Objective: The objective of this study is to construct the simulated patient training curriculum for OSCE examination for undergraduate nursing students and to explore the theoretical and practical foundation. Methods...Objective: The objective of this study is to construct the simulated patient training curriculum for OSCE examination for undergraduate nursing students and to explore the theoretical and practical foundation. Methods: To establish TSP training curriculum and SSP training curriculum, 30 experts were invited to finish the questionnaires which were proved by Delphi Method. Findings: We established the training curriculum of TSP and SSP, and set the weight of various curricula and teaching contents. Conclusions: The experts considered that the degree and importance of these two training curricula were comparable. This conclusion lays the foundation for applying these curricula to teaching practice and clinical practice, and enhancing the teaching outcome of undergraduate nursing students. Implications: This study provided a new way of assessing the clinic ability of nursing students.展开更多
Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent stud...Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent studies have also indicated a tumor-suppressive role of PKCs via unclear molecular mechanisms.In this study,we found that PKCαinhibition enhances CD8+T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice.We further identified PKCαas a critical regulator of programmed cell death-ligand 1(PD-L1)and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression.We demonstrated that PKCα-mediated PD-L1 phosphorylation promotes PD-L1 degradation throughβtransducin repeat-containing protein.Notably,the efficacy of PKCαinhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity in vivo.Clinical analysis revealed that PKCαexpression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer.This study demonstrated the antitumor capability of PKCα,identified potential therapeutic strategies to avoid tumor evasion via PKC-targeted therapies,and provided a proof of concept for targeting PKCαin combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer,especially TNBC.展开更多
Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and ident...Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(SacSaccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUB1 depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,providing a new therapeutic strategy for treating metastatic CRC through targeting SUB1.展开更多
Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males.Immune-checkpoint inhibitors(ICIs)that target programmed cell death protein-1(PD-1)or programmed cell death-ligan...Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males.Immune-checkpoint inhibitors(ICIs)that target programmed cell death protein-1(PD-1)or programmed cell death-ligand 1(PD-L1)have achieved impressive efficacy in the treatment of non-small-cell lung cancer(NSCLC)(Pardoll,2012;Champiat et al.,2016;Gao et al.,2022).Although ICIs are usually well tolerated,they are often accompanied by immune-related adverse events(irAEs)(Doroshow et al.,2019).Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system(O'Kane et al.,2017;Puzanov et al.,2017).展开更多
Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even contradic-tory.Multi-dimensional analyses are required to comprehensively elucidate its value and underlyi...Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even contradic-tory.Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.Methods:We collected 49 RNA-seq datasets,40 cell line types data and 70 scRNA pan-cancer datasets public available,including 17 HCC datasets(1754 tumor samples),and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics.APOA1 impacting on the HCC tumor microenvironment(TME)was analyzed using intensive data mining.Methylation sequencing,flow cy-tometry,quantitative PCR,western blot,immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.Results:The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC,primarily involved in choles-terol efflux.Consistent findings at histology,serology,and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCc.Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC.The cell cycle,DNA replication,mismatch repair pathways,and tumor cell proliferation were less observed in the HCC APOAihigh subgroup.The favorable immunoregulatory abilities of APOA1 showed interesting findings:a positive correlation between APOA1 and anti-tumor immune cells(NK,CD8+T cells)and a negative association with immune cells exerting immunosuppressive effects,including M2 macrophages.Conclusion:This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments.Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinicai target for HCC assessment and intervention in the future.展开更多
