Background:This study aims to analyze the genotypes and antibiotic resistance characteristics of Clostridioides difficile(C.difficile)isolated from children under 5 years old with diarrhea in Yunnan Province.Methods:F...Background:This study aims to analyze the genotypes and antibiotic resistance characteristics of Clostridioides difficile(C.difficile)isolated from children under 5 years old with diarrhea in Yunnan Province.Methods:Fecal samples from children under 5 years of age with diarrhea in Kunming city from 2013-2019 were collected for anaerobic culture,isolation,and identification of C.difficile.The antibiotic susceptibility tests and molecular typing of isolated strains were also performed.Results:44 strains of C.difficile were isolated from 896 fecal samples.Of these,40 strains(90.9%)were positive for both tcdA and tcdB,while 4 strains(9.1%)were negative for both.All isolates were negative for cdtA and cdtB.The isolates were classified into 13 STs,the predominant types were ST3(13 strains,29.5%),ST35(8 strains,18.2%),and ST54(5 strains,11.4%).All the strains were susceptible to metronidazole,amoxicillin/clavulanic acid,vancomycin,and amoxicillin.The highest resistance rate was observed against gentamicin(86.36%),followed by polymyxin E(84.09%),quinupristin-dalfopristin(61.36%),and ceftazidime(36.36%).Some patients with diarrhea had C.difficile co-infections with other pathogens,including norovirus,adenovirus,rotavirus or Salmonella or Escherichia coli.Conclusion:C.difficile strains isolated from children under 5 years of age are mostly toxigenic,and the MLST results are highly diverse.Monitoring and prevention of C.difficile should be strengthened.展开更多
Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it t...Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in Chuan-Dian rhombic block and concerned Xianshuihe-Anninghe-Xiaojiang seismic belt, as well as in Jinshajiang-Honghe seismic belt. Multiple mainshock type （MMT） mainly distributes in western Yunnan, and Longlin and Lancang areas in Tengchong-Baoshan block in west of Nujiang-Lancangjiang fault zone. A few isolated earthquake type （IET） mainly occurred in northwestern Sichuan and there is no IET occurred in Yunnan region. In northwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in west segment of South Tianshan in Xinjiang region. Some MMT also occurred in this area in the intersection of Kalpin block and the Puchang fault zone. It takes IET as the major in middle Tianshan in Xinjiang. Along the Qilianshan seismic belt, most of sequences are MAT. In Qinghai region, it takes MAT as the major, but the regional feature of the spatial distribution of sequence types is not very clear. In North China, it takes MAT as the major in Yinshan-Yanshan-Bohai seismic belt, north edge of North China, and in Hebei plain seismic belt, as well as in sub-plate of lower river area of Yangtze River. In intersection of north segment of Shanxi seismic belt and the NW-trending Yinshan-Yanshan-Bohai seismic belt, there are several moderate or strong MMT with magnitude from 5.0 to 6.0 occurred. In south of North China around the latitude line of 35°N, it takes IET as the major. The spatial distribution of sequence types is relevant to the patterns of tectonic movements. MAT is mostly produced by the ruptures of locked units or asperities or the neonatal separating segments inside the fault zones. MMT is generally relevant to the conjugate structures or intersection of many tectonic settings. Further extension of simple fault often produces IET. Spatial distribution of sequence types is also correlative to the regional and deep environment of crustal medium to some extent. MAT mainly distributes in high velocity area in upper crust or in the transition zone between high velocity area and low velocity area, MMT mostly occurred in the low velocity area in upper crust.展开更多
AIM To investigate the material basis and mechanism underlying the therapeutic effect of DLC in T2DM.METHODS T2DM was triggered in rats using a high-sugar,high-fat diet alongside 35 mg/kg streptozotocin.The effect of ...AIM To investigate the material basis and mechanism underlying the therapeutic effect of DLC in T2DM.METHODS T2DM was triggered in rats using a high-sugar,high-fat diet alongside 35 mg/kg streptozotocin.The effect of DLC on the intestinal microbiota in T2DM rats was analyzed via 16S rDNA sequencing.Targeted metabolomics was conducted to evaluate the impact of DLC on the levels of nine short-chain fatty acids(SCFAs).Untargeted metabolomics examined DLC-induced alterations in fecal metabolites and associated metabolic pathways.Additionally,Spearman’s correlation analysis assessed gut microbiota and fecal metabolite relationships.RESULTS DLC significantly attenuated pathological weight loss,reduced fasting blood glucose levels,restored blood sugar homeostasis,and ameliorated dyslipidemia in T2DM rats.The 16S rDNA sequencing revealed that DLC enhanced microbial diversity and reversed intestinal dysbiosis.Targeted metabolomics indicated decreased acetic acid and propionic acid levels and increased butyric acid,isobutyric acid,and 2-methylbutyric acid levels after DLC treatment.Untargeted metabolomics revealed 57 metabolites with altered expression associated with amino acid,carbohydrate,purine,and biotin pathways.The Spearman analysis demonstrated significant links between specific gut microbiota taxa and fecal metabolites.CONCLUSION DLC may exert hypoglycemic effects by modulating intestinal flora genera,SCFA levels,and fecal metabolites.展开更多
