Objective The present study aimed to estimate the association between susceptibility to migraine and the 12nucleotide insertion/deletion （indel） polymorphism in promoter region ofα 2B -adrenergic receptor gene （AD...Objective The present study aimed to estimate the association between susceptibility to migraine and the 12nucleotide insertion/deletion （indel） polymorphism in promoter region ofα 2B -adrenergic receptor gene （ADRA2B）.Methods A case-control study was carried out in Chinese Han population,including 368 cases of migraine and 517 controls.Genomic DNA was extracted from blood samples,and DNA fragments containing the site of polymorphism were amplified by PCR.Data were adjusted for sex,age,migraine history and family history,and analyzed using a logistic regression model.Results There was no association between indel polymorphism and migraine,at either the allele or the genotype level.Conclusion These findings do not support a functional significance of ADRA2B indel polymorphism at position-4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.展开更多
This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN case...This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.展开更多
Objective To investigate the 23 bp and 12 bp insertion/deletion(indel)mutations within the bovine prion protein(PRNP)gene in Chinese dairy cows,and to detect the associations of two indel mutations with BSE susceptibi...Objective To investigate the 23 bp and 12 bp insertion/deletion(indel)mutations within the bovine prion protein(PRNP)gene in Chinese dairy cows,and to detect the associations of two indel mutations with BSE susceptibility and milk performance.Methods Based on bovine PRNP gene sequence,two pairs of primers for testing the 23 bp and 12 bp indel mutations were designed.The PCR amplification and agarose electrophoresis were carried out to distinguish the different genotypes within the mutations.Moreover,based on previous data from other cattle breeds and present genotypic and allelic frequencies of two indels mutations in this study,the corrections between the two indel mutations and BSE susceptibility were tested,as well as the relationships between the mutations and milk performance traits were analyzed in this study based on the statistical analyses.Results In the analyzed Chinese Holstein population,the frequencies of two"del"alleles in 23 bp and 12 bp indel muations were more frequent.The frequency of haplotype of 23del-12del was higher than those of 23del-12ins and 23ins-12del.From the estimated r2and D’values,two indel polymorphisms were linked strongly in the Holstein population(D’=57.5%,r2=0.257).Compared with the BSE-affected cattle populations from the reported data,the significant differences of genotypic and allelic frequencies were found among present Holstein and some BSE-affected populations(P<0.05 or P<0.01).Similarly,there were significant frequency distribution differences of genotypes and alleles among Chinese Holstein and several previous reported healthy dairy cattle(P<0.05 or P<0.01).Moreover,association of genotype and combined genotypes of two indel polymorphisms with milk performance and resistant mastitis traits were analyzed in Holstein population,but no significant differences were found(P>0.05).Conclusions These observations revealed that the influence of two indel mutations within the bovine PRNP gene on BSE depended on the breed and they did not affect the milk production traits,which layed the foundation for future selection of resistant animals,and for improving health conditions for dairy breeding against BSE in China.展开更多
Due to the virtues of no stutter peaks,low rates of mutation,and short amplicon sizes,insertion/deletion(InDei)polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human ident...Due to the virtues of no stutter peaks,low rates of mutation,and short amplicon sizes,insertion/deletion(InDei)polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications(Wang et al.,2021).Herein,a self-developed panel of 43 InDei loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing(HCB)including 301 random healthy individuals.展开更多
Objective: The aim of this work is to determine whether the angiotensin converting enzyme(ACE) I/D(insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease(CHD) in the Qinghai...Objective: The aim of this work is to determine whether the angiotensin converting enzyme(ACE) I/D(insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease(CHD) in the Qinghai Han Chinese. Methods: This study enrolled 59 CHD patients and 193 CHD controls from Qinghai Cardiovascular Diseases Vocational Hospital. Blood samples were collected from each of the patient and control groups. The ACE-I/D polymorphism was detected by polymerase chain reaction(PCR). Results: The genotype frequencies of ACE-I/D for II, ID, DD in patients and controls were 0.475, 0.441, 0.085 and 0.430, 0.446, 0.124, respectively. The allelic frequencies of I and D were 0.650, 0.350 and 0.695, 0.305, respectively. The OR of ID, DD and D alleles relative to II for CHD was 1.116(0.604-2.060), 1.619(0.564-4.648) and 1.211(0.777-1.889). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between the patient and control groups. Conclusion: There is no relation between ACE-I/D polymorphism and CHD in current Qinghai Han Chinese.展开更多
Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the ge...Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.展开更多
Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain contr...Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95％ confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.展开更多