The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for hi...The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose （FPG） levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects （1027 men, and 2433 women, aged 35-75 years old） who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose （IFG） was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels （lowest tertiles, FPG： 5.376 ± 0.018; middle tertiles, 5.324± 0.018; highest tertiles, 5.276±0.018mmol/L; P = 0.001）. Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level （OR： 1.75; 95% CI： 1.20-2.56）. In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.展开更多
Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inheri...Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inherited risk component to SCD.Signal transducer and activators of transcription 5 A(STAT5A)is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes.In this study,we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations.Based on the screening results,an insertion/deletion polymorphism(rs3833144)in 3’UTR of STAT5A was selected as the candidate variant.A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations.Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk(odds ratio(OR)=1.54;95%confidence interval(CI)=1.18-2.01;P=0.000955).Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A,and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant.On the other hand,the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144,and eQTL analysis showed the higher expression of both genes in samples with deletion allele.Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription.Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.展开更多
A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An i...A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An intriguing chemoselective dearomative hydroarylation of 2-phenyl indoles is presented.Th dearomative hydroarylation protocol rapidly delivers valuable spirocycles with carbon-carbon doub bonds from readily accessible aromatic precursors in a single step.展开更多
Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this ...Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this study,we developed a six-dye multiplex typing system consisting of 34 autosomal InDels and Amelogenin for forensic application.The contained InDels were specifically selected for Chinese population with the MAF≥0.25 in East Asia,which do not overlap with the markers of Investigator^(■)DIPplex kit.The typing system was named as GoldeneyeTM DNA ID System 35InDel Kit,and a series of developmental validation studies including repeatability/reproducibility,concordance,accuracy,sensitivity,stability,species specificity and population genetics were conducted on this kit.We confirmed that the 35InDel kit is precise,sensitive,species specific and robust for forensic practice.Moreover,the 35InDel kit is capable of typing DNA extracted from forensic routine case-type samples as well as degraded samples and mixture samples.All markers are proved to be highly polymorphic with an average observed heterozygosity(He)of 0.4582.The combined power of discrimination(CPD)is 0.999999999999978 and the combined power of exclusion in duos(CPE_(D))and trios(CPE_(T))are 0.978837 and 0.999573,respectively,which are higher than those of the Investigator^(■)DIPplex kit.Thus,the GoldeneyeTM DNA ID System 35InDel kit is suitable for forensic human identification and could serve as a supplementary typing system for paternity testing.展开更多
Sudden cardiac death(SCD)is defined as an unexpected natural death without any obvious non-cardiac causes that occurs within 1 h with witnessed symptom onset or within 24 h without witnessed symptom onset.Genetic stud...Sudden cardiac death(SCD)is defined as an unexpected natural death without any obvious non-cardiac causes that occurs within 1 h with witnessed symptom onset or within 24 h without witnessed symptom onset.Genetic studies conducted during the past decade have markedly illuminated the genetic basis of the cardiac disorders associated with SCD.Macrophage migration inhibitory factor(MIF)is an upstream immunoregulatory cytokine associated with the pathogenesis of many inflammatory diseases including atherosclerosis and myocardial infarction.Previous studies have reported that the functional -794(CATT)_(5-8) polymorphism in MIF is unrelated to sudden infant deth syndrome susceptibility.However,there are no reports concerning the association between the polymorphism and adult SCD susceptibility.In the current study,we investigated the association between the-794(CATT)_(5-8) polymorphism and adult SCD susceptibility using 79 adult SCD cases and 313 healthy controls.All samples were analysed using a conventional polymerase chain reaction(PCR)technique.We found that CATT_(6) and 5-6 were the most common allele and genotype in both groups,respectively,while no significant association was found between the-794(CATT)_(5-8) polymorphism and SCD susceptibility.We also summarized the allele frequencies of 794(CATT)_(5-8) in cohorts of healthy people from different countries and found that the allele frequency distributions of the polymorphism in Chinese populations were quite different from that of American and European populations(P=0.005,P=0.0001,respectively),but similar to Japanese populations(P=0.827).In conclusion,this study indicates that the-794(CATT)_(5-8) polymorphism may not be associated with adult SCD susceptibility in Chinese populations.Different allele frequency distributions of the polymorphism in multiple populations may provide a useful reference for further genetic association studies.展开更多