In this paper, the complete convergence for the weighted sums of independent and identically distributed random variables in Stout [9] is improved and extended under NOD setup.The more optimal moment condition is give...In this paper, the complete convergence for the weighted sums of independent and identically distributed random variables in Stout [9] is improved and extended under NOD setup.The more optimal moment condition is given. The main results also hold for END sequence.展开更多
In this paper, we investigate the problem of approximating solutions of the equations of Lipschitzian ψ-strongly accretive operators and fixed points of Lipschitzian ψ-hemicontractive operators by lshikawa type iter...In this paper, we investigate the problem of approximating solutions of the equations of Lipschitzian ψ-strongly accretive operators and fixed points of Lipschitzian ψ-hemicontractive operators by lshikawa type iterative sequences with errors. Our results unify, improve and extend the results obtained previously by several authors including Li and Liu (Acta Math. Sinica 41 (4)(1998), 845-850), and Osilike (Nonlinear Anal. TMA, 36(1)(1999), 1-9), and also answer completely the open problems mentioned by Chidume (J. Math. Anal. Appl. 151 (2)(1990), 453-461).展开更多
In this paper, based on the results of tomographic image of Tangshan and Xingtai areas, the relations between thecharacteristics of the two strong earthquake sequences and their three-dimensional velocity structures a...In this paper, based on the results of tomographic image of Tangshan and Xingtai areas, the relations between thecharacteristics of the two strong earthquake sequences and their three-dimensional velocity structures are studied.The research results indicate that:① Mosaic distribution of low-velocity bodies and high-velocity bodies, especially the existence of high-velocity bodies with large size in crust are the common basis of development of thetwo earthquake sequences. ② Scale, depth, and heterogeneity of high-velocity and low-velocity bodies are theimportant factors to effect the characteristic of earthquake sequences. ③ The depth of the high-velocity body inTangshan area is less than that in Xingtai area, which is the principal reason why the dominant focal depth and thebiggest focal depth of Tangshan earthquake sequence are less than Xingtai's. ④ The depth of the high-velocitybodies in Ninghe area is more than that in Tangshan-Luanxian area, which lead to the biggest magnitude and epicentral intensity are lower. These results could be helpful for predicting the main shock of strong swarm-typeearthquakes and later strong aftershocks.展开更多
The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the e...The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the extension, there is a unique PEST sequence (Glu31-Cys46), which is composed of an amino terminal Pro-rich segment and a carboxyl terminal Ser-cluster. Substitution of either half of the PEST sequence with Ala residues by cassette mutagenesis reduced the apparent molecular size of L-type GATA-6 on SDS-polyacrylamide gel-electrophoresis. However, the effect of substitution of the Pro-rich segment was much more significant;the mobility increase of the Pro-rich segment on the gel was 13% while that of the Ser-cluster was 8%. Substitution of each amino acid residue demonstrated that the effect of Pro substitution is greater than that of the Ser and Thr residues. Such increased mobility of L-type GATA-6 in the presence of a detergent may apparently correlate with the decrease in transcription activity in vivo as determined by means of luciferase reporter gene assay. The activity of ΔAla (with Ala residues instead of the PEST sequence) was reduced to one fifth of that of ΔA (with the PEST sequence). These results suggest that the PEST sequence of L-type GATA-6 does not function as a constitutive protein degradation signal, but rather plays structural and functional roles in the activation of gene expression on the GATA responsive promoter.展开更多
