Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank...Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank,sarcopenia was diagnosed according to European and Asian Working Groups for Sarcopenia criteria.Social isolation was assessed using standardized questionnaires,including questions on solitude,frequency of social activities,contact with others,and marital status(for the CLHLS only).Results During the follow-up period,8,249 deaths occurred in the CLHLS and 26,670 deaths in the UK Biobank groups.While no significant interaction was observed between sarcopenia and social isolation in predicting all-cause mortality in the CLHLS cohort,the association between social isolation and mortality was stronger among individuals with sarcopenia in the UK Biobank(P-interaction=0.03,relative risk due to interaction:0.23,95%confidence interval[CI]:0.06–0.41).Further joint analyses showed that participants with sarcopenia and high levels of social isolation had the highest mortality risk(hazard ration[HR]:1.99;95%CI:[1.74–2.28]in the CLHLS and 1.69[1.55–1.85]in the UK Biobank)compared to those without either condition.Conclusion The combination of social isolation and sarcopenia synergistically increases the risk of mortality in middle-aged and older adults across diverse populations.展开更多
In order to realize simultaneous quantitative detection of various enteroviruses from water samples, a real-time reverse transcriptionpolymerase chain reaction （real-time RT-PCR） method was developed with universal ...In order to realize simultaneous quantitative detection of various enteroviruses from water samples, a real-time reverse transcriptionpolymerase chain reaction （real-time RT-PCR） method was developed with universal primer pairs designed based on the highly conserved non-coding region sequences of genome targeting poliovirus, coxsackievirus and enterovirus 71. The recombinant plasmid was constructed as enterovirus DNA standard by cloning poliovirus cDNA into a pMD18-T vector. The real-time RT-PCR method utilizing SYBR Green I was optimized. As a result of a series of examinations, the detection limit of the method was found to be 2.31 genome equivalent copy （GEC）/μL, the intraand inter-assay variations were lower than 2% and 5%, respectively, and enteroviruses were well distinguished from other microorganisms. There was a good linear relationship （r 2 = 0.997） between the logarithm of viral density and cycle threshold in a wide range of 2.31 × 10 0 to 2.31 × 10 9 GEC/μL. The validity of the method was further proved by its application for the detection of enteroviruses from various practical water samples.展开更多
Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA1...Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31 st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may cocirculate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.展开更多
Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can...Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.展开更多
Enterovirus 71 （EV71） is a common cause of Hand, foot, and mouth disease （HFMD） and may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic divers...Enterovirus 71 （EV71） is a common cause of Hand, foot, and mouth disease （HFMD） and may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity of EV71, we determined and analyzed the complete VP1 sequences （891 nueleotides） from nine EV71 strains isolated in Fuyang, China. We found that nine EV71 strains isolated were over 98% homologous at the nucleotide level and 93%-100% homologous tO members of the C4 subgenogroup. At the amino acid level, these Fuyang strains were 99% -100% homologous to one another, 97%-100% homologous to members of the C4 subgenogroup, and the histidine（H） at amino acid position 22 was conserved among the Fuyang strains. The results indicate that Fuyang isolates belong to genotype C4, and an H at position 22 appears to be a marker for the Fuyang strains.展开更多
Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontan...Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,展开更多
Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitinati...Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. Therefore, whether the effect of EVs 3C on RIG-I is associated with TRIM25 expression is worth to be further investigated. Here, we demonstrate that 3C proteins of EV71 and coxsackievirus B3(CVB3) reduced not only RIG-I expression but also TRIM25 expression through protease cleavage activity, while overexpression of TRIM25 restored RIG-I expression and IFN-b production reduced by 3C proteins. Further investigation confirmed that the two amino acids and functional domains in TRIM25 required for RIG-I ubiquitination and TRIM25 structural conformation were essential for the recovery of RIG-I expression. Moreover, we also observed that TRIM25 could rescue RIG-I expression reduced by 3C proteins of CVA6 and EV-D68 but not CVA16. Our findings provide an insightful interpretation of 3C-mediated host innate immune suppression and support TRIM25 as an attractive target against multiple EVs infection.展开更多
An 8-month survey was conducted to detect and quantify enteroviruses in Tianjin coastal seawaters of Bohai Bay to assess coastal water quality. Ten water samples were collected from Bohai Bay for the detection and qua...An 8-month survey was conducted to detect and quantify enteroviruses in Tianjin coastal seawaters of Bohai Bay to assess coastal water quality. Ten water samples were collected from Bohai Bay for the detection and quantification of enteroviruses by conventional reverse transcription polymerase chain reaction （RT-PCR） and SYBR Green real-time quantitative RT-PCR （qRT-PCR）. Total viral nucleic acid was extracted from 500 mL of seawater samples concentrated by Centricon plus-70 centrifugal filter devices. The viral recovery rate was 29.1% based on viral seeding study. The centrifugal ultrafiltration method applied is effective for viral recovery from small volume of polluted water, which may have broader applications to monitoring human virus in aquatic environment. Our results indicated that there was a severe viral contamination in seawater of Bohai Bay. Enteroviruses were detected at concentrations ranging from 1.7 × 10^6 to 6.3 × 10^7 copies/L by qRT-PCR. Sequencing analyses identified that all of the twenty clones as poliovirus type 2. This is the first quantitative report of human viruses in coastal waters of a metropolitan city in China. This study emphasized the importance for the local and central governmertts to monitor and assess the water quality.展开更多
