The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion...The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.展开更多
Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in...Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).展开更多
Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being s...Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.展开更多
Plant viruses pose significant threats to agriculture,with many vectored by insect pests.The entry of viruses and their encoded proteins into the host nucleus is a critical step for promoting some viral replication an...Plant viruses pose significant threats to agriculture,with many vectored by insect pests.The entry of viruses and their encoded proteins into the host nucleus is a critical step for promoting some viral replication and enabling systemic infection.Laodelphax striatellus,also known as the small brown planthopper(SBPH),is an efficient vector for rice stripe virus(RSV),one of the most damaging viruses of rice.In this study,we demonstrate that RSV infection induces the expression of genes in both the classical and non-classical nuclear import pathways of SBPH.A gene belonging to the importinβfamily,importin 5(LsIPO5),was upregulated by 84%in SBPH midguts infected with RSV.The nuclear localization signal(NLS,^(168)YRSPSKKRHKYV^(179))is located within the nonstructural protein NS3 directly bound to LsIPO5,thereby facilitating NS3nuclear entry.Moreover,a RING-type E3 ligase(LsRING)in SBPH,which mediated the ubiquitination of NS3 in the insect vector,enhanced NS3 binding to LsIPO5 and facilitated NS3 perinuclear localization.Combined treatment of SBPH with both ds IPO5 and ds RING significantly reduced RSV loads,highlighting the importance of LsIPO5 and NS3 ubiquitination cooperation in facilitating viral replication.Our findings provide new insights into synergistic molecular mechanisms that govern RSV infection and suggest potential therapeutic targets to control viral transmission through their insect vectors.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic effi...Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.展开更多
Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Down...Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.展开更多
Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,va...Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].展开更多
Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs a...Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.展开更多
Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in...Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.展开更多
Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To over...Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.展开更多
DealEdrtor,Dear Editor,Spodoptera litura,commonly known as the tobacco cutworm,is a polyphagous agricultural pest worldwide,causing significant economic losses to a wide range of crops.Over the past decades,S.litura h...DealEdrtor,Dear Editor,Spodoptera litura,commonly known as the tobacco cutworm,is a polyphagous agricultural pest worldwide,causing significant economic losses to a wide range of crops.Over the past decades,S.litura has developed high resistance levels to multiple chemical insecticides(Li et al.,2024),and shown low susceptibility to transgenic Bacillus thuringiensis(Bt)cotton(Wan et al.,2008).展开更多
This paper introduces a novel fractional-order model based on the Caputo-Fabrizio(CF)derivative for analyzing computer virus propagation in networked environments.The model partitions the computer population into four...This paper introduces a novel fractional-order model based on the Caputo-Fabrizio(CF)derivative for analyzing computer virus propagation in networked environments.The model partitions the computer population into four compartments:susceptible,latently infected,breaking-out,and antivirus-capable systems.By employing the CF derivative—which uses a nonsingular exponential kernel—the framework effectively captures memory-dependent and nonlocal characteristics intrinsic to cyber systems,aspects inadequately represented by traditional integer-order models.Under Lipschitz continuity and boundedness assumptions,the existence and uniqueness of solutions are rigorously established via fixed-point theory.We develop a tailored two-step Adams-Bashforth numerical scheme for the CF framework and prove its second-order accuracy.Extensive numerical simulations across various fractional orders reveal that memory effects significantly influence virus transmission and control dynamics;smaller fractional orders produce more pronounced memory effects,delaying both infection spread and antivirus activation.Further theoretical analysis,including Hyers-Ulam stability and sensitivity assessments,reinforces the model’s robustness and identifies key parameters governing virus dynamics.The study also extends the framework to incorporate stochastic effects through a stochastic CF formulation.These results underscore fractional-order modeling as a powerful analytical tool for developing robust and effective cybersecurity strategies.展开更多
