ThePigeon-InspiredOptimization(PIO)algorithmconstitutes ametaheuristic method derived fromthe homing behaviour of pigeons.Initially formulated for three-dimensional path planning in unmanned aerial vehicles(UAVs),the ...ThePigeon-InspiredOptimization(PIO)algorithmconstitutes ametaheuristic method derived fromthe homing behaviour of pigeons.Initially formulated for three-dimensional path planning in unmanned aerial vehicles(UAVs),the algorithmhas attracted considerable academic and industrial interest owing to its effective balance between exploration and exploitation,coupled with advantages in real-time performance and robustness.Nevertheless,as applications have diversified,limitations in convergence precision and a tendency toward premature convergence have become increasingly evident,highlighting a need for improvement.This reviewsystematically outlines the developmental trajectory of the PIO algorithm,with a particular focus on its core applications in UAV navigation,multi-objective formulations,and a spectrum of variantmodels that have emerged in recent years.It offers a structured analysis of the foundational principles underlying the PIO.It conducts a comparative assessment of various performance-enhanced versions,including hybrid models that integrate mechanisms from other optimization paradigms.Additionally,the strengths andweaknesses of distinct PIOvariants are critically examined frommultiple perspectives,including intrinsic algorithmic characteristics,suitability for specific application scenarios,objective function design,and the rigor of the statistical evaluation methodologies employed in empirical studies.Finally,this paper identifies principal challenges within current PIO research and proposes several prospective research directions.Future work should focus on mitigating premature convergence by refining the two-phase search structure and adjusting the exponential decrease of individual numbers during the landmark operator.Enhancing parameter adaptation strategies,potentially using reinforcement learning for dynamic tuning,and advancing theoretical analyses on convergence and complexity are also critical.Further applications should be explored in constrained path planning,Neural Architecture Search(NAS),and other real-worldmulti-objective problems.For Multi-objective PIO(MPIO),key improvements include controlling the growth of the external archive and designing more effective selection mechanisms to maintain convergence efficiency.These efforts are expected to strengthen both the theoretical foundation and practical versatility of PIO and its variants.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
Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)r...Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.展开更多
NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-l...NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-like PRRSV evolved,named the L1A variant.The phylogenetics,epidemic status,and pathogenicity of the LA variants were subsequently comprehensively evaluated.Based on the results of the ORF5 phylogenetic analysis,the L1A variants were classified as NADC34-like PPRSV.All the strains had the same discontinuous 131-aa deletion in the NSP2 region(similar to that in the NADC30).Recombination analysis revealed that the L1A variants were recombinant viruses that contained an NADC30-like PRRSV skeleton,a nonstructural protein-encoding gene region obtained in part from JXA1-like PRRSV and a ORF2-ORF6 gene region partly obtained from NADC34-like PRRSV and that exhibited similar recombination patterns.We successfully isolated the L1A variant TZJ2756 from PAMs and Marc-145 cells.In animal experiments,TZJ2756 exhibited moderate pathogenicity in piglets,causing obvious clinical symptoms,namely,persistent fever,significantly reduced body weight,interstitial edema and severe interstitial pneumonia in the lungs,and prolonged high-load viremia.L1A variants have been detected in at least 12 provinces in China and share many similar epidemiological characteristics with the American L1C variant.This research will enhance our understanding of the prevalence of L1A variants and furnish valuable data for the ongoing monitoring of NADC34-like PRRSV in China.展开更多
Basal melting and calving are the main pathways for mass loss in Antarctic ice shelves.Basal channels,as detailed variations in basal melting,mutually promote basal melting and calving,thereby weakening the stability ...Basal melting and calving are the main pathways for mass loss in Antarctic ice shelves.Basal channels,as detailed variations in basal melting,mutually promote basal melting and calving,thereby weakening the stability of ice shelves.Therefore,it is necessary to calculate and statistically analyze basal melting,basal channels,and calving events across all Antarctic ice shelves and examine the correlation among these three factors.This study utilizes various data sources to calculate the Basal Channel Density(BCD)and average basal melt rate of all Antarctic ice shelves during 2010-2020,as well as the spatial correlation between basal melting,basal channels,and calving.We found that ice shelves along the Amundsen Sea and Bellingshausen Sea have higher basal melt rates and basal channel densities,while other sea areas have lower values.This is mainly influenced by seabed topography and Circumpolar Deep Water.Excluding(CDW)extreme calving events,there is a positive correlation among basal melting,basal channels,and calving in coastal ice shelves across different sea areas,with a correlation coefficient exceeding 0.67.This indicates that basal melting and basal channels are major factors causing ice shelf calving.Our results emphasize the importance of the impact of basal melting,basal channels,and calving on ice shelf stability,and they provide a significant reference for further research on ice shelf-ocean interactions.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