The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic a...The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic and preventive strategies.In this study,our initial attempts to introduce a NanoLuc luciferase(NLuc)reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies.We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus.Therefore,we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71(EV-A71),coxsackievirus A10(CVA10),coxsackievirus A7(CVA7),coxsackievirus A16(CVA16),namely EV-A71-HiBiT,CVA16-HiBiT,CVA10-HiBiT,CVA7-HiBiT,and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency.Notably,the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses.A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics.Moreover,these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages.In addition,the HiBiT-tagged viruses were successfully tested in antiviral drug assays,and the sensitivity of the viruses to drugs was not affected by the HiBiT tag.Ultimately,our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal,convenient,and invaluable method for advancing research in the realm of enterovirus virology.Furthermore,HiBiT-tagged enteroviruses exhibit great potential for diverse applications,including the development of antivirals and the elucidation of viral infection mechanisms.展开更多
Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one mi...Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported annually.Before 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).展开更多
AIM： To search for new antiviral agents from traditional Chinese medicine, specifically anti-enterovirosuses agents. METHODS： The aqueous extracts （AE） of more than 100 traditionally used medicinal plants in China...AIM： To search for new antiviral agents from traditional Chinese medicine, specifically anti-enterovirosuses agents. METHODS： The aqueous extracts （AE） of more than 100 traditionally used medicinal plants in China were evaluated for their in vitro anti-Coxsackie virus B3 activities with a MTT-based colorimetric assay. RESULTS： The test for AE of 16 plants exhibited anti- Coxsackie virus B3 activities at different magnitudes of potency. They can inhibit three steps （inactivation, adsorption and replication） during the infection. Among the 16 plants, Sargentodoxa cuneata （Oliv.） Rehd. et Wils., Sophora tonkinensis Gapnep., Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtorniurn fortunei J, sm. also have activity against other enterovirus, including Coxsackie virus 135, Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated that all tested AE had CC50 values higher than their EC50 values. CONCLUSION： The sixteen traditionally used medicinal plants in China possessed antMral activity, and some of them merit further investigations.展开更多
After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evid...After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.展开更多
For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5' non-coding region were desi...For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5' non-coding region were designed by analyzing enteroviral genomes, and then they were used to enzymatically amplify RNA from 31 prototype enteroviral strains and enteroviruses (EV) in cerebrospinal fluid (CSF) of 34 cases of aseptic meningitis and 11 cases of aseptic encephalitis. The RT-PCR products generated with these enteroviral primers were analyzed by agar gel electrophoresis and dot blot hybridization analysis. 31 EV strains showed an obvious monoclonal amplification band, and all dot blot hybridization results were positive. Four other viruses and cells cultured were all negative. The study of sensitivity of the RT-PCR showed that amplification production were positive to 10(-2)- 10(-3) 50% tissue culture infective doses. With this assay, 21(61.8%) of 34 aseptic meningitis and 8 (72. 7%) of 11 aseptic encephalitis contained EV RNA in CSF samples. Two cases of meningitis and one of encephalitis with EV infection were still positive during convalescence. Our results suggest that this RT-PCR method was a fast, sensitive and specific technique for detection of common EV infection.展开更多
Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied i...Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied in 3596 AFP patients in 64 districts of Uttar-Pradesh, India, to observe indirect relationship of AFP with wild polio as well as NPEV. A recent study suggests the need to investigate polio virus negative but NPEV positive AFP cases. Methods: The lab results of the stool samples of these children were line listed and analysed to observe the association of various factors with respect to presence of paralysis on 60 follow-up days. Taking zero OPV dose AFP cases as a biological base, we studied the relationship of presence of paralysis at 60 follow-up days to that of presence of NPEV in stool samples while polio virus was present or absent. Results: 70 of the 86 AFP cases (81%) with zero OPV dose and having only NPEV isolated in stool samples were having paralysis at 60 follow-up days. There were 4.54% (162) AFP cases, which did not carry any polio