There exist three problems in the calculation of lateral vibration of the train-track time-variant system athome and abroad and the method to solve them is presented. Spatially coupling vibration analysis model of tra...There exist three problems in the calculation of lateral vibration of the train-track time-variant system athome and abroad and the method to solve them is presented. Spatially coupling vibration analysis model of train-track time-variant system is put forward. Each vehicle is modeled as a multi-body system with 26 degrees of freedomand the action of coupler is also considered. The track structure is modeled as an assembly of track elements with 30degrees of freedom, then the spatially coupling vibration matrix equation of the train-track time-variant system is es-tablished on the basis of the principle of total potential energy with stationary value and the "set-in-right-position"rule. The track vertical geometric irregularity is considered as the excitation source of the vertical vibration of thesystem, and the hunting wave of car bogie frame is taken as the excitation source of lateral vibration of the system.The spatially coupling vibration matrix equation of the system is solved by Wilson-θ direct integration method. Theapproximation of the calculated results to the spot test results demonstrates the feasibility and effectiveness of thepresented analysis method. Finally, some other vibration responses of the system are also obtained.展开更多
Recently,inspired by a modified generalized shift-splitting iteration method for complex symmetric linear systems,we propose two variants of the modified generalized shift-splitting iteration(MGSS)methods for solving ...Recently,inspired by a modified generalized shift-splitting iteration method for complex symmetric linear systems,we propose two variants of the modified generalized shift-splitting iteration(MGSS)methods for solving com-plex symmetric linear systems.One is a parameterized MGSS iteration method and the other is a modified parameterized MGSS iteration method.We prove that the proposed methods are convergent under appropriate constraints on the parameters.In addition,we also give the eigenvalue distributions of differ-ent preconditioned matrices to verify the effectiveness of the preconditioners proposed in this paper.展开更多
Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Ph...Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Phytohemagglutinin-M,Gibco)stimulated blood T lymphocytes by Giemsa trypsin Giemsa banding and Ag-NOR banding on 580 couples with a history of idiopathic recurrent pregnancy loss and 240 couples from the general population.Thirty good chromosomal spreads were captured,karyotyped,and analyzed.The karyotypes were designated using the International System for Human Cytogenomic Nomenclature 2024.Pearson Chi-square test was used to compare the frequency of chromosomal polymorphism variations in the idiopathic recurrent pregnancy loss group with the general population group.Results:A conventional cytogenetic investigation revealed that 45.43%of couples experiencing idiopathic recurrent pregnancy loss presented with various types of chromosomal polymorphic variants,compared to 11.88%in the general population.The overall frequency of these chromosomal polymorphic variants was significantly higher in the idiopathic recurrent pregnancy loss group compared to the general population group(OR 9.97,95%CI 6.99-14.21;P<0.05).Additionally,the prevalence of polymorphic variants was higher among males(49.14%)than females(41.72%)(P=0.01).Conclusions:Chromosomal polymorphic analysis may play a crucial role in the assessment and careful clinical management of cases with idiopathic recurrent pregnancy loss,especially when no other conclusive reasons are identified during the initial evaluation.Therefore,heteromorphism should not be overlooked while investigating the causes of idiopathic recurrent pregnancy loss.展开更多
OBJECTIVE:To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs(TCHs)as an alternative to conventional medicine(CM)in children with cough variant asthma(CVA).METHODS:Randomiz...OBJECTIVE:To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs(TCHs)as an alternative to conventional medicine(CM)in children with cough variant asthma(CVA).METHODS:Randomized controlled trial(RCT)studies that were published from their inceptions to March 31,2020,were identified from the electronic databases of China National Knowledge Infrastructure,Wangfang,Pub Med,and Cochrane Central Library.The primary outcome of the review was the total effective rate(TER),and the secondary outcomes were immunoglobulin E(Ig E),peak expiratory flow(PEF),adverse drug reactions,and relapse rates of interventions.RESULTS:For the Meta-analysis,13 studies involving 992 children with CVA were included.In terms of TER and Ig E,the experimental interventions of TCH,when compared with the control interventions of CM,on pediatric CVA were found to be significantly effective(P<0.0001),whereas for spirometry,PEF was not significantly improved in the TCH group(P=0.48).The incident rates of adverse drug reaction and relapse were found to be significantly lower in the TCH group than those in the CM group(P=0.02 and P<0.0001,respectively).CONCLUSION:Compared with CM therapy,the effects of TCH therapy on pediatric CVA were significantly beneficial in terms of TER and Ig E,but not for PEF,and the methodological quality of included studies was poor.Therefore,the results should be interpreted with caution.More randomized controlled trials with rigorous experimental methodologies are required for objectivity in the future.展开更多
