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
Rabies,a persistent and historic global zoonosis,continues to impose a significant public health burden,particularly in resource-limited regions.The causative agent,rabies virus(RABV;genus Lyssavirus,family Rhabdoviri...Rabies,a persistent and historic global zoonosis,continues to impose a significant public health burden,particularly in resource-limited regions.The causative agent,rabies virus(RABV;genus Lyssavirus,family Rhabdoviridae),possesses a surface glycoprotein(G)that is pivotal for virus entry and pathogenesis.Rabies virus glycoprotein(RABV-G)mediates binding to host cell receptor(s)and acidic-pH-dependent membrane fusion,enabling the release of RNA genome into the host cytoplasm.It is also the main target for neutralizing antibodies and the major component of rabies vaccines.In this review,we systematically summarize the structural features,functional mechanisms,and antiviral targeting strategies of RABV-G,emphasizing recent structural insights into its conformational dynamics.Key neutralizing epitopes and their recognition by monoclonal antibodies are discussed,along with antiviral strategies,including entry inhibitors,antibody therapies,and advanced vaccine platforms.Accumulating structural analyses indicate that the pH-dependent and reversible conformational transitions of this classⅢviral fusion protein underlie both viral infectivity and vulnerability to immune intervention.Collectively,available data establish that neutralizing epitopes on RABV-G are conformationally defined and dynamically regulated during fusion,thereby constraining viral entry and dictating the effectiveness of antibody-and entry inhibitor–mediated neutralization.Together,these findings establish RABV-G as the primary determinant of rabies virus virulence and immune control.By exploring the structural framework and prospective treatment modalities,we aim to enhance our understanding of rabies virus,particularly the glycoprotein G,and support ongoing initiatives to alleviate the burden of rabies,offering renewed optimism in the battle against this formidable infectious disease.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
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
Influenza viruses are a major cause of respiratory illness,with significant public health impact due to their ability to cause pandemics.This dialogue brought together experts including Professors George Fu Gao,Stephe...Influenza viruses are a major cause of respiratory illness,with significant public health impact due to their ability to cause pandemics.This dialogue brought together experts including Professors George Fu Gao,Stephen Cusack,Mark von Itzstein,Ervin Fodor,Jonathan Grimes,Aartjan J.W.te Velthuis,and Tao Deng to decode the pressing scientific challenges and future directions in influenza research.They discussed how structural studies of the influenza polymerase have advanced our understanding of viral RNA transcription and replication.These insights are crucial for developing new antiviral drugs,with a particular focus on targeting the polymerase and its interactions with host factors like acidic nuclear phosphoprotein 32(ANP32).The dialogue also highlighted the potential of artificial intelligence(AI)to assist in designing small-molecule drugs,offering new strategies for combating influenza.Future research will continue to unravel the complexities of the polymerase’s role in replication,aiming to translate these findings into effective therapies and resilient public health strategies.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
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
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
Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially i...Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.展开更多
A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(da...A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.展开更多
AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected p...AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.展开更多
Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Cu...Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Currently,there is no commercial vaccine or specific treatment available to prevent ZIKV infection.Therefore,controlling the epidemic's spread relies on preventing mosquitoes from transmitting the virus.Although various studies have explored the transmission of ZIKV between mosquitoes and vertebrate hosts,comprehensive research on potential mosquito-to-mosquito transmission of ZIKV remains limited.In this study,we conducted systematic laboratory investigations to assess the ability of ZIKV to spread among mosquitoes,and to evaluate the impact of ZIKV infection on mosquito development.Our findings revealed that ZIKV can be transmitted between Aedes aegypti mosquitoes both vertically and horizontally,through oviposition and contact between mosquitoes of the same or opposite sex.Additionally,we observed that ZIKV infection resulted in a reduction in the number of mosquito eggs but an increase in their size.The widespread distribution of ZIKV in infected mosquitoes and the altered levels of hormone related genes following viral infection were noted,which may contribute to viral transmission among mosquitoes and affect mosquito development.This research provides systematic experimental evidence of ZIKV transmission among mosquitoes,which is crucial for developing novel strategies to disrupt the spread of orthoflaviviruses and other mosquitoborne pathogens.展开更多
Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive imm...Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and ...Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and mechanism of A.annua leaf methanol extracts(AALME)against IAV in vitro and in vivo.Our results revealed that AALME exhibits potent anti-IAV activity by interacting with IAV particles.Mechanistically,AALME directly targets the IAV nucleoprotein(NP)protein and abolishes the nuclear import of IAV NP.AALME profoundly suppresses IAV-induced mitochondrial apoptosis via suppressing ROS-mediated AIF-dependent pathways.More importantly,we found that AALME plays a crucial role in protecting mice from IAV infection and mitigating IAV pathogenicity.This current work provides mechanistic insight into the mechanism by which AALME controls IAV infection in vitro and in vivo,potentially contributing to the development of antiviral treatments for IAV infection.展开更多
BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated l...BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated liver cirrhosis because of their self-renewal and multidirectional differentiation potential.AIM To explore the safety and effect of treating liver cirrhosis with HBV by hUC-MSCs.METHODS Twenty-four participants were recruited,divided into 3 groups,and injected with different amounts of hUC-MSCs via the peripheral vein.Therapy was administered 3 times.A 24-week follow-up examination of each patient’s liver function,coagulation function,general condition,and immune system was performed.Adverse events were also recorded.A 2-year survival assessment was subsequently performed.RESULTS Infusion therapy rapidly improved liver function.Serum albumin transiently increased on days 57 and 85 but returned to baseline by day 169,while prothrombin time activity demonstrated sustained improvement from day 29 through day 169.Interleukin-8 levels decreased persistently throughout treatment.All dosage groups achieved 100%6-month survival;2-year survival rates were 66.7%(low-dose),100%(medium-dose),and 87.5%(high-dose).The interaction between dosage and efficacy was weak.Notably,the improvement in liver function was statistically significant and sustained for almost 3 months,suggesting clinically meaningful therapeutic durability.CONCLUSION hUC-MSCs can be considered a safe treatment for patients with decompensated liver cirrhosis associated with HBV.However,larger-scale randomized controlled trials are needed to prove its therapeutic effect.展开更多
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 National Natural Science Foundation of China(grant numbers 82272333 to G.L.and 32100114 to F.Y.)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(grant number ZYGD23022 to G.L.)the National Postdoctoral Program for Innovative Talents of China(grant number BX20230243 to S.L.)。
文摘Rabies,a persistent and historic global zoonosis,continues to impose a significant public health burden,particularly in resource-limited regions.The causative agent,rabies virus(RABV;genus Lyssavirus,family Rhabdoviridae),possesses a surface glycoprotein(G)that is pivotal for virus entry and pathogenesis.Rabies virus glycoprotein(RABV-G)mediates binding to host cell receptor(s)and acidic-pH-dependent membrane fusion,enabling the release of RNA genome into the host cytoplasm.It is also the main target for neutralizing antibodies and the major component of rabies vaccines.In this review,we systematically summarize the structural features,functional mechanisms,and antiviral targeting strategies of RABV-G,emphasizing recent structural insights into its conformational dynamics.Key neutralizing epitopes and their recognition by monoclonal antibodies are discussed,along with antiviral strategies,including entry inhibitors,antibody therapies,and advanced vaccine platforms.Accumulating structural analyses indicate that the pH-dependent and reversible conformational transitions of this classⅢviral fusion protein underlie both viral infectivity and vulnerability to immune intervention.Collectively,available data establish that neutralizing epitopes on RABV-G are conformationally defined and dynamically regulated during fusion,thereby constraining viral entry and dictating the effectiveness of antibody-and entry inhibitor–mediated neutralization.Together,these findings establish RABV-G as the primary determinant of rabies virus virulence and immune control.By exploring the structural framework and prospective treatment modalities,we aim to enhance our understanding of rabies virus,particularly the glycoprotein G,and support ongoing initiatives to alleviate the burden of rabies,offering renewed optimism in the battle against this formidable infectious disease.
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Influenza viruses are a major cause of respiratory illness,with significant public health impact due to their ability to cause pandemics.This dialogue brought together experts including Professors George Fu Gao,Stephen Cusack,Mark von Itzstein,Ervin Fodor,Jonathan Grimes,Aartjan J.W.te Velthuis,and Tao Deng to decode the pressing scientific challenges and future directions in influenza research.They discussed how structural studies of the influenza polymerase have advanced our understanding of viral RNA transcription and replication.These insights are crucial for developing new antiviral drugs,with a particular focus on targeting the polymerase and its interactions with host factors like acidic nuclear phosphoprotein 32(ANP32).The dialogue also highlighted the potential of artificial intelligence(AI)to assist in designing small-molecule drugs,offering new strategies for combating influenza.Future research will continue to unravel the complexities of the polymerase’s role in replication,aiming to translate these findings into effective therapies and resilient public health strategies.
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.
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.