virus but were having NPEV isolated in the stool samples and paralysis at 60 follow-up days. 79% (75/95) of zero OPV dose children, who were having residual weakness at 60 follow-up days, were carrying both polio virus as well as NPEV in their stool samples. Total AFP cases, having residual weakness at 60 follow-up days and having NPEV in stool samples, decreased with increase in OPV doses;a behavior similar to what wild polio viruses (WPV) have to OPV. Conclusions: Maybe polio like NPEV is active for causing severe paralysis in children and is responding to the OPV. As is evident in the studies by M. Margalith, B. Fattal et al. [1] that there is an antibody response to the enteroviruses, we can think of coming out with a vaccine against the enteroviruses. Therefore, enterovirus vaccine can be produced on similar lines to that of OPV, as now we have enough isolates of NPEV. Effective NPEV surveillance system also needs to be in place.展开更多
Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of entero...Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of enteroviruses deposited in the international database GenBank （www.ncbi.nlm.nih.gov/Genbank） was conducted to develop specific primers for the detection of these viruses.The specificity and sensitivity of the method were tested using coxackicvirus B3 strain Nancy,environmental isolate of human hepatitis A virus and human rotavirus strain WA.Seventy sewage samples were analyzed.Results:Enterovirus genome was detected in all positive samples.The genome of enterovirus was not detected in negative samples.The level of detection of these viruses was 10<sup>2</sup> TCID<sub>50</sub>mI..Conclusions:The development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.展开更多
The multi-terminal direct current(DC)grid has extinctive superiorities over the traditional alternating current system in integrating large-scale renewable energy.Both the DC circuit breaker(DCCB)and the current flow ...The multi-terminal direct current(DC)grid has extinctive superiorities over the traditional alternating current system in integrating large-scale renewable energy.Both the DC circuit breaker(DCCB)and the current flow controller(CFC)are demanded to ensure the multiterminal DC grid to operates reliably and flexibly.However,since the CFC and the DCCB are all based on fully controlled semiconductor switches(e.g.,insulated gate bipolar transistor,integrated gate commutated thyristor,etc.),their separation configuration in the multiterminal DC grid will lead to unaffordable implementation costs and conduction power losses.To solve these problems,integrated equipment with both current flow control and fault isolation abilities is proposed,which shares the expensive and duplicated components of CFCs and DCCBs among adjacent lines.In addition,the complicated coordination control of CFCs and DCCBs can be avoided by adopting the integrated equipment in themultiterminal DC grid.In order to examine the current flow control and fault isolation abilities of the integrated equipment,the simulation model of a specific meshed four-terminal DC grid is constructed in the PSCAD/EMTDC software.Finally,the comparison between the integrated equipment and the separate solution is presented a specific result or conclusion needs to be added to the abstract.展开更多
Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies...Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.展开更多
Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numeri...Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numerical parameter analysis is conducted on the key influencing factors of the vibration isolation hole(VIH),which include hole diameter,hole net spacing,hole depth,hole number,hole arrangement,and soil parameters.The results indicate that a smaller ratio of net spacing to hole diameter,the deeper the hole,the multi-row hole,the hole adoption of staggered arrangements,and better site soil conditions can enhance the efficiency of the VIH barrier.The average maximum vibration reduction efficiency within the vibration isolation area can reach 42.2%.The vibration safety of adjacent oil pipelines during a dynamic compaction projection was evaluated according to existing standards,and the measurement of the VIH was recommended to reduce excessive vibration.The single-row vibration isolation scheme and three-row staggered arrangement with the same hole parameters are suggested according to different cases.The research findings can serve as a reference for the vibration safety analysis,assessment,and control of adjacent underground facilities under the influence of strong surface impact loads.展开更多
BACKGROUND Frailty has become a significant public health issue.The recent increase in the number of frail older adults has led to increased attention being paid to psycho-logical care services in communities.The soci...BACKGROUND Frailty has become a significant public health issue.The recent increase in the number of frail older adults has led to increased attention being paid to psycho-logical care services in communities.The social isolation of pre-frail older adults can impact their psychological distress.AIM To explore the mediating effect of health literacy between social isolation and psychological distress among communitydwelling older adults with pre-frailty.METHODS This descriptive cross-sectional study was conducted with 254 pre-frail older individuals aged 60 years and over.Social isolation,health literacy,and psycholo-gical distress were comprehensively measured using the Lubben Social Network Scale-6,12-item Short-Form Health Literacy Questionnaire,and the Kessler Psy-chological Distress Scale-10.Data were evaluated using the SPSS 27.0 package program and the PROCESS macro tool.Descriptive statistical analyses,correlation analyses,and bootstrap mediation tests were used to assess associations between the variables.RESULTS The results showed that social isolation had an effect on health literacy among pre-frail older adults(β=0.240,P<0.001),social isolation impact on psycho-logical distress pre-frail older adults(β=-0.415,P<0.001);health literacy was identified effect on psychological distress among pre-frail older persons(β=-0.307,P<0.001).Health literacy partially mediated the relationship between social isolation and psychological distress among community-dwelling older adults with pre-frailty,with a mediation effect of-0.074,accounting for 17.83%of the total effect.展开更多