The custom-designed single nucleotide polymorphism(SNP)panel amplified 231 autosomal SNPs in one PCR reaction and subsequently sequenced with massively parallel sequencing(MPS)technology and Ion Torrent personal genom...The custom-designed single nucleotide polymorphism(SNP)panel amplified 231 autosomal SNPs in one PCR reaction and subsequently sequenced with massively parallel sequencing(MPS)technology and Ion Torrent personal genome machine(PGM).SNPs were chosen from SNPforID,IISNP,HapMap,dbSNP,and related published literatures.Full concordance was obtained between available MPS calling and Sanger sequencing with 9947A and 9948 controls.Ten SNPs(rs4606077,rs334355,rs430046,rs2920816,rs4530059,rs1478829,rs1498553,rs7141285,rs12714757 and rs2189011)with low coverage or heterozygote imbalance should be optimized or excluded from the panel.Sequence data had sufficiently high coverage and gave reliable SNP calling for the remaining 221 loci with the custom MPS-SNP panel.A default DNA input amount of 10 ng per reaction was recommended by Ampliseq technology but sensitivity testing revealed positive results from as little as 1 ng input DNA.Mixture testing with this panel is possible through analysis of the F MAR(frequency of major allele reads)values at most loci with enough high coverage depth and low level of sequencing noise.These results indicate the potential advantage of the custom MPS-SNP assays and Ion Torrent PGM platform for forensic study.展开更多
Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizat...Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizative remote arylcarboxylation of nonactivated arenes including naphthalenyl-and phenyl-bearing aromatics with CO_(2) under mild conditions through a radical-polar crossover cascade(RPCC).This reductive dearomatization protocol rapidly delivers a broad range of spirocyclic and valuable carboxylic acid derivatives from readily accessible aromatic precursors with generally good regioselectivity and chemoselectivity.展开更多
文摘Objective: The objective of this study is to construct the simulated patient training curriculum for OSCE examination for undergraduate nursing students and to explore the theoretical and practical foundation. Methods: To establish TSP training curriculum and SSP training curriculum, 30 experts were invited to finish the questionnaires which were proved by Delphi Method. Findings: We established the training curriculum of TSP and SSP, and set the weight of various curricula and teaching contents. Conclusions: The experts considered that the degree and importance of these two training curricula were comparable. This conclusion lays the foundation for applying these curricula to teaching practice and clinical practice, and enhancing the teaching outcome of undergraduate nursing students. Implications: This study provided a new way of assessing the clinic ability of nursing students.
基金supported by grants from the National Natural Science Foundation of China(82173853,82173379,82373914,82073892)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-2-002,2021-I2M-1e026 and 2021-I2M-1e016,China)+2 种基金CAMS Central Public-interest Scientific Institution Basal Research Fund(2018PT35004,China)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China)Peking Union Medical College Graduate Innovation Fund(2019-1007-05,China).
文摘Protein kinase Cα(PKCα)regulates diverse biological functions of cancer cells and is a promising therapeutic target.However,clinical trials of PKC-targeted therapies have not yielded satisfactory results.Recent studies have also indicated a tumor-suppressive role of PKCs via unclear molecular mechanisms.In this study,we found that PKCαinhibition enhances CD8+T-cell-mediated tumor evasion and abolishes antitumor activity in immunocompetent mice.We further identified PKCαas a critical regulator of programmed cell death-ligand 1(PD-L1)and found that it enhances T-cell-dependent antitumor immunity in breast cancer by interacting with PD-L1 and suppressing PD-L1 expression.We demonstrated that PKCα-mediated PD-L1 phosphorylation promotes PD-L1 degradation throughβtransducin repeat-containing protein.Notably,the efficacy of PKCαinhibitors was intensified by synergizing with anti-PD-L1 mAb therapy to boost antitumor T-cell immunity in vivo.Clinical analysis revealed that PKCαexpression is positively correlated with T-cell function and the interferon-gamma signature in patients with breast cancer.This study demonstrated the antitumor capability of PKCα,identified potential therapeutic strategies to avoid tumor evasion via PKC-targeted therapies,and provided a proof of concept for targeting PKCαin combination with anti-PD-L1 mAb therapy as a potential therapeutic approach against breast cancer,especially TNBC.
