Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway

Objective Keshan disease(KD)is a myocardial mitochondrial disease closely related to insufficient selenium(Se)and protein intake.PTEN induced putative kinase 1(PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body.This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury.Methods A low Se and low protein animal model was established.One hundred Wistar rats were randomly divided into 5 groups(control group,low Se group,low protein group,low Se+low protein group,and corn from KD area group).The JC-1 method was used to detect the mitochondrial membrane potential(MMP).ELISA was used to detect serum creatine kinase MB(CK-MB),cardiac troponin I(cTnI),and mitochondrial-glutamicoxalacetic transaminase(M-GOT)levels.RT-PCR and Western blot analysis were used to detect the expression of PINK1,Parkin,sequestome 1(P62),and microtubule-associated proteins1A/1B light chain 3B(MAP1LC3B).Results The MMP was significantly decreased and the activity of CK-MB,cTnI,and M-GOT significantly increased in each experimental group(low Se group,low protein group,low Se+low protein group and corn from KD area group)compared with the control group(P<0.05 for all).The mRNA and protein expression levels of PINK1,Parkin and MAP1LC3B were profoundly increased,and those of P62 markedly decreased in the experimental groups compared with the control group(P<0.05 for all).Conclusion Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Murine model of acute myocarditis and cerebral cortical neuron edema induced by coxsackievirus B4

Globally, coxsackievirus B4 （CV-B4） has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system （CNS） complications, which remain poorly studied and understood. In the present study, we established an institute for Cancer Research （ICR） mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. in addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-y and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.

Time Series and Spatial Epidemiological Analysis of the Prevalence of Iodine Deficiency Disorders in China

Objective To recognize the spatial and temporal characteristics of iodine deficiency disorders(IDD),China national IDD surveillance data for the years of 1995–2018 were analyzed.Methods Time series analysis was used to describe and predict the IDD related indicators,and spatial analysis was used to analyze the spatial distribution of salt iodine levels.Results In China,the median urinary iodine concentration increased in 1995–1997,then decreased to adequate levels,and are expected to remain appropriate in 2019–2022.The goiter rate continually decreased and is expected to be maintained at a low level.Since 2002,the coverage rates of iodized salt and the consumption rates of qualified iodized salt(the percentage of qualified iodized salt in all tested salt) increased and began to decline in 2012;they are expected to continue to decrease.Spatial epidemiological analysis indicated a positive spatial correlation in 2016–2018 and revealed feature regarding the spatial distribution of salt related indicators in coastal areas and areas near iodine-excess areas.Conclusions Iodine nutrition in China showed gradual improvements.However,a recent decline has been observed in some areas following changes in the iodized salt supply in China.In the future,more regulations regarding salt management should be issued to strengthen IDD control and prevention measures,and avoid the recurrence of IDD.

Cold weather and Kashin-Beck disease

Kashin-Beck disease(KBD)is an endemic osteoarthropathy.Its distribution region covers a long and narrow belt on the Pacific side and belongs to continental climate with short summer,long frost period,and large temperature differences between day and night.In particular,KBD patients are typically scattered in the rural areas with seasonal features such as cold winters and rainy autumns.Etiological studies have demonstrated that the carrier of pathogenic factors is the grains produced in endemic areas.Risk factors for KBD include fungal contamination of grains due to poor storage conditions associated with cold weather.The epidemiological characteristics of KBD include agricultural area,early age of onset,gender equality,family aggregation,regional differences,and annual fluctuations.A series of preventive measures have been successfully taken in the past decades.National surveillance data indicate that the annual incidence of KBD is gradually declining.

Disease and Economic Burden of Kashin-Beck Disease—China,2021

What is already known about this topic?Kashin-Beck disease(KBD)is a chronic and degenerative osteoarthropathy characterized by cartilage degeneration.It is an endemic disease that is highly prevalent among the Chinese population and poses a significant health risk.What is added by this report?This is the first national report on the economic burden of KBD in China.According to the data from 2021,KBD has caused significant disease and economic burdens.The most substantial reduction in healthy life expectancy was observed among patients with degree II severity and those aged 60 years and older,resulting in a total indirect economic burden of 112.74 million Chinese Yuan(CNY).What are the implications for public health practice?The results of this study will contribute to informing the development of tailored prevention and control strategies by the government.These strategies will include targeted policies and recommendations for appropriate healthcare and financial subsidies,which will be based on the demographic characteristics of the endemic areas.

A brief procedure for big data analysis of gene expression

There are a lot of biological and experimental data from genomics, proteomics, drug screening, medicinal chemistry, etc. A large amount of data must be analyzed by special methods of statistics, bioinformatics, and computer science. Big data analysis is an effective way to build scientific hypothesis and explore internal mechanism.Here, gene expression is taken as an example to illustrate the basic procedure of the big data analysis.