Objective:To investigate the effects and potential mechanisms of action of Panax notoginseng(Burk)F.H.Chen(P.notoginseng,San Qi)flowers in type 2 diabetes mellitus(T2DM)using network pharmacology,in vivo experiments,a...Objective:To investigate the effects and potential mechanisms of action of Panax notoginseng(Burk)F.H.Chen(P.notoginseng,San Qi)flowers in type 2 diabetes mellitus(T2DM)using network pharmacology,in vivo experiments,and RNA sequencing(RNA-seq).Methods:Network pharmacology analysis was performed to identify and correlate the drug targets of flower buds of P.notoginseng(PNF)with T2DM disease targets and to predict the key targets and pathways involved in the therapeutic effects of PNF in T2DM.In vivo experiments were conducted to assess the effects of PNF on glucose and lipid metabolism in mice with T2DM.RNA-seq was performed,and the results were integrated with network pharmacology data to assess the therapeutic mechanisms of PNF in T2DM.The results from transcriptomics and network pharmacology were validated using real-time polymerase chain reaction.Results:A total of 27 intersecting targets were identified by overlapping 35 drug targets with T2DM targets.Further topological analysis using the Centiscape 2.2 tool revealed five core targets,including signal transducer and activator of transcription 3(STAT3).Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis indicated that the JAK/STAT signaling pathway is a key mechanism underlying the therapeutic effects of PNF in T2DM.In vivo experiments confirmed that PNF effectively regulates glycolipid metabolism in a mouse model of diabetes.KEGG pathway enrichment analysis of RNA-seq data highlighted the JAK2/STAT3 and PI3K/AKT pathway as a potential mechanism.PNF high-dose(PNFH)increased the gene expression levels of PIK3R1 and AKT2,decreased the expression of PCK1,JAK2,and STAT3,and showed a trend toward increasing INSR expression without reaching statistical significance.Conclusion:PNF improves glycolipid metabolism disorders in T2DM,potentially by modulating the JAK2/STAT3 and PI3K/AKT signaling pathway.展开更多
高等院校作为国家科技人才孵化及汇集的重要场所,肩负着为国育人、为党育才的使命。运用科学、技术与社会(Science,Technology and Society)跨学科的教学和实践活动探索地方应用型高校培养创新科技人才的新途径,能使学生在理解科学和技...高等院校作为国家科技人才孵化及汇集的重要场所,肩负着为国育人、为党育才的使命。运用科学、技术与社会(Science,Technology and Society)跨学科的教学和实践活动探索地方应用型高校培养创新科技人才的新途径,能使学生在理解科学和技术的基础上更好地应对社会问题和挑战。在STS教育理念下,可以通过以下措施进一步探索和实践科技创新人才培养路径:优化专业结构,完善专业动态调整机制,提高专业办学与经济社会发展的契合度;完善“平台+模块”的课程建设架构,创新实践教学体系;建立协同育人机制,加强师资队伍建设;深化拔尖人才培养模式改革,完善教学评价制度。展开更多
Different genetic types of meter-scale cyclic sequences in stratigraphic records result from episodic accumulation of strata related to Milankovitch cycles. The distinctive fabric natures of facies succession result f...Different genetic types of meter-scale cyclic sequences in stratigraphic records result from episodic accumulation of strata related to Milankovitch cycles. The distinctive fabric natures of facies succession result from the sedimentation governed by different sediment sources and sedimentary dynamic conditions in different paleogeographical backgrounds, corresponding to high-frequency sea-level changes. Naturally, this is the fundamental criterion for the classification of genetic types of meter-scale cyclic sequences. The widespread development in stratigraphic records and the regular vertical stacking patterns in long-term sequences, the evolution characters of earth history and the genetic types reflected by specific fabric natures of facies successions in different paleogeographical settings, all that show meter-scale cyclic sequences are not only the elementary working units in stratigraphy and sedimentology, but also the replenishment and extension of parasequence of sequence stratigraphy. Two genetic kinds of facies succession for meter-scale cyclic sequence in neritic-facies strata of carbonate and clastic rocks, are normal grading succession mainly formed by tidal sedimentation and inverse grading succession chiefly made by wave sedimentation, and both of them constitute generally shallowing upward succession, the thickness of which ranges from several tens of centimeters to several meters. The classification of genetic types of meter-scale cyclic sequence could be made in terms of the fabric natures of facies succession, and carbonate meter-scale cyclic sequences could be divided into four types: L-M type, deep-water asymmetrical type, subtidal type and peritidal type. Clastic meter-scale cyclic sequences could be grouped into two types: tidal-dynamic type and wave-dynamic type. The boundaries of meter-scale cyclic sequences are marked by instantaneous punctuated surface formed by non-deposition resulting from high-frequency level changes, which include instantaneous exposed punctuated surface, drowned punctuated surface as well as their relative surface. The development of instantaneous punctuated surface used as the boundary of meter-scale cyclic sequence brings about the limitations of Walter's Law on the explanation of facies distribution in time and space, and reaffirm the importance of Sander's Rule on analysis of stratigraphic records. These non-continuous surface could be traced for long distance and some could be correlative within same basin range. The study of meter-scale cyclic sequences and their regularly vertical stacking patterns in long-term sequences indicate that the research into cyclicity of stratigraphic records is a useful way to get more regularity from stratigraphic records that are frequently complex as well as non-integrated.展开更多
Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asia...Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.展开更多
基金supported by Yunnan Provincial Key Research and Development Program(grant No.202503AP140034)Infectious Disease Spectrum and Epidemiology Project of YNCDC(grant No.YNAPM2025-003).