An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acylox...An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acyloxy esters in moderate to high yields with a broad substrate scope.All starting materials are readily available,and the reactions can be conducted in the open air at room temperature.展开更多
A blue light-induced formal insertion reaction ofα-siloxy carbene into the C—H bond of 1,3-diketones has been reported.Under the irradiation of blue light,acylsilane converts toα-siloxy carbene,which then undergoes...A blue light-induced formal insertion reaction ofα-siloxy carbene into the C—H bond of 1,3-diketones has been reported.Under the irradiation of blue light,acylsilane converts toα-siloxy carbene,which then undergoes formal C—H bond insertion reaction with the enol form of 1,3-diketone.This method uses readily available and relative stable acylsilane as car-bene precursor,which features a simple and metal-free approach under mild conditions.Moreover,the synthetic potential of this protocol has been demonstrated by performing the reaction on a gram scale with comparable high yield.展开更多
Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand o...Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand obesity in Chinese type 2 diabetic mellitus(T2DM) using an improved experiment method. MethodsFrom June 2016 to March 2018,300 T2DM patientswith DKD [DKD( +)]and 300 T2DM patients withoutDKD [DKD ( - )] were selected from China-JapanFriendship Hospital. The improved Triple Primer Methodthat combined PCR with capillary electrophoresis was establishedin this study to detect the ACE genotype. Therelevant clinical data as well as the frequencies of genotypeand allele of ACE gene I /D polymorphism betweenthe two groups were statistically analyzed. Patients werefurther grouped based on smoking status and obesity formultivariate regression.展开更多
The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C_(2)-or C_(3)-positon has been developed in this paper.This highly site-selective C-H carbenoid functionalization is determine...The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C_(2)-or C_(3)-positon has been developed in this paper.This highly site-selective C-H carbenoid functionalization is determined by both the Rh-catalyst species and auxiliary groups.[Cp∗RhCl_(2)]_(2) and coordinating pyrimidyl group direct the C-H carbenoid functionalization to occur at the C_(2)-position,while Rh2OAc4 and noncoordinating benzyl group lead the reaction to occur at the C_(3)-position of the indoles.This regioselective C−H functionalization strategy is of significant importance for the discovery of indole drugs.展开更多
Uronic acids are prevalent components of crucial glycoconjugates,pivotal in various biological processes.In nature,NDP-uronic acids,the nucleosides-activated uronic acids,serve as glycosylation donors catalyzed by uro...Uronic acids are prevalent components of crucial glycoconjugates,pivotal in various biological processes.In nature,NDP-uronic acids,the nucleosides-activated uronic acids,serve as glycosylation donors catalyzed by uronosyltransferases(UATs)to construct glycans containing uronic acids.Despite their biological importance,the synthesis of naturally occurring NDP-uronic acids on a large scale remains challenging.Here,we developed an oxidation reaction insertion strategy for the efficient synthesis of NDP-uronic acids,and 11 NDP-uronic acids were successfully prepared in good yield and on a large scale.The prepared NDP-uronic acids can be used to explore new uronosyltransferases and synthesize uronic acids containing carbohydrates for fundamental research.展开更多
The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause ...The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause the branched architecture of ears in maize,such mutations also change the normal phenotypic performance of the tassels.In the present study,a natural maize mutant with branched ears,named branched ear1(be1),was characterized.be1 shows several branched ears at the base of the central ear with unchanged architecture of the tassels.Besides,both the branched and central ears of be1 possess regularly arranged kerels.The phenotypic characteristics of be1 differ completely from those reported mutants of fasciated ears or RAMOSA-like ears in maize.An SEM survey at the very early development stage showed that meristems with three protrusions,similar to the BM in tassels,were present during the development of the branched ears in be1.Gene mapping and sequence alignment suggested that TEOSINTE BRANCHED1(TB1)was the candidate gene of BE1.Further verification showed that a be1-specific 31 bp deletion at the downstream of BE1 led to statistically reduced expression of this gene in the immature ear,which serves as the potential causal reason for the branched ears of be1.CRISPR/Cas9-based gene editing downstream of TB1 complemented the phenotypic architecture of branched ears,suggesting that TB1 was the target of BE1,and it was named as Zm TB1be1.The results of the present study implied a novel function of TB1 in female inforescence development,rather than shaping the plant architecture in maize.Meanwhile,further functional dissection of ZmTB1be1might shed new light on TB1,the most famous domestication related gene in maize.展开更多
