Hepatocellular carcinoma(HCC)is the second cause of cancer-related mortality.The diagnosis of HCC depends mainly on-fetoprotein,which is limited in its diagnostic and screening capabilities.There is an urgent need for...Hepatocellular carcinoma(HCC)is the second cause of cancer-related mortality.The diagnosis of HCC depends mainly on-fetoprotein,which is limited in its diagnostic and screening capabilities.There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment.New targets of therapy could enhance survival and create future alternative curative methods.In silico analysis provides both;discovery of biomarkers,and understanding of the molecular pathways,to pave the way for treatment development.This review discusses the role of in silico analysis in the discovery of biomarkers,molecular pathways,and the role the author has contributed to this area of research.It also discusses future aspirations and current limitations.A literature review was conducted on the topic using various databases(PubMed,Science Direct,and Wiley Online Library),searching in various reviews,and editorials on the topic,with overviewing the author’s own published and unpublished work.This review discussed the steps of the validation process from in silico analysis to in vivo validation,to incorporation into clinical practice guidelines.In addition,reviewing the recent lines of research of bioinformatic studies related to HCC.In conclusion,the genetic,molecular and epigenetic markers discoveries are hot areas for HCC research.Bioinformatics will enhance our ability to accomplish this understanding in the near future.We face certain limitations that we need to overcome.展开更多
Simple sequence repeats(SSRs) defined as sequence repeat units between 1 and 6 bp occur abundantly in both coding and non-coding regions in eukaryotic genomes and these repeats can affect gene expression. In this st...Simple sequence repeats(SSRs) defined as sequence repeat units between 1 and 6 bp occur abundantly in both coding and non-coding regions in eukaryotic genomes and these repeats can affect gene expression. In this study, ESTs(expressed sequence tags) of Betula pendula(silver birch) were analyzed for in silico mining of ESTSSRs, protein annotation, open reading frames(ORFs),designing primers, and identifying codon repetitions. In B.pendula, the frequency of ESTs containing SSRs was 7.8 %with an average of 1SSR/4. 78 kb of EST sequences. A total of 188 SSRs was identified by using MISA software and dinucleotide SSR motifs(65.9 %) were found to be the most abundant type of repeat motif followed by tri-(27.1 %),tetra-(4.8 %), and penta-(2.2 %) motifs. Based on ORF analysis, 175 of 178 sequences were predicted as ORFs and the most frequent SSRs were detected in 50 UTR(58.43 %),followed by in ORF(31.46 %) and in 30UTR(8.43 %). 102 of 178 ESTs were annotated as ribosomal protein, transport protein, membrane protein, carrier protein, binding protein,and transferase protein. For a total of 102 SSRs(57.3 %)with significant matches, a set of 102 primers(100 %) with forward and reverse strands was designed by using Primer 3 software. Serine(Ser, 19.6 %) was predominant in putative encoded amino acids and most of amino acids showed nonpolar(35.3 %) nature. Our data provide resources for B.pendula and can be useful for in silico comparative analyses of Betulaceae species, including SSR mining.展开更多
Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrentl...Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a ubiquitous bacterium that affects nearly half of the world’s population with a high morbidity and mortality rate.Polymorphisms within the tumor necrosis factor-alpha(TNF-A...BACKGROUND Helicobacter pylori(H.pylori)is a ubiquitous bacterium that affects nearly half of the world’s population with a high morbidity and mortality rate.Polymorphisms within the tumor necrosis factor-alpha(TNF-A)promoter region are considered a possible genetic basis for this disease.AIM To functionally characterize the genetic variations in the TNF-A 5’-region(-584 to+107)of Sudanese patients infected with H.pylori using in silico tools.METHODS An observational study was carried out in major public and private hospitals in Khartoum state.A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy.Genomic DNA was extracted.Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H.pylori infection in the Sudanese population.Furthermore,Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5’-region(-584 to+107)of TNF-A in H.pylori-infected patients.Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region.A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation.Also,a multivariate logistic regression model was constructed to estimate odds ratios and their 95%confidence intervals for the association between TNF-A-1030,sociodemographic characteristics and H.pylori infection.Differences were statistically significant if P<0.05.Statistical analyses were performed using Stata version 11 software.RESULTS A total of seven single nucleotide polymorphisms were observed in the TNF-A 5’-region of Sudanese patients infected with H.pylori.Only one of them(T>A,-76)was located at the in silico-predicted promoter region(-146 to+10),and it was predicted to alter transcription factor binding sites and composite regulatory elements.A novel mutation(A>T,+27)was detected in the 5’untranslated region,and it could affect the post-transcriptional regulatory pathways.Genotyping of TNF-A-1030 showed a lack of significant association between-1030T and susceptibility to H.pylori and gastric cancer in the studied population(P=0.1756)and(P=0.8116),respectively.However,a significant association was detected between T/C genotype and H.pylori infection(39.34%vs 19.67%,odds ratio=2.69,95%confidence interval:1.17-6.17,P=0.020).Mammalian conservation was observed for the(-146 to+10)region in chimpanzee(99.4%),rhesus monkey(95.6%),cow(91.8%),domesticated dog(89.3%),mouse(84.3%),rat(82.4%)and opossum(78%).CONCLUSION Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.展开更多
As coronavirus disease 2019(COVID-19) threatens human health globally,infectious disorders have become one of the most challenging problem for the medical community.Natural products(NP) have been a prolific source of ...As coronavirus disease 2019(COVID-19) threatens human health globally,infectious disorders have become one of the most challenging problem for the medical community.Natural products(NP) have been a prolific source of antimicrobial agents with widely divergent structures and a range of vast biological activities.A dataset comprising 618 articles,including 646 NP-based compounds from 672 species of natural sources with biological activities against 21 infectious pathogens from five categories,was assembled through manual selection of published articles.These data were used to identify 268 NP-based compounds classified into ten groups,which were used for network pharmacology analysis to capture the most promising lead-compounds such as agelasine D,dicumarol,dihydroartemisinin and pyridomycin.The distribution of maximum Tanimoto scores indicated that compounds which inhibited parasites exhibited low diversity,whereas the chemistries inhibiting bacteria,fungi,and viruses showed more structural diversity.A total of 331 species of medicinal plants with compounds exhibiting antimicrobial activities were selected to classify the family sources.The family Asteraceae possesses various compounds against C.neoformans,the family Anacardiaceae has compounds against Salmonella typhi,the family Cucurbitacea against the human immunodeficiency virus(HIV),and the family Ancistrocladaceae against Plasmodium.This review summarizes currently available data on NPbased antimicrobials against refractory infections to provide information for further discovery of drugs and synthetic strategies for anti-infectious agents.展开更多
Dry-cured ham has been described as a good source of bioactive peptides and taste-active compounds.Some of them are dipeptides and tripeptides that are released in a large amount from different muscle proteins due to ...Dry-cured ham has been described as a good source of bioactive peptides and taste-active compounds.Some of them are dipeptides and tripeptides that are released in a large amount from different muscle proteins due to the action of exopeptidases during the dry-cured ham processing.The potential of dipeptides and tripeptides to exert bioactivities and impart taste characteristics to dry-cured ham has been evaluated using the BIOPEP database,since in silico approaches are a time-and cost-effective alternative to empirical approaches.Most of the studied dipeptides and tripeptides showed ACE and DPP inhibitory activities as well as imparted bitter taste.In fact,more than one bioactivity and/or taste could be assigned to a given peptide sequence,and there could be a correlation between both,like ACE inhibitory and bitter EA,EI and LG peptides.Furthermore,several dipeptides such as EK,KP,LA,PL,PP,RG,and VE,among others,were found to be multifunctional(ACE and DPP IV inhibitory)which would be determined by their structure,sequence and amino acid composition.In silico analysis evidences the relevance of dipeptides and tripeptides in the bioactivity and taste of dry-cured hams,but further empirical assays including in vitro and in vivo studies are necessary to confirm such theoretical results.Possible degradation of the small peptides during gastrointestinal digestion and intestinal absorption as well as interactions with the food matrix could reduce their bioavailability and bioaccessibility,and modify their biological activities.展开更多
Recent advances in the development of high-throughput tools have significantly revolutionized our understanding of molecular mech- anisms underlying normal and dysfunctional biological processes. Here we present a nov...Recent advances in the development of high-throughput tools have significantly revolutionized our understanding of molecular mech- anisms underlying normal and dysfunctional biological processes. Here we present a novel computational tool, transcription factor search and analysis tool (TrFAST), which was developed for the in silico analysis of transcription factor binding sites (TFBSs) of sig- naling pathway-specific TFs. TrFAST facilitates searching as well as comparative analysis of regulatory motifs through an exact pattern matching algorithm followed by the graphical representation of matched binding sites in multiple