文摘Background:This study aims to analyze the genotypes and antibiotic resistance characteristics of Clostridioides difficile(C.difficile)isolated from children under 5 years old with diarrhea in Yunnan Province.Methods:Fecal samples from children under 5 years of age with diarrhea in Kunming city from 2013-2019 were collected for anaerobic culture,isolation,and identification of C.difficile.The antibiotic susceptibility tests and molecular typing of isolated strains were also performed.Results:44 strains of C.difficile were isolated from 896 fecal samples.Of these,40 strains(90.9%)were positive for both tcdA and tcdB,while 4 strains(9.1%)were negative for both.All isolates were negative for cdtA and cdtB.The isolates were classified into 13 STs,the predominant types were ST3(13 strains,29.5%),ST35(8 strains,18.2%),and ST54(5 strains,11.4%).All the strains were susceptible to metronidazole,amoxicillin/clavulanic acid,vancomycin,and amoxicillin.The highest resistance rate was observed against gentamicin(86.36%),followed by polymyxin E(84.09%),quinupristin-dalfopristin(61.36%),and ceftazidime(36.36%).Some patients with diarrhea had C.difficile co-infections with other pathogens,including norovirus,adenovirus,rotavirus or Salmonella or Escherichia coli.Conclusion:C.difficile strains isolated from children under 5 years of age are mostly toxigenic,and the MLST results are highly diverse.Monitoring and prevention of C.difficile should be strengthened.
基金Joint Seismological Science Foundation of China (105076) and continued subject ″Statistic Features of Aftershock Sequences and Forecast of the Large Aftershocks″ (2004BA601B01-04-02), Ministry of Science and Technology of China in the 10th Five-Year Plan.
文摘Based on 294 earthquake sequences with magnitude greater than or equal to 5.0 occurred in Chinese mainland since 1970, the spatial distribution features of sequence types have been studied. In southwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in Chuan-Dian rhombic block and concerned Xianshuihe-Anninghe-Xiaojiang seismic belt, as well as in Jinshajiang-Honghe seismic belt. Multiple mainshock type （MMT） mainly distributes in western Yunnan, and Longlin and Lancang areas in Tengchong-Baoshan block in west of Nujiang-Lancangjiang fault zone. A few isolated earthquake type （IET） mainly occurred in northwestern Sichuan and there is no IET occurred in Yunnan region. In northwestern China, it takes mainshock-aftershock sequence type （MAT） as the major in west segment of South Tianshan in Xinjiang region. Some MMT also occurred in this area in the intersection of Kalpin block and the Puchang fault zone. It takes IET as the major in middle Tianshan in Xinjiang. Along the Qilianshan seismic belt, most of sequences are MAT. In Qinghai region, it takes MAT as the major, but the regional feature of the spatial distribution of sequence types is not very clear. In North China, it takes MAT as the major in Yinshan-Yanshan-Bohai seismic belt, north edge of North China, and in Hebei plain seismic belt, as well as in sub-plate of lower river area of Yangtze River. In intersection of north segment of Shanxi seismic belt and the NW-trending Yinshan-Yanshan-Bohai seismic belt, there are several moderate or strong MMT with magnitude from 5.0 to 6.0 occurred. In south of North China around the latitude line of 35°N, it takes IET as the major. The spatial distribution of sequence types is relevant to the patterns of tectonic movements. MAT is mostly produced by the ruptures of locked units or asperities or the neonatal separating segments inside the fault zones. MMT is generally relevant to the conjugate structures or intersection of many tectonic settings. Further extension of simple fault often produces IET. Spatial distribution of sequence types is also correlative to the regional and deep environment of crustal medium to some extent. MAT mainly distributes in high velocity area in upper crust or in the transition zone between high velocity area and low velocity area, MMT mostly occurred in the low velocity area in upper crust.