Introduction: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a neuroregressive disorder associated with subacute encephalopathy, confusion, dysarthria, and dysphagia, as well as occasional external ophtha...Introduction: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a neuroregressive disorder associated with subacute encephalopathy, confusion, dysarthria, and dysphagia, as well as occasional external ophthalmoplegia or supranuclear facial nerve palsy. It may progress to severe rigidity, dystonia, and quadriparesis. Combination therapy of high-dose thiamine and biotin helps to control the symptoms and prevent progression of the disease. Methods: This retrospective, cross-sectional study was conducted at King Fahad Medical City in Riyadh, Saudi Arabia, to investigate the demographic, clinical features, treatment response, outcomes, and predictive factors of BTBGD in the pediatric population. Results: Twenty-five records of pediatric patients diagnosed with BTBGD were included in the study. The most common symptoms observed at presentation were ataxia in 13 patients (52%), followed by developmental regression in 11 patients (44%), and seizures in 7 patients (28%). Statistically significant associations were found between patient’s age of presentation, seizures at presentation, lactate level and their health outcomes. Multivariate logistic regression analysis revealed significant differences in patient outcomes (prognosis) based on their age at presentation, seizures, and lactate levels (p Conclusion: This study reported BTBGD in 25 pediatric patients in Saudi Arabia. Age at presentation, seizures, and lactate levels were found to be significantly associated with patient health outcomes. Increasing public awareness of the condition, particularly among parents and pediatricians, is imperative. Early diagnosis, along with timely management using biotin and thiamine supplementation, promotes improved health outcomes and prevents progressive neurodegeneration and death.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
Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have i...Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become “inactive HBsAg carriers”. However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.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
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
The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KC...The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.展开更多
Models that predict a forest stand’s evolution are essential for developing plans for sustainable management.A simple mathematical framework was developed that con-siders the individual tree and stand basal area unde...Models that predict a forest stand’s evolution are essential for developing plans for sustainable management.A simple mathematical framework was developed that con-siders the individual tree and stand basal area under random resource competition and is based on two assumptions:(1)a sigmoid-type stochastic process governs tree and stand basal area dynamics of living and dying trees,and(2)the total area that a tree may potentially occupy determines the number of trees per hectare.The most effective method to satisfy these requirements is formalizing each tree diameter and potentially occupied area using Gompertz-type stochastic differential equations governed by fixed and mixed-effect parameters.Data from permanent experimental plots from long-term Lithuania experiments were used to construct the tree and stand basal area models.The new models were relatively unbiased for live trees of all species,including silver birch(Betula pen-dula Roth)and downy birch(Betula pubescens Ehrh.),[spruce(Picea abies),and pine(Pinus sylvestris)].Less reliable predic-tions were made for the basal area of dying trees.Pines gave the highest accuracy prediction of mean basal area among all live trees.The mean basal area prediction for all dying trees was lower than that for live trees.Among all species,pine also had the best average basal area prediction accuracy for live trees.Newly developed basal area growth and yield models can be recommended despite their complex formulation and implementation challenges,particularly in situations when data is scarce.This is because the newly observed plot provides sufficient information to calibrate random effects.展开更多
Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endother...Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.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
Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untr...Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untranslated regions(3'UTRs)on alternative polyadenylation(APA)of m RNA remains lacking.In this study,we analyze 10,199 tumor samples across 32 cancer types and identify 1333 somatic single nucleotide variants(SNVs)associated with abnormal 3'UTR APA.Mechanistically,these 3'UTR SNVs can alter cisregulatory elements,such as the poly(A)signal and UGUA motif,leading to changes in APA.Minigene assays confirm that 3'UTR SNVs in multiple genes,including RPS23 and CHTOP,induce aberrant APA.Among affected genes,62 exhibit differential stability between tandem 3'UTR isoforms,including HSPA4and UCK2,validated by experimental assays.Finally,we establish that SNV-related abnormal APA usage serves as an additional layer of expression regulation for tumor-suppressor gene HMGN2 in breast cancer.Collectively,this study reveals 3'UTR APA as a critical mechanism mediating the functional impact of somatic noncoding variants in human cancers.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
Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous famil...Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous family with biallelic variants in MED16 identified by exome sequencing.The affected individuals present with global developmental delay,intellectual disability,and dysmorphisms.To assess the pathogenicity of the variants,functional studies are performed in Drosophila and patient-derived cells.The fly ortholog med16 is expressed in neurons and some glia of the developing central nervous system(CNS).Loss of med16 leads to a reduction in eclosion and lifespan,as well as impaired synaptic transmission.In neurons differentiated from the patient-derived induced pluripotent stem cells(iPSCs),the neurite outgrowth is impaired and rescued by expression of exogenous MED16.The patient-associated variants behave as loss-of-function(LoF)alleles in flies and iPSCs.Additionally,the transcription of genes related to neuronal maturation and function is preferentially altered in patient cells relative to differentiated H9 controls.In summary,our findings support that MED16 is important for appropriate development and function,and that biallelic MED16 variants cause a neurodevelopmental disease.展开更多
基金supported by the National Natural Science Foundation of China under grant number 62066016the Natural Science Foundation of Hunan Province of China under grant number 2024JJ7395+2 种基金International and Regional Science and Technology Cooperation and Exchange Program of the Hunan Association for Science and Technology under grant number 025SKX-KJ-04Hunan Provincial Postgraduate Research Innovation Project under grant numberCX20251611Liye Qin Bamboo Slips Research Special Project of JishouUniversity 25LYY03.
文摘ThePigeon-InspiredOptimization(PIO)algorithmconstitutes ametaheuristic method derived fromthe homing behaviour of pigeons.Initially formulated for three-dimensional path planning in unmanned aerial vehicles(UAVs),the algorithmhas attracted considerable academic and industrial interest owing to its effective balance between exploration and exploitation,coupled with advantages in real-time performance and robustness.Nevertheless,as applications have diversified,limitations in convergence precision and a tendency toward premature convergence have become increasingly evident,highlighting a need for improvement.This reviewsystematically outlines the developmental trajectory of the PIO algorithm,with a particular focus on its core applications in UAV navigation,multi-objective formulations,and a spectrum of variantmodels that have emerged in recent years.It offers a structured analysis of the foundational principles underlying the PIO.It conducts a comparative assessment of various performance-enhanced versions,including hybrid models that integrate mechanisms from other optimization paradigms.Additionally,the strengths andweaknesses of distinct PIOvariants are critically examined frommultiple perspectives,including intrinsic algorithmic characteristics,suitability for specific application scenarios,objective function design,and the rigor of the statistical evaluation methodologies employed in empirical studies.Finally,this paper identifies principal challenges within current PIO research and proposes several prospective research directions.Future work should focus on mitigating premature convergence by refining the two-phase search structure and adjusting the exponential decrease of individual numbers during the landmark operator.Enhancing parameter adaptation strategies,potentially using reinforcement learning for dynamic tuning,and advancing theoretical analyses on convergence and complexity are also critical.Further applications should be explored in constrained path planning,Neural Architecture Search(NAS),and other real-worldmulti-objective problems.For Multi-objective PIO(MPIO),key improvements include controlling the growth of the external archive and designing more effective selection mechanisms to maintain convergence efficiency.These efforts are expected to strengthen both the theoretical foundation and practical versatility of PIO and its variants.
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.
