【背景】酪蛋白水解蛋白酶L(caseinolytic protease L,ClpL)是热休克蛋白100(heat shock protein 100,HSP100)家族成员,参与多种细胞内生物学过程包括应激耐受反应、长期存活、毒力和抗生素抗性等,在病原菌的致病过程中发挥重要作用。...【背景】酪蛋白水解蛋白酶L(caseinolytic protease L,ClpL)是热休克蛋白100(heat shock protein 100,HSP100)家族成员,参与多种细胞内生物学过程包括应激耐受反应、长期存活、毒力和抗生素抗性等,在病原菌的致病过程中发挥重要作用。【目的】阐明HSP100/ClpL对猪链球菌2型(Streptococcus suis type 2)强毒株的应激耐受和毒力的影响。【方法】利用温敏自杀质粒pSET4s构建了SsClpL基因缺失株ΔclpL;利用大肠杆菌-猪链球菌穿梭质粒pSET2构建了互补株CΔclpL;比较亲本株SS2-1、ΔclpL和CΔclpL在各种应激环境(高温、氧化性应激和酸应激)和血液中的生存能力;利用小鼠感染模型和体内竞争试验评价clpL缺失前后细菌的毒力变化。【结果】clpL缺失后,SS2在各种应激环境中的生存能力明显减弱;同时在猪全血中的存活能力也显著降低;对BALB/c小鼠的致病力有所降低,在体内的定殖能力明显降低。【结论】SsClpL与猪链球菌的应激耐受和致病性密切相关。展开更多
Given their unique structure-dependent properties,strategically designing semiconductor-based photocatalysts,which expose highly reactive crystalline facets,is widely used to tune their performance.Herein,AgBr/Ag/TiO_...Given their unique structure-dependent properties,strategically designing semiconductor-based photocatalysts,which expose highly reactive crystalline facets,is widely used to tune their performance.Herein,AgBr/Ag/TiO_(2){100}nanorods Z-scheme heterojunction composites were prepared via hydrothermal and in situ facet-induced reduction.Transmission electron microscopy,X-ray diffraction,X-ray photoelectron spectroscopy,electron paramagnetic resonance spectroscopy,and density functional theory calculations reveal that the selective exposure of TiO_(2){100}facets with abundant oxygen vacancies(OV)promotes the formation of metallic silver on the interfaces between AgBr and TiO_(2){100}.Metallic silver can mediate interfacial charge transfer by facilitating the photogenerated carrier recombination of the conduction band of TiO_(2){100}and the valence band of AgBr.As a result,a Z-scheme heterojunction is formed in AgBr/Ag/TiO_(2){100}.The AgBr/Ag/TiO_(2){100}exhibits faster degradation of tetracycline in aqueous solution compared to pristine AgBr,TiO_(2){101},TiO_(2){100}and AgBr/TiO_(2){101}p-n heterojunctions.This is attributed to the effect of the Z-scheme heterojunction on prolonging the lifetime of photogenerated carriers,which is confirmed by femtosecond transient absorption spectroscopy.The photocatalytic mechanism and degradation pathways are discussed along with a toxicity assessment of the intermediates.Overall,this work develops a new approach for designing Z-scheme heterojunction photocatalysts via selective facet control of anatase TiO_(2).展开更多
Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Alt...Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.展开更多
Optimizing the orientation of β-Ga_(2)O_(3) has emerged as an effective strategy to design high-performance β-Ga_(2)O_(3) device,but the orientation growth mechanism and approach have not been revealed yet.Herein,by...Optimizing the orientation of β-Ga_(2)O_(3) has emerged as an effective strategy to design high-performance β-Ga_(2)O_(3) device,but the orientation growth mechanism and approach have not been revealed yet.Herein,by employing AlN buffer layer,the highly preferred orientation of β-Ga_(2)O_(3)(100)film rather than(-201)film is realized on 4H-SiC substrate at low sputtering power and temperature.Because β-Ga_(2)O_(3)(100)film exhibits a slower growth speed than(-201)film,the former possesses the higher dangling bond