The ubiquitination of proteins,followed by their degradation via the proteasome or autophagosome,is a key mechanism for the posttranslational regulation of proteins in cells.The specificity of this process is primaril...The ubiquitination of proteins,followed by their degradation via the proteasome or autophagosome,is a key mechanism for the posttranslational regulation of proteins in cells.The specificity of this process is primarily dictated by the E3 ubiquitin ligases,which are classified into three main types:the really interesting new gene(RING),the RING-between-RING(RBR),and the homologous to the human papillomavirus E6 protein-associated protein(E6-AP)carboxyl terminus(HECT).Among the RING-type E3 ubiquitin ligases are the membrane-associated or membrane-proximal RING-CH(MARCH)proteins,which regulate the trafficking and levels of cellular and viral proteins,including immune receptors,innate immune response proteins,and viral glycoproteins[1].Eleven MARCH proteins,named MARCH1-11,are encoded in the human genome,and some of them(primarily MARCH8 along with MARCH1 and MARCH2)have been implicated in antiviral defense against RNA viruses such as human immunodeficiency virus(HIV-1),influenza virus,Ebola virus,SARS-CoV-2,and respiratory syncytial virus(RSV)[2].展开更多
Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by...Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by the World Organization for Animal Health(WOAH).The causative agent,Epizootic Hemorrhagic Disease Virus(EHDV),belongs to the genus Orbivirus within the family Reoviridae and possesses a viral genome comprising ten double-stranded RNA(dsRNA)segments(JiménezCabello et al.2023).To date,ten distinct serotypes of EHDV,designated as EHDV-1,2,and 4 through 11,have been identified globally(Anthony et al.2009;Maan et al.2017;Shirafuji et al.2017;Yang et al.2020).展开更多
Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation tran...Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.展开更多
Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exh...Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.展开更多
Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional va...Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses,whereas messenger RNA(mRNA)vaccines have demonstrated significant advantages due to their short development periods,straightforward production,and low costs.After the outbreak of the COVID-19 pandemic,multiple mRNA vaccines,including Pfizer-BioNTech and Moderna,rapidly received emergency use authorization,validating their feasibility.The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikóand Drew Weissman,underscoring the efficacy of mRNA vaccine technology.In 2024,the U.S.Food and Drug Administration(FDA)approval of Moderna's respiratory syncytial virus(RSV)mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation.This review article summarizes the design,clinical research,and future challenges of mRNA vaccines for respiratory viruses,delving into antigen design,mRNA delivery systems,and advancements in vaccines for multiple respiratory viruses,including innovations in self-amplifying mRNA and circular mRNA vaccines.Additionally,the development of combination vaccines is underway,aiming to provide protection against multiple viruses through a single administration.Despite the significant progress in mRNA vaccine development,challenges remain regarding raw material costs,stability,and delivery efficiency.In the future,with technological advancements and the accumulation of clinical experience,the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized,thereby enhancing their safety and efficacy.展开更多
BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investi...BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.展开更多
基金supported by the Russian Science Foundation(Grant No.24-25-20087 to V.K.)。
文摘The highly conserved human leukocyte antigen-A2(HLA-A2)-restricted epitope NS3-1073 represents a promising candidate for a therapeutic vaccine against hepatitis C virus(HCV).In this study,we engineered a set of fusion proteins based on the artificial self-assembling peptide(SAP),which were expressed in Escherichia coli and spontaneously self-assembled into nanosized particles displaying HCV epitopes,including NS3-1073.To enhance immunogenicity,we incorporated the T helper epitope PADRE into the construct.Alpha-helical linkers were introduced between SAP and the epitopes to facilitate proper protein folding.Notably,a helical linker with a high supercoiling propensity enabled soluble expression of the fusion protein containing both the NS3-1073 and PADRE epitopes,allowing purification of the in vivo-formed nanoparticles by metal affinity chromatography.Human dendritic cells derived from peripheral blood monocytes showed robust activation in response to the fusion proteins and preferentially stimulated T lymphocytes toward a Th1-biased immune response.In mice,immunization with nanoparticles carrying NS3-1073 induced splenocyte proliferation in response to in vitro stimulation with a mixture of NS3 peptides.These results demonstrate that recombinant nanoparticle-based carriers presenting the NS3-1073 epitope can be produced in bacterial systems and hold strong potential as a foundation for a therapeutic HCV vaccine.