基金supported by grants from the National Key Research and Development Program of China(No.2023YFC3606300,No.2022YFC3600300)the National Natural Science Foundation of China(No.82325043)the National Key Research and Development Program of Hubei Province(2022BCA036)。
文摘Objective This study aims to investigate the joint associations of sarcopenia and social isolation with mortality risk.Methods Using data from the Chinese Longitudinal Healthy Longevity Survey(CLHLS)and the UK Biobank,sarcopenia was diagnosed according to European and Asian Working Groups for Sarcopenia criteria.Social isolation was assessed using standardized questionnaires,including questions on solitude,frequency of social activities,contact with others,and marital status(for the CLHLS only).Results During the follow-up period,8,249 deaths occurred in the CLHLS and 26,670 deaths in the UK Biobank groups.While no significant interaction was observed between sarcopenia and social isolation in predicting all-cause mortality in the CLHLS cohort,the association between social isolation and mortality was stronger among individuals with sarcopenia in the UK Biobank(P-interaction=0.03,relative risk due to interaction:0.23,95%confidence interval[CI]:0.06–0.41).Further joint analyses showed that participants with sarcopenia and high levels of social isolation had the highest mortality risk(hazard ration[HR]:1.99;95%CI:[1.74–2.28]in the CLHLS and 1.69[1.55–1.85]in the UK Biobank)compared to those without either condition.Conclusion The combination of social isolation and sarcopenia synergistically increases the risk of mortality in middle-aged and older adults across diverse populations.
基金supported by the National Natural Sci-ence Foundation of China (No. 50908185)the National Program of Water Pollution Control (No. 2008ZX07317-004)+2 种基金the Basic Research Foundation of Xi’an University of Architecture and Technology (No. JC0910)the Research Foundation for Talented Scholars of Xi’an University of Architecture and Technology (No. RC0824)the Program for Changjiang Scholars and Innovative Research Team in University (No. IRT0853)
文摘In order to realize simultaneous quantitative detection of various enteroviruses from water samples, a real-time reverse transcriptionpolymerase chain reaction （real-time RT-PCR） method was developed with universal primer pairs designed based on the highly conserved non-coding region sequences of genome targeting poliovirus, coxsackievirus and enterovirus 71. The recombinant plasmid was constructed as enterovirus DNA standard by cloning poliovirus cDNA into a pMD18-T vector. The real-time RT-PCR method utilizing SYBR Green I was optimized. As a result of a series of examinations, the detection limit of the method was found to be 2.31 genome equivalent copy （GEC）/μL, the intraand inter-assay variations were lower than 2% and 5%, respectively, and enteroviruses were well distinguished from other microorganisms. There was a good linear relationship （r 2 = 0.997） between the logarithm of viral density and cycle threshold in a wide range of 2.31 × 10 0 to 2.31 × 10 9 GEC/μL. The validity of the method was further proved by its application for the detection of enteroviruses from various practical water samples.
基金supported by the TOTAL foundation,and the Grants from the National Science and Technology Major Project of China(2017ZX10103009-002)the "One Belt One Road" Project(153831KYSB20170043)of the Chinese Academy of Sciencesthe133 Project of Institut Pasteur of Shanghai,CAS.
文摘Hand, foot and mouth disease(HFMD) is a major public health concern in China. The most predominant enteroviruses that cause HFMD have traditionally been attributed to enterovirus A71(EVA71) and coxsackievirus A16(CVA16). Since its first large outbreak in 2008, the dominant HFMD pathogens are constantly changing. In 2013 and 2015, CVA6 exceeded both EVA71 and CVA16 to become the leading cause of HFMD in some provinces. However, there still lacks a comprehensive overview on the molecular epidemiology and evolution of HFMD-related enteroviruses at the national level. In this study, we performed systematic epidemiological analyses of HFMD-related enteroviruses using the data of 64 published papers that met the inclusion criteria, and conducted phylogenetic analyses based on 12,080 partial VP1 sequences identified in China before 31 st June 2018. We found that EVA71 prevalence has decreased sharply but other enteroviruses have increased rapidly from 2008 to 2016 and that one subtype of each enterovirus is represented during the epidemic. In addition, four genotypes EVA71_C4, CVA16_B1, CVA6_D and CVA10_C are the most predominant enterovirus strains and collectively they cause over 90% of all HFMD cases in China according to the phylogenetic trees using representative partial VP1 sequences. These four major enterovirus genotypes have different geographical distributions, and they may cocirculate with other genotypes and serotypes. These results suggest that more molecular epidemiological studies should be performed on several enteroviruses simultaneously, and such information should have implications for virological surveillance, disease management, vaccine development and policy-making on the prevention and control of HFMD.