BACKGROUND Difficulty of colonoscopy insertion(DCI)significantly affects colonoscopy effectiveness and serves as a key quality indicator.Predicting and evaluating DCI risk preoperatively is crucial for optimizing intr...BACKGROUND Difficulty of colonoscopy insertion(DCI)significantly affects colonoscopy effectiveness and serves as a key quality indicator.Predicting and evaluating DCI risk preoperatively is crucial for optimizing intraoperative strategies.AIM To evaluate the predictive performance of machine learning(ML)algorithms for DCI by comparing three modeling approaches,identify factors influencing DCI,and develop a preoperative prediction model using ML algorithms to enhance colonoscopy quality and efficiency.METHODS This cross-sectional study enrolled 712 patients who underwent colonoscopy at a tertiary hospital between June 2020 and May 2021.Demographic data,past medical history,medication use,and psychological status were collected.The endoscopist assessed DCI using the visual analogue scale.After univariate screening,predictive models were developed using multivariable logistic regression,least absolute shrinkage and selection operator(LASSO)regression,and random forest(RF)algorithms.Model performance was evaluated based on discrimination,calibration,and decision curve analysis(DCA),and results were visualized using nomograms.RESULTS A total of 712 patients(53.8%male;mean age 54.5 years±12.9 years)were included.Logistic regression analysis identified constipation[odds ratio(OR)=2.254,95%confidence interval(CI):1.289-3.931],abdominal circumference(AC)(77.5–91.9 cm,OR=1.895,95%CI:1.065-3.350;AC≥92 cm,OR=1.271,95%CI:0.730-2.188),and anxiety(OR=1.071,95%CI:1.044-1.100)as predictive factors for DCI,validated by LASSO and RF methods.Model performance revealed training/validation sensitivities of 0.826/0.925,0.924/0.868,and 1.000/0.981;specificities of 0.602/0.511,0.510/0.562,and 0.977/0.526;and corresponding area under the receiver operating characteristic curves(AUCs)of 0.780(0.737-0.823)/0.726(0.654-0.799),0.754(0.710-0.798)/0.723(0.656-0.791),and 1.000(1.000-1.000)/0.754(0.688-0.820),respectively.DCA indicated optimal net benefit within probability thresholds of 0-0.9 and 0.05-0.37.The RF model demonstrated superior diagnostic accuracy,reflected by perfect training sensitivity(1.000)and highest validation AUC(0.754),outperforming other methods in clinical applicability.CONCLUSION The RF-based model exhibited superior predictive accuracy for DCI compared to multivariable logistic and LASSO regression models.This approach supports individualized preoperative optimization,enhancing colonoscopy quality through targeted risk stratification.展开更多
Insertion and deletion(indel) mutations, which can trigger single nucleotide substitutions on the flanking regions of genes, may generate abundant materials for disease defense, reproduction, species survival and evol...Insertion and deletion(indel) mutations, which can trigger single nucleotide substitutions on the flanking regions of genes, may generate abundant materials for disease defense, reproduction, species survival and evolution. However, genetic and evolutionary mechanisms of indels remain elusive. We establish a comparative genome-transcriptome-alignment approach for a large-scale identification of indels in Monopterus population. Over 2000 indels in 1738 indel genes, including 1-21 bp deletions and 1-15 bp insertions, were detected. Each indel gene had ～1.1 deletions/insertions, and 2-4 alleles in population. Frequencies of deletions were prominently higher than those of insertions on both genome and population levels. Most of the indels led to in frame mutations with multiples of three and majorly occurred in non-domain regions, indicating functional constraint or tolerance of the indels. All indel genes showed higher expression levels than non-indel genes during sex reversal. Slide window analysis of global expression levels in gonads showed a significant positive correlation with indel density in the genome. Moreover, indel genes were evolutionarily conserved and evolved slowly compared to nonindel genes. Notably, population genetic structure of indels revealed divergent evolution of Monopterus population, as bottleneck effect of biogeographic isolation by Taiwan Strait, China.展开更多
Due to its specific characteristics, such as ma-ternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it har...Due to its specific characteristics, such as ma-ternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it harbors. Rare mutation (excluding parallel mutation) occur-ring at multiple times in different haplogroups could thus be a potential reading error according to the mtDNA phylogeny. This experience has been widely used in double-checking the credibility of the rare mutations in human mtDNA sequences. However, no test has been performed so far for the feasibility of applying this strategy to the rare insertion/deletion (indel) events in mtDNA sequences. In this study, we attempted to relate the rare indels in mtDNAs to their haplogroup status in a total of 2352 individuals from 50 populations in China. Our results show that the insertion of A at position 16259 is restricted to a subclade of haplogroup C and can be verified. The other indel polymorphisms, which occur in the repeat of the deleted or inserted nucleotide(s), may not be distin-guished from phantom mutations from a phylogenetic point of view. Independently and multiply sequencing the frag-ment with the indel is the best and the most reliable way for confirmation.展开更多
The atom-economical C-F insertion chemistry is emerged as a promising technology for the synthesis of various fluorinated scaffolds,which have wide applications both in the academic and the industrial com-munities.The...The atom-economical C-F insertion chemistry is emerged as a promising technology for the synthesis of various fluorinated scaffolds,which have wide applications both in the academic and the industrial com-munities.The past three years have witnessed rapid developments in this field.This highlight provides an overview on the evolution according to the fluorinating agents used.展开更多