基金supported by the National Natural Science Foundation of China(82073229,82072623)。
文摘Metastasis accounts for the major cause of colorectal cancer(CRC)related mortality due to the lack of effective treatments.In this study,we integrated the single-cell RNA-seq(sc RNA-seq)and bulk RNA-seq data and identified the transcriptional coactivator SUB1 homolog(SacSaccharomyces cerevisiae)/PC4(positive cofactor 4)associated with CRC metastasis.Elevated SUB1 expression was correlated with advanced tumor stage and poor survival in CRC.In vivo and vitro assays showed that SUB1 depletion could inhibit the invasive and metastatic abilities of CRC cells.SUB1 activated NF-κB signaling and its transcriptional target genes CXCL1 and CXCL3 to drive CRC metastasis.Mechanistically,SUB1 integrated with the E3 ubiquitin-protein ligase UBR5 and increased its protein level in CRC cells.Subsequently,the increased UBR5mainly mediated Lys11-linked polyubiquitination and degradation of NF-κB negative regulator UBXN1,thus to activate the NF-κB signaling.Overall,our study demonstrated that SUB1 promoted CRC progression by modulating UBR5/UBXN1 and activating NF-κB signaling,providing a new therapeutic strategy for treating metastatic CRC through targeting SUB1.
文摘Lung cancer remains the leading cause of cancer deaths worldwide and is the most common cancer in males.Immune-checkpoint inhibitors(ICIs)that target programmed cell death protein-1(PD-1)or programmed cell death-ligand 1(PD-L1)have achieved impressive efficacy in the treatment of non-small-cell lung cancer(NSCLC)(Pardoll,2012;Champiat et al.,2016;Gao et al.,2022).Although ICIs are usually well tolerated,they are often accompanied by immune-related adverse events(irAEs)(Doroshow et al.,2019).Non-specific activation of the immune system produces off-target immune and inflammatory responses that can affect virtually any organ or system(O'Kane et al.,2017;Puzanov et al.,2017).
基金The studies involving human participants were reviewed and approved by the Institutional Ethics Committee of the leading medical center(Shanghai Easterm Hepatobiliary Surgery Hospital,EHBHKY2020-02-012).
文摘Background:Current knowledge on apolipoprotein A1(APOA1)in hepatocellular carcinoma(HCC)is fragmented and even contradic-tory.Multi-dimensional analyses are required to comprehensively elucidate its value and underlying mechanism.Methods:We collected 49 RNA-seq datasets,40 cell line types data and 70 scRNA pan-cancer datasets public available,including 17 HCC datasets(1754 tumor samples),and enrolled 73 pairs of HCC tissue and 516 blood samples independently from our clinics.APOA1 impacting on the HCC tumor microenvironment(TME)was analyzed using intensive data mining.Methylation sequencing,flow cy-tometry,quantitative PCR,western blot,immunohistochemistry and clinical chemistry assays were conducted for wet experimental investigation.Results:The APOA1 ontology fingerprint indicated that it played various crucial biological roles in HCC,primarily involved in choles-terol efflux.Consistent findings at histology,serology,and clinical follow-up revealed that high APOA1 was a good prognosis indicator of HCc.Hypermethylation in the APOA1 promoter region was found in clinical samples which is in accordance with the reduction of APOA1 in HCC.The cell cycle,DNA replication,mismatch repair pathways,and tumor cell proliferation were less observed in the HCC APOAihigh subgroup.The favorable immunoregulatory abilities of APOA1 showed interesting findings:a positive correlation between APOA1 and anti-tumor immune cells(NK,CD8+T cells)and a negative association with immune cells exerting immunosuppressive effects,including M2 macrophages.Conclusion:This is an integrative multidimensional exploration of APOA1 using bioinformatics and experiments.Both the prognostic value and anti-tumor effects based on APOA1 panoramic exploration in the HCC TME demonstrate a new potential clinicai target for HCC assessment and intervention in the future.
