3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is l...3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is lower bainite plates or polygonal ferrite containing quantities of dispersed cementite particles, mixed with a few of low carbon martensite laths or ferrite, depending on the heat input. The hardness and the tensile strength of the weld metal are higher than those of the base metal, and monotonously increase as the heat input decreases. No softened zone exists in heat affected zone (HAZ). Compared with the base metal, although the grains of laser weld are much larger, the toughness of the weld metal is higher within a large range of heat input. Furthermore, as the heat input increases, the toughness of the weld metal rises to a maximum value, at which point the percentage of lower bainite is the highest, and then drops.展开更多
OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations...OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations.METHODS In order to apply the IBGC model in mice,we introduced S602 W point mutation into the mouse Slc20a2.Mice(3months old)with homozygous mutation developed brain calcification as similar as IBGC in human.The SYM decoction was diluted and added into the drinking water of 2-week-old homozygous Slc20a2 KI mice for 5months.Another group of homozygous Slc20a2 KI mice were set as control and received no treatment.After 5months,to analyze the effect of the SYM decoction on brain calcification,pathological sections with the brain of Slc20a2 KI mice were made and stained.RESULTS Calcified nodules were not seen in the brain of Slc20a2 KI mice that received SYM decoction treatment,while the control group developed multiple calcifications in the thalamus region.CONCLUSION SYM decoction produced preventive effect on the formation of calcified nodules in IBGC model mice,which might be useful for the treatment of IBGC caused by SLC20A2 mutations.展开更多
A novel cycloartane, named sphaerophysone A, 9, 19-cycloart-7b, 24b, 25-triol-1-en-3- one, was isolated from the ethanol extract of Sphaerophysa salsula DC. The structure was elucidated on the basis of spectral evide...A novel cycloartane, named sphaerophysone A, 9, 19-cycloart-7b, 24b, 25-triol-1-en-3- one, was isolated from the ethanol extract of Sphaerophysa salsula DC. The structure was elucidated on the basis of spectral evidences and confirmed by X-ray analysis, the stereochemistry of the compound was also defined by X-ray analysis.展开更多
Amyloid-βpeptide(Aβ)oligomers,characteristic symptom of Alzheimer’s disease(AD),have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD.However,due to their trans...Amyloid-βpeptide(Aβ)oligomers,characteristic symptom of Alzheimer’s disease(AD),have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD.However,due to their transient and heterogeneous nature,the high-resolution structures and exact pathogenic processes of Aβ oligomers are currently unknown.Using light-controlled molecular tweezers(LMTs),we describe a method for precisely capturing specific Aβ oligomers produced from synthetic Aβ and AD animal models.Light irradiation can activate LMTs,which are composed of two Aβ-targeting pentapeptides(KLVFF)motifs and a rigid azobenzene(azo)derivative,to form a tweezer-like cis configuration that preferentially binds to specific oligomers matching the space of the tweezers via multivalent interactions of KLVFF motifs with the oligomers.Surprisingly,cis-LMTs can immobilize the captured oligomers in transgenic Caenorhabditis elegans under light irradiation.The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via reversible photoisomerization,which would improve the understanding of the toxic mechanisms of Aβoligomers and development of oligomer-targeted diagnosis and therapy.展开更多
Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reas...Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD.展开更多
基金This work was supported by the‘973'ScienceTechnology Development Plan of the National Basic Research Foundation(No.1998061500)the 985'Foundation of Tsinghua University.
文摘3 mm thick 400 MPa grade ultrafine grained ferritic steel plates were bead-on-plate welded by CO2 laser with heat input of 120-480 J/mm. The microstructures of the weld metal mainly consist of bainite, which form is lower bainite plates or polygonal ferrite containing quantities of dispersed cementite particles, mixed with a few of low carbon martensite laths or ferrite, depending on the heat input. The hardness and the tensile strength of the weld metal are higher than those of the base metal, and monotonously increase as the heat input decreases. No softened zone exists in heat affected zone (HAZ). Compared with the base metal, although the grains of laser weld are much larger, the toughness of the weld metal is higher within a large range of heat input. Furthermore, as the heat input increases, the toughness of the weld metal rises to a maximum value, at which point the percentage of lower bainite is the highest, and then drops.