Temperature is an important environmental factor affecting heading date of rice.Despite its importance,genes responsible for temperature-sensitive heading in rice have remained elusive.Our previous study identified a ...Temperature is an important environmental factor affecting heading date of rice.Despite its importance,genes responsible for temperature-sensitive heading in rice have remained elusive.Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures.A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97(ZS97).However,the function of this natural variant in controlling temperature sensitivity has not been verified.In this study,we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97.Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51.One-hybrid assays in yeast,ChIP-quantitative polymerase chain reaction,electrophoretic mobility shift,and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1.We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51,offering an explanation for how the 9.5-kb insertion affects temperature sensitivity.We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China,possibly accounting for their strong temperature sensitivity.These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding.展开更多
The studypresents theHalfMax InsertionHeuristic (HMIH) as a novel approach to solving theTravelling SalesmanProblem (TSP). The goal is to outperform existing techniques such as the Farthest Insertion Heuristic (FIH) a...The studypresents theHalfMax InsertionHeuristic (HMIH) as a novel approach to solving theTravelling SalesmanProblem (TSP). The goal is to outperform existing techniques such as the Farthest Insertion Heuristic (FIH) andNearest Neighbour Heuristic (NNH). The paper discusses the limitations of current construction tour heuristics,focusing particularly on the significant margin of error in FIH. It then proposes HMIH as an alternative thatminimizes the increase in tour distance and includes more nodes. HMIH improves tour quality by starting withan initial tour consisting of a ‘minimum’ polygon and iteratively adding nodes using our novel Half Max routine.The paper thoroughly examines and compares HMIH with FIH and NNH via rigorous testing on standard TSPbenchmarks. The results indicate that HMIH consistently delivers superior performance, particularly with respectto tour cost and computational efficiency. HMIH’s tours were sometimes 16% shorter than those generated by FIHand NNH, showcasing its potential and value as a novel benchmark for TSP solutions. The study used statisticalmethods, including Friedman’s Non-parametric Test, to validate the performance of HMIH over FIH and NNH.This guarantees that the identified advantages are statistically significant and consistent in various situations. Thiscomprehensive analysis emphasizes the reliability and efficiency of the heuristic, making a compelling case for itsuse in solving TSP issues. The research shows that, in general, HMIH fared better than FIH in all cases studied,except for a few instances (pr439, eil51, and eil101) where FIH either performed equally or slightly better thanHMIH. HMIH’s efficiency is shown by its improvements in error percentage (δ) and goodness values (g) comparedto FIH and NNH. In the att48 instance, HMIH had an error rate of 6.3%, whereas FIH had 14.6% and NNH had20.9%, indicating that HMIH was closer to the optimal solution. HMIH consistently showed superior performanceacross many benchmarks, with lower percentage error and higher goodness values, suggesting a closer match tothe optimal tour costs. This study substantially contributes to combinatorial optimization by enhancing currentinsertion algorithms and presenting a more efficient solution for the Travelling Salesman Problem. It also createsnew possibilities for progress in heuristic design and optimization methodologies.展开更多
基金supported by the National Natural Science Foundation of China(No.30800621)China Postdoctoral Science Foundation(No.20080431121,200902530)
文摘Objective The present study aimed to estimate the association between susceptibility to migraine and the 12nucleotide insertion/deletion （indel） polymorphism in promoter region ofα 2B -adrenergic receptor gene （ADRA2B）.Methods A case-control study was carried out in Chinese Han population,including 368 cases of migraine and 517 controls.Genomic DNA was extracted from blood samples,and DNA fragments containing the site of polymorphism were amplified by PCR.Data were adjusted for sex,age,migraine history and family history,and analyzed using a logistic regression model.Results There was no association between indel polymorphism and migraine,at either the allele or the genotype level.Conclusion These findings do not support a functional significance of ADRA2B indel polymorphism at position-4825 relative to the start codon in the far upstream region of the promoter in the present migraine subjects.
文摘This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.
基金supported by the National Natural Science Foundation of China (Grant No. 31272408 30972080)+2 种基金the National 863 Program of China (Grant No. 2013AA102505)the Program of National Beef Cattle and yak Industrial Technology System (CARS-38)the Agricultural Science and Technology Innovation Projects of Shanxi Province (No. 2012NKC01-13).