文摘The association between dyslipidemia and elevated fasting glucose in type 2 diabetes is well known. In non-diabetes, whether this association still exists, and whether dyslipidemia is an independent risk factor for high fasting plasma glucose （FPG） levels are not clear. This cross-sectional study recruited 3460 non-diabetic Chinese subjects （1027 men, and 2433 women, aged 35-75 years old） who participated in a health survey. Men and women were classified into tertiles by levels of plasma lipids respectively. In women, the prevalence of impaired fasting glucose （IFG） was decreased with increased HDL-C. A stepwise increase in HDL-C was associated with decreasing FPG levels （lowest tertiles, FPG： 5.376 ± 0.018; middle tertiles, 5.324± 0.018; highest tertiles, 5.276±0.018mmol/L; P = 0.001）. Reversely, FPG levels increased from lowest tertiles to highest tertiles of LDL-C, TC, and TG. we found that women in the first tertile with lower HDL-C level had a 1.75-fold increase in risk of IFG compared with non-diabetic women in the third tertile with higher HDL-C level （OR： 1.75; 95% CI： 1.20-2.56）. In men, no significant association was found. We took age, BMI, waist/hip ratio, education, smoking, alcohol drinking, and physical exercise as adjusted variables. In Chinese non-diabetic women, dyslipidemia is independently associated with high levels of FPG; TG, HDL-C, and LDL-C are predictors of IFG independent of BMI and waist/hip ratio.
基金This study was funded by National Natural Science Foundation of China[grant numbers 81772029 and 81572767]Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inherited risk component to SCD.Signal transducer and activators of transcription 5 A(STAT5A)is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes.In this study,we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations.Based on the screening results,an insertion/deletion polymorphism(rs3833144)in 3’UTR of STAT5A was selected as the candidate variant.A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations.Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk(odds ratio(OR)=1.54;95%confidence interval(CI)=1.18-2.01;P=0.000955).Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A,and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant.On the other hand,the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144,and eQTL analysis showed the higher expression of both genes in samples with deletion allele.Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription.Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.
基金the financial supports from the National Natural Science Foundation of China(Nos.22022111,21871257,21801240)the Natural Science Foundation of Fujian Province(No.2020J02008)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB20000000)。
文摘A visible-light-induced spirocyclizative hydroarylation via reductive dearomatization of a series of non activated arenes including 2-phenyl indoles and naphthalene derivatives under mild conditions is de scribed.An intriguing chemoselective dearomative hydroarylation of 2-phenyl indoles is presented.Th dearomative hydroarylation protocol rapidly delivers valuable spirocycles with carbon-carbon doub bonds from readily accessible aromatic precursors in a single step.
基金This study was supported by grants from the National Youth Top-Notch Talent of Ten Thousand Program[grant number WRQB2019]the Youth Science and Technology Innovation Leader of Ten Thousand Program[grant number 2018RA2102],China.
文摘Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this study,we developed a six-dye multiplex typing system consisting of 34 autosomal InDels and Amelogenin for forensic application.The contained InDels were specifically selected for Chinese population with the MAF≥0.25 in East Asia,which do not overlap with the markers of Investigator^(■)DIPplex kit.The typing system was named as GoldeneyeTM DNA ID System 35InDel Kit,and a series of developmental validation studies including repeatability/reproducibility,concordance,accuracy,sensitivity,stability,species specificity and population genetics were conducted on this kit.We confirmed that the 35InDel kit is precise,sensitive,species specific and robust for forensic practice.Moreover,the 35InDel kit is capable of typing DNA extracted from forensic routine case-type samples as well as degraded samples and mixture samples.All markers are proved to be highly polymorphic with an average observed heterozygosity(He)of 0.4582.The combined power of discrimination(CPD)is 0.999999999999978 and the combined power of exclusion in duos(CPE_(D))and trios(CPE_(T))are 0.978837 and 0.999573,respectively,which are higher than those of the Investigator^(■)DIPplex kit.Thus,the GoldeneyeTM DNA ID System 35InDel kit is suitable for forensic human identification and could serve as a supplementary typing system for paternity testing.