基金supported by the National Key Research and Development Program of China (2021YFD1800200)the National Natural Science Foundation of China (32170539)。
文摘Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).
基金supported by the Natural Science Foundation of Heilongjiang Province,China (YQ2022C040)。
文摘Oral immunization is an alternative or supplementary approach that can significantly improve dog vaccination coverage,especially for free-roaming dogs.Safe and effective oral rabies vaccines for dogs are still being sought.In our previous studies,we generated a genetically modified rabies virus(RABV) ERA strain,rERAG_(333E),containing a mutation from arginine(Arg,R) to glutamic acid(Glu,E) at residue 333 of the G protein(G_(333E)).Our previous results demonstrated that rERAG_(333E) was safe for adult mice and dogs,and oral vaccination with rERAG_(333E) induced a strong and long-lasting protective immune response in dogs.Here,we further investigated the safety and immunogenicity of rERAG_(333E) in nontarget species,including suckling mice,rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.Suckling mice studies demonstrated that the G_(333E) mutation significantly reduced the virulence of the ERA strain.All of the suckling mice aged 10 days and above survived and showed no apparent signs of disease after intracerebral inoculation with rERAG_(333E).Animal studies demonstrated that rERAG_(333E) was safe in rhesus monkeys,foxes,raccoon dogs,piglets,goats,and sheep.None of those animals inoculated orally with 10 times the intended field dose of rERAG_(333E) showed abnormal clinical signs before and after the booster immunization with Rabvac 3,an inactivated rabies vaccine.Meanwhile,oral inoculation with rERAG_(333E) induced strong neutralizing antibody(NA) responses to RABV in rhesus monkeys,foxes,raccoon dogs,and piglets.These results demonstrated that rERAG_(333E) has the potential to serve as a safe oral rabies vaccine for dogs.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20240902 and BK20240904)the National Natural Science Foundation of China(32272533)。
文摘Plant viruses pose significant threats to agriculture,with many vectored by insect pests.The entry of viruses and their encoded proteins into the host nucleus is a critical step for promoting some viral replication and enabling systemic infection.Laodelphax striatellus,also known as the small brown planthopper(SBPH),is an efficient vector for rice stripe virus(RSV),one of the most damaging viruses of rice.In this study,we demonstrate that RSV infection induces the expression of genes in both the classical and non-classical nuclear import pathways of SBPH.A gene belonging to the importinβfamily,importin 5(LsIPO5),was upregulated by 84%in SBPH midguts infected with RSV.The nuclear localization signal(NLS,^(168)YRSPSKKRHKYV^(179))is located within the nonstructural protein NS3 directly bound to LsIPO5,thereby facilitating NS3nuclear entry.Moreover,a RING-type E3 ligase(LsRING)in SBPH,which mediated the ubiquitination of NS3 in the insect vector,enhanced NS3 binding to LsIPO5 and facilitated NS3 perinuclear localization.Combined treatment of SBPH with both ds IPO5 and ds RING significantly reduced RSV loads,highlighting the importance of LsIPO5 and NS3 ubiquitination cooperation in facilitating viral replication.Our findings provide new insights into synergistic molecular mechanisms that govern RSV infection and suggest potential therapeutic targets to control viral transmission through their insect vectors.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金Supported by the earmarked fund for CARS(No.CARS-48)the National Natural Science Foundation of China(No.32202964)。