文摘Objective To investigate the 23 bp and 12 bp insertion/deletion(indel)mutations within the bovine prion protein(PRNP)gene in Chinese dairy cows,and to detect the associations of two indel mutations with BSE susceptibility and milk performance.Methods Based on bovine PRNP gene sequence,two pairs of primers for testing the 23 bp and 12 bp indel mutations were designed.The PCR amplification and agarose electrophoresis were carried out to distinguish the different genotypes within the mutations.Moreover,based on previous data from other cattle breeds and present genotypic and allelic frequencies of two indels mutations in this study,the corrections between the two indel mutations and BSE susceptibility were tested,as well as the relationships between the mutations and milk performance traits were analyzed in this study based on the statistical analyses.Results In the analyzed Chinese Holstein population,the frequencies of two"del"alleles in 23 bp and 12 bp indel muations were more frequent.The frequency of haplotype of 23del-12del was higher than those of 23del-12ins and 23ins-12del.From the estimated r2and D’values,two indel polymorphisms were linked strongly in the Holstein population(D’=57.5%,r2=0.257).Compared with the BSE-affected cattle populations from the reported data,the significant differences of genotypic and allelic frequencies were found among present Holstein and some BSE-affected populations(P<0.05 or P<0.01).Similarly,there were significant frequency distribution differences of genotypes and alleles among Chinese Holstein and several previous reported healthy dairy cattle(P<0.05 or P<0.01).Moreover,association of genotype and combined genotypes of two indel polymorphisms with milk performance and resistant mastitis traits were analyzed in Holstein population,but no significant differences were found(P>0.05).Conclusions These observations revealed that the influence of two indel mutations within the bovine PRNP gene on BSE depended on the breed and they did not affect the milk production traits,which layed the foundation for future selection of resistant animals,and for improving health conditions for dairy breeding against BSE in China.
基金This study was supported by the National Natural Science Foundation of China(No.81373248).
文摘Due to the virtues of no stutter peaks,low rates of mutation,and short amplicon sizes,insertion/deletion(InDei)polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications(Wang et al.,2021).Herein,a self-developed panel of 43 InDei loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing(HCB)including 301 random healthy individuals.
基金supported by Qinghai Science & Technology Support Program(2015-SF-124)Basic Applied Study Foundation of Qinghai(2016-ZJ-706)
文摘Objective: The aim of this work is to determine whether the angiotensin converting enzyme(ACE) I/D(insertion/deletion) polymorphism is associated with the susceptibility to congenital heart disease(CHD) in the Qinghai Han Chinese. Methods: This study enrolled 59 CHD patients and 193 CHD controls from Qinghai Cardiovascular Diseases Vocational Hospital. Blood samples were collected from each of the patient and control groups. The ACE-I/D polymorphism was detected by polymerase chain reaction(PCR). Results: The genotype frequencies of ACE-I/D for II, ID, DD in patients and controls were 0.475, 0.441, 0.085 and 0.430, 0.446, 0.124, respectively. The allelic frequencies of I and D were 0.650, 0.350 and 0.695, 0.305, respectively. The OR of ID, DD and D alleles relative to II for CHD was 1.116(0.604-2.060), 1.619(0.564-4.648) and 1.211(0.777-1.889). There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between the patient and control groups. Conclusion: There is no relation between ACE-I/D polymorphism and CHD in current Qinghai Han Chinese.
文摘Genetic,environmental and demographic factors contribute to the development of essential hypertension.Genetic polymorphism of Rennin-angiotensin-aldosterone system(RAAS)has been extensively studied to determine the genetic susceptibility to hypertension.The insertion/deletion(I/D)angiotensin converting enzyme(ACE)polymorphism has been established as a cardiovascular risk factor in some population,but its association with essential hypertension is controversial.This study sought to determine the association of I/D polymorphism of the ACE gene in south Indian essential hypertensive subjects.A total of 208 clinically diagnosed essential hypertensive patients without any associated diseases and 220 healthy control subjects were included in this study.Distribution and allelic frequency of Insertion(I)and Deletion(D)polymorphism at the 287 base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed.The distribution of II,ID,DD genotypes of ACE gene was 28.3%,32.6%and 38.9%respectively in essential hypertensive patients and to 53.6%,26.3%and 20%in controls.The allele frequency for D allele is 0.58 in essential hypertension as compared to 0.34 of control subjects.The genotype and allele frequency of ACE gene polymorphism is significantly differed in patients when compared to controls.In conclusion,the I/D polymorphism of ACE gene is associated with Indian essential hypertension.