density and the lower nucleation energy,and a large conversion barrier exists between these two ori-entations.Moreover,the AlN buffer layer can suppress the surface oxidation of the 4H-SiC substrate and eliminate the strain of β-Ga_(2)O_(3)(100)film,which further reduces the nucleation energy and en-larges the conversion barrier.Meanwhile,the AlN buffer layer can increase the oxygen vacancy formation energy and decrease the oxygen vacancy concentration of β-Ga_(2)O_(3)(100)film.Consequently,the solar-blind photodetector based on the oriented film exhibits the outstanding detectivity of 1.22×10^(12) Jones and photo-to-dark current ratio of 1.11×10^(5),which are the highest among the reported β-Ga_(2)O_(3) solar-blind photodetector on the SiC substrate.Our results offer in-depth insights into the preferred orientation growth mechanism,and provide an effective way to design high-quality β-Ga_(2)O_(3)(100)orientation film and high-performance solar-blind photodetector.展开更多
文摘【背景】酪蛋白水解蛋白酶L(caseinolytic protease L,ClpL)是热休克蛋白100(heat shock protein 100,HSP100)家族成员,参与多种细胞内生物学过程包括应激耐受反应、长期存活、毒力和抗生素抗性等,在病原菌的致病过程中发挥重要作用。【目的】阐明HSP100/ClpL对猪链球菌2型(Streptococcus suis type 2)强毒株的应激耐受和毒力的影响。【方法】利用温敏自杀质粒pSET4s构建了SsClpL基因缺失株ΔclpL;利用大肠杆菌-猪链球菌穿梭质粒pSET2构建了互补株CΔclpL;比较亲本株SS2-1、ΔclpL和CΔclpL在各种应激环境(高温、氧化性应激和酸应激)和血液中的生存能力;利用小鼠感染模型和体内竞争试验评价clpL缺失前后细菌的毒力变化。【结果】clpL缺失后,SS2在各种应激环境中的生存能力明显减弱;同时在猪全血中的存活能力也显著降低;对BALB/c小鼠的致病力有所降低,在体内的定殖能力明显降低。【结论】SsClpL与猪链球菌的应激耐受和致病性密切相关。
文摘Given their unique structure-dependent properties,strategically designing semiconductor-based photocatalysts,which expose highly reactive crystalline facets,is widely used to tune their performance.Herein,AgBr/Ag/TiO_(2){100}nanorods Z-scheme heterojunction composites were prepared via hydrothermal and in situ facet-induced reduction.Transmission electron microscopy,X-ray diffraction,X-ray photoelectron spectroscopy,electron paramagnetic resonance spectroscopy,and density functional theory calculations reveal that the selective exposure of TiO_(2){100}facets with abundant oxygen vacancies(OV)promotes the formation of metallic silver on the interfaces between AgBr and TiO_(2){100}.Metallic silver can mediate interfacial charge transfer by facilitating the photogenerated carrier recombination of the conduction band of TiO_(2){100}and the valence band of AgBr.As a result,a Z-scheme heterojunction is formed in AgBr/Ag/TiO_(2){100}.The AgBr/Ag/TiO_(2){100}exhibits faster degradation of tetracycline in aqueous solution compared to pristine AgBr,TiO_(2){101},TiO_(2){100}and AgBr/TiO_(2){101}p-n heterojunctions.This is attributed to the effect of the Z-scheme heterojunction on prolonging the lifetime of photogenerated carriers,which is confirmed by femtosecond transient absorption spectroscopy.The photocatalytic mechanism and degradation pathways are discussed along with a toxicity assessment of the intermediates.Overall,this work develops a new approach for designing Z-scheme heterojunction photocatalysts via selective facet control of anatase TiO_(2).
基金supported by the National Key Research and Development Program of China(No.2023YFC2506504)the National Natural Science Foundation of China(No.82370255,and No.U24A20646)the Shanghai Science and Technology Commission Project(No.23410761200).