Understanding the functional effects of genetic variants is crucial in modern genomics and genetics. Transcription factor binding sites （TFBSs） are one of the most important cis-regulatory elements. While multiple t...Understanding the functional effects of genetic variants is crucial in modern genomics and genetics. Transcription factor binding sites （TFBSs） are one of the most important cis-regulatory elements. While multiple tools have been developed to assess functional effects of genetic variants at TFBSs, they usually assume that each variant works in isolation and neglect the potential ＂interference＂ among multiple variants within the same TFBS. In this study, we presented COPE-TFBS （Context-Oriented Predictor for variant Effect on Transcription Factor Binding Site）, a novel method that considers sequence context to accurately predict variant effects on TFBSs. We systematically re-analyzed the sequencing data from both the 1000 Genomes Project and the Genotype-Tissue Expression （GTEx） Project via COPE-TFBS, and identified numbers of novel TFBSs, transformed TFBSs and discordantly annotated TFBSs resulting from multiple variants, further highlighting the necessity of sequence context in accurately annotating genetic variants.展开更多
Stream cipher, DNA cryptography and DNA analysis are the most important R&D fields in both Cryptography and Bioinformatics. HC-256 is an emerged scheme as the new generation of stream ciphers for advanced network ...Stream cipher, DNA cryptography and DNA analysis are the most important R&D fields in both Cryptography and Bioinformatics. HC-256 is an emerged scheme as the new generation of stream ciphers for advanced network security. From a random sequencing viewpoint, both sequences of HC-256 and real DNA data may have intrinsic pseudo-random properties respectively. In a recent decade, many DNA sequencing projects are developed on cells, plants and animals over the world into huge DNA databases. Researchers notice that mammalian genomes encode thousands of large noncoding RNAs (lncRNAs), interact with chromatin regulatory complexes, and are thought to play a role in localizing these complexes to target loci across the genome. It is a challenge target using higher dimensional visualization tools to organize various complex interactive properties as visual maps. The Variant Map System (VMS) as an emerging scheme is systematically proposed in this paper to apply multiple maps that used four Meta symbols as same as DNA or RNA representations. System architecture of key components and core mechanism on the VMS are described. Key modules, equations and their I/O parameters are discussed. Applying the VM System, two sets of real DNA sequences from both sample human (noncoding DNA) and corn (coding DNA) genomes are collected in comparison with pseudo DNA sequences generated by HC-256 to show their intrinsic properties in higher levels of similar relationships among relevant DNA sequences on 2D maps. Sample 2D maps are listed and their characteristics are illustrated under controllable environment. Visual results are briefly analyzed to explore their intrinsic properties on selected genome sequences.展开更多
The paper gives a detail analysis on the necessity of rapid hydraulic support design, and presents a computer-aided rapid variant design system for hydraulic support. The system integrates the type selection and embod...The paper gives a detail analysis on the necessity of rapid hydraulic support design, and presents a computer-aided rapid variant design system for hydraulic support. The system integrates the type selection and embodiment design of hydraulic support. Case-based reasoning and rule-based reasoning are the main reasoning methods. Several crucial problems are discussed.展开更多
The production model of“multi-specification and low-quantity”is becoming the main trend of manufacturing industry.As a key activity in the manufacturing chain,traditional computer aided process planning(CAPP)system ...The production model of“multi-specification and low-quantity”is becoming the main trend of manufacturing industry.As a key activity in the manufacturing chain,traditional computer aided process planning(CAPP)system fails to adapt to the production model of customization.Therefore,a novel method for variant design of process planning was proposed to develop CAPP system based on Tabular Layouts of Article Characteristics(Sach-Merk Leisten in German and SML for short). With the support of standard database of master process planning documents which are developed by parameterization technique, and instance process planning for special product(instance product)can be generated automatically by the sub-system of variant de- sign of process planning.Finally,a CAPP system was developed for process design of rotor of steam turbine to validate the feasibil- ity and applicability of the method.展开更多
In this paper the generalized Bianchi's identities for the variant constrained system (GBIVOS)w ith non-invariant action integral and constraint conditions was derived, and the strong and weak conservation laws fo...In this paper the generalized Bianchi's identities for the variant constrained system (GBIVOS)w ith non-invariant action integral and constraint conditions was derived, and the strong and weak conservation laws for such system was deduced. The preliminary applications of the GBIVCS to the case for some models of field theories was given. The Dirac constraint of such system was discussed.展开更多
BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare subtype of extranodal lymphoma.In particular,the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow in...BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare subtype of extranodal lymphoma.In particular,the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow involvement.However,central nervous system(CNS)involvement is uncommon in this variant compared to the Western variant.Here,we report a case of typical Asian variant IVLBCL with highly suspected CNS involvement and discuss the nature of the disease and its genetic aberration.CASE SUMMARY A 67-year-old female patient complained of gradually worsening cognitive impairment.While hospitalized,she developed a high fever and showed marked bicytopenia.Intracranial imaging revealed a suspected leptomeningeal disease.Although no malignant cells were found in the cerebrospinal fluid(CSF),the protein and lactate dehydrogenase levels in CSF were increased.Bone marrow examination revealed an increased number of hemophagocytic histiocytes,and 18F-fluorodeoxyglucose(FDG)positron emission tomography with computerized tomography scan revealed increased FDG uptake in both adrenal glands,the liver,and the right ethmoid sinus.A tissue biopsy showed atypical large lymphoid cells with prominent nucleoli in the vessels,and the tumor cells were positive for CD20,BCL2,BCL6,and IRF4/MUM1.In addition,targeted sequencing identified MYD88,TET2,and PIM1 mutations.Consequently,we diagnosed the patient with the Asian variant of IVLBCL with highly suspected CNS involvement.CONCLUSION Suspicion of IVLBCL and immediate diagnosis lead to timely treatment.Moreover,careful CNS examination at diagnosis is recommended.展开更多
Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be a...Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be accompanied by clinical symptoms such as dysmenorrhea,fatigue,dysuria,deep dyspareunia,and infertility.Due to the complex etiology and the yet-unknown pathogenesis of endometriosis,and the treatment effect is not ideal,causing significant physical and mental harm to reproductive-age women;thus,it has become a hot research topic.Endometriosis is still a mysterious disease of unknown origin and pathogenesis.Genetic factors are known to affect the manifestation and progression of endometriosis.A selection of genetic studies revealed genetic mutations and polymorphisms of endometriosis and their effects on the risk of developing this disease.This paper aimed to discuss the genetic variants associated with the risk of endometriosis and provided information to enrich the gene spectrum of endometriosis.展开更多
Objective:A comprehensive and updated systematic review is needed to evaluate the effectiveness and safety of HuangQiXiXin decoction(HQXXD)for cough variant asthma(CVA).The aim of this systematic review protocol is to...Objective:A comprehensive and updated systematic review is needed to evaluate the effectiveness and safety of HuangQiXiXin decoction(HQXXD)for cough variant asthma(CVA).The aim of this systematic review protocol is to comprehensively assess the effectiveness and safety of HQXXD for CVA.Methods:An overall search for studies in main English and Chinese electronic databases from their inception to January 2021 will be performed.Randomized controlled trials regarding HQXXD for CVA will be included.We will use RevMan 5.3 software to perform statistical analysis and meta-analysis.Results:The findings of this systematic review will be disseminated through peer-reviewed publications.Conclusion:The systematic review will provide more evidence regarding the effectiveness and safety of HQXXD for CVA.展开更多
The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findin...The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.展开更多
Based on the concept of discrete adiabatic invariant, this paper studies the perturbation to Mei symmetry and Mei adiabatic invariants of the discrete generalized Birkhoffian system. The discrete Mei exact invariant i...Based on the concept of discrete adiabatic invariant, this paper studies the perturbation to Mei symmetry and Mei adiabatic invariants of the discrete generalized Birkhoffian system. The discrete Mei exact invariant induced from the Mei symmetry of the system without perturbation is given. The criterion of the perturbation to Mei symmetry is established and the discrete Mei adiabatic invariant induced from the perturbation to Mei symmetry is obtained. Meanwhile, an example is discussed to illustrate the application of the results.展开更多
BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the ...BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.展开更多
Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research....Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.展开更多
BACKGROUND The evolutionary mutational changes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since its emergence in Chhattisgarh,India in 2020 have warranted the need for the characterization of every ...BACKGROUND The evolutionary mutational changes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since its emergence in Chhattisgarh,India in 2020 have warranted the need for the characterization of every lineage/sublineage that has evolved until February 2024.AIM To unravel the evolutionary pathway of SARS-CoV-2 in Chhattisgarh from 2020 to February 2024.METHODS A total of 635 coronavirus disease 2019 cases obtained between 2020 and February 2024 were investigated by whole genome sequencing.RESULTS Whole genome sequencing analysis identified the evolution of SARS-CoV-2 into seventeen lineages from 2020 to 2024.SARS-CoV-2 initially emerged in Chhattisgarh in its Alpha(B.1.1.7)variant in 2020.Thereafter,it continuously underwent periodical mutational changes in the spike gene to further differentiate into various lineages/sublineages,viz.,Kappa,Delta,BA.1,and BA.2 in 2021;the Omicron lineage(BA.5,BA.2.12.1,BA.2.75,BQ.1,and XBB)in 2022;the new Omicron lineage(XBB.1.5,XBB.1.16,XBB.1.9.1,and XBB.2.3)in 2023;and finally to JN.1 in January and February 2024.The predominant lineages over these 4 years were BA.1.1.7(Alpha)in 2020,B.1.617.2(Delta)in the period between 2021 and mid-2022,B.1.1.529(Omicron)in late 2022 to 2023,and Omicron-JN.1 in early 2024.The presently circulating JN.1 lineage was observed harboring exclusive predominant mutations of E4554K,A570V,P621A,and P1143 L with 99%CONCLUSION SARS-CoV-2 from 2020 to 2024 has evolved into 17 lineages/sublineages in Chhattisgarh.The presently circulating JN.1 harbored 40 mutations,especially E554K,A570V,P621S,and P1143 L,capacitating the virus with features of host cell entry,stability,replication,rapid transmissibility,and crucial immune evasion.Therefore,earlier immunity from either vaccination or prior infection may not protect against the current lineage and increases the possibility of future outbreaks.Thus,the periodical genomic surveillance of SARS-CoV-2 is essential for the genomic blueprint of the circulating virus,which may help in updating the vaccine strain and various basic research for developing appropriate therapeutics and diagnostics.展开更多