基金supported by the National Natural Science Foundation of China(Nos.32371573 and 32171497)。
文摘Photoperiod serves as an essential environmental cue that facilitates seasonal acclimatization and thermoregulation in birds.However,its effects on basal and substrate metabolism in Zebra Finches(Taeniopygia guttata)remain unclear.To explore the influence of photoperiod on basal metabolism and substrate metabolism in Zebra Finches,basal metabolic rate(BMR),body mass,cellular metabolic activities,and substrate metabolism were investigated under different photoperiods.After one week of exposure to a short photoperiod,Zebra Finches exhibited a temporary decrease in BMR,gross energy intake,digestible energy intake,and digestibility,although body mass remained unchanged throughout the experiment.After four weeks of acclimation,no significant differences were observed among different groups in state 4 respiration,cytochrome c oxidase activity,citrate synthase activity,avian uncoupling protein expression,or circulating triiodothyronine and thyroxine hormone levels.In terms of substrate metabolism,short photoperiod-exposed finches showed increased pectoral muscle glycogen content and elevated serum triglyceride and free fatty acid levels,accompanied by a decrease in body fat.No differences were detected in serum glucose levels or in the activity and mRNA levels of carnitine palmityltransferase-1 andβ-hydroxyacyl Co-A dehydrogenase.These findings suggest that changes in photoperiod may serve as signals for substrate metabolism remodeling,while having only transient effects on basal metabolism in Zebra Finches.
基金supported by grants from the National Natural Science Foundation of China(32172890 and 32002315)the National Key Research and Development Program of China(2022YFF0711004)+3 种基金the Natural Science Foundation of Heilongjiang Province,China(YQ2022C042)the State Key Laboratory of Veterinary Biotechnology Foundation of China(SKLVBF202208)the Postdoctoral Fellowship Program of CPSF,China(GZC20233062)the National Center of Technology Innovation for Pigs,China(NCTIP-XD/C09)。
文摘NADC34-like porcine reproductive and respiratory syndrome virus(PRRSV),which first appeared in China in 2017,is currently one of the main epidemic strains in China.In this study,we found that a new variant of NADC34-like PRRSV evolved,named the L1A variant.The phylogenetics,epidemic status,and pathogenicity of the LA variants were subsequently comprehensively evaluated.Based on the results of the ORF5 phylogenetic analysis,the L1A variants were classified as NADC34-like PPRSV.All the strains had the same discontinuous 131-aa deletion in the NSP2 region(similar to that in the NADC30).Recombination analysis revealed that the L1A variants were recombinant viruses that contained an NADC30-like PRRSV skeleton,a nonstructural protein-encoding gene region obtained in part from JXA1-like PRRSV and a ORF2-ORF6 gene region partly obtained from NADC34-like PRRSV and that exhibited similar recombination patterns.We successfully isolated the L1A variant TZJ2756 from PAMs and Marc-145 cells.In animal experiments,TZJ2756 exhibited moderate pathogenicity in piglets,causing obvious clinical symptoms,namely,persistent fever,significantly reduced body weight,interstitial edema and severe interstitial pneumonia in the lungs,and prolonged high-load viremia.L1A variants have been detected in at least 12 provinces in China and share many similar epidemiological characteristics with the American L1C variant.This research will enhance our understanding of the prevalence of L1A variants and furnish valuable data for the ongoing monitoring of NADC34-like PRRSV in China.
基金The National Natural Science Foundation of China No.42406251the Fundamental Research Funds for the Central Universities under contract No.2042025kf0079 and 2042025kf0080+2 种基金the Postdoctoral Fellowship Program of CPSF under contract No.GZC20241257the Postdoctoral Fellowship Program of CPSF under contract No.GZC20241257the Key Laboratory of Polar Environment Monitoring and Public Governance(Wuhan University),the Ministry of Education Open Fund under contract Nos 202403 and 202405.
文摘Basal melting and calving are the main pathways for mass loss in Antarctic ice shelves.Basal channels,as detailed variations in basal melting,mutually promote basal melting and calving,thereby weakening the stability of ice shelves.Therefore,it is necessary to calculate and statistically analyze basal melting,basal channels,and calving events across all Antarctic ice shelves and examine the correlation among these three factors.This study utilizes various data sources to calculate the Basal Channel Density(BCD)and average basal melt rate of all Antarctic ice shelves during 2010-2020,as well as the spatial correlation between basal melting,basal channels,and calving.We found that ice shelves along the Amundsen Sea and Bellingshausen Sea have higher basal melt rates and basal channel densities,while other sea areas have lower values.This is mainly influenced by seabed topography and Circumpolar Deep Water.Excluding(CDW)extreme calving events,there is a positive correlation among basal melting,basal channels,and calving in coastal ice shelves across different sea areas,with a correlation coefficient exceeding 0.67.This indicates that basal melting and basal channels are major factors causing ice shelf calving.Our results emphasize the importance of the impact of basal melting,basal channels,and calving on ice shelf stability,and they provide a significant reference for further research on ice shelf-ocean interactions.