文摘Background: Several studies have investigated the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with peripheral vascular disease (PVD); however, the results remain controversial. Therefore, we conducted the current meta-analysis to evaluate this relationship in the general population of different ethnicities. Methods: We searched PubMed, Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies. Random-effect models were applied to estimate the pooled odds ratio (OR) with a 95％ confidence interval (CI), regardless of between-study heterogeneity. Results: A total of 13 studies with 1966 cases and 6129 controls were included in this meta-analysis. The pooled ORs for the association between ACE I/D polymorphism and PVD risk were not statistically significant in the overall population under all genetic models. In further ethnicity-stratified analyses, we found a statistically significant association of ACE I/D polymorphism with PVD susceptibility in Asians under most models. However, the association among Caucasians did not reach statistical significance. Conclusion: ACE I/D polymorphism might be associated with susceptibility to PVD in the Asian population, but there was no clear evidence indicating a similar significant relationship among Caucasians.
文摘An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acyloxy esters in moderate to high yields with a broad substrate scope.All starting materials are readily available,and the reactions can be conducted in the open air at room temperature.
文摘A blue light-induced formal insertion reaction ofα-siloxy carbene into the C—H bond of 1,3-diketones has been reported.Under the irradiation of blue light,acylsilane converts toα-siloxy carbene,which then undergoes formal C—H bond insertion reaction with the enol form of 1,3-diketone.This method uses readily available and relative stable acylsilane as car-bene precursor,which features a simple and metal-free approach under mild conditions.Moreover,the synthetic potential of this protocol has been demonstrated by performing the reaction on a gram scale with comparable high yield.
文摘Objective To explore the interaction of angiotensinconverting enzyme (ACE) insertion /deletion(I /D) polymorphism( rs1799752 ) with diabetic kidney disease(DKD) development as well as its interaction with smokingand obesity in Chinese type 2 diabetic mellitus(T2DM) using an improved experiment method. MethodsFrom June 2016 to March 2018,300 T2DM patientswith DKD [DKD( +)]and 300 T2DM patients withoutDKD [DKD ( - )] were selected from China-JapanFriendship Hospital. The improved Triple Primer Methodthat combined PCR with capillary electrophoresis was establishedin this study to detect the ACE genotype. Therelevant clinical data as well as the frequencies of genotypeand allele of ACE gene I /D polymorphism betweenthe two groups were statistically analyzed. Patients werefurther grouped based on smoking status and obesity formultivariate regression.
基金CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2022-I2M-1-013,2022-I2M-1-014,2022-I2M-2-002).
文摘The switchable cross-coupling of indoles and pyridotriazoles through carbene insertion at C_(2)-or C_(3)-positon has been developed in this paper.This highly site-selective C-H carbenoid functionalization is determined by both the Rh-catalyst species and auxiliary groups.[Cp∗RhCl_(2)]_(2) and coordinating pyrimidyl group direct the C-H carbenoid functionalization to occur at the C_(2)-position,while Rh2OAc4 and noncoordinating benzyl group lead the reaction to occur at the C_(3)-position of the indoles.This regioselective C−H functionalization strategy is of significant importance for the discovery of indole drugs.
基金financially supported by National Natural Science Foundation of China(No.22207113 to J.Zhang)Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110588to J.Zhang)Natural Science Foundation of Shanghai Municipality(No.22ZR1474000 to L.Wen)。
文摘Uronic acids are prevalent components of crucial glycoconjugates,pivotal in various biological processes.In nature,NDP-uronic acids,the nucleosides-activated uronic acids,serve as glycosylation donors catalyzed by uronosyltransferases(UATs)to construct glycans containing uronic acids.Despite their biological importance,the synthesis of naturally occurring NDP-uronic acids on a large scale remains challenging.Here,we developed an oxidation reaction insertion strategy for the efficient synthesis of NDP-uronic acids,and 11 NDP-uronic acids were successfully prepared in good yield and on a large scale.The prepared NDP-uronic acids can be used to explore new uronosyltransferases and synthesize uronic acids containing carbohydrates for fundamental research.
基金supported by the Special Key Project for Technological Innovation and Application Development in Chongqing,China(CSTB2022TIAD-KPX0011)the Special Fund for Youth Team of the Southwest Universities,China(SWU-XJPY202306)+1 种基金the Natural Science Foundation of Chongqing,China(cstc2021jcyj-msxmX0583)the Fundamental Research Funds for the Central Universities of Southwest University,China(S202210635326)。
文摘The female inflorescence,or ear,of maize develops no branch meristem(BM),which differs from the male inforescence,or tassel.While the mutations of some well documented genes,such as fea2/3/4 and ramosa1/2/3,can cause the branched architecture of ears in maize,such mutations also change the normal phenotypic performance of the tassels.In the present study,a natural maize mutant with branched ears,named branched ear1(be1),was characterized.be1 shows several branched ears at the base of the central ear with unchanged architecture of the tassels.Besides,both the branched and central ears of be1 possess regularly arranged kerels.The phenotypic characteristics of be1 differ completely from those reported mutants of fasciated ears or RAMOSA-like ears in maize.An SEM survey at the very early development stage showed that meristems with three protrusions,similar to the BM in tassels,were present during the development of the branched ears in be1.Gene mapping and sequence alignment suggested that TEOSINTE BRANCHED1(TB1)was the candidate gene of BE1.Further verification showed that a be1-specific 31 bp deletion at the downstream of BE1 led to statistically reduced expression of this gene in the immature ear,which serves as the potential causal reason for the branched ears of be1.CRISPR/Cas9-based gene editing downstream of TB1 complemented the phenotypic architecture of branched ears,suggesting that TB1 was the target of BE1,and it was named as Zm TB1be1.The results of the present study implied a novel function of TB1 in female inforescence development,rather than shaping the plant architecture in maize.Meanwhile,further functional dissection of ZmTB1be1might shed new light on TB1,the most famous domestication related gene in maize.