Novel astrovirus and paramyxovirus in Mongolian gerbils(Meriones unguiculatus)from China

DEAR EDITOR,Mongolian gerbils(Meriones unguiculatus)are small rodents belonging to the family Muridae and widely inhabit typical steppes and desert grasslands across northern China.Yet,few viruses in wild M.unguiculatus have been reported.Using meta-transcriptomic sequencing we identified two novel RNA viruses:an astrovirus,denoted Gerbil astrovirus(GeAstV).

Pathogen genomic surveillance elucidates the origins, transmission and evolution of emerging viral agents in China

In the past twenty years, numerous novel zoonotic viral agents with pandemic potential have emerged in China, such as the severe acute respiratory syndrome(SARS) coronavirus and, more recently, the avian-origin influenza A/H7N9 virus, which have caused outbreaks among humans with high morbidity and mortality. In addition, several emerging and re-emerging viral pathogens have also been imported into China from travelers, e.g. the Middle East respiratory syndrome(MERS) coronavirus and Zika virus(ZIKV). Herein, we review these emerging viral pathogens in China and focus on how surveillance by pathogen genomics has been employed to discover and annotate novel pathogenic agents, identify natural reservoirs, monitor the transmission events and delineate their evolution and adaption to the human host. We also highlight the application of genomic sequencing in the recent Ebola epidemics in Western Africa. In summary, genomic sequencing has become a standard research tool in the field of emerging infectious diseases which has been proven invaluable in containing these viral infections and reducing burden of disease in humans and animals. Genomic surveillance of pathogenic agents will serve as a key epidemiological and research tool in the modern era of precision infectious diseases and in the future studies of virosphere.

The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas

Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.

Seroprevalence of influenza viruses in Shandong,Northern China during the COVID-19 pandemic

Nonpharmaceutical interventions(NPIs)have been commonly deployed to prevent and control the spread of the coronavirus disease 2019(COVID-19),resulting in a worldwide decline in influenza prevalence.However,the influenza risk in China warrants cautious assessment.We conducted a cross-sectional,seroepidemiological study in Shandong Province,Northern China in mid-2021.Hemagglutination inhibition was performed to test antibodies against four influenza vaccine strains.A combination of descriptive and meta-analyses was adopted to compare the seroprevalence of influenza antibodies before and during the COVID-19 pandemic.The overall seroprevalence values against A/H1N1pdm09,A/H3N2,B/Victoria,and B/Yamagata were 17.8%(95%CI 16.2%–19.5%),23.5%(95%CI 21.7%–25.4%),7.6%(95%CI 6.6%–8.7%),and 15.0(95%CI 13.5%–16.5%),respectively,in the study period.The overall vaccination rate was extremely low(2.6%).Our results revealed that antibody titers in vaccinated participants were significantly higher than those in unvaccinated individuals(P<0.001).Notably,the meta-analysis showed that antibodies against A/H1N1pdm09 and A/H3N2 were significantly low in adults after the COVID-19 pandemic(P<0.01).Increasing vaccination rates and maintaining NPIs are recommended to prevent an elevated influenza risk in China.

Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges

Since the 20th century,humans have lived through five pandemics caused by influenza A viruses(IAVs)(H1N1/1918,H2N2/1957,H3N2/1968,and H1N1/2009)and the coronavirus(CoV)severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).IAVs and CoVs both have broad host ranges and share multiple hosts.Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs,further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk.Moreover,SARS-CoV-2 may maintain longterm circulation in humans as seasonal IAVs.Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden.Herein,we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs,further affecting virus evolution and disease dynamics and burden,calling for active virus surveillance and countermeasures for future public health challenges.

Genomic characterizations of H4 subtype avian influenza viruses from live poultry markets in Sichuan province of China, 2014–2015

Dear Editor,Avian influenza viruses (AIVs) have posed a serious threat to poultry production and public health. To date, more than fourteen AIV subtypes that are able to infect human beings have been documented. Also, it is suggested that new subtypes may be reported in the future, owing to the migration of wild birds and live poultry transportation (Gao, 2018).Poultry may act as a potential incubator for novel subtypes of avian influenza virus (Bi et al., 2016a; Bi et al., 2016b; Liu et al., 2014a; Su et al., 2017). Up to date, the H7N9 AIV emerged in February 2013 has caused 1,567 human cases,with a fatality rate of 39.2%(http://www.who.int/influenza/

The Initial Case of COVID-19—Shulan City,Jilin Province,China,May 8,2020

Coronavirus disease 2019(COVID-19)was designated a global pandemic by the World Health Organization(WHO)on March 11,2020(1).After great effort,COVID-19 has been well-controlled in China,but new challenges have emerged due to increasing numbers of imported cases from outside of China.On May 8,the Health Commission of Jilin Province reported a confirmed COVID-19 case of a 45-year-old laundry woman from Shulan City in the northeast of China.This case was suspected to be associated with a possible importation event.