文摘目的探究肌层浸润性膀胱癌(muscle-invasive bladder cancer,MIBC)分子亚型特异性,为不同MIBC分子亚型患者的治疗提供指导。方法基于MIBC分子分型方法中的UNC分型法,应用转录组测序数据,将48例MIBC患者分为2种分子亚型即Basal型和Luminal型,并进行差异表达分析以探究MIBC特异性的lncRNAs,并进一步探讨其分子特征和临床意义。结合单细胞质谱流式细胞术(single-cell mass cytometry,CyTOF)和镜像质谱流式细胞术(imaging mass cytometry,IMC)分析MBNL1-AS1高表达组和低表达组Basal型MIBC患者的免疫微环境异质性。结果基于分子分型法筛选发现了在MIBC特异性表达的lncRNA MBNL1-AS1,其低表达与Basal型MIBC患者的不良预后密切相关(P=0.022)。且进一步分析转录组测序数据后发现,在Basal型MIBC中,MBNL1-AS1低表达组具有去分化(P=0.008)、高干性(P=0.020)和高增殖(P=0.010)的特征。MBNL1-AS1低表达组的Basal型MIBC患者的免疫评分与NK CD56bright细胞和Treg细胞的评分呈负相关(P<0.05),而MBNL1-AS1高表达组的B细胞和CD8+T细胞相关基因的表达水平较高。高维度单细胞蛋白质组学分析结果显示,MBNL1-AS1低表达的Basal型MIBC患者表现出较高的Treg细胞亚群丰度(P=0.016)。结论MBNL1-AS1低表达组的Basal型MIBC患者具有去分化、高干性、高增殖和免疫抑制的特点。MBNL1-AS1具有作为Basal型MIBC免疫响应生物标志物的潜能。
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.
文摘Introduction: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a neuroregressive disorder associated with subacute encephalopathy, confusion, dysarthria, and dysphagia, as well as occasional external ophthalmoplegia or supranuclear facial nerve palsy. It may progress to severe rigidity, dystonia, and quadriparesis. Combination therapy of high-dose thiamine and biotin helps to control the symptoms and prevent progression of the disease. Methods: This retrospective, cross-sectional study was conducted at King Fahad Medical City in Riyadh, Saudi Arabia, to investigate the demographic, clinical features, treatment response, outcomes, and predictive factors of BTBGD in the pediatric population. Results: Twenty-five records of pediatric patients diagnosed with BTBGD were included in the study. The most common symptoms observed at presentation were ataxia in 13 patients (52%), followed by developmental regression in 11 patients (44%), and seizures in 7 patients (28%). Statistically significant associations were found between patient’s age of presentation, seizures at presentation, lactate level and their health outcomes. Multivariate logistic regression analysis revealed significant differences in patient outcomes (prognosis) based on their age at presentation, seizures, and lactate levels (p Conclusion: This study reported BTBGD in 25 pediatric patients in Saudi Arabia. Age at presentation, seizures, and lactate levels were found to be significantly associated with patient health outcomes. Increasing public awareness of the condition, particularly among parents and pediatricians, is imperative. Early diagnosis, along with timely management using biotin and thiamine supplementation, promotes improved health outcomes and prevents progressive neurodegeneration and death.
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Molecular virology methods including polymerase chain reaction, cloning and sequencing have revolutionised our understanding of viral genome variation. In the case of hepatitis B virus (HBV), sequencing studies have identified a number of virus variants normally found during the natural course of chronic infection. The appearance of the precore stop codon (with G-for-A substitution at position 1896) and basal core promoter (BCP) (with A-for-T and G-for-A, at positions 1762 and 1764, respectively) variants which reduce or abrogate hepatitis B e antigen (HBeAg) production, heralds the initiation of the seroconversion phase from HBeAg to anti-HBe positivity. The gradual removal of the tolerogenic effect of HBeAg leads to the awakening of the immune response (immune clearance phase). Most patients after HBeAg seroconversion become “inactive HBsAg carriers”. However during the course of infection precore and/or BCP variants may emerge and be selected leading to HBeAg negative chronic hepatitis B (CHB) with high viremia levels (reactivation phase). The prevalence of HBeAg negative CHB has been increasing over the last few decades and has become the commonest type of HBV infection in many countries of the world. This probably reflects the aging of existing HBV carriers and the effective prevention measures restricting new HBV infections. Frequent acute exacerbations accompanied by high viral replication, elevated alanine aminotransferase levels and histological activity are a common feature of HBeAg negative CHB leading to cirrhosis much faster than in HBeAg positive CHB patients.
