BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to invest...BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.展开更多
miRNAs regulate a variety of biological processes through pairing-based regulation of gene expression at the 3＇ end of the noncoding region of the target miRNA, miRNAs were found to be abnormally expressed in ischemi...miRNAs regulate a variety of biological processes through pairing-based regulation of gene expression at the 3＇ end of the noncoding region of the target miRNA, miRNAs were found to be abnormally expressed in ischemia/reperfusion injury models. High-throughput sequencing is a recently developed method for sequencing miRNAs and has been widely used in the analysis of miRNAs. In this study, ischemia/reperfusion injury models were intracerebroventricularly injected with 50 pg/kg apelin-13. High-throughput sequencing showed that 357 known miRNAs were differentially expressed among rat models, among which 78 changed to 〉 2-fold or 〈 0.5-fold. Quantita- tive real-time polymerase chain reaction was selected to confirm the expression levels of four miRNAs that were differentially expressed, the results of which were consistent with the results of high-throughput sequencing. Gene Ontology analysis revealed that the predicted targets of the different miRNAs are particularly associated with cellular process, metabolic process, single-organism process, cell, and binding. Kyoto Encyclopedia of Gene and Genome analysis showed that the target genes are involved in metabolic pathways, mitogen-ac- tivated protein kinase signaling pathway, calcium signaling pathway, and nuclear factor-KB signaling pathway. Our findings suggest that differentially expressed miRNAs and their target genes play an important role in ischemia/reperfusion injury and neuroprotection by apelin-13.展开更多
Although genome-wide association studies are widely used to mine genes for quantitative traits,the effects to be estimated are confounded,and the methodologies for detecting interactions are imperfect.To address these...Although genome-wide association studies are widely used to mine genes for quantitative traits,the effects to be estimated are confounded,and the methodologies for detecting interactions are imperfect.To address these issues,the mixed model proposed here first estimates the genotypic effects for AA,Aa,and aa,and the genotypic polygenic background replaces additive and dominance polygenic backgrounds.Then,the estimated genotypic effects are partitioned into additive and dominance effects using a one-way analysis of variance model.This strategy was further expanded to cover QTN-by-environment interactions(QEIs)and QTN-by-QTN interactions(QQIs)using the same mixed-model framework.Thus,a three-variance-component mixed model was integrated with our multi-locus random-SNP-effect mixed linear model(mrMLM)method to establish a new methodological framework,3VmrMLM,that detects all types of loci and estimates their effects.In Monte Carlo studies,3VmrMLM correctly detected all types of loci and almost unbiasedly estimated their effects,with high powers and accuracies and a low false positive rate.In re-analyses of 10 traits in 1439 rice hybrids,detection of 269 known genes,45 known gene-by-environment interactions,and 20 known gene-by-gene interactions strongly validated 3VmrMLM.Further analyses of known genes showed more small(67.49%),minor-allele-frequency(35.52%),and pleiotropic(30.54%)genes,with higher repeatability across datasets(54.36%)and more dominance loci.In addition,a heteroscedasticity mixed model in multiple environments and dimension reduction methods in quite a number of environments were developed to detect QEIs,and variable selection under a polygenic background was proposed for QQI detection.This study provides a new approach for revealing the genetic architecture of quantitative traits.展开更多
Inmost existingmethods and softwares of genome-wide association studies(GWAS)fordetecting quantitative trait nucleotides(QTNs),QTN-by-environment interactions(QEls),and QTN-by-QTN interactions(QQIs),only the allele su...Inmost existingmethods and softwares of genome-wide association studies(GWAS)fordetecting quantitative trait nucleotides(QTNs),QTN-by-environment interactions(QEls),and QTN-by-QTN interactions(QQIs),only the allele substitution effect and its interaction-related effects are detected and estimated,conditional on method-specific polygenic background control,leading to confounding in effect estimation and insufficient polygenic background control(Li et al.,2022;Supplemental Tables 1-3).展开更多
Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a-4J were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited high...Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a-4J were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, the most phototoxic compound 4d and 4j individually showed ICso values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength （λmax 〉 650 nm）, high phototoxicitv, low dark cvtotoxicitv and ~ood water-solubility.展开更多
基金Supported by National Natural Science Foundation of China(General Program),No.82070631.
文摘BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.