文摘Decapod Iridescent Virus 1(DIV1)is a recently discovered virus recognized for its high infectivity in Macrobrachium rosenbergii.A thermal treatment was performed on DIV1-infected M.rosenbergii,and the therapeutic efficacy was evaluated.In the DIV1 challenge experiment,the mortality rate in the challenged group was found to be 2.6 times greater than that in the control group,with the viral load in deceased individuals exceeding 5.41×10^(7)copies/μg-DNA.The thermal treatment(TT)was administered at 36℃for a duration of 16 d,followed by a temperature restoration(TR)period at 26℃for 3 d.On the first day at 36℃,an average viral concentration of 5.34×10 copies/μg-DNA was detected in the survived individuals.RNA-seq analysis showed a significant upregulation of genes related to the lysosome pathway,including sialin-like isoform x2(slc17a5),beta-galactosidase-1-like protein 2(glb1),putative glucosylceramidase 3(gba),sphingomyelin phosphodiesterase-like isoform x2(smpd1),betahexosaminidase subunit alpha-like(hexa_b)and legumain-like protein(lgmn),following a transient suppression period induced by thermal stress.Upon reaching 36℃,the activation of heat shock protein 70(hsp70)and heat shock protein 90(hsp90a)was observed.Concomitantly,genes that implicated in energy production critical for DIV1 replication,such as hexokinase(hk)and microsomal glutathione stransferase 3-like isoform x2(gst),were inhibited.These results collectively suggest that TT/TR treatments eliminated DIV1 in M.rosenbergii by activating the organism’s innate immune response and suppressing virus replication.This study provides a theoretical basis for utilizing thermal therapy in the management of viral infections in M.rosenbergii breeding programs,thereby facilitating the development of new strains resistant to DIV1.
文摘Oncology Research Editorial Office Published:23 March 2026 The published article titled“MicroRNA 125a-5p Inhibits Cell Proliferation and Induces Apoptosis in Hepatitis B Virus-Related Hepatocellular Carcinoma by Downregulation of ErbB3”has been retracted from Oncology Research,Vol.27,No.4,2019,pp.449-458.DOI:10.3727/096504017X15016337254623 URL:https://www.techscience.com/or/v27n4/48558.
文摘Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].
文摘Rabies is a zoonotic disease with an estimated global mortality of 59,000 people annually and a burden of more than 3.7 million disability-adjusted life years(DALYs)that is caused by a neurotropic lyssavirus[1].Dogs are the primary source of human rabies,as more than 95%of human cases can be traced to dogs[2,3].China faces a substantial burden of rabies,having endured three major human rabies epidemics,which occurred in the 1950s,1981,and 2007[4].Implementation of various prevention and control measures has decreased the number of human rabies cases from 3,300 in 2007 to 167 in 2024.In China.
基金supported by the National Natural Science Foundation of China,No.82471327the Natural Science Foundation of ShandongProvince,No.ZR2024MH200(both to SL).
文摘Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke.Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity,resulting in enduring neurological deficits.Recent findings from our research indicate that inhibition of Rho-associated kinase(ROCK)2 facilitates neuroprotection in different models of central nervous system diseases.In addition,our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons.However,it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis.In this study,we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus(AAV)vector(AAV-sh.ROCK2).We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo.Furthermore,AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury.Notably,AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury.Mechanistically,AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression.Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis,highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.