sequences up to 50 kb in length. TrFAST is proficient in reducing the number of comparisons by the exact pattern matching strategy. In contrast to the pre-existing tools that find TFBS in a single sequence, TrFAST seeks out the desired pattern in multiple sequences simultaneously. It counts the GC con- tent within the given multiple sequence data set and assembles the combinational details of consensus sequence(s) located at these regions, thereby generating a visual display based on the abundance of unique pattern. Comparative regulatory region analysis of multi- ple orthologous sequences simultaneously enhances the features of TrFAST and provides a significant insight into study of conservation of non-coding cis-regulatory elements. TrFAST is freely available at http://www.fi-pk.com/trfast.html.展开更多
Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,...Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,DEFB126 gene polymorphisms have not been extensively studied.Therefore,the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation.Screening was performed by semen analysis,karyotype analysis,and Y microdeletion detection,and 102 fertile men and 106 men with asthenozoospermia in Chengdu,China,were selected for DEFB126 gene sequence analyses.Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected.rs11467417(317-318 del/del),rs11467497(163-166 wt/del),c.152T>C,and c.227A>G were significantly different between the control and asthenozoospermia groups,likely representing high-risk genetic factors for asthenozoospermia among males.DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion.The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus,and the rs11467417 binucleotide deletion produces a non-stop messenger RNA(mRNA).The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces.Based on in silico analysis,the amino acids 51M and 76K are located in the highly conserved domain;c.152T>C(M51T)and c.227A>G(K76R)are predicted to be damaging and capable of changing alternative splice,structural and posttranslational modification sites of the RNA,as well as the secondary structure,structural stability,and hydrophobicity of the protein,suggesting that these mutations are associated with asthenozoospermia.展开更多
文摘Hepatocellular carcinoma(HCC)is the second cause of cancer-related mortality.The diagnosis of HCC depends mainly on-fetoprotein,which is limited in its diagnostic and screening capabilities.There is an urgent need for a biomarker that detects early HCC to give the patients a chance for curative treatment.New targets of therapy could enhance survival and create future alternative curative methods.In silico analysis provides both;discovery of biomarkers,and understanding of the molecular pathways,to pave the way for treatment development.This review discusses the role of in silico analysis in the discovery of biomarkers,molecular pathways,and the role the author has contributed to this area of research.It also discusses future aspirations and current limitations.A literature review was conducted on the topic using various databases(PubMed,Science Direct,and Wiley Online Library),searching in various reviews,and editorials on the topic,with overviewing the author’s own published and unpublished work.This review discussed the steps of the validation process from in silico analysis to in vivo validation,to incorporation into clinical practice guidelines.In addition,reviewing the recent lines of research of bioinformatic studies related to HCC.In conclusion,the genetic,molecular and epigenetic markers discoveries are hot areas for HCC research.Bioinformatics will enhance our ability to accomplish this understanding in the near future.We face certain limitations that we need to overcome.
文摘Simple sequence repeats(SSRs) defined as sequence repeat units between 1 and 6 bp occur abundantly in both coding and non-coding regions in eukaryotic genomes and these repeats can affect gene expression. In this study, ESTs(expressed sequence tags) of Betula pendula(silver birch) were analyzed for in silico mining of ESTSSRs, protein annotation, open reading frames(ORFs),designing primers, and identifying codon repetitions. In B.pendula, the frequency of ESTs containing SSRs was 7.8 %with an average of 1SSR/4. 78 kb of EST sequences. A total of 188 SSRs was identified by using MISA software and dinucleotide SSR motifs(65.9 %) were found to be the most abundant type of repeat motif followed by tri-(27.1 %),tetra-(4.8 %), and penta-(2.2 %) motifs. Based on ORF analysis, 175 of 178 sequences were predicted as ORFs and the most frequent SSRs were detected in 50 UTR(58.43 %),followed by in ORF(31.46 %) and in 30UTR(8.43 %). 102 of 178 ESTs were annotated as ribosomal protein, transport protein, membrane protein, carrier protein, binding protein,and transferase protein. For a total of 102 SSRs(57.3 %)with significant matches, a set of 102 primers(100 %) with forward and reverse strands was designed by using Primer 3 software. Serine(Ser, 19.6 %) was predominant in putative encoded amino acids and most of amino acids showed nonpolar(35.3 %) nature. Our data provide resources for B.pendula and can be useful for in silico comparative analyses of Betulaceae species, including SSR mining.