基金Supported by the National Natural Science Foundation of China,No.82160771NATCM's Project of High-Level Construction of Key TCM Disciplines:Traditional Medicine of Chinese Minority(Zhuang Medicine),No.zyyzdxk-2023165+7 种基金Guangxi One Thousand Young and Middle-Aged College and University Backbones Teachers Cultivation Program,No.[2019]5Guangxi Traditional Chinese Medicine Multidisciplinary Cross Innovation Team Project,No.GZKJ2309Guangxi Key R&D Plan Project,No.AB21196016Guangxi Key Discipline of Traditional Chinese Medicine Zhuang Pharmacy,No.GZXK-Z-20-64The First-Class Subject of Traditional Chinese Medicine(Ethnic Pharmacy)in Guangxi,No.[2018]12Guangxi Science and Technology Base and Talent Special Project,No.AD20238058 and No.AD21238031the Third Batch of Cultivating High-level Talent Teams in the“Qi Huang Project”of the Guangxi University of Chinese Medicine,No.202406and Huang Danian Style Teacher Team From Universities in Guangxi Zhuang Autonomous Region“Traditional Chinese Medicine Inheritance and Innovation Teacher Team”,No.[2023]31.
文摘AIM To investigate the material basis and mechanism underlying the therapeutic effect of DLC in T2DM.METHODS T2DM was triggered in rats using a high-sugar,high-fat diet alongside 35 mg/kg streptozotocin.The effect of DLC on the intestinal microbiota in T2DM rats was analyzed via 16S rDNA sequencing.Targeted metabolomics was conducted to evaluate the impact of DLC on the levels of nine short-chain fatty acids(SCFAs).Untargeted metabolomics examined DLC-induced alterations in fecal metabolites and associated metabolic pathways.Additionally,Spearman’s correlation analysis assessed gut microbiota and fecal metabolite relationships.RESULTS DLC significantly attenuated pathological weight loss,reduced fasting blood glucose levels,restored blood sugar homeostasis,and ameliorated dyslipidemia in T2DM rats.The 16S rDNA sequencing revealed that DLC enhanced microbial diversity and reversed intestinal dysbiosis.Targeted metabolomics indicated decreased acetic acid and propionic acid levels and increased butyric acid,isobutyric acid,and 2-methylbutyric acid levels after DLC treatment.Untargeted metabolomics revealed 57 metabolites with altered expression associated with amino acid,carbohydrate,purine,and biotin pathways.The Spearman analysis demonstrated significant links between specific gut microbiota taxa and fecal metabolites.CONCLUSION DLC may exert hypoglycemic effects by modulating intestinal flora genera,SCFA levels,and fecal metabolites.
基金Supported by the National Natural Science Foundation of China(11271161)
文摘In this paper, the complete convergence for the weighted sums of independent and identically distributed random variables in Stout [9] is improved and extended under NOD setup.The more optimal moment condition is given. The main results also hold for END sequence.
基金supported by the Teaching and Research Award Fund for Outstanding Young Teachers in Higher Educations of MOE,P.R.C.the National Natural Science Foundation of P.R.C.No.19801023
文摘In this paper, we investigate the problem of approximating solutions of the equations of Lipschitzian ψ-strongly accretive operators and fixed points of Lipschitzian ψ-hemicontractive operators by lshikawa type iterative sequences with errors. Our results unify, improve and extend the results obtained previously by several authors including Li and Liu (Acta Math. Sinica 41 (4)(1998), 845-850), and Osilike (Nonlinear Anal. TMA, 36(1)(1999), 1-9), and also answer completely the open problems mentioned by Chidume (J. Math. Anal. Appl. 151 (2)(1990), 453-461).