基金supported by the National Science and Technology Major Project of China(No.2018ZX10201001-010,No.2017ZX10103009-005,No.2018ZX10713001-007)the National Natural Science Fund for Distinguished Young Scholars of China(No.81525023)+4 种基金the National Natural Science Foundation of China(No.81473031)the Program of Shanghai Academic/Technology Research Leader(No.18XD1400300)the Li Ka Shing Oxford Global Health Programme(No.B9RST00-B900.57)the Chinese Preventive Medicine Association(No:20101801)supported by CAS Pioneer Hundred Talents Program
文摘Enteroviruses(EVs)species A are a major public health issue in the Asia–Pacific region and cause frequent epidemics of hand,foot and mouth disease(HFMD)in China.Mild infections are common in children;however,HFMD can also cause severe illness that affects the central nervous system.To molecularly characterize EVs,a prospective HFMD virological surveillance program was performed in China between 2013 and 2016.Throat swabs,rectal swabs and stool samples were collected from suspected HFMD patients at participating hospitals.EVs were detected using generic real-time and nested reverse transcription-polymerase chain reactions(RT-PCRs).Then,the complete VP1 regions of enterovirus A71(EV-A71),coxsackievirus A16(CVA16)and CVA6 were sequenced to analyze amino acid changes and construct a viral molecular phylogeny.Of the 2836 enrolled HFMD patients,2,517(89%)were EV positive.The most frequently detected EVs were CVA16(32.5%,819),CVA6(31.2%,785),and EV-A71(20.4%,514).The subgenogroups CVA16B1 b,CVA6D3 a and EV-A71C4 a were predominant in China and recombination was not observed in the VP1 region.Sequence analysis revealed amino acid variations at the 30,29 and 44 positions in the VP1 region of EV-A71,CVA16 and CVA6(compared to the respective prototype strains Br Cr,G10 and Gdula),respectively.Furthermore,in 21 of 24(87.5%)identified EV-A71 samples,a known amino acid substitution(D31 N)that may enhance neurovirulence was detected.Our study provides insights about the genetic characteristics of common HFMD-associated EVs.However,the emergence and virulence of the described mutations require further investigation.
基金Scientific Research Fund of Institute of Pathogen Biology(2008IPB108)
文摘Enterovirus 71 （EV71） is a common cause of Hand, foot, and mouth disease （HFMD） and may also cause severe neurological diseases, such as encephalitis and poliomyelitis-like paralysis. To examine the genetic diversity of EV71, we determined and analyzed the complete VP1 sequences （891 nueleotides） from nine EV71 strains isolated in Fuyang, China. We found that nine EV71 strains isolated were over 98% homologous at the nucleotide level and 93%-100% homologous tO members of the C4 subgenogroup. At the amino acid level, these Fuyang strains were 99% -100% homologous to one another, 97%-100% homologous to members of the C4 subgenogroup, and the histidine（H） at amino acid position 22 was conserved among the Fuyang strains. The results indicate that Fuyang isolates belong to genotype C4, and an H at position 22 appears to be a marker for the Fuyang strains.
基金supported by National Foundation of China (project No.2013ZX10004-202)National Basic Research Program of China (973 Program,2011CB504902)National Natural Science Foundation of China (project Nos.30900063,81101303,81373049)
文摘Hand, foot, and mouth disease （HFMD） is a common contagious illness which occurs worldwide both sporadically and in epidemics. The disease mainly affects, children and the typical symptoms, which may resolve spontaneously, include mucocutaneous papulovesicular lesions on the hands, feet, mouth, and buttocks. In rare cases, however, the patients may also develop neurological complications such as neurogenic pulmonary edema,
基金The study was supported by the National Natural Science Foundation of China(No.81672004 and 81930062)the Science and Technology Department of Jilin Province(20190101003JH)the Key Laboratory of Molecular Virology,Jilin Province(20102209)。
文摘Enteroviruses(EVs) 3C proteins suppress type I interferon(IFN) responses mediated by retinoid acid-inducible gene I(RIG-I), while an E3 ubiquitin ligase, tripartite motif protein 25(TRIM25)-mediated RIG-I ubiquitination is essential for RIG-I antiviral activity. Therefore, whether the effect of EVs 3C on RIG-I is associated with TRIM25 expression is worth to be further investigated. Here, we demonstrate that 3C proteins of EV71 and coxsackievirus B3(CVB3) reduced not only RIG-I expression but also TRIM25 expression through protease cleavage activity, while overexpression of TRIM25 restored RIG-I expression and IFN-b production reduced by 3C proteins. Further investigation confirmed that the two amino acids and functional domains in TRIM25 required for RIG-I ubiquitination and TRIM25 structural conformation were essential for the recovery of RIG-I expression. Moreover, we also observed that TRIM25 could rescue RIG-I expression reduced by 3C proteins of CVA6 and EV-D68 but not CVA16. Our findings provide an insightful interpretation of 3C-mediated host innate immune suppression and support TRIM25 as an attractive target against multiple EVs infection.