基金This work was funded by the Key Project of National Natural Science Foundation of China[grant number 81830117]Joint Funds of National Natural Science Foundation of China[grant number U22A20365]+3 种基金National Natural Science Foundation of China[grant numbers 8220140209,82274499]Guangdong Basic and Applied Basic Research Foundation[grant number 2021A1515110082]China Postdoctoral Science Foundation[grant number 2022M711534]Science&Technical Plan of Guangzhou,Guangdong,China[grant number 201903010069].
文摘Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.
文摘BACKGROUND Helicobacter pylori(H.pylori)is a ubiquitous bacterium that affects nearly half of the world’s population with a high morbidity and mortality rate.Polymorphisms within the tumor necrosis factor-alpha(TNF-A)promoter region are considered a possible genetic basis for this disease.AIM To functionally characterize the genetic variations in the TNF-A 5’-region(-584 to+107)of Sudanese patients infected with H.pylori using in silico tools.METHODS An observational study was carried out in major public and private hospitals in Khartoum state.A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy.Genomic DNA was extracted.Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H.pylori infection in the Sudanese population.Furthermore,Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5’-region(-584 to+107)of TNF-A in H.pylori-infected patients.Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region.A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation.Also,a multivariate logistic regression model was constructed to estimate odds ratios and their 95%confidence intervals for the association between TNF-A-1030,sociodemographic characteristics and H.pylori infection.Differences were statistically significant if P<0.05.Statistical analyses were performed using Stata version 11 software.RESULTS A total of seven single nucleotide polymorphisms were observed in the TNF-A 5’-region of Sudanese patients infected with H.pylori.Only one of them(T>A,-76)was located at the in silico-predicted promoter region(-146 to+10),and it was predicted to alter transcription factor binding sites and composite regulatory elements.A novel mutation(A>T,+27)was detected in the 5’untranslated region,and it could affect the post-transcriptional regulatory pathways.Genotyping of TNF-A-1030 showed a lack of significant association between-1030T and susceptibility to H.pylori and gastric cancer in the studied population(P=0.1756)and(P=0.8116),respectively.However,a significant association was detected between T/C genotype and H.pylori infection(39.34%vs 19.67%,odds ratio=2.69,95%confidence interval:1.17-6.17,P=0.020).Mammalian conservation was observed for the(-146 to+10)region in chimpanzee(99.4%),rhesus monkey(95.6%),cow(91.8%),domesticated dog(89.3%),mouse(84.3%),rat(82.4%)and opossum(78%).CONCLUSION Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.
基金supported by the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences (CI2021A04013)the Fundamental Research Funds for the Central Public Welfare Research Institutes (L2021029)。
文摘As coronavirus disease 2019(COVID-19) threatens human health globally,infectious disorders have become one of the most challenging problem for the medical community.Natural products(NP) have been a prolific source of antimicrobial agents with widely divergent structures and a range of vast biological activities.A dataset comprising 618 articles,including 646 NP-based compounds from 672 species of natural sources with biological activities against 21 infectious pathogens from five categories,was assembled through manual selection of published articles.These data were used to identify 268 NP-based compounds classified into ten groups,which were used for network pharmacology analysis to capture the most promising lead-compounds such as agelasine D,dicumarol,dihydroartemisinin and pyridomycin.The distribution of maximum Tanimoto scores indicated that compounds which inhibited parasites exhibited low diversity,whereas the chemistries inhibiting bacteria,fungi,and viruses showed more structural diversity.A total of 331 species of medicinal plants with compounds exhibiting antimicrobial activities were selected to classify the family sources.The family Asteraceae possesses various compounds against C.neoformans,the family Anacardiaceae has compounds against Salmonella typhi,the family Cucurbitacea against the human immunodeficiency virus(HIV),and the family Ancistrocladaceae against Plasmodium.This review summarizes currently available data on NPbased antimicrobials against refractory infections to provide information for further discovery of drugs and synthetic strategies for anti-infectious agents.