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supported by grants from the National Natural Science Foundation of China(Grant No.82273458 to Jinfei Chen)the Start-up Fund for the Recruited Talents of the First Affiliated Hospital of Wenzhou Medical University(Grant No.2021QD025 to Jinfei Chen)。
文摘The KCNQ family of genes(KCNQ1–KCNQ5),encoding voltage-gated K+(Kv)channels,have been demonstrated to play potential pathophysiological roles in cancers.However,the associations between genetic variants located in KCNQ family genes and gastric cancer survival remain unclear.In this study,a large-scale cohort comprising 1135 Chinese gastric cancer patients was enrolled to identify genetic variants in KCNQ family genes associated with overall survival(OS).Based on the survival evaluation of all five KCNQ family genes,KCNQ1 was selected for subsequent genetic analysis.In both Cox regression model and stepwise Cox regression model used to evaluate survival-related genetic variants,we found that KCNQ1 rs10832417G>T was associated with an increased OS in gastric cancer patients(adjusted hazards ratio[HR]=0.84,95%confidence interval[CI]:0.72–0.98,P=0.023).Subsequently,a nomogram was constructed to enhance the prognostic capacity and clinical translation of rs10832417 variants.The rs10832417 T allele was predicted to increase the minimum free energy of the secondary structure.Furthermore,we observed that gastric cancer patients with downregulated KCNQ1expression had a poorer survival across multiple public datasets.The findings of the present study indicate that KCNQ1 rs10832417 may serve as an independent prognostic predictor of gastric cancer,providing novel insights into the progression and survival of the disease.
基金supported by the Horizon Europe Framework Programme(HORIZON),call Teaming for Excellence(HORIZONWIDERA-2022-ACCESS-01-two-stage)-Creation of the Centre of Excellence in Smart Forestry“Forest 4.0”No.101059985″This research was cofunded by FOREST 4.0-“Ekscelencijos centras tvariai miško bioekonomikai vystyti”(Nr.10-042-P-0002).
文摘Models that predict a forest stand’s evolution are essential for developing plans for sustainable management.A simple mathematical framework was developed that con-siders the individual tree and stand basal area under random resource competition and is based on two assumptions:(1)a sigmoid-type stochastic process governs tree and stand basal area dynamics of living and dying trees,and(2)the total area that a tree may potentially occupy determines the number of trees per hectare.The most effective method to satisfy these requirements is formalizing each tree diameter and potentially occupied area using Gompertz-type stochastic differential equations governed by fixed and mixed-effect parameters.Data from permanent experimental plots from long-term Lithuania experiments were used to construct the tree and stand basal area models.The new models were relatively unbiased for live trees of all species,including silver birch(Betula pen-dula Roth)and downy birch(Betula pubescens Ehrh.),[spruce(Picea abies),and pine(Pinus sylvestris)].Less reliable predic-tions were made for the basal area of dying trees.Pines gave the highest accuracy prediction of mean basal area among all live trees.The mean basal area prediction for all dying trees was lower than that for live trees.Among all species,pine also had the best average basal area prediction accuracy for live trees.Newly developed basal area growth and yield models can be recommended despite their complex formulation and implementation challenges,particularly in situations when data is scarce.This is because the newly observed plot provides sufficient information to calibrate random effects.