基金the Chinese Clinical Trial Registry(No.ChiCTR2000040109)approved by the Hospital Ethics Committee(No.20210130017).
文摘BACKGROUND Difficulty of colonoscopy insertion(DCI)significantly affects colonoscopy effectiveness and serves as a key quality indicator.Predicting and evaluating DCI risk preoperatively is crucial for optimizing intraoperative strategies.AIM To evaluate the predictive performance of machine learning(ML)algorithms for DCI by comparing three modeling approaches,identify factors influencing DCI,and develop a preoperative prediction model using ML algorithms to enhance colonoscopy quality and efficiency.METHODS This cross-sectional study enrolled 712 patients who underwent colonoscopy at a tertiary hospital between June 2020 and May 2021.Demographic data,past medical history,medication use,and psychological status were collected.The endoscopist assessed DCI using the visual analogue scale.After univariate screening,predictive models were developed using multivariable logistic regression,least absolute shrinkage and selection operator(LASSO)regression,and random forest(RF)algorithms.Model performance was evaluated based on discrimination,calibration,and decision curve analysis(DCA),and results were visualized using nomograms.RESULTS A total of 712 patients(53.8%male;mean age 54.5 years±12.9 years)were included.Logistic regression analysis identified constipation[odds ratio(OR)=2.254,95%confidence interval(CI):1.289-3.931],abdominal circumference(AC)(77.5–91.9 cm,OR=1.895,95%CI:1.065-3.350;AC≥92 cm,OR=1.271,95%CI:0.730-2.188),and anxiety(OR=1.071,95%CI:1.044-1.100)as predictive factors for DCI,validated by LASSO and RF methods.Model performance revealed training/validation sensitivities of 0.826/0.925,0.924/0.868,and 1.000/0.981;specificities of 0.602/0.511,0.510/0.562,and 0.977/0.526;and corresponding area under the receiver operating characteristic curves(AUCs)of 0.780(0.737-0.823)/0.726(0.654-0.799),0.754(0.710-0.798)/0.723(0.656-0.791),and 1.000(1.000-1.000)/0.754(0.688-0.820),respectively.DCA indicated optimal net benefit within probability thresholds of 0-0.9 and 0.05-0.37.The RF model demonstrated superior diagnostic accuracy,reflected by perfect training sensitivity(1.000)and highest validation AUC(0.754),outperforming other methods in clinical applicability.CONCLUSION The RF-based model exhibited superior predictive accuracy for DCI compared to multivariable logistic and LASSO regression models.This approach supports individualized preoperative optimization,enhancing colonoscopy quality through targeted risk stratification.
基金supported by the National Natural Science Foundation of China (31571280 and 31771370)National Key Technologies R&D Program and Hubei Province Science and Technology project
文摘Insertion and deletion(indel) mutations, which can trigger single nucleotide substitutions on the flanking regions of genes, may generate abundant materials for disease defense, reproduction, species survival and evolution. However, genetic and evolutionary mechanisms of indels remain elusive. We establish a comparative genome-transcriptome-alignment approach for a large-scale identification of indels in Monopterus population. Over 2000 indels in 1738 indel genes, including 1-21 bp deletions and 1-15 bp insertions, were detected. Each indel gene had ～1.1 deletions/insertions, and 2-4 alleles in population. Frequencies of deletions were prominently higher than those of insertions on both genome and population levels. Most of the indels led to in frame mutations with multiples of three and majorly occurred in non-domain regions, indicating functional constraint or tolerance of the indels. All indel genes showed higher expression levels than non-indel genes during sex reversal. Slide window analysis of global expression levels in gonads showed a significant positive correlation with indel density in the genome. Moreover, indel genes were evolutionarily conserved and evolved slowly compared to nonindel genes. Notably, population genetic structure of indels revealed divergent evolution of Monopterus population, as bottleneck effect of biogeographic isolation by Taiwan Strait, China.