A Reemergent Case of COVID-19—Harbin City,Heilongjiang Province,China,April 9,2020

As of February 22,a total of 198 confirmed COVID-19 cases were reported in Harbin,Heilongjiang Province,and no new local cases were reported in Harbin over the next 54 days(1).However,on April 9,a newly confirmed COVID-19 case was reported with an unknown source of infection(2).The patient,a 54-year-old male,developed a fever on March 28 with the highest recorded temperature at 37.5℃.On April 7,the symptoms worsened and included dyspnea,cough,sputum,chest pain,and other symptoms,though he did not experience chest distress,heart palpitations,nausea and vomiting,abdominal pain or diarrhea.He went to the fever clinic of the Harbin Second Hospital and was admitted to the isolation ward with a temperature of 37.2°C.The patient also had a history of diabetes.

Genomic characterization of SARS-CoV-2 identified in a reemerging COVID-19 outbreak in Beijing's Xinfadi market in 2020

After 56 days without coronavirus disease 2019(COVID-19)cases,reemergent cases were reported in Beijing,China on June 11,2020.Here,we report the genetic characteristics of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)sequenced from the clinical specimens of 4 human cases and 2 environmental samples.The nucleotide similarity among six SARS-CoV-2 genomes ranged from 99.98%to 99.99%.Compared with the reference strain of SARS-CoV-2(GenBank No.NC_045512),all six genome sequences shared the same substitutions at nt241(C→T),nt3037(C→T),nt14408(C→T),nt23403(A→G),nt28881(G→A),nt28882(G→A),and nt28883(G→C),which are the characteristic nucleotide substitutions of L-lineage European branch I.This was also proved by themaximum likelihood phylogenetic tree based on the full-length genome of SARS-CoV-2.They also have a unique shared nucleotide substitution,nt6026(C→T),which is the characteristic nucleotide substitution of SARS-CoV-2 in Beijing's Xinfadi outbreak.It is noteworthy that there is an amino acid D614Gmutation caused by nt23403 substitution in all six genomes,which may enhance the virus's infectivity in humans and help it become the leading strain of the virus to spread around the world today.It is necessary to continuously monitor the genetic variation of SARS-CoV-2,focusing on the influence of key mutation sites of SARS-CoV-2 on viral transmission,clinical manifestations,severity,and course of disease.

Identification of a novel hepacivirus in Mongolian gerbil(Meriones unguiculatus)from Shaanxi,China

Dear Editor,Hepaciviruses,members of the family Flaviviridae,are enveloped viruses containing a single-stranded positive-sense RNA genome of approximately 8.9-10.5 kb in size(Simmonds et al.,2017).To date,15species(Hepacivirus A-N,and P)have been documented within the Hepacivirus genus that show distinct host ranges,including primates,bats,horses,donkeys,cows,and various rodents(Hartlage et al.,2016).

CASCIRE surveillance network and work on avian influenza viruses

Studies on influenza virus by Chinese Academy of Sciences(CAS)could be traced back as early as 2005 by the CAS Key Laboratory of Pathogenic Microbiology and Immunology(CASPMI),who discovered that Qinghai-like Clade 2.2H5N1 subtype highly pathogenic avian influenza virus(HPAIV)first caused severe outbreak in wild birds in Qinghai Lake(Liu et al.,2005).

Intra-host Ebola viral adaption during human infection

The onsite next generation sequencing(NGS)of Ebola virus(EBOV)genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin,transmission,and evolution of this virus.Herein,we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015,during the late phase of the outbreak.The surviving EBOV patients had a recovery process characterized by decreasing viremia,fever,and biochemical parameters.EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection,including the previously described short stretches of 13 serial TNC mutations.Remarkably,within individual patients,samples collected during the early phase of infection possessed Ts at these nucleotide sites,whereas they were replaced by Cs in samples collected in the later phase,suggesting that these short stretches of TNC mutations could emerge independently.In addition,up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently.Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions.

长江流域湿地越冬候鸟中禽流感病毒的生态学研究

候鸟是A型禽流感病毒的自然宿主和储存库.为了深入了解我国候鸟禽流感病毒的流行规律及生态特点,本研究对长江流域越冬候鸟中的禽流感病毒进行长期监测,于2013~2017年间采集8000多份样本并分离出122株禽流感病毒.结果表明,长江流域越冬候鸟中禽流感病毒多样性丰富,监测期间发现8种HA亚型和8种NA亚型、18种HA-NA亚型组合.对其中108株病毒全基因组的分析表明,越冬地禽流感病毒基因组具有复杂的多样性,其中部分片段连续多个越冬季持续流行于候鸟中.进一步的系统发育分析表明越冬地禽流感病毒重配复杂且不同亚型重配模式截然不同.进化分析发现越冬候鸟病毒的一些基因片段与北美野鸟流行毒株高度相近,表明野鸟中禽流感病毒曾发生跨洲基因扩散.此外,家禽中流行的高致病H5和低致病H9禽流感病毒,跨越家禽/候鸟界面传播至野鸟中.综上,本研究是长江流域越冬候鸟大规模禽流感病毒监测的代表性工作,数年的监测数据凸显越冬候鸟在禽流感病毒生态分布中的重要作用,研究成果可为禽流感新毒株的突现提供早期预警.