基金financially supported by grants from the National Natural Science Foundation of China (Nos.32371573,32171497,and 31971420)。
文摘Food is a critical environmental factor that influences animal survival,especially for small passerines due to their high mass-specific metabolic rates.Basal metabolic rate(BMR)reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget.Some birds have been shown to employ compensatory mechanisms during food shortages,temporarily reducing these selfmaintenance expenditures without using hypothermia.However,the mechanisms of BMR adjustment remain unexplored.In the present study,we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows(Passer montanus)by comparing a control group to groups fasted for 6,12,18,and 24 h.We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities,mitochondrial substrate supply,and changes in serum thyroid hormones during fasting.Our data indicated that fasting groups had significantly lower body mass,BMR,body temperature,and body fat content.Furthermore,fasting groups had significantly lower glycogen levels,mitochondrial state 4 respiration and cytochrome c oxidase(CCO)activity in the liver,and CCO activity in pectoral muscle.The levels of avian uncoupling protein(avUCP)m RNA were significantly reduced,while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups.Furthermore,the groups subjected to fasting exhibited significantly lower levels of serum glucose,triglyceride,thyroxine(T_(4)),and triiodothyronine(T_(3)).Positive correlations were observed between the following pairs of variables:log BMR and log body mass,log body mass and log body fat,log BMR and log state 4 respiration in the liver,log BMR and log CCO activity in the liver and muscle,log BMR and log av-UCP m RNA expression,whereas a negative correlation was observed between log BMR and log myostatin level.In addition,a positive correlation was also detected between log T_(3) and each of the following:log BMR,state 4 respiration,and log CCO activity in the liver.Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.
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financially supported by the National Key R&D Program of China(2023YFC3603300,2021YFA0909300)National Natural Science Foundation of China(92249302,32370592,32400437)China Postdoctoral Science Foundation(BX20230073 and 2023M740709)。
文摘Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untranslated regions(3'UTRs)on alternative polyadenylation(APA)of m RNA remains lacking.In this study,we analyze 10,199 tumor samples across 32 cancer types and identify 1333 somatic single nucleotide variants(SNVs)associated with abnormal 3'UTR APA.Mechanistically,these 3'UTR SNVs can alter cisregulatory elements,such as the poly(A)signal and UGUA motif,leading to changes in APA.Minigene assays confirm that 3'UTR SNVs in multiple genes,including RPS23 and CHTOP,induce aberrant APA.Among affected genes,62 exhibit differential stability between tandem 3'UTR isoforms,including HSPA4and UCK2,validated by experimental assays.Finally,we establish that SNV-related abnormal APA usage serves as an additional layer of expression regulation for tumor-suppressor gene HMGN2 in breast cancer.Collectively,this study reveals 3'UTR APA as a critical mechanism mediating the functional impact of somatic noncoding variants in human cancers.
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supported by the National Key R&D Program of China (2020YFA0112500 and 2021YFA1100400)the National Natural Science Foundation of China (32271019 and 12411530079)+6 种基金the Natural Science Foundation of Shanghai Municipality (22ZR1462600)supported by the Natural Science Foundation of Hunan Province, China (2022JJ40206)Ruixin project of Hunan Provincial Maternal and Child Health Care Hospital (2023RX01)supported by the Clinical Research Center Projects for Genetic Birth Defects and Rare Diseases in Hunan Province (2023SK4053)Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1010)supported by the Model Organisms Screening Center of the UDN by U54NS093793 of the NIH (NINDS)supported by the Office of Research Infrastructure Programs of the NIH (awards R24 OD022005 and R24 OD031447).
文摘Mediator Complex Subunit 16(MED16,MIM:604062)is a member of the Mediator complex,which controls many aspects of transcriptional activity in all eukaryotes.Here,we report two individuals from a non-consanguineous family with biallelic variants in MED16 identified by exome sequencing.The affected individuals present with global developmental delay,intellectual disability,and dysmorphisms.To assess the pathogenicity of the variants,functional studies are performed in Drosophila and patient-derived cells.The fly ortholog med16 is expressed in neurons and some glia of the developing central nervous system(CNS).Loss of med16 leads to a reduction in eclosion and lifespan,as well as impaired synaptic transmission.In neurons differentiated from the patient-derived induced pluripotent stem cells(iPSCs),the neurite outgrowth is impaired and rescued by expression of exogenous MED16.The patient-associated variants behave as loss-of-function(LoF)alleles in flies and iPSCs.Additionally,the transcription of genes related to neuronal maturation and function is preferentially altered in patient cells relative to differentiated H9 controls.In summary,our findings support that MED16 is important for appropriate development and function,and that biallelic MED16 variants cause a neurodevelopmental disease.