文摘Due to its specific characteristics, such as ma-ternal inheritance and absence of recombination, each mtDNA belongs to certain monophyletic clade in the rooted mtDNA tree (haplogroup) according to the mutations it harbors. Rare mutation (excluding parallel mutation) occur-ring at multiple times in different haplogroups could thus be a potential reading error according to the mtDNA phylogeny. This experience has been widely used in double-checking the credibility of the rare mutations in human mtDNA sequences. However, no test has been performed so far for the feasibility of applying this strategy to the rare insertion/deletion (indel) events in mtDNA sequences. In this study, we attempted to relate the rare indels in mtDNAs to their haplogroup status in a total of 2352 individuals from 50 populations in China. Our results show that the insertion of A at position 16259 is restricted to a subclade of haplogroup C and can be verified. The other indel polymorphisms, which occur in the repeat of the deleted or inserted nucleotide(s), may not be distin-guished from phantom mutations from a phylogenetic point of view. Independently and multiply sequencing the frag-ment with the indel is the best and the most reliable way for confirmation.
基金The Tertiary Education Scientific Research Project of Guangzhou Municipal Education Bureau(No.202235305)is gratefully acnowledged for financial support.
文摘The atom-economical C-F insertion chemistry is emerged as a promising technology for the synthesis of various fluorinated scaffolds,which have wide applications both in the academic and the industrial com-munities.The past three years have witnessed rapid developments in this field.This highlight provides an overview on the evolution according to the fluorinating agents used.
基金supported by the Laboratory of Lingnan Modern Agriculture Project(NT2021001)Guangdong Province Basic and Applied Basic Research Fund-Provincial and Municipal Joint Fund Project(2023A1515110882)+3 种基金Guangzhou Science and Technology Plan Project(2023A04J0811)Guangdong Province Rural Revitalization Strategy Special Fund Seed Industry Revitalization Project(2022-NPY-00-013)Natural Science Foundation of Zhejiang Pro-vince(LY22C130006)Key Laboratory of New Rice Breeding Technologies in Guangdong Province(2023B1212060042).
文摘Temperature is an important environmental factor affecting heading date of rice.Despite its importance,genes responsible for temperature-sensitive heading in rice have remained elusive.Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures.A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97(ZS97).However,the function of this natural variant in controlling temperature sensitivity has not been verified.In this study,we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97.Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51.One-hybrid assays in yeast,ChIP-quantitative polymerase chain reaction,electrophoretic mobility shift,and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1.We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51,offering an explanation for how the 9.5-kb insertion affects temperature sensitivity.We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China,possibly accounting for their strong temperature sensitivity.These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding.
基金the Centre of Excellence in Mobile and e-Services,the University of Zululand,Kwadlangezwa,South Africa.
文摘The studypresents theHalfMax InsertionHeuristic (HMIH) as a novel approach to solving theTravelling SalesmanProblem (TSP). The goal is to outperform existing techniques such as the Farthest Insertion Heuristic (FIH) andNearest Neighbour Heuristic (NNH). The paper discusses the limitations of current construction tour heuristics,focusing particularly on the significant margin of error in FIH. It then proposes HMIH as an alternative thatminimizes the increase in tour distance and includes more nodes. HMIH improves tour quality by starting withan initial tour consisting of a ‘minimum’ polygon and iteratively adding nodes using our novel Half Max routine.The paper thoroughly examines and compares HMIH with FIH and NNH via rigorous testing on standard TSPbenchmarks. The results indicate that HMIH consistently delivers superior performance, particularly with respectto tour cost and computational efficiency. HMIH’s tours were sometimes 16% shorter than those generated by FIHand NNH, showcasing its potential and value as a novel benchmark for TSP solutions. The study used statisticalmethods, including Friedman’s Non-parametric Test, to validate the performance of HMIH over FIH and NNH.This guarantees that the identified advantages are statistically significant and consistent in various situations. Thiscomprehensive analysis emphasizes the reliability and efficiency of the heuristic, making a compelling case for itsuse in solving TSP issues. The research shows that, in general, HMIH fared better than FIH in all cases studied,except for a few instances (pr439, eil51, and eil101) where FIH either performed equally or slightly better thanHMIH. HMIH’s efficiency is shown by its improvements in error percentage (δ) and goodness values (g) comparedto FIH and NNH. In the att48 instance, HMIH had an error rate of 6.3%, whereas FIH had 14.6% and NNH had20.9%, indicating that HMIH was closer to the optimal solution. HMIH consistently showed superior performanceacross many benchmarks, with lower percentage error and higher goodness values, suggesting a closer match tothe optimal tour costs. This study substantially contributes to combinatorial optimization by enhancing currentinsertion algorithms and presenting a more efficient solution for the Travelling Salesman Problem. It also createsnew possibilities for progress in heuristic design and optimization methodologies.