文摘In this paper, based on the results of tomographic image of Tangshan and Xingtai areas, the relations between thecharacteristics of the two strong earthquake sequences and their three-dimensional velocity structures are studied.The research results indicate that:① Mosaic distribution of low-velocity bodies and high-velocity bodies, especially the existence of high-velocity bodies with large size in crust are the common basis of development of thetwo earthquake sequences. ② Scale, depth, and heterogeneity of high-velocity and low-velocity bodies are theimportant factors to effect the characteristic of earthquake sequences. ③ The depth of the high-velocity body inTangshan area is less than that in Xingtai area, which is the principal reason why the dominant focal depth and thebiggest focal depth of Tangshan earthquake sequence are less than Xingtai's. ④ The depth of the high-velocitybodies in Ninghe area is more than that in Tangshan-Luanxian area, which lead to the biggest magnitude and epicentral intensity are lower. These results could be helpful for predicting the main shock of strong swarm-typeearthquakes and later strong aftershocks.
文摘The transcriptional factor GATA-6 gene produces two translational isoforms from a single mRNA through ribosomal leaky scanning. L-type GATA-6 has an extension of 146 amino acid residues at its amino terminus. In the extension, there is a unique PEST sequence (Glu31-Cys46), which is composed of an amino terminal Pro-rich segment and a carboxyl terminal Ser-cluster. Substitution of either half of the PEST sequence with Ala residues by cassette mutagenesis reduced the apparent molecular size of L-type GATA-6 on SDS-polyacrylamide gel-electrophoresis. However, the effect of substitution of the Pro-rich segment was much more significant;the mobility increase of the Pro-rich segment on the gel was 13% while that of the Ser-cluster was 8%. Substitution of each amino acid residue demonstrated that the effect of Pro substitution is greater than that of the Ser and Thr residues. Such increased mobility of L-type GATA-6 in the presence of a detergent may apparently correlate with the decrease in transcription activity in vivo as determined by means of luciferase reporter gene assay. The activity of ΔAla (with Ala residues instead of the PEST sequence) was reduced to one fifth of that of ΔA (with the PEST sequence). These results suggest that the PEST sequence of L-type GATA-6 does not function as a constitutive protein degradation signal, but rather plays structural and functional roles in the activation of gene expression on the GATA responsive promoter.
基金supported by the Creation and Talent Introduction Base of Prevention and Treatment of Diabetes and Its Complications withTraditional Chinese Medicine(B20055).
文摘Objective:To investigate the effects and potential mechanisms of action of Panax notoginseng(Burk)F.H.Chen(P.notoginseng,San Qi)flowers in type 2 diabetes mellitus(T2DM)using network pharmacology,in vivo experiments,and RNA sequencing(RNA-seq).Methods:Network pharmacology analysis was performed to identify and correlate the drug targets of flower buds of P.notoginseng(PNF)with T2DM disease targets and to predict the key targets and pathways involved in the therapeutic effects of PNF in T2DM.In vivo experiments were conducted to assess the effects of PNF on glucose and lipid metabolism in mice with T2DM.RNA-seq was performed,and the results were integrated with network pharmacology data to assess the therapeutic mechanisms of PNF in T2DM.The results from transcriptomics and network pharmacology were validated using real-time polymerase chain reaction.Results:A total of 27 intersecting targets were identified by overlapping 35 drug targets with T2DM targets.Further topological analysis using the Centiscape 2.2 tool revealed five core targets,including signal transducer and activator of transcription 3(STAT3).Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis indicated that the JAK/STAT signaling pathway is a key mechanism underlying the therapeutic effects of PNF in T2DM.In vivo experiments confirmed that PNF effectively regulates glycolipid metabolism in a mouse model of diabetes.KEGG pathway enrichment analysis of RNA-seq data highlighted the JAK2/STAT3 and PI3K/AKT pathway as a potential mechanism.PNF high-dose(PNFH)increased the gene expression levels of PIK3R1 and AKT2,decreased the expression of PCK1,JAK2,and STAT3,and showed a trend toward increasing INSR expression without reaching statistical significance.Conclusion:PNF improves glycolipid metabolism disorders in T2DM,potentially by modulating the JAK2/STAT3 and PI3K/AKT signaling pathway.