Barley(Hordeum vulgare L.)employs the Na^(+)transporter HvHKT1;1,which is an N^(+)-selective transporter.This study characterized the full-length HvHKT1;1(HvHKT1;1-FL)and three mRNA variants(HvHKT1;1-V1,-V2,and-V3),wh...Barley(Hordeum vulgare L.)employs the Na^(+)transporter HvHKT1;1,which is an N^(+)-selective transporter.This study characterized the full-length HvHKT1;1(HvHKT1;1-FL)and three mRNA variants(HvHKT1;1-V1,-V2,and-V3),which encode polypeptides of 64.7,54.0,40.5,and 32.9 kDa,respectively.Tissue-specific expression profiling revealed that HvHKT1;1-FL is the most abundant transcript across leaf,sheath,and root tissues under normal conditions,with the highest expression in leaves.Under 150 mM NaCl stress,HvHKT1;1-FL and its variants showed a dynamic,time-dependent expression pattern,with peak leaf expression at 2 h,sheath expression at 12 h,and root expression at 2 h,suggesting their roles in early stress response.Functional analysis using two-electrode voltage-clamp measurements demonstrated thatHvHKT1;1-FL is highly selective for Na^(+),withminimal conductance for K^(+),Li^(+),Rb^(+),or Cs^(+).It demonstrated high Na^(+)transport efficiency,characterized by higher Vmax and lower Km values,while the variants showed reducedNa^(+)currents,lowerVmax,and higherKmvalues,indicating decreasedNa^(+)transport capacity.Reversal potential analyses further confirmed Na^(+)selectivity,with HvHKT1;1-FL displaying the strongest preference for Na^(+).Notably,while all variants retained Na^(+)selectivity,they showed reduced efficiency,as indicated by a more negative reversal potential in low Na^(+)conditions.These findings highlight the functional diversity among HvHKT1;1 variants,with HvHKT1;1-FL playing a dominant role in Na^(+)transport.The tissue-specific regulation of these variants under salinity stress underscores their importance in barley’s adaptive responses.展开更多
Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune press...Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.展开更多
Congenital heart disease(CHD)is the mnost comman birth defect,with 34%of cases attrib utedto genetic variants.NOTCH1,a multi-domain transmembrane protein,regulates heart developmert bycontrolling the differantiation a...Congenital heart disease(CHD)is the mnost comman birth defect,with 34%of cases attrib utedto genetic variants.NOTCH1,a multi-domain transmembrane protein,regulates heart developmert bycontrolling the differantiation and migration of myocardial mesoderm cells,and different variants are presentin differnt types of CHD.In this review,we aim to provide a detailed description of NOTCH1 structuraldomains and their functions,highlighting NOTCH1 variants in CHD and the molecular mechanisms throughwhich they contribute to CHD occurrence,NOTCH1 has two main domains,the NOTCH extracellulardomain(NBCD)and the NOTCH intracellular domain(NICD).NECD facilitates ligand binding and NICDformation,while the NICD functions as a transcrip tion factor,forming complexes with co-factors in thenucleus to initiate gene transcription.Amnong the NOTCH1 variants associated with CHD occurrence,most are loss-of-function variants.Moreover,most of the variants are located in theEGF-like domain.Themolecular mechanism behind the NOTCH1 variant-associated CHD occurrence appears to be either due to aloss-of-function or missense variant.In the loss-of-function mutations,NOTCH1 haploinsufficiency is notedand directly reduces theNICD production,causing CHD ocaurrence.In the less common case of missensevariant,only a mild NOTCH1 malfuncticn is observed,but insufficient to directly lead to CHD occurrence.However,when a missense variant is combined with a risk factor,such as exposure to an environmentaltoxin,the cumulative effect can lead to CHD.Understanding the genetic and molecular mechanisms linkingNOTCH1 variants to CHD is crucial for improving clinical management and patient quality of life.展开更多
基金Project (50078006) supported by the National Natural Science Foundation of China Project (2001G029) supported by the Foundation of the Science and Technology Section of the Railway Bureau
文摘There exist three problems in the calculation of lateral vibration of the train-track time-variant system athome and abroad and the method to solve them is presented. Spatially coupling vibration analysis model of train-track time-variant system is put forward. Each vehicle is modeled as a multi-body system with 26 degrees of freedomand the action of coupler is also considered. The track structure is modeled as an assembly of track elements with 30degrees of freedom, then the spatially coupling vibration matrix equation of the train-track time-variant system is es-tablished on the basis of the principle of total potential energy with stationary value and the "set-in-right-position"rule. The track vertical geometric irregularity is considered as the excitation source of the vertical vibration of thesystem, and the hunting wave of car bogie frame is taken as the excitation source of lateral vibration of the system.The spatially coupling vibration matrix equation of the system is solved by Wilson-θ direct integration method. Theapproximation of the calculated results to the spot test results demonstrates the feasibility and effectiveness of thepresented analysis method. Finally, some other vibration responses of the system are also obtained.
基金supported by the National Natural Science Foundation of China(Grant No.12371378)by the Natural Science Foundation of Fujian Province(Grant Nos.2024J01980,2024J08242).
文摘Recently,inspired by a modified generalized shift-splitting iteration method for complex symmetric linear systems,we propose two variants of the modified generalized shift-splitting iteration(MGSS)methods for solving com-plex symmetric linear systems.One is a parameterized MGSS iteration method and the other is a modified parameterized MGSS iteration method.We prove that the proposed methods are convergent under appropriate constraints on the parameters.In addition,we also give the eigenvalue distributions of differ-ent preconditioned matrices to verify the effectiveness of the preconditioners proposed in this paper.