文摘Objective The pathogenesis and progression of heart failure(HF)are governed by complex,interconnected biological pathways,with dysregulated immune responses and maladaptive cardiac remodeling playing central roles.Although specific inflammatory mediators have been implicated in modulating critical features of cardiac remodeling—such as cardiomyocyte hypertrophy and extracellular matrix fibrosis—the precise molecular mechanisms driving these processes remain incompletely characterized.Methods Integrated bioinformatics analysis of HF and hypertrophic cardiomyopathy(HCM)transcriptomic datasets identified pathologically relevant candidate genes.A protein-protein interaction(PPI)network was constructed from these candidates using the STRING database,followed by module analysis.Serum S100 calcium-binding protein A9(S100A9)protein expression in HF patients was quantified by Western blotting under reducing conditions.The functional relevance of prioritized genes was subsequently validated through:(i)in vitro cyclic mechanical stretch in primary neonatal rat cardiomyocytes,and(ii)in vivo pressure overload modeling via transverse aortic constriction(TAC)in mice.Results Bioinformatics analysis of HF and HCM datasets revealed a significant association between immune function and cardiac remodeling.Using CytoNCA,we identified core genes,among which the top 25 included multiple inflammatory pathway-related factors,such as S100A9 and Toll-like receptor 2(TLR2).Notably,S100A9 levels were significantly elevated in the serum of HF patients and in mechanically stretched cardiomyocytes.This increase correlated with upregulated expression of hypertrophy-related markers,including atrial natriuretic peptide(ANP).Furthermore,mechanical stretch-induced S100A9 upregulation markedly enhanced TLR2 expression in cardiomyocytes.Importantly,TLR2 inhibition substantially attenuated the mechanical stretch-induced upregulation of S100A9 mRNA expression,as well as the subsequent hypertrophic and inflammatory responses in cardiomyocytes.Conclusion The inflammatory mediators S100A9 and TLR2 engage in reciprocal activation that amplifies the hypertrophic response in mechanically stretched cardiomyocytes.This pathogenic cross-talk exacerbates maladaptive remodeling and likely accelerates HF progression.
基金supported by the National Key Research and Development Program of China(No.2021YFA0715600)the National Natural Science Foundation of China(Nos.62274125,52192611)+2 种基金the Guangdong Basic and Applied Basic Research Fund(No.2023A1515030084)the Key Research and Development Program of Shaanxi Province(Grant No.2024GX-YBXM-410)the fund of the State Key Laboratory of Solidification Processing in NWPU(No.SKLSP202220).
文摘Optimizing the orientation of β-Ga_(2)O_(3) has emerged as an effective strategy to design high-performance β-Ga_(2)O_(3) device,but the orientation growth mechanism and approach have not been revealed yet.Herein,by employing AlN buffer layer,the highly preferred orientation of β-Ga_(2)O_(3)(100)film rather than(-201)film is realized on 4H-SiC substrate at low sputtering power and temperature.Because β-Ga_(2)O_(3)(100)film exhibits a slower growth speed than(-201)film,the former possesses the higher dangling bond density and the lower nucleation energy,and a large conversion barrier exists between these two ori-entations.Moreover,the AlN buffer layer can suppress the surface oxidation of the 4H-SiC substrate and eliminate the strain of β-Ga_(2)O_(3)(100)film,which further reduces the nucleation energy and en-larges the conversion barrier.Meanwhile,the AlN buffer layer can increase the oxygen vacancy formation energy and decrease the oxygen vacancy concentration of β-Ga_(2)O_(3)(100)film.Consequently,the solar-blind photodetector based on the oriented film exhibits the outstanding detectivity of 1.22×10^(12) Jones and photo-to-dark current ratio of 1.11×10^(5),which are the highest among the reported β-Ga_(2)O_(3) solar-blind photodetector on the SiC substrate.Our results offer in-depth insights into the preferred orientation growth mechanism,and provide an effective way to design high-quality β-Ga_(2)O_(3)(100)orientation film and high-performance solar-blind photodetector.