基金The project supported by National Natural Science Foundation of China grants(31230045and 81271252)the National Science&Technology Pillar Program duringthe 12th Five-year Plan Period(2012BAI09B04)
文摘OBJECTIVE To establish Idiopathic basal ganglia calcification(IBGC′s)disease model in mouse,and investigate the effect of Chinese herbal medicine formula SYM to prevent brain calcification caused by SLC20A2 mutations.METHODS In order to apply the IBGC model in mice,we introduced S602 W point mutation into the mouse Slc20a2.Mice(3months old)with homozygous mutation developed brain calcification as similar as IBGC in human.The SYM decoction was diluted and added into the drinking water of 2-week-old homozygous Slc20a2 KI mice for 5months.Another group of homozygous Slc20a2 KI mice were set as control and received no treatment.After 5months,to analyze the effect of the SYM decoction on brain calcification,pathological sections with the brain of Slc20a2 KI mice were made and stained.RESULTS Calcified nodules were not seen in the brain of Slc20a2 KI mice that received SYM decoction treatment,while the control group developed multiple calcifications in the thalamus region.CONCLUSION SYM decoction produced preventive effect on the formation of calcified nodules in IBGC model mice,which might be useful for the treatment of IBGC caused by SLC20A2 mutations.
文摘A novel cycloartane, named sphaerophysone A, 9, 19-cycloart-7b, 24b, 25-triol-1-en-3- one, was isolated from the ethanol extract of Sphaerophysa salsula DC. The structure was elucidated on the basis of spectral evidences and confirmed by X-ray analysis, the stereochemistry of the compound was also defined by X-ray analysis.
基金National Natural Science Foundation of China,Grant/Award Numbers:21771105,22377053Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20170103The Six Talent Peaks Project in Jiangsu Province,Grant/Award Number:SWYY-043。
文摘Amyloid-βpeptide(Aβ)oligomers,characteristic symptom of Alzheimer’s disease(AD),have been identified as the most neurotoxic species and significant contributors to neurodegeneration in AD.However,due to their transient and heterogeneous nature,the high-resolution structures and exact pathogenic processes of Aβ oligomers are currently unknown.Using light-controlled molecular tweezers(LMTs),we describe a method for precisely capturing specific Aβ oligomers produced from synthetic Aβ and AD animal models.Light irradiation can activate LMTs,which are composed of two Aβ-targeting pentapeptides(KLVFF)motifs and a rigid azobenzene(azo)derivative,to form a tweezer-like cis configuration that preferentially binds to specific oligomers matching the space of the tweezers via multivalent interactions of KLVFF motifs with the oligomers.Surprisingly,cis-LMTs can immobilize the captured oligomers in transgenic Caenorhabditis elegans under light irradiation.The LMTs may serve as spatiotemporally controllable molecular tools to extract specific native oligomers for the structure and function studies via reversible photoisomerization,which would improve the understanding of the toxic mechanisms of Aβoligomers and development of oligomer-targeted diagnosis and therapy.
基金Science Fund for Creative Research Groups of the National Natural Science Foundation of China,Grant/Award Number:81521004National Natural Science Foundation of China,Grant/Award Numbers:81922061,82172992,81903391,81702266+2 种基金Research Unit of Prospective Cohort of Cardiovascular Diseases and Cancers,Chinese Academy of Medical Sciences,Grant/Award Number:2019RU038Natural Science Foundation of Jiangsu Province,Grant/Award Numbers:BK20211253,BK20190148Postgraduate Research&Practice Innovation Program of Jiangsu Province,Grant/Award Number:KYCX18_0195。
文摘Background:Epigenetic alterations have been shown to contribute immensely to human carcinogenesis.Dynamic and reversible N6-methyladenosine(m6A)RNA modification regulates gene expression and cell fate.However,the reasons for activation of KIAA1429(also known as VIRMA,an RNA methyltransferase)and its underlying mechanism in lung adenocarcinoma(LUAD)remain largely unexplored.In this study,we aimed to clarify the oncogenic role of KIAA1429 in the tumorigenesis of LUAD.Methods:Whole-genome sequencing and transcriptome sequencing of LUAD data were used to analyze the gene amplification of RNA methyltransferase.The in vitro and in vivo functions of KIAA1429 were investigated.Transcriptome sequencing,methylated RNA immunoprecipitation sequencing(MeRIP-seq),m6A dot blot assays and RNA immunoprecipitation(RIP)were performed to confirm the modified gene mediated by KIAA1429.RNA stability assays were used to detect the half-life of the target gene.Results:Copy number amplification drove higher expression of KIAA1429 in LUAD,whichwas correlatedwith poor overall survival.Manipulating the expression of KIAA1429 could regulate the proliferation and metastasis of LUAD.Mechanistically,the target genes of KIAA1429-mediated m6A modification were confirmed by transcriptome sequencing and MeRIP-seq assays.We also revealed that KIAA1429 could regulate BTG2 expression in an m6A-dependent manner.Knockdown of KIAA1429 significantly decreased the m6A levels of BTG2 mRNA,leading to enhanced YTH m6A RNA binding protein 2(YTHDF2,the m6A“reader”)-dependent BTG2 mRNA stability and promoted the expression of BTG2;thus,participating in the tumorigenesis of LUAD.Conclusions:Our data revealed the activation mechanism and important role of KIAA1429 in LUAD tumorigenesis,which may provide a novel view on the targeted molecular therapy of LUAD.