基金funded by the Technology Development Board(TDB)of India's Ministry of Science and Technology(TDB/M-25/2018-19).
文摘Objective:To investigate the potential link between chromosomal polymorphisms in couples who had a medical history of idiopathic recurrent pregnancy loss.Methods:Cytogenetic investigation was conducted with mitogen(Phytohemagglutinin-M,Gibco)stimulated blood T lymphocytes by Giemsa trypsin Giemsa banding and Ag-NOR banding on 580 couples with a history of idiopathic recurrent pregnancy loss and 240 couples from the general population.Thirty good chromosomal spreads were captured,karyotyped,and analyzed.The karyotypes were designated using the International System for Human Cytogenomic Nomenclature 2024.Pearson Chi-square test was used to compare the frequency of chromosomal polymorphism variations in the idiopathic recurrent pregnancy loss group with the general population group.Results:A conventional cytogenetic investigation revealed that 45.43%of couples experiencing idiopathic recurrent pregnancy loss presented with various types of chromosomal polymorphic variants,compared to 11.88%in the general population.The overall frequency of these chromosomal polymorphic variants was significantly higher in the idiopathic recurrent pregnancy loss group compared to the general population group(OR 9.97,95%CI 6.99-14.21;P<0.05).Additionally,the prevalence of polymorphic variants was higher among males(49.14%)than females(41.72%)(P=0.01).Conclusions:Chromosomal polymorphic analysis may play a crucial role in the assessment and careful clinical management of cases with idiopathic recurrent pregnancy loss,especially when no other conclusive reasons are identified during the initial evaluation.Therefore,heteromorphism should not be overlooked while investigating the causes of idiopathic recurrent pregnancy loss.
文摘OBJECTIVE:To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs(TCHs)as an alternative to conventional medicine(CM)in children with cough variant asthma(CVA).METHODS:Randomized controlled trial(RCT)studies that were published from their inceptions to March 31,2020,were identified from the electronic databases of China National Knowledge Infrastructure,Wangfang,Pub Med,and Cochrane Central Library.The primary outcome of the review was the total effective rate(TER),and the secondary outcomes were immunoglobulin E(Ig E),peak expiratory flow(PEF),adverse drug reactions,and relapse rates of interventions.RESULTS:For the Meta-analysis,13 studies involving 992 children with CVA were included.In terms of TER and Ig E,the experimental interventions of TCH,when compared with the control interventions of CM,on pediatric CVA were found to be significantly effective(P<0.0001),whereas for spirometry,PEF was not significantly improved in the TCH group(P=0.48).The incident rates of adverse drug reaction and relapse were found to be significantly lower in the TCH group than those in the CM group(P=0.02 and P<0.0001,respectively).CONCLUSION:Compared with CM therapy,the effects of TCH therapy on pediatric CVA were significantly beneficial in terms of TER and Ig E,but not for PEF,and the methodological quality of included studies was poor.Therefore,the results should be interpreted with caution.More randomized controlled trials with rigorous experimental methodologies are required for objectivity in the future.
基金supported by funds from the National Key R&D Program of China (2016YFC0901603)the China 863 Program (2015AA020108)+1 种基金the State Key Laboratory of Protein and Plant Gene Researchsupported in part by the National Program for Support of Top-notch Young Professionals
文摘Understanding the functional effects of genetic variants is crucial in modern genomics and genetics. Transcription factor binding sites （TFBSs） are one of the most important cis-regulatory elements. While multiple tools have been developed to assess functional effects of genetic variants at TFBSs, they usually assume that each variant works in isolation and neglect the potential ＂interference＂ among multiple variants within the same TFBS. In this study, we presented COPE-TFBS （Context-Oriented Predictor for variant Effect on Transcription Factor Binding Site）, a novel method that considers sequence context to accurately predict variant effects on TFBSs. We systematically re-analyzed the sequencing data from both the 1000 Genomes Project and the Genotype-Tissue Expression （GTEx） Project via COPE-TFBS, and identified numbers of novel TFBSs, transformed TFBSs and discordantly annotated TFBSs resulting from multiple variants, further highlighting the necessity of sequence context in accurately annotating genetic variants.
文摘Stream cipher, DNA cryptography and DNA analysis are the most important R&D fields in both Cryptography and Bioinformatics. HC-256 is an emerged scheme as the new generation of stream ciphers for advanced network security. From a random sequencing viewpoint, both sequences of HC-256 and real DNA data may have intrinsic pseudo-random properties respectively. In a recent decade, many DNA sequencing projects are developed on cells, plants and animals over the world into huge DNA databases. Researchers notice that mammalian genomes encode thousands of large noncoding RNAs (lncRNAs), interact with chromatin regulatory complexes, and are thought to play a role in localizing these complexes to target loci across the genome. It is a challenge target using higher dimensional visualization tools to organize various complex interactive properties as visual maps. The Variant Map System (VMS) as an emerging scheme is systematically proposed in this paper to apply multiple maps that used four Meta symbols as same as DNA or RNA representations. System architecture of key components and core mechanism on the VMS are described. Key modules, equations and their I/O parameters are discussed. Applying the VM System, two sets of real DNA sequences from both sample human (noncoding DNA) and corn (coding DNA) genomes are collected in comparison with pseudo DNA sequences generated by HC-256 to show their intrinsic properties in higher levels of similar relationships among relevant DNA sequences on 2D maps. Sample 2D maps are listed and their characteristics are illustrated under controllable environment. Visual results are briefly analyzed to explore their intrinsic properties on selected genome sequences.