文摘高等院校作为国家科技人才孵化及汇集的重要场所,肩负着为国育人、为党育才的使命。运用科学、技术与社会(Science,Technology and Society)跨学科的教学和实践活动探索地方应用型高校培养创新科技人才的新途径,能使学生在理解科学和技术的基础上更好地应对社会问题和挑战。在STS教育理念下,可以通过以下措施进一步探索和实践科技创新人才培养路径:优化专业结构,完善专业动态调整机制,提高专业办学与经济社会发展的契合度;完善“平台+模块”的课程建设架构,创新实践教学体系;建立协同育人机制,加强师资队伍建设;深化拔尖人才培养模式改革,完善教学评价制度。
基金ThestudyisjointlysupportedbyNationalNaturalScienceFoundationofChina (No .4980 2 0 1 2 )andMinistryofSciencesandTechnology (SSER
文摘Different genetic types of meter-scale cyclic sequences in stratigraphic records result from episodic accumulation of strata related to Milankovitch cycles. The distinctive fabric natures of facies succession result from the sedimentation governed by different sediment sources and sedimentary dynamic conditions in different paleogeographical backgrounds, corresponding to high-frequency sea-level changes. Naturally, this is the fundamental criterion for the classification of genetic types of meter-scale cyclic sequences. The widespread development in stratigraphic records and the regular vertical stacking patterns in long-term sequences, the evolution characters of earth history and the genetic types reflected by specific fabric natures of facies successions in different paleogeographical settings, all that show meter-scale cyclic sequences are not only the elementary working units in stratigraphy and sedimentology, but also the replenishment and extension of parasequence of sequence stratigraphy. Two genetic kinds of facies succession for meter-scale cyclic sequence in neritic-facies strata of carbonate and clastic rocks, are normal grading succession mainly formed by tidal sedimentation and inverse grading succession chiefly made by wave sedimentation, and both of them constitute generally shallowing upward succession, the thickness of which ranges from several tens of centimeters to several meters. The classification of genetic types of meter-scale cyclic sequence could be made in terms of the fabric natures of facies succession, and carbonate meter-scale cyclic sequences could be divided into four types: L-M type, deep-water asymmetrical type, subtidal type and peritidal type. Clastic meter-scale cyclic sequences could be grouped into two types: tidal-dynamic type and wave-dynamic type. The boundaries of meter-scale cyclic sequences are marked by instantaneous punctuated surface formed by non-deposition resulting from high-frequency level changes, which include instantaneous exposed punctuated surface, drowned punctuated surface as well as their relative surface. The development of instantaneous punctuated surface used as the boundary of meter-scale cyclic sequence brings about the limitations of Walter's Law on the explanation of facies distribution in time and space, and reaffirm the importance of Sander's Rule on analysis of stratigraphic records. These non-continuous surface could be traced for long distance and some could be correlative within same basin range. The study of meter-scale cyclic sequences and their regularly vertical stacking patterns in long-term sequences indicate that the research into cyclicity of stratigraphic records is a useful way to get more regularity from stratigraphic records that are frequently complex as well as non-integrated.
基金This work was supported by the grants from the Special Project of Ministry of Health (No.201302009)and the National Natural Science Foundation of China (No. 81700300).
文摘Primary hyperoxaluria type 1(PH1)is a rare but devastating autosomal recessive inherited disease caused by mutations in gene AGXT.Pathogenic mutations of AGXT were mostly reported in Caucasian but infrequently in Asian,especially in Chinese.To update the genotypes of PH1 in the Chinese population,we collected and identified 7 Chinese probands with PH1 from 2013 to 2017 in our center,five of whom had delayed diagnosis and failed in kidney transplantation.Samples of peripheral blood DNA from the 7 patients and their family members were collected and sequencing analysis was performed to test the mutations of gene AGXT.Western blotting and enzyme activity analysis were conducted to evaluate the function of the mutations.Furthermore,a systematic review from 1998 to 2017 was performed to observe the genetic characteristics between Chinese and Caucasian. The results showed that a total of 12 mutations were identified in the 7 pedigrees.To the best of ourknowledge,2 novel variants of A GXT,p.Gly41 Trp and p.Leu33Met,were first reported.Bioinformatics and functional analysis showed that only 7 mutations led to a reduced expression of alanine-glyoxylate amino transferase (AGT)at a protein level.The systematic review revealed significant population heterogeneity in PH1.In conclusion,new genetic subtypes and genetic characteristics of PH1 are updated in the Chinese population. Furthermore,a genotype-phenotype correlation is found in PH1.
