinal nerve fibre layer(RNFL),and ganglion cell and inner plexiform layer(GCIPL).By searching druggable gene lists,the ChEMBL database,and the ClinicalTrials.gov database,the druggability and clinical development activity of the identified proteins were systematically evaluated.Results:Eighteen proteins were identified with significant associations with POAG risk after multiple comparison adjustments.The ORs per standard deviation increase in protein levels ranged from 0.39(95%CI:0.24–0.62;P=7.70×10^(-5))for phospholipase C gamma 1(PLCG1)to 1.29(95%CI:1.16–1.44;P=6.72×10^(-6))for nidogen-1(NID1).Bidirectional MR indicated that reverse causality did not interfere with the results of the main MR analyses.Five proteins exhibited strong co-localization evidence(PH4≥0.8):protein sel-1 homolog 1(SEL1L),tyrosine-protein kinase receptor UFO(AXL),nidogen-1(NID1)and FAD-linked sulfhydryl oxidase ALR(GFER)were negatively associated with POAG risk,while roundabout homolog 1(ROBO1)showed a positive association.The phenotype scanning did not reveal any confounding factors between pQTLs and POAG.Further,validation analyses identified nine proteins causally related to POAG traits,with five proteins including interleukin-18 receptor 1(IL18R1),interleukin-1 receptor type 1(IL1R1),phospholipase C gamma 1(PLCG1),ribonuclease pancreatic(RNASE1),serine protease inhibitor Kazal-type 6(SPINK6)revealing consistent directional associations.In addition,18 causal proteins were highlighted for their druggability,of which 5 proteins are either already approved drugs or in clinical trials and 13 proteins are novel drug targets.Conclusions:This study identifies 18 plasma proteins as potential therapeutic targets for POAG,particularly emphasizing the role of genomic and proteomic integration in drug discovery.Future experimental and clinical studies should be conducted to validate the efficacy of these proteins and to conduct more comprehensive proteomic explorations,thus taking a significant leap toward innovative POAG treatments.
基金funded by the Hainan Province Clinical Medical Center(82171084)the National Natural Science Foundation of China(82371086).
文摘Background:Diabetic retinopathy(DR)urgently needs novel and effective therapeutic targets.Integrated analyses of plasma proteomic and genetic markers can clarify the causal relevance of proteins and discover novel targets for diseases,but no systematic screening for DR has been performed.Methods:Summary statistics of plasma protein quantitative trait loci(pQTL)were derived from two extensive genome-wide analysis study(GWAS)datasets and one systematic review,with over 100 thousand participants covering thousands of plasma proteins.DR data were sourced from the largest FinnGen study,comprising 10,413 DR cases and 308,633 European controls.Genetic instrumental variables were identified using multiple filters.In the two-sample MR analysis,Wald ratio and inverse variance-weighted(IVW)MR were utilized to investigate the causality of plasma proteins with DR.Bidirectional MR,Bayesian Co-localization,and phenotype scanning were employed to test for potential reverse causality and confounding factors in the main MR analyses.By systemically searching druggable gene lists,the ChEMBL database,DrugBank,and Gene Ontology database,the druggability and relevant functional pathways of the identified proteins were systematically evaluated.Results:Genetically predicted levels of 24 proteins were significantly associated with DR risk at a false discovery rate<0.05 including 11 with positive associations and 13 with negative associations.For each standard deviation increase in plasm protein levels,the odds ratios(ORs)for DR varied from 0.51(95%CI:0.36-0.73;P=2.22×10-5)for tubulin polymerization-promoting protein family member 3(TPPP3)to 2.02(95%CI:1.44-2.83;P=5.01×10-5)for olfactomedin like 3(OLFML3).Bidirectional MR indicated there was no reverse causality that interfered with the results of the main MR analyses.Four proteins exhibited strong co-localization evidence(PH4≥0.8):cytoplasmic tRNA synthetase(WARS),acrosin binding protein(ACRBP),and intercellular adhesion molecule 1(ICAM1)were negatively associated with DR risk,while neurogenic locus notch homolog protein 2(NOTCH2)showed a positive association.No confounding factors were detected between pQTLs and DR according to the phenotypic scan.Drugability assessments highlighted 6 proteins already in drug development endeavor and 18 novel drug targets,with metalloproteinase inhibitor 3(TIMP)currently in phase I clinical trials for DR.GO analysis identified 18 of 24 plasma proteins enriching 22 pathways related to cell differentiation and proliferation regulation.Conclusions:Twenty-four promising drug targets for DR were identified,including four plasma proteins with particular co-localization evidence.These findings offer new insights into DR's etiology and therapeutic targeting,exemplifying the value of genomic and proteomic data in drug target discovery.
基金supported by the Natural Science Foundation of Hebei Province(F2010000306,F2012201089)the Hebei Province Department of Education Fund(ZH2011205)
文摘Organic polymer solar materials are shown to exhibit better solubility in mixed solvents than in pure ones,which affects the performance of their solar cells.In this article,poly[N-9-hepta-decanyl-2,7-carbazole-alt-5,5-(4.7-di-2-thienyI-2,l,3-benzothiadiazole)(PCDTBT0)and[6,6]-phenyl-C71-butyric acid methyl ester(PC_(71)BM)are used as active layer materials in solar cells.To optimize the performance of these active materials,the ratio of chloroform(CF)to chlorobenzene used as solvents to dissolve PCDTBT,and PC_(71)BM is varied,which is shown to affect power conversion efficiency(PCE).The solar cell that shows the best performance with a PCE as high as 6.82%is produced using a volume ratio of CF to chlorobenzene of1:1.
基金the Key Research and Development Projects of Hebei Province(Grant No.19214301D)the Key Project of Science and Technology Research in Higher Education Institutions of Hebei Province(Grant No.ZD2022024)+3 种基金the Natural Science Foundation of Hebei Province(Grant Nos A2019405059,A2022405002)the Starting Fund for Independent Doctoral Research of Hebei Agricultural University(PY2021005)the General Projects of Hebei North University(Grant No.XJ2021001)the Innovation and Entrepreneurship Training Program for College Students of Hebei North University(Grant Nos 202210092007,S202210092006).
文摘Transparent conductive films(TCFs)are crucial components of solar cells.In this study,F,Cl,and Ga codoped ZnO(FCGZO)TCFs were deposited onto a glass substrate using the sol-gel spin-coating method and rapid thermal annealing.The effects of F-doping content on the structural,morphological,electrical,and optical properties of FCGZO films were examined by XRD,TEM,FE-SEM,PL spectroscopy,XPS,Hall effects testing,and UVeviseNIR spectroscopy.All prepared ZnO films exhibited a hexagonal wurtzite structure and preferentially grew along the c axis perpendicular to the substrate.Changes in the doping concentration of F changed the interplanar crystal spacing and O vacancies in the film.At a doping ratio of 2%(in mole),the F,Cl,and Ga co-doped ZnO film exhibited the best photoelectric performance,with a carrier concentration of 2.62×10^(20)cm^(-3),mobility of 14.56 cm^(2)/(V·s),and resistivity of 1.64×10^(-3)Ucm.The average transmittance(AT)in the 380-1600 nm region nearly 90%with air as the reference,and the optical band gap was 3.52 eV.