基金The Korea Centers for Disease Control and Prevention,Grant/Award Number:2022-ER1701-00,2022-NI-041-02,2024-ER1702-00 and 2025-NI-014-00。
文摘Background:Humanized mouse models are essential for studying the human immune response and antibody development.However,conventional models show limited B cell maturation and antigen-specific humoral responses.To overcome these limitations,we used the NOG-EXL mice expressing human interleukin 3(IL-3)and granulocyte-macrophage colony-stimulating factor(GM-CSF)to enhance myeloid and B-cell lineage differentiation.Methods:Human CD34^(+)hematopoietic stem cells(HSC)were transplanted into NOG-EXL mice to produce humanized immune systems.After immune cell reconstitution was confirmed across 12 weeks,the mice were immunized twice with inactivated severe fever with thrombocytopenia syndrome virus(SFTSV)antigens.Peripheral blood mononuclear cells and splenocytes were analyzed using multicolor flow cytometry to assess human immune cell subsets.Antigen-specific immunoglobulin G(IgG)production was quantified using enzyme-linked immunosorbent assay(ELISA),and virus-specific B cells were isolated using antigen-labeled recombinant protein probes.Results:Twelve weeks after transplantation of HSCs into NOG-EXL mice,they exhibited robust engraftment of human leukocytes,including T,B,and dendritic cells,compared to NOG mice.Unlike NOG mice,humanized NOG-EXL mice exhibited an increase in human IgG levels,indicating the production of human antibody responses to antigens.Humanized NOG-EXL mice were immunized twice every 2 weeks with inactivated SFTSV,and antigen-specific human antibodies against the virus were detected in the mouse sera by ELISA.Sera from SFTSV-immunized humanized mice demonstrated neutralizing activity against SFTSV,confirming the induction of functional virus-specific neutralizing antibodies.Antigen-binding IgG-positive human B cells were isolated from mouse splenocytes using recombinant protein probes.Conclusion:This model provides a valuable platform for evaluating humoral immunity and isolating B cells using high-affinity human monoclonal antibodies without genetic engineering.
基金supported by the National Natural Science Foundation of China(32071477,32272634).
文摘DealEdrtor,Dear Editor,Spodoptera litura,commonly known as the tobacco cutworm,is a polyphagous agricultural pest worldwide,causing significant economic losses to a wide range of crops.Over the past decades,S.litura has developed high resistance levels to multiple chemical insecticides(Li et al.,2024),and shown low susceptibility to transgenic Bacillus thuringiensis(Bt)cotton(Wan et al.,2008).
基金supported and funded by the Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University(IMSIU)(grant number IMSIU-DDRSP2601).
文摘This paper introduces a novel fractional-order model based on the Caputo-Fabrizio(CF)derivative for analyzing computer virus propagation in networked environments.The model partitions the computer population into four compartments:susceptible,latently infected,breaking-out,and antivirus-capable systems.By employing the CF derivative—which uses a nonsingular exponential kernel—the framework effectively captures memory-dependent and nonlocal characteristics intrinsic to cyber systems,aspects inadequately represented by traditional integer-order models.Under Lipschitz continuity and boundedness assumptions,the existence and uniqueness of solutions are rigorously established via fixed-point theory.We develop a tailored two-step Adams-Bashforth numerical scheme for the CF framework and prove its second-order accuracy.Extensive numerical simulations across various fractional orders reveal that memory effects significantly influence virus transmission and control dynamics;smaller fractional orders produce more pronounced memory effects,delaying both infection spread and antivirus activation.Further theoretical analysis,including Hyers-Ulam stability and sensitivity assessments,reinforces the model’s robustness and identifies key parameters governing virus dynamics.The study also extends the framework to incorporate stochastic effects through a stochastic CF formulation.These results underscore fractional-order modeling as a powerful analytical tool for developing robust and effective cybersecurity strategies.
基金partly supported by the United States National Institutes of Health(P20 GM134974 to RKJ).
文摘The ubiquitination of proteins,followed by their degradation via the proteasome or autophagosome,is a key mechanism for the posttranslational regulation of proteins in cells.The specificity of this process is primarily dictated by the E3 ubiquitin ligases,which are classified into three main types:the really interesting new gene(RING),the RING-between-RING(RBR),and the homologous to the human papillomavirus E6 protein-associated protein(E6-AP)carboxyl terminus(HECT).Among the RING-type E3 ubiquitin ligases are the membrane-associated or membrane-proximal RING-CH(MARCH)proteins,which regulate the trafficking and levels of cellular and viral proteins,including immune receptors,innate immune response proteins,and viral glycoproteins[1].Eleven MARCH proteins,named MARCH1-11,are encoded in the human genome,and some of them(primarily MARCH8 along with MARCH1 and MARCH2)have been implicated in antiviral defense against RNA viruses such as human immunodeficiency virus(HIV-1),influenza virus,Ebola virus,SARS-CoV-2,and respiratory syncytial virus(RSV)[2].