基金supported by the National Natural Science Foundation of China,No.81501018 and 816712276the Natural Science Foundation of Shandong Province of China,No.ZR2013CQ031 and ZR2014HL040
文摘miRNAs regulate a variety of biological processes through pairing-based regulation of gene expression at the 3＇ end of the noncoding region of the target miRNA, miRNAs were found to be abnormally expressed in ischemia/reperfusion injury models. High-throughput sequencing is a recently developed method for sequencing miRNAs and has been widely used in the analysis of miRNAs. In this study, ischemia/reperfusion injury models were intracerebroventricularly injected with 50 pg/kg apelin-13. High-throughput sequencing showed that 357 known miRNAs were differentially expressed among rat models, among which 78 changed to 〉 2-fold or 〈 0.5-fold. Quantita- tive real-time polymerase chain reaction was selected to confirm the expression levels of four miRNAs that were differentially expressed, the results of which were consistent with the results of high-throughput sequencing. Gene Ontology analysis revealed that the predicted targets of the different miRNAs are particularly associated with cellular process, metabolic process, single-organism process, cell, and binding. Kyoto Encyclopedia of Gene and Genome analysis showed that the target genes are involved in metabolic pathways, mitogen-ac- tivated protein kinase signaling pathway, calcium signaling pathway, and nuclear factor-KB signaling pathway. Our findings suggest that differentially expressed miRNAs and their target genes play an important role in ischemia/reperfusion injury and neuroprotection by apelin-13.
基金supported by the National Natural Science Foundation of China(32070557 and 31871242)the Fundamental Research Funds for the Central Universities(2662020ZKPY017)+1 种基金the Huazhong Agricultural University Scientific&Technological Self-Innovation Foundation(2014RC020)the State Key Laboratory of Cotton Biology Open Fund(CB2021B01).
文摘Although genome-wide association studies are widely used to mine genes for quantitative traits,the effects to be estimated are confounded,and the methodologies for detecting interactions are imperfect.To address these issues,the mixed model proposed here first estimates the genotypic effects for AA,Aa,and aa,and the genotypic polygenic background replaces additive and dominance polygenic backgrounds.Then,the estimated genotypic effects are partitioned into additive and dominance effects using a one-way analysis of variance model.This strategy was further expanded to cover QTN-by-environment interactions(QEIs)and QTN-by-QTN interactions(QQIs)using the same mixed-model framework.Thus,a three-variance-component mixed model was integrated with our multi-locus random-SNP-effect mixed linear model(mrMLM)method to establish a new methodological framework,3VmrMLM,that detects all types of loci and estimates their effects.In Monte Carlo studies,3VmrMLM correctly detected all types of loci and almost unbiasedly estimated their effects,with high powers and accuracies and a low false positive rate.In re-analyses of 10 traits in 1439 rice hybrids,detection of 269 known genes,45 known gene-by-environment interactions,and 20 known gene-by-gene interactions strongly validated 3VmrMLM.Further analyses of known genes showed more small(67.49%),minor-allele-frequency(35.52%),and pleiotropic(30.54%)genes,with higher repeatability across datasets(54.36%)and more dominance loci.In addition,a heteroscedasticity mixed model in multiple environments and dimension reduction methods in quite a number of environments were developed to detect QEIs,and variable selection under a polygenic background was proposed for QQI detection.This study provides a new approach for revealing the genetic architecture of quantitative traits.
基金This work was supported by the National Natural Science Foundation of China(32070557,31871242)the Huazhong Agricultural University Scientific&Technological Self-InnovationFoundation(2014RC020).
文摘Inmost existingmethods and softwares of genome-wide association studies(GWAS)fordetecting quantitative trait nucleotides(QTNs),QTN-by-environment interactions(QEls),and QTN-by-QTN interactions(QQIs),only the allele substitution effect and its interaction-related effects are detected and estimated,conditional on method-specific polygenic background control,leading to confounding in effect estimation and insufficient polygenic background control(Li et al.,2022;Supplemental Tables 1-3).
基金supported by the National Natural Science Foundation of China (No. 81172950)the Project of Science and Technology Commission of Shanghai (Nos. 11431920401 and 11430723201)
文摘Ten new water-soluble amino acid conjugates of pyropheophorbide-a ethers 4a-4J were synthesized and investigated for their in vitro photodynamic antitumor activity. The results showed that all compounds exhibited higher phototoxicity and lower dark toxicity against three kinds of tumor cell lines than BPD-MA. In particular, the most phototoxic compound 4d and 4j individually showed ICso values of 41 nmol/L and 33 nmol/L against HCT116 cell, which represented 7.8- and 9.7-fold increase of antitumor potency compared to BPD-MA, respectively, suggesting that they were promising photosensitizers for PDT applications because of their strong absorption at long wavelength （λmax 〉 650 nm）, high phototoxicitv, low dark cvtotoxicitv and ~ood water-solubility.