文摘Diel investigations of water environments are one means to holistically understand the dynamics and functional roles of phytoplankton,bacteria and viruses in these ecosystems.They have the potential to substantially impact carbon(C),nitrogen(N)and phosphorus(P)biogeochemistry through their respective roles.This study characterizes the phytoplankton,bacteria and virus communities and the elemental composition of various C,N and P nutrients flow over three diel cycles in tropical urban lake.Our results show that ratios of C:N:P fluctuated strongly from the lack of dissolved organic phosphorus(DOP)and PO_(4).Specifically,green algae peaked during day time and exudate dissolved organic matter(DOM)that strongly modulate dissolved organic carbon(DOC):DOP ratio to diel DOP limitation.Multiple linear regression and Stella modelling emphasize the roles of viruses together with Synechococcus as important nutrient recyclers of NH_(4)and PO_(4)in nutrients-limited waters.Respective normalised surface PO_(4)and combined surface and bottom NH_(4)concentration selected both viruses and Synechococcus as important drivers.Process model of N and P biogeochemical cycles can achieve 69%and 57%similar to observed concentration of NH_(4)and PO_(4),respectively.A short latent period of 9 hr was calculated,in addition to the calibrated high infectivity of viruses to Synechococcus.Taken together,the rapid turn-over between Synechococcus and viruses has biogeochemical significance,where the rapid recycling of essential nutrients allows for shortcuts in the N and P cycle,supporting a wide range of microbes.
基金Natural science foundation of Inner Mongolia(2024LHMS06018)The basic scientific research funding for directly affiliated universities in the Inner Mongolia(JY20250094)。
文摘A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500.
基金Supported by the Self-funded Research Project of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region(No.Z2016325).
文摘AIM:To investigate the etiology of ocular pathogens and to establish the various pathogens present in human immunodeficiency virus(HIV)patients with cytomegalovirus retinitis(CMVR).METHODS:A total of 17 HIV-infected patients with concomitant eye disorders were enrolled.Patients were divided into CMVR group(10 patients,18 eyes)and non-CMVR group(7 patients,9 eyes)based on clinical manifestations and the presence of cytomegalovirus(CMV)-DNA in ocular specimens.The viral load of CMV was assessed using polymerase chain reaction in aqueous humor,vitreous fluid,and peripheral blood samples of patients in the CMVR group.Additionally,peripheral blood CD4^(+)T cell counts were measured in both groups.RESULTS:In the CMVR group,the CMV-DNA load in the vitreous and aqueous humor samples was substantially higher than in the peripheral blood samples(P<0.01).CMVDNA load in the aqueous humor and vitreous samples of the two eyes in the CMVR group was determined to be statistically significant(10 patients,16 eyes,P=0.018,0.012).Peripheral blood CD4^(+)T cell counts in the CMVR group were adversely linked with the CMV-DNA load in both the aqueous humor and peripheral blood(P=0.005,0.048).Compared with the non-CMVR group,the peripheral blood CD4^(+)T cell count in the CMVR group decreased significantly(P=0.014).The peripheral blood CD4^(+)T cell count exceeded 300 cells/μL in 85.71%of non-CMVR patients,whereas it was below 100 cells/μL in 90.00%of the CMVR group.The intraocular specimens of the patients who underwent CMVR testing did not include any additional infections.CONCLUSION:In HIV-associated CMVR patients,there may exist alternative,yet unidentified,infection pathways for intraocular CMV in addition to the conventional route.The substantial difference in CMV-DNA load between the eyes of most CMVR patients suggests that CMV may originate from different sources in each eye.The proportion of peripheral blood CD4^(+)T cells in HIV patients is negatively correlated with the quantity of CMV viruses in their eyes.The peripheral blood count of<100 cells/μL indicates a considerable increase in the risk of concurrent CMVR.Multi-ocular pathogen presentations are uncommon in HIV individuals with CMVR.
基金supported by National Key Research and Development Program of China,China(2024YFD1800102,2022YFD1800105 and 2022YFD1801500)National Natural Science Foundation of China,China(32372993 and 32030107)Fundamental Research Funds for the Central Universities,China(2662023PY005).
文摘Zika virus(ZIKV)is a mosquito-borne virus belonging to the genus Orthoflavivirus,and the family Flaviviridae.It commonly presents with febrile-like symptoms,neurological issues,and pregnancy complications in humans.Currently,there is no commercial vaccine or specific treatment available to prevent ZIKV infection.Therefore,controlling the epidemic's spread relies on preventing mosquitoes from transmitting the virus.Although various studies have explored the transmission of ZIKV between mosquitoes and vertebrate hosts,comprehensive research on potential mosquito-to-mosquito transmission of ZIKV remains limited.In this study,we conducted systematic laboratory investigations to assess the ability of ZIKV to spread among mosquitoes,and to evaluate the impact of ZIKV infection on mosquito development.Our findings revealed that ZIKV can be transmitted between Aedes aegypti mosquitoes both vertically and horizontally,through oviposition and contact between mosquitoes of the same or opposite sex.Additionally,we observed that ZIKV infection resulted in a reduction in the number of mosquito eggs but an increase in their size.The widespread distribution of ZIKV in infected mosquitoes and the altered levels of hormone related genes following viral infection were noted,which may contribute to viral transmission among mosquitoes and affect mosquito development.This research provides systematic experimental evidence of ZIKV transmission among mosquitoes,which is crucial for developing novel strategies to disrupt the spread of orthoflaviviruses and other mosquitoborne pathogens.