基金supported by the National Key Research and Development Program of China(2022YFF0710500 and 2023YFF0724603)the Key Research&Development Program of Heilongjiang Province,China(Innovation Base)(JD2023SJ10)the Central Public-interest Scientific Institution Basal Research,China(1610302023003)。
文摘Epizootic Hemorrhagic Disease(EHD),a vector-borne disease affecting both wild and domestic ruminants,is transmitted by biting midges of the genus Culicoides.Since 2008,it has been classified as a notifiable disease by the World Organization for Animal Health(WOAH).The causative agent,Epizootic Hemorrhagic Disease Virus(EHDV),belongs to the genus Orbivirus within the family Reoviridae and possesses a viral genome comprising ten double-stranded RNA(dsRNA)segments(JiménezCabello et al.2023).To date,ten distinct serotypes of EHDV,designated as EHDV-1,2,and 4 through 11,have been identified globally(Anthony et al.2009;Maan et al.2017;Shirafuji et al.2017;Yang et al.2020).
基金financially supported by the National Natural Science Foundation of China(82127802,22374157)Strategic Priority Research Program,CAS(XDB0540000,XDC0170000)CAS Youth Interdisciplinary Team(JCTD-2022-13).In addition,Xin Zhou acknowledges the support from the Tencent Foundation through the XPLORER PRIZE.
文摘Magnetic resonance imaging(MRI)is a powerful tool for diagnosing and monitoring brain diseases,but its low sensitivity can hinder early detection.To address this challenge,we utilized chemical exchange saturation transfer(CEST)MRI,which greatly enhances sensitivity for detecting low-concentration compounds.In this study,we developed a CEST contrast agent based on a recombinant adeno-associated viruses(rAAVs)encoding the protamine-1(PRM1)MRI reporter gene.CEST MRI revealed that PRM1 contrast agent effectively highlighted caudate putamen region after injection of the rAAVs into the mouse brain,clearly distinguishing it from the surrounding tissue,with no observable damage.This method provides a sensitive,metal-free CEST contrast agent for in vivo brain cell detection,demonstrating potential for both diagnostic and therapeutic applications in brain diseases.
基金National Natural Science Foundation of China,No.32271148(to JW)the National Key Research and the Development Program of China,No.2023M740625(to ML)+1 种基金the Natural Science Foundation of Guangdong Province,Nos.2021B1515120050(to HW)and 2023A1515110782(to ML)and Key R&D Program of Ningxia Hui Autonomous Region,No.2024BEG02027(to JW).
文摘Astrocytes are the most abundant glial cells in the central nervous system.They perform a diverse array of functions,with a critical role in structural integrity,synapse formation,and neurotransmission.These cells exhibit substantial regional heterogeneity and display variable responses to different neurological diseases.Such diversity in astrocyte morphology and function is essential for understanding both normal brain function and the underlying mechanisms of neurological disorders.To investigate this heterogeneity,we developed a novel method for the selective and sparse labeling of astrocytes in various brain regions.This technique utilizes a dual adeno-associated virus system that allows for the expression of Cre recombinase and enhanced green fluorescent protein under the control of the glial fibrillary acidic protein(GfaABC1D)promoter.The system was tested in C57BL/6J mice and successfully labeled astrocytes across multiple brain regions.The method enabled the detailed visualization of individual astrocytes-including their intricate peripheral processes-through three-dimensional reconstructions from confocal microscopy images.Furthermore,the labeling efficiency of this dual adeno-associated virus technology was validated by examining astrocyte function in a spared nerve injury model and through chemogenetic modulation.This innovative approach holds great promise for future research because it enables a more comprehensive understanding of astrocyte variation not only in spared nerve injury but also in a broad spectrum of neurological diseases.The ability to selectively label and study astrocytes in different brain regions provides a powerful tool for exploring the complexities of these essential cells and their roles in physiological and pathological conditions.