文摘The paper gives a detail analysis on the necessity of rapid hydraulic support design, and presents a computer-aided rapid variant design system for hydraulic support. The system integrates the type selection and embodiment design of hydraulic support. Case-based reasoning and rule-based reasoning are the main reasoning methods. Several crucial problems are discussed.
文摘The production model of“multi-specification and low-quantity”is becoming the main trend of manufacturing industry.As a key activity in the manufacturing chain,traditional computer aided process planning(CAPP)system fails to adapt to the production model of customization.Therefore,a novel method for variant design of process planning was proposed to develop CAPP system based on Tabular Layouts of Article Characteristics(Sach-Merk Leisten in German and SML for short). With the support of standard database of master process planning documents which are developed by parameterization technique, and instance process planning for special product(instance product)can be generated automatically by the sub-system of variant de- sign of process planning.Finally,a CAPP system was developed for process design of rotor of steam turbine to validate the feasibil- ity and applicability of the method.
基金This work was supported by Beijing Science Foundation of the People's Republie of China.
文摘In this paper the generalized Bianchi's identities for the variant constrained system (GBIVOS)w ith non-invariant action integral and constraint conditions was derived, and the strong and weak conservation laws for such system was deduced. The preliminary applications of the GBIVCS to the case for some models of field theories was given. The Dirac constraint of such system was discussed.
基金The institutional review board of Chungbuk National University Hospital approved this study(approval number.CBNUH 2023-04-024)informed written consent was obtained from the patient for publication of this report and any accompanying images.
文摘BACKGROUND Intravascular large B-cell lymphoma(IVLBCL)is a rare subtype of extranodal lymphoma.In particular,the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow involvement.However,central nervous system(CNS)involvement is uncommon in this variant compared to the Western variant.Here,we report a case of typical Asian variant IVLBCL with highly suspected CNS involvement and discuss the nature of the disease and its genetic aberration.CASE SUMMARY A 67-year-old female patient complained of gradually worsening cognitive impairment.While hospitalized,she developed a high fever and showed marked bicytopenia.Intracranial imaging revealed a suspected leptomeningeal disease.Although no malignant cells were found in the cerebrospinal fluid(CSF),the protein and lactate dehydrogenase levels in CSF were increased.Bone marrow examination revealed an increased number of hemophagocytic histiocytes,and 18F-fluorodeoxyglucose(FDG)positron emission tomography with computerized tomography scan revealed increased FDG uptake in both adrenal glands,the liver,and the right ethmoid sinus.A tissue biopsy showed atypical large lymphoid cells with prominent nucleoli in the vessels,and the tumor cells were positive for CD20,BCL2,BCL6,and IRF4/MUM1.In addition,targeted sequencing identified MYD88,TET2,and PIM1 mutations.Consequently,we diagnosed the patient with the Asian variant of IVLBCL with highly suspected CNS involvement.CONCLUSION Suspicion of IVLBCL and immediate diagnosis lead to timely treatment.Moreover,careful CNS examination at diagnosis is recommended.
基金This work was financially supported by the Sci-Tech Planning Project of Jiaxing,China(2019AY32008 to BH),and the Res-Training Project of JUMC,China(JUMC2020-06 to DC).
文摘Endometriosis is defined as the presence of endometrium-like tissue outside the uterus,80%of which occur in the ovaries.It is characterized by an estrogen-dependent produces periodic and repeated bleeding,and may be accompanied by clinical symptoms such as dysmenorrhea,fatigue,dysuria,deep dyspareunia,and infertility.Due to the complex etiology and the yet-unknown pathogenesis of endometriosis,and the treatment effect is not ideal,causing significant physical and mental harm to reproductive-age women;thus,it has become a hot research topic.Endometriosis is still a mysterious disease of unknown origin and pathogenesis.Genetic factors are known to affect the manifestation and progression of endometriosis.A selection of genetic studies revealed genetic mutations and polymorphisms of endometriosis and their effects on the risk of developing this disease.This paper aimed to discuss the genetic variants associated with the risk of endometriosis and provided information to enrich the gene spectrum of endometriosis.
基金supported by the Scientific Research Project from the Health Commission of Wuxi(No.Q202055)Project of Clinical Research and Preparation in Jiangyin Hospital of Traditional Chinese Medicine(No.Z202109).
文摘Objective:A comprehensive and updated systematic review is needed to evaluate the effectiveness and safety of HuangQiXiXin decoction(HQXXD)for cough variant asthma(CVA).The aim of this systematic review protocol is to comprehensively assess the effectiveness and safety of HQXXD for CVA.Methods:An overall search for studies in main English and Chinese electronic databases from their inception to January 2021 will be performed.Randomized controlled trials regarding HQXXD for CVA will be included.We will use RevMan 5.3 software to perform statistical analysis and meta-analysis.Results:The findings of this systematic review will be disseminated through peer-reviewed publications.Conclusion:The systematic review will provide more evidence regarding the effectiveness and safety of HQXXD for CVA.