基金supported by the National High Technology Research and Development Program (863) of China(No.2006AA09Z170)
文摘An 8-month survey was conducted to detect and quantify enteroviruses in Tianjin coastal seawaters of Bohai Bay to assess coastal water quality. Ten water samples were collected from Bohai Bay for the detection and quantification of enteroviruses by conventional reverse transcription polymerase chain reaction （RT-PCR） and SYBR Green real-time quantitative RT-PCR （qRT-PCR）. Total viral nucleic acid was extracted from 500 mL of seawater samples concentrated by Centricon plus-70 centrifugal filter devices. The viral recovery rate was 29.1% based on viral seeding study. The centrifugal ultrafiltration method applied is effective for viral recovery from small volume of polluted water, which may have broader applications to monitoring human virus in aquatic environment. Our results indicated that there was a severe viral contamination in seawater of Bohai Bay. Enteroviruses were detected at concentrations ranging from 1.7 × 10^6 to 6.3 × 10^7 copies/L by qRT-PCR. Sequencing analyses identified that all of the twenty clones as poliovirus type 2. This is the first quantitative report of human viruses in coastal waters of a metropolitan city in China. This study emphasized the importance for the local and central governmertts to monitor and assess the water quality.
基金supported by the National Natural Science Foundation of China(grant nos.82002135 and 82172250).
文摘The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications,enabling the development of effective therapeutic and preventive strategies.In this study,our initial attempts to introduce a NanoLuc luciferase(NLuc)reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies.We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus.Therefore,we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71(EV-A71),coxsackievirus A10(CVA10),coxsackievirus A7(CVA7),coxsackievirus A16(CVA16),namely EV-A71-HiBiT,CVA16-HiBiT,CVA10-HiBiT,CVA7-HiBiT,and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency.Notably,the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses.A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics.Moreover,these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages.In addition,the HiBiT-tagged viruses were successfully tested in antiviral drug assays,and the sensitivity of the viruses to drugs was not affected by the HiBiT tag.Ultimately,our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal,convenient,and invaluable method for advancing research in the realm of enterovirus virology.Furthermore,HiBiT-tagged enteroviruses exhibit great potential for diverse applications,including the development of antivirals and the elucidation of viral infection mechanisms.
基金supported by the key research project of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(Grant no:GWVI-3,GWVI-11.1-09)approved by the Ethics Committees of Shanghai Municipal Center for Disease Control and Prevention(Ethics Number,2023-44)。
文摘Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific region.In the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported annually.Before 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).
文摘AIM： To search for new antiviral agents from traditional Chinese medicine, specifically anti-enterovirosuses agents. METHODS： The aqueous extracts （AE） of more than 100 traditionally used medicinal plants in China were evaluated for their in vitro anti-Coxsackie virus B3 activities with a MTT-based colorimetric assay. RESULTS： The test for AE of 16 plants exhibited anti- Coxsackie virus B3 activities at different magnitudes of potency. They can inhibit three steps （inactivation, adsorption and replication） during the infection. Among the 16 plants, Sargentodoxa cuneata （Oliv.） Rehd. et Wils., Sophora tonkinensis Gapnep., Paeonia veitchii Lynch, Spatholobus suberectus Dunn. and Cyrtorniurn fortunei J, sm. also have activity against other enterovirus, including Coxsackie virus 135, Polio virus I, Echo virus 9 and Echo virus 29. Cell cytotoxic assay demonstrated that all tested AE had CC50 values higher than their EC50 values. CONCLUSION： The sixteen traditionally used medicinal plants in China possessed antMral activity, and some of them merit further investigations.
文摘After decades of research, functional dyspepsia (FD) remains one of the most elusive gastrointestinal disorders. Endoscopic appearance of mild inflammation of the gastric mucosa without ulceration and microscopic evidence of mild chronic inflammation are often considered as normal findings since no etiology could be found other than H. Pylori. Enteroviruses infect the gastrointestinal tract and have been shown to persist in the stomach of symptomatic patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we evaluated FD patients with and without the diagnosis of ME/CFS, and were able to support the viral protein staining with finding of double-stranded RNA in 63% of the same stomach biopsies by immunoperoxidase staining. Furthermore, we clarified the possible cross-reaction with creatine kinase brain subtype (CKB), present in parietal cells, using antibody competition experiments and western blot analysis of stomach proteins. Viral protein+ and dsRNA+ biopsies were infectious in SCID mice. More research is needed to elucidate the mechanism of enterovirus infection of the stomach associated with FD and chronic gastritis.