基金Grants from the Ministry of Science and Technology of the People's Republic of China,Grant/Award Number:2021YFA1300301 and 2018YFA0507101National Natural Science Foundation of China,Grant/Award Number:31730054 and 31770900Beijing Natural Science Foundation,Grant/Award Number:5212016。
文摘Respiratory infectious diseases frequently erupt on a global scale,with RNA viruses,such as SARS-CoV-2,RSV,and influenza viruses,posing challenges to vaccine development due to their high mutation rates.Traditional vaccine development cycles are lengthy and struggle to keep pace with rapidly evolving viruses,whereas messenger RNA(mRNA)vaccines have demonstrated significant advantages due to their short development periods,straightforward production,and low costs.After the outbreak of the COVID-19 pandemic,multiple mRNA vaccines,including Pfizer-BioNTech and Moderna,rapidly received emergency use authorization,validating their feasibility.The Nobel Prize in Physiology or Medicine in 2023 was awarded to Katalin Karikóand Drew Weissman,underscoring the efficacy of mRNA vaccine technology.In 2024,the U.S.Food and Drug Administration(FDA)approval of Moderna's respiratory syncytial virus(RSV)mRNA vaccine marked the immense potential of mRNA technology in vaccine innovation.This review article summarizes the design,clinical research,and future challenges of mRNA vaccines for respiratory viruses,delving into antigen design,mRNA delivery systems,and advancements in vaccines for multiple respiratory viruses,including innovations in self-amplifying mRNA and circular mRNA vaccines.Additionally,the development of combination vaccines is underway,aiming to provide protection against multiple viruses through a single administration.Despite the significant progress in mRNA vaccine development,challenges remain regarding raw material costs,stability,and delivery efficiency.In the future,with technological advancements and the accumulation of clinical experience,the design strategies and delivery systems of mRNA vaccines are expected to be continuously optimized,thereby enhancing their safety and efficacy.
文摘BACKGROUND To prevent mother to child transmission(MTCT)of human immunodeficiency virus(HIV),sustained maternal viral load suppression(VLS)and early HIV testing among HIV exposed infants(HEI)is critical.AIM To investigate maternal viral load results and infant HIV testing uptake at 6-weeks,and 9-months and 18-months in Rwanda.METHODS Between 2015 and 2022,VLS(<200 copies/mL)was measured among pregnant women living with HIV(WLHIV)from 38-healthcare facilities.Viral loads(VL)were measured at 6-months,12-months and 24-months,respectively.For maternal VL,the unit of analysis was visit-pair,and the pairs were created to define those with VL<200 copies/mL at two consecutive visits as having sustained VLS,persistent viremia(VL≥200 copies/mL at two consecutive visits),viral rebound(VL<200 copies/mL at prior visit only)and newly suppressed(VL<200 copies/mL at subsequent visit only).HEI were considered to have persistent HIV testing if they had all three HIV tests.Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio(aIRR)and 95%CI for factors associated with sustained VLS and persistent HIV testing.RESULTS A total of 1145 mother-infant pairs were analyzed.Infant HIV testing uptake at 6-weeks,9-months and 18-months was 1145(100.0%),1089(95.1%),1006(87.9%)respectively.Nine hundred ninety-nine HEI(87.3%)tested for HIV persistently.At 18-months,the incidence of HIV among HEI was 8(0.7%).Of 1145 mothers,1076(94.0%)had≥2 VL results making a total of 2010 visit-pairs(142-single;934-double visit-pairs).The incidence rate of sustained VLS,persistent viremia,viral rebound and new suppression were 91.0%,1.3%,3.6%and 4.0%respectively.Maternal disclosure of HIV status(aIRR=1.08,95%CI:1.02-1.14)was associated with increased likelihood of sustained VLS.Having peer support(aIRR=1.0595%CI:1.01-1.10)was associated with persistent HIV testing among HEI.CONCLUSION Sustained VLS is high among pregnant WLHIV in Rwanda.The low incidence of HIV among HEI may be attributed to high VLS levels.Targeted interventions,including enhanced HIV disclosure and peer support,are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.