基金Supported by Shenzhen Medical Research Fund,No.D2301010Shenzhen Science and Technology Program,No.RCYX20231211090346060。
文摘Chronic hepatitis B virus(HBV)infection remains a major health burden worldwide.To establish a persistence infection,HBV needs to evade both adaptive and innate immune surveillance.Multiple mechanisms for adaptive immunity evasion have been established,but how HBV evades the innate surveillance is less clear.There are three types of host cells involving in the innate immune responses against HBV infection:Hepatocytes,hepatic nonparenchymal cells and conventional innate immune cells.Among these,hepatocytes are the only target cells that are susceptible to HBV infection and the only confirmed site where HBV replication takes place.This review focuses on the hepatocyte-intrinsic innate immunity;one of the earliest host defense responses.After entering hepatocytes,the viral components can be sensed by the cellular pattern recognition receptors.This triggers downstream antiviral responses capable of inhibiting viral replication and even degrading the viral DNA genome directly or indirectly.However,HBV has evolved a variety of sophisticated strategies to evade intracellular immune defense,resulting in the establishment of infection.Here,we provide insights into the mechanisms of the intrinsic innate immune response of hepatocytes and how HBV escapes these defense mechanisms.Hopefully,this will lay the foundation for the development of novel anti-HBV therapies.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金supported by grants from the National Natural Science Foundation of China(32170937)Shenzhen Medical Research Fund(SMRF,A2303015)+3 种基金Pearl River Talent Project of Guangdong Province(2021QN02Y426)Shenzhen Peacock Plan Project(827/000655)to Liang Yethe Yunnan Provincial Key Areas Science and Technology Plan Project(202303AC100025)Yunnan Scholar of Yunling(YNWRYLXZ-2019-019)to Rongping Zhang.
文摘Artemisia annua L.is a medicinal herb with multiple therapeutic applications,whereas its antiinfluenza A virus(IAV)efficiency and mechanism of action are still unclear.Here,we investigated the inhibition activity and mechanism of A.annua leaf methanol extracts(AALME)against IAV in vitro and in vivo.Our results revealed that AALME exhibits potent anti-IAV activity by interacting with IAV particles.Mechanistically,AALME directly targets the IAV nucleoprotein(NP)protein and abolishes the nuclear import of IAV NP.AALME profoundly suppresses IAV-induced mitochondrial apoptosis via suppressing ROS-mediated AIF-dependent pathways.More importantly,we found that AALME plays a crucial role in protecting mice from IAV infection and mitigating IAV pathogenicity.This current work provides mechanistic insight into the mechanism by which AALME controls IAV infection in vitro and in vivo,potentially contributing to the development of antiviral treatments for IAV infection.
基金Supported by the Foundation of Health Commission of Hubei Province,No.WJ2019H053Natural Science Foundation of Hubei Province,No.2023AFB169+1 种基金Foundation of Health Commission of Hubei Province,No.ZY2021Q019Open Fund Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells,Taihe Hospital,No.2024SCOF008.
文摘BACKGROUND Large number of decompensated liver cirrhosis patients in China have been diagnosed with hepatitis B virus(HBV).Human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)can possibly cure decompensated liver cirrhosis because of their self-renewal and multidirectional differentiation potential.AIM To explore the safety and effect of treating liver cirrhosis with HBV by hUC-MSCs.METHODS Twenty-four participants were recruited,divided into 3 groups,and injected with different amounts of hUC-MSCs via the peripheral vein.Therapy was administered 3 times.A 24-week follow-up examination of each patient’s liver function,coagulation function,general condition,and immune system was performed.Adverse events were also recorded.A 2-year survival assessment was subsequently performed.RESULTS Infusion therapy rapidly improved liver function.Serum albumin transiently increased on days 57 and 85 but returned to baseline by day 169,while prothrombin time activity demonstrated sustained improvement from day 29 through day 169.Interleukin-8 levels decreased persistently throughout treatment.All dosage groups achieved 100%6-month survival;2-year survival rates were 66.7%(low-dose),100%(medium-dose),and 87.5%(high-dose).The interaction between dosage and efficacy was weak.Notably,the improvement in liver function was statistically significant and sustained for almost 3 months,suggesting clinically meaningful therapeutic durability.CONCLUSION hUC-MSCs can be considered a safe treatment for patients with decompensated liver cirrhosis associated with HBV.However,larger-scale randomized controlled trials are needed to prove its therapeutic effect.