文摘For rapid diagnosis of enteroviral infection in clinic practice, we developed a reverse transcription and polymerase chain reaction (RT-PCR) assay.Primers homologous to the conserved 5' non-coding region were designed by analyzing enteroviral genomes, and then they were used to enzymatically amplify RNA from 31 prototype enteroviral strains and enteroviruses (EV) in cerebrospinal fluid (CSF) of 34 cases of aseptic meningitis and 11 cases of aseptic encephalitis. The RT-PCR products generated with these enteroviral primers were analyzed by agar gel electrophoresis and dot blot hybridization analysis. 31 EV strains showed an obvious monoclonal amplification band, and all dot blot hybridization results were positive. Four other viruses and cells cultured were all negative. The study of sensitivity of the RT-PCR showed that amplification production were positive to 10(-2)- 10(-3) 50% tissue culture infective doses. With this assay, 21(61.8%) of 34 aseptic meningitis and 8 (72. 7%) of 11 aseptic encephalitis contained EV RNA in CSF samples. Two cases of meningitis and one of encephalitis with EV infection were still positive during convalescence. Our results suggest that this RT-PCR method was a fast, sensitive and specific technique for detection of common EV infection.
文摘Background: While we are inching towards global eradication of polio, the paralysis due to non-polio viruses (NPEV) poses greater challenge. Factors responsible for causing Acute Flaccid Paralysis (AFP) were studied in 3596 AFP patients in 64 districts of Uttar-Pradesh, India, to observe indirect relationship of AFP with wild polio as well as NPEV. A recent study suggests the need to investigate polio virus negative but NPEV positive AFP cases. Methods: The lab results of the stool samples of these children were line listed and analysed to observe the association of various factors with respect to presence of paralysis on 60 follow-up days. Taking zero OPV dose AFP cases as a biological base, we studied the relationship of presence of paralysis at 60 follow-up days to that of presence of NPEV in stool samples while polio virus was present or absent. Results: 70 of the 86 AFP cases (81%) with zero OPV dose and having only NPEV isolated in stool samples were having paralysis at 60 follow-up days. There were 4.54% (162) AFP cases, which did not carry any polio virus but were having NPEV isolated in the stool samples and paralysis at 60 follow-up days. 79% (75/95) of zero OPV dose children, who were having residual weakness at 60 follow-up days, were carrying both polio virus as well as NPEV in their stool samples. Total AFP cases, having residual weakness at 60 follow-up days and having NPEV in stool samples, decreased with increase in OPV doses;a behavior similar to what wild polio viruses (WPV) have to OPV. Conclusions: Maybe polio like NPEV is active for causing severe paralysis in children and is responding to the OPV. As is evident in the studies by M. Margalith, B. Fattal et al. [1] that there is an antibody response to the enteroviruses, we can think of coming out with a vaccine against the enteroviruses. Therefore, enterovirus vaccine can be produced on similar lines to that of OPV, as now we have enough isolates of NPEV. Effective NPEV surveillance system also needs to be in place.
文摘Objective:To study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples.Methods: Nucleotide sequence analysis of enteroviruses deposited in the international database GenBank （www.ncbi.nlm.nih.gov/Genbank） was conducted to develop specific primers for the detection of these viruses.The specificity and sensitivity of the method were tested using coxackicvirus B3 strain Nancy,environmental isolate of human hepatitis A virus and human rotavirus strain WA.Seventy sewage samples were analyzed.Results:Enterovirus genome was detected in all positive samples.The genome of enterovirus was not detected in negative samples.The level of detection of these viruses was 10<sup>2</sup> TCID<sub>50</sub>mI..Conclusions:The development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.
基金supported in part by Natural Science Foundation of Jiangsu Province under Grant BK20230255Natural Science Foundation of Shandong Province under Grant ZR2023QE281.
文摘The multi-terminal direct current(DC)grid has extinctive superiorities over the traditional alternating current system in integrating large-scale renewable energy.Both the DC circuit breaker(DCCB)and the current flow controller(CFC)are demanded to ensure the multiterminal DC grid to operates reliably and flexibly.However,since the CFC and the DCCB are all based on fully controlled semiconductor switches(e.g.,insulated gate bipolar transistor,integrated gate commutated thyristor,etc.),their separation configuration in the multiterminal DC grid will lead to unaffordable implementation costs and conduction power losses.To solve these problems,integrated equipment with both current flow control and fault isolation abilities is proposed,which shares the expensive and duplicated components of CFCs and DCCBs among adjacent lines.In addition,the complicated coordination control of CFCs and DCCBs can be avoided by adopting the integrated equipment in themultiterminal DC grid.In order to examine the current flow control and fault isolation abilities of the integrated equipment,the simulation model of a specific meshed four-terminal DC grid is constructed in the PSCAD/EMTDC software.Finally,the comparison between the integrated equipment and the separate solution is presented a specific result or conclusion needs to be added to the abstract.