文摘The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.
基金Project supported by the Fundamental Research Funds for the Central Universities of China (Grant No. 09CX04018A)
文摘Based on the concept of discrete adiabatic invariant, this paper studies the perturbation to Mei symmetry and Mei adiabatic invariants of the discrete generalized Birkhoffian system. The discrete Mei exact invariant induced from the Mei symmetry of the system without perturbation is given. The criterion of the perturbation to Mei symmetry is established and the discrete Mei adiabatic invariant induced from the perturbation to Mei symmetry is obtained. Meanwhile, an example is discussed to illustrate the application of the results.
基金Supported by Patronage of the Autonomous University of Nayarit,Quality Postgraduate Program with resources from the 15%Special Tax allocated to the UAN 2022.
文摘BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.
基金supported by the Key Project of the National Natural Science Foundation of China(82030030)the National Natural Science Foundation of China(82171836)+1 种基金the Science and Technology Department of Sichuan Province(2024NSFSC0648)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC20002).
文摘Multiple nucleotide variants(MNVs)are frequently misannotated as separate single-nucleotide variants(SNVs)by widely utilized variant-calling pipelines,presenting substantial challenges in genetic testing and research.The role of MNVs in genetic diagnosis remains inadequately characterized,particularly within large disease cohorts.In this study,we comprehensively investigate codon-level MNVs(cMNVs)across 157 hearing loss(HL)-related genes in 11,467 HL cases and 7258 controls from the Chinese Deafness Gene Consortium(CDGC)cohort.A total of 116 cMNVs are identified,occurring in 29.07%of HL cases.Among them,56.03%of cMNVs exhibit functional consequences distinct from constituent SNVs.Moreover,amino acid substitutions exclusive to cMNVs cause more substantial physicochemical disruptions than those associated with SNVs.Notably,51 cMNVs show pathogenicity classifications that diverge from at least one constituent SNV,impacting genetic interpretation in 145 cases.Pathogenicity interpretation of cMNV facilitates definitive genetic diagnoses in eight HL cases that would otherwise have been subject to misdiagnoses or missed diagnoses.These findings provide critical insights into the genomic characteristics,functional impacts,and diagnostic implications of cMNVs,underscoring their clinical significance in genetic diagnosis and emphasizing the necessity for comprehensive and accurate detection and interpretation of cMNVs in genetic testing and research.
文摘BACKGROUND The evolutionary mutational changes of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)since its emergence in Chhattisgarh,India in 2020 have warranted the need for the characterization of every lineage/sublineage that has evolved until February 2024.AIM To unravel the evolutionary pathway of SARS-CoV-2 in Chhattisgarh from 2020 to February 2024.METHODS A total of 635 coronavirus disease 2019 cases obtained between 2020 and February 2024 were investigated by whole genome sequencing.RESULTS Whole genome sequencing analysis identified the evolution of SARS-CoV-2 into seventeen lineages from 2020 to 2024.SARS-CoV-2 initially emerged in Chhattisgarh in its Alpha(B.1.1.7)variant in 2020.Thereafter,it continuously underwent periodical mutational changes in the spike gene to further differentiate into various lineages/sublineages,viz.,Kappa,Delta,BA.1,and BA.2 in 2021;the Omicron lineage(BA.5,BA.2.12.1,BA.2.75,BQ.1,and XBB)in 2022;the new Omicron lineage(XBB.1.5,XBB.1.16,XBB.1.9.1,and XBB.2.3)in 2023;and finally to JN.1 in January and February 2024.The predominant lineages over these 4 years were BA.1.1.7(Alpha)in 2020,B.1.617.2(Delta)in the period between 2021 and mid-2022,B.1.1.529(Omicron)in late 2022 to 2023,and Omicron-JN.1 in early 2024.The presently circulating JN.1 lineage was observed harboring exclusive predominant mutations of E4554K,A570V,P621A,and P1143 L with 99%CONCLUSION SARS-CoV-2 from 2020 to 2024 has evolved into 17 lineages/sublineages in Chhattisgarh.The presently circulating JN.1 harbored 40 mutations,especially E554K,A570V,P621S,and P1143 L,capacitating the virus with features of host cell entry,stability,replication,rapid transmissibility,and crucial immune evasion.Therefore,earlier immunity from either vaccination or prior infection may not protect against the current lineage and increases the possibility of future outbreaks.Thus,the periodical genomic surveillance of SARS-CoV-2 is essential for the genomic blueprint of the circulating virus,which may help in updating the vaccine strain and various basic research for developing appropriate therapeutics and diagnostics.
基金supported by JSPS KAKENHI Grant Number JP20K06708 to Maki Katsuhara,and an OU fellowship to Shahin Imran.