基金The Natural Science Foundation of China[grant numbers 81572767,81502431,81172898 and 81571848]Priority Aca-demic Program Development of Jiangsu Higher Education Institutions.
文摘Sudden cardiac death(SCD)is defined as an unexpected natural death without any obvious non-cardiac causes that occurs within 1 h with witnessed symptom onset or within 24 h without witnessed symptom onset.Genetic studies conducted during the past decade have markedly illuminated the genetic basis of the cardiac disorders associated with SCD.Macrophage migration inhibitory factor(MIF)is an upstream immunoregulatory cytokine associated with the pathogenesis of many inflammatory diseases including atherosclerosis and myocardial infarction.Previous studies have reported that the functional -794(CATT)_(5-8) polymorphism in MIF is unrelated to sudden infant deth syndrome susceptibility.However,there are no reports concerning the association between the polymorphism and adult SCD susceptibility.In the current study,we investigated the association between the-794(CATT)_(5-8) polymorphism and adult SCD susceptibility using 79 adult SCD cases and 313 healthy controls.All samples were analysed using a conventional polymerase chain reaction(PCR)technique.We found that CATT_(6) and 5-6 were the most common allele and genotype in both groups,respectively,while no significant association was found between the-794(CATT)_(5-8) polymorphism and SCD susceptibility.We also summarized the allele frequencies of 794(CATT)_(5-8) in cohorts of healthy people from different countries and found that the allele frequency distributions of the polymorphism in Chinese populations were quite different from that of American and European populations(P=0.005,P=0.0001,respectively),but similar to Japanese populations(P=0.827).In conclusion,this study indicates that the-794(CATT)_(5-8) polymorphism may not be associated with adult SCD susceptibility in Chinese populations.Different allele frequency distributions of the polymorphism in multiple populations may provide a useful reference for further genetic association studies.
基金supported by grants from the National Natu-ral Science Foundation of China[grant number 81330073],[grant number 81302620]the Ministry of Science and Technology of China[grant number 2016YFC0800703]the Science and Technology Commission of Shanghai Municipality[grant number 14DZ2270800].
文摘The custom-designed single nucleotide polymorphism(SNP)panel amplified 231 autosomal SNPs in one PCR reaction and subsequently sequenced with massively parallel sequencing(MPS)technology and Ion Torrent personal genome machine(PGM).SNPs were chosen from SNPforID,IISNP,HapMap,dbSNP,and related published literatures.Full concordance was obtained between available MPS calling and Sanger sequencing with 9947A and 9948 controls.Ten SNPs(rs4606077,rs334355,rs430046,rs2920816,rs4530059,rs1478829,rs1498553,rs7141285,rs12714757 and rs2189011)with low coverage or heterozygote imbalance should be optimized or excluded from the panel.Sequence data had sufficiently high coverage and gave reliable SNP calling for the remaining 221 loci with the custom MPS-SNP panel.A default DNA input amount of 10 ng per reaction was recommended by Ampliseq technology but sensitivity testing revealed positive results from as little as 1 ng input DNA.Mixture testing with this panel is possible through analysis of the F MAR(frequency of major allele reads)values at most loci with enough high coverage depth and low level of sequencing noise.These results indicate the potential advantage of the custom MPS-SNP assays and Ion Torrent PGM platform for forensic study.
基金the financial support from NSFC(grant nos.21871257,22022111,and 21801240)the Natural Science Foundation of Fujian Province(grant no.2020J02008)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB20000000).
文摘Visible-light-induced reductive dearomatization of nonactivated arenes is a very challenging transformation and remains in its infancy.Herein,we report a novel strategy to achieve a visible-light-induced spirocyclizative remote arylcarboxylation of nonactivated arenes including naphthalenyl-and phenyl-bearing aromatics with CO_(2) under mild conditions through a radical-polar crossover cascade(RPCC).This reductive dearomatization protocol rapidly delivers a broad range of spirocyclic and valuable carboxylic acid derivatives from readily accessible aromatic precursors with generally good regioselectivity and chemoselectivity.