基金supported by the National Natural Science Foundation of China(82322059)the Chinese Academy of Medical·Sciences Innovation Fund for Medical Sciences(2021-I2M-1-010)+1 种基金the National Key Research and Development Program of China(2021YFC2500500)the National High Level Hospital Clinical Research Funding(2023-GSPRC-19).
文摘Objective Observational studies have shown inconsistent associations of loneliness or social isolation(SI)with ischemic heart disease(IHD),with unknown mediators.Methods Using data from genome-wide association studies of predominantly European ancestry,we performed a bidirectional two-sample Mendelian Randomization(MR)study to estimate causal effects of loneliness(N=487,647)and SI traits on IHD(N=184,305).SI traits included whether individuals lived alone,participated in various types of social activities,and how often they had contact with friends or family(N=459,830 to 461,369).A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators,including metabolic,behavioral and psychological factors.Results Loneliness increased IHD risk(OR=2.129;95%confidence interval[CI]:1.380 to 3.285),mediated by body fat percentage,waist-hip ratio,total cholesterol,and low-density lipoprotein cholesterol.For SI traits,only fewer social activities increased IHD risk(OR=1.815;95%CI:1.189 to 2.772),mediated by hypertension,high-density lipoprotein cholesterol,triglycerides,fasting insulin,and smoking cessation.No reverse causality of IHD with loneliness and SI was found.Conclusion These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD,with several mediators as prioritized targets for intervention.
基金National Natural Science Foundation of China under Grant Nos.52078386 and 52308496SINOMACH Youth Science and Technology Fund under Grant No.QNJJ-PY-2022-02+2 种基金Young Elite Scientists Sponsorship Program under Grant No.BYESS2023432Fund of State Key Laboratory of Precision Blasting and Hubei Key Laboratory of Blasting Engineering,Jianghan University under Grant No.PBSKL2023A9Fund of China Railway Construction Group Co.,Ltd.under Grant No.LX19-04b。
文摘Strong surface impact will produce strong vibration,which will pose a threat to the safety of nearby buried pipelines and other important lifeline projects.Based on the verified numerical method,a comprehensive numerical parameter analysis is conducted on the key influencing factors of the vibration isolation hole(VIH),which include hole diameter,hole net spacing,hole depth,hole number,hole arrangement,and soil parameters.The results indicate that a smaller ratio of net spacing to hole diameter,the deeper the hole,the multi-row hole,the hole adoption of staggered arrangements,and better site soil conditions can enhance the efficiency of the VIH barrier.The average maximum vibration reduction efficiency within the vibration isolation area can reach 42.2%.The vibration safety of adjacent oil pipelines during a dynamic compaction projection was evaluated according to existing standards,and the measurement of the VIH was recommended to reduce excessive vibration.The single-row vibration isolation scheme and three-row staggered arrangement with the same hole parameters are suggested according to different cases.The research findings can serve as a reference for the vibration safety analysis,assessment,and control of adjacent underground facilities under the influence of strong surface impact loads.
基金Supported by the Scientific Research Fund of Zhejiang Provincial Education Department,No.Y202351104and Huzhou Science and Technology Plan Project,No.2023GZ67。
文摘BACKGROUND Frailty has become a significant public health issue.The recent increase in the number of frail older adults has led to increased attention being paid to psycho-logical care services in communities.The social isolation of pre-frail older adults can impact their psychological distress.AIM To explore the mediating effect of health literacy between social isolation and psychological distress among communitydwelling older adults with pre-frailty.METHODS This descriptive cross-sectional study was conducted with 254 pre-frail older individuals aged 60 years and over.Social isolation,health literacy,and psycholo-gical distress were comprehensively measured using the Lubben Social Network Scale-6,12-item Short-Form Health Literacy Questionnaire,and the Kessler Psy-chological Distress Scale-10.Data were evaluated using the SPSS 27.0 package program and the PROCESS macro tool.Descriptive statistical analyses,correlation analyses,and bootstrap mediation tests were used to assess associations between the variables.RESULTS The results showed that social isolation had an effect on health literacy among pre-frail older adults(β=0.240,P<0.001),social isolation impact on psycho-logical distress pre-frail older adults(β=-0.415,P<0.001);health literacy was identified effect on psychological distress among pre-frail older persons(β=-0.307,P<0.001).Health literacy partially mediated the relationship between social isolation and psychological distress among community-dwelling older adults with pre-frailty,with a mediation effect of-0.074,accounting for 17.83%of the total effect.