文摘Barley(Hordeum vulgare L.)employs the Na^(+)transporter HvHKT1;1,which is an N^(+)-selective transporter.This study characterized the full-length HvHKT1;1(HvHKT1;1-FL)and three mRNA variants(HvHKT1;1-V1,-V2,and-V3),which encode polypeptides of 64.7,54.0,40.5,and 32.9 kDa,respectively.Tissue-specific expression profiling revealed that HvHKT1;1-FL is the most abundant transcript across leaf,sheath,and root tissues under normal conditions,with the highest expression in leaves.Under 150 mM NaCl stress,HvHKT1;1-FL and its variants showed a dynamic,time-dependent expression pattern,with peak leaf expression at 2 h,sheath expression at 12 h,and root expression at 2 h,suggesting their roles in early stress response.Functional analysis using two-electrode voltage-clamp measurements demonstrated thatHvHKT1;1-FL is highly selective for Na^(+),withminimal conductance for K^(+),Li^(+),Rb^(+),or Cs^(+).It demonstrated high Na^(+)transport efficiency,characterized by higher Vmax and lower Km values,while the variants showed reducedNa^(+)currents,lowerVmax,and higherKmvalues,indicating decreasedNa^(+)transport capacity.Reversal potential analyses further confirmed Na^(+)selectivity,with HvHKT1;1-FL displaying the strongest preference for Na^(+).Notably,while all variants retained Na^(+)selectivity,they showed reduced efficiency,as indicated by a more negative reversal potential in low Na^(+)conditions.These findings highlight the functional diversity among HvHKT1;1 variants,with HvHKT1;1-FL playing a dominant role in Na^(+)transport.The tissue-specific regulation of these variants under salinity stress underscores their importance in barley’s adaptive responses.
基金National Science and Technology Infrastructure of China,Grant/Award Number:National Pathogen Resource Center-NPRC-32National Key Research and Development Program of China,Grant/Award Number:2023YFF0724800CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-035。
文摘Background:New variants of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continue to drive global epidemics and pose significant health risks.The pathogenicity of these variants evolves under immune pressure and host factors.Understanding these changes is crucial for epidemic control and variant research.Methods:Human angiotensin-converting enzyme 2(hACE2)transgenic mice were in-tranasally challenged with the original strain WH-09 and the variants Delta,Beta,and Omicron BA.1,while BALB/c mice were challenged with Omicron subvariants BA.5,BF.7,and XBB.1.To compare the pathogenicity differences among variants,we con-ducted a comprehensive analysis that included clinical symptom observation,meas-urement of viral loads in the trachea and lungs,evaluation of pulmonary pathology,analysis of immune cell infiltration,and quantification of cytokine levels.Results:In hACE2 mice,the Beta variant caused significant weight loss,severe lung inflammation,increased inflammatory and chemotactic factor secretion,greater mac-rophage and neutrophil infiltration in the lungs,and higher viral loads with prolonged shedding duration.In contrast,BA.1 showed a significant reduction in pathogenicity.The BA.5,BF.7,and XBB.1 variants were less pathogenic than the WH-09,Beta,and Delta variants when infected in BALB/c mice.This was evidenced by reduced weight loss,diminished pulmonary pathology,decreased secretion of inflammatory factors and chemokines,reduced macrophage and neutrophil infiltration,as well as lower viral loads in both the trachea and lungs.Conclusion:In hACE2 mice,the Omicron variant demonstrated the lowest pathogenic-ity,while the Beta variant exhibited the highest.Pathogenicity of the Delta variant was comparable to the original WH-09 strain.Among BALB/c mice,Omicron subvari-ants BA.5,BF.7,and XBB.1 showed no statistically significant differences in virulence.
基金the National Natural Science Foundation of China,GrantNos.82100321 and 82370353.
文摘Congenital heart disease(CHD)is the mnost comman birth defect,with 34%of cases attrib utedto genetic variants.NOTCH1,a multi-domain transmembrane protein,regulates heart developmert bycontrolling the differantiation and migration of myocardial mesoderm cells,and different variants are presentin differnt types of CHD.In this review,we aim to provide a detailed description of NOTCH1 structuraldomains and their functions,highlighting NOTCH1 variants in CHD and the molecular mechanisms throughwhich they contribute to CHD occurrence,NOTCH1 has two main domains,the NOTCH extracellulardomain(NBCD)and the NOTCH intracellular domain(NICD).NECD facilitates ligand binding and NICDformation,while the NICD functions as a transcrip tion factor,forming complexes with co-factors in thenucleus to initiate gene transcription.Amnong the NOTCH1 variants associated with CHD occurrence,most are loss-of-function variants.Moreover,most of the variants are located in theEGF-like domain.Themolecular mechanism behind the NOTCH1 variant-associated CHD occurrence appears to be either due to aloss-of-function or missense variant.In the loss-of-function mutations,NOTCH1 haploinsufficiency is notedand directly reduces theNICD production,causing CHD ocaurrence.In the less common case of missensevariant,only a mild NOTCH1 malfuncticn is observed,but insufficient to directly lead to CHD occurrence.However,when a missense variant is combined with a risk factor,such as exposure to an environmentaltoxin,the cumulative effect can lead to CHD.Understanding the genetic and molecular mechanisms linkingNOTCH1 variants to CHD is crucial for improving clinical management and patient quality of life.