基金Funds received from grant AGL2017--89381-R and FEDER funds from the Spanish Ministry of Economy,Industry and Competitiveness.
文摘Dry-cured ham has been described as a good source of bioactive peptides and taste-active compounds.Some of them are dipeptides and tripeptides that are released in a large amount from different muscle proteins due to the action of exopeptidases during the dry-cured ham processing.The potential of dipeptides and tripeptides to exert bioactivities and impart taste characteristics to dry-cured ham has been evaluated using the BIOPEP database,since in silico approaches are a time-and cost-effective alternative to empirical approaches.Most of the studied dipeptides and tripeptides showed ACE and DPP inhibitory activities as well as imparted bitter taste.In fact,more than one bioactivity and/or taste could be assigned to a given peptide sequence,and there could be a correlation between both,like ACE inhibitory and bitter EA,EI and LG peptides.Furthermore,several dipeptides such as EK,KP,LA,PL,PP,RG,and VE,among others,were found to be multifunctional(ACE and DPP IV inhibitory)which would be determined by their structure,sequence and amino acid composition.In silico analysis evidences the relevance of dipeptides and tripeptides in the bioactivity and taste of dry-cured hams,but further empirical assays including in vitro and in vivo studies are necessary to confirm such theoretical results.Possible degradation of the small peptides during gastrointestinal digestion and intestinal absorption as well as interactions with the food matrix could reduce their bioavailability and bioaccessibility,and modify their biological activities.
基金supported by Higher Education Commission, Pakistan(Grant No.20-1493/R&D/09)
文摘Recent advances in the development of high-throughput tools have significantly revolutionized our understanding of molecular mech- anisms underlying normal and dysfunctional biological processes. Here we present a novel computational tool, transcription factor search and analysis tool (TrFAST), which was developed for the in silico analysis of transcription factor binding sites (TFBSs) of sig- naling pathway-specific TFs. TrFAST facilitates searching as well as comparative analysis of regulatory motifs through an exact pattern matching algorithm followed by the graphical representation of matched binding sites in multiple sequences up to 50 kb in length. TrFAST is proficient in reducing the number of comparisons by the exact pattern matching strategy. In contrast to the pre-existing tools that find TFBS in a single sequence, TrFAST seeks out the desired pattern in multiple sequences simultaneously. It counts the GC con- tent within the given multiple sequence data set and assembles the combinational details of consensus sequence(s) located at these regions, thereby generating a visual display based on the abundance of unique pattern. Comparative regulatory region analysis of multi- ple orthologous sequences simultaneously enhances the features of TrFAST and provides a significant insight into study of conservation of non-coding cis-regulatory elements. TrFAST is freely available at http://www.fi-pk.com/trfast.html.
文摘Idiopathic asthenozoospermia,a common factor in male infertility,is characterized by altered sperm motility function in fresh ejaculate.Although theβ-defensin 126(DEFB126)protein is associated with asthenozoospermia,DEFB126 gene polymorphisms have not been extensively studied.Therefore,the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation.Screening was performed by semen analysis,karyotype analysis,and Y microdeletion detection,and 102 fertile men and 106 men with asthenozoospermia in Chengdu,China,were selected for DEFB126 gene sequence analyses.Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected.rs11467417(317-318 del/del),rs11467497(163-166 wt/del),c.152T>C,and c.227A>G were significantly different between the control and asthenozoospermia groups,likely representing high-risk genetic factors for asthenozoospermia among males.DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion.The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus,and the rs11467417 binucleotide deletion produces a non-stop messenger RNA(mRNA).The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces.Based on in silico analysis,the amino acids 51M and 76K are located in the highly conserved domain;c.152T>C(M51T)and c.227A>G(K76R)are predicted to be damaging and capable of changing alternative splice,structural and posttranslational modification sites of the RNA,as well as the secondary structure,structural stability,and hydrophobicity of the protein,suggesting that these mutations are associated with asthenozoospermia.