Molecular surveillance of coxsackievirus A16 in southern China, 2008-2019.

A national surveillance system on hand, foot, and mouth disease (HFMD) was launched in 2008 in China. Since then, millions of HFMD cases have been reported each year, with enterovirus A71 (EV-A71), coxsackievirus A16 (CV-A16), and coxsackievirus A6 (CV-A6) as the major causative pathogens. Long-term surveillance of viral infection rates and genetic changes is essential for understanding the disease epidemiology pattern. Here, we analyzed molecular surveillance data on CV-A16 covering a period of 12 years (2008-2019) in Guangdong, China, one of the regions reporting the largest number of HFMD cases. Full VP1 sequences of 456 strains were determined to examine the genetic diversity and changes in the distribution of CV-A16 variants. Our study revealed an irregular pattern of CV-A16 infections in Guangdong. Different from the cyclic epidemics observed in some Asia-Pacific regions, there was a continuously high CV-A16 infection rate from 2008 to 2014, and after a period of lower epidemic activity in 2015-2017, an upsurge of CV-A16 infection was observed in 2018-2019. Cocirculation of subgenotypes B1a and B1b was observed, but while subgenotype B1a was predominant from 2008 to 2012, it appears to have been replaced by B1b, which has circulated as the predominant subgenotype since 2013. Phylogenetic analysis showed that most of the circulating CV-A16 strains are endemic, with occasional transmission between neighboring regions. The re-emergence of B1a in 2016-2019 in Guangdong was likely the result of introduction(s) from Southeast Asia. These results highlight the importance of continuous molecular surveillance from different areas, which will improve our understanding of the origin of the epidemic and facilitate the development of strategies for HFMD disease control.

K2S2O8-Promoted Aryl Thioamides Synthesis from Aryl Aldehydes Using Thiourea as the Sulfur Source.

Thiourea as a sulfur atom transfer reagent was applied for the synthesis of aryl thioamides through a three-component coupling reaction with aryl aldehydes and N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMAC). The reaction could tolerate various functional groups and gave moderate to good yields of desired products under the transition-metal-free condition.

Elucidation of echovirus 30's origin and transmission during the 2012 aseptic meningitis outbreak in Guangdong, China, through continuing environmental surveillance.

An aseptic meningitis outbreak occurred in Luoding City of Guangdong, China, in 2012, and echovirus type 30 (ECHO30) was identified as the major causative pathogen. Environmental surveillance indicated that ECHO30 was detected in the sewage of a neighboring city, Guangzhou, from 2010 to 2012 and also in Luoding City sewage samples (6/43, 14%) collected after the outbreak. In order to track the potential origin of the outbreak viral strains, we sequenced the VP1 genes of 29 viral strains from clinical patients and environmental samples. Sequence alignments and phylogenetic analyses based on VP1 gene sequences revealed that virus strains isolated from the sewage of Guangzhou and Luoding cities matched well the clinical strains from the outbreak, with high nucleotide sequence similarity (98.5% to 100%) and similar cluster distribution. Five ECHO30 clinical strains were clustered with the Guangdong environmental strains but diverged from strains from other regions, suggesting that this subcluster of viruses most likely originated from the circulating virus in Guangdong rather than having been more recently imported from other regions. These findings underscore the importance of long-term, continuous environmental surveillance and genetic analysis to monitor circulating enteroviruses.

Prevalence of nonpolio enteroviruses in the sewage of Guangzhou city, China, from 2009 to 2012.

The human-pathogenic viruses in urban sewage have been extensively monitored to obtain information on circulating viruses in human communities. Enteroviruses (EVs) excreted by patients who present with diverse clinical syndromes can remain infectious in the environment for several weeks, and limited data on circulating environmental EVs are available. A 4-year (2009 to 2012) surveillance study was conducted to detect nonpolio enteroviruses (NPEVs) in the urban sewage of Guangzhou city, China. After the viruses in the sewage samples were concentrated and isolated, molecular identification was used to detect and type the NPEVs. During the 4-year study, 17 different NPEV serotypes were identified in the sewage of Guangzhou city. The most common serotypes were echovirus 11 (ECHO11), ECHO6, ECHO7, and ECHO12 and coxsackie group B viruses 5 (CVB5) and CVB3. The predominant serotypes were influenced by spatial and temporal factors and differed each year. CVB5 was commonly detected in 2009 and 2010 but was rarely isolated in 2011 and 2012. In contrast, CVB3 was not observed in 2009 and 2010 but was increasingly detected in 2011 and 2012. Our study provides an overview of the serotype distribution and circulation patterns of NPEVs in the sewage of Guangzhou, China. In the absence of a systematic EV disease surveillance system, the detection and characterization of sewage-borne NPEVs will help us better understand the changes in EV disease trends and the epidemic background of circulating EVs, which could help interpret the EV trends and warn of future outbreaks in this area.

Bibliometric Analysis in the Field of Rural Revitalization: Current Status, Progress, and Prospects.

Rural areas play an important role in global sustainable development. In recent years, however, rural development has experienced global crises, such as issues in public education, health care, roads, water and sanitation, along with environmental pollution and a lack of natural resources. It is therefore important to promote rural revitalization in the process of modernization. To objectively reveal the current research status in the field of rural revitalization, we analyzed relevant publications in the Web of Science from 1991 to 2021. The results are as follows: (1) In the past 30 years, the number of publications on rural vitalization has increased, and the period from 1991 to 2021 can be divided into three stages, the initial period (1991-2004), the development period (2005-2016), and the high-yield period (2017-2021). (2) Research on rural revitalization covered 60 countries or regions around the world, involving a total of 3099 authors. China, the United States, and Canada published most of the articles. (3) High-frequency keywords were migration, management, and urbanization, indicating that scientists considered the role of sustainable urban and rural development, policy formulation, and urbanization. We highlight that for the development of the field of rural vitalization, scientists need to further strengthen theoretical research, fully absorb the development achievements of advanced countries and regions, understand the laws and trends of urban and rural development in their own countries, and explore new paths to achieve rural vitalization.

Emergence and continuous evolution of genotype 1E rubella viruses in China.

In China, rubella vaccination was introduced into the national immunization program in 2008, and a rubella epidemic occurred in the same year. In order to know whether changes in the genotypic distribution of rubella viruses have occurred in the postvaccination era, we investigate in detail the epidemiological profile of rubella in China and estimate the evolutionary rate, molecular clock phylogeny, and demographic history of the predominant rubella virus genotypes circulating in China using Bayesian Markov chain Monte Carlo phylodynamic analyses. 1E was found to be the predominant rubella virus genotype since its initial isolation in China in 2001, and no genotypic shift has occurred since then. The results suggest that the global 1E genotype may have diverged in 1995 and that it has evolved at a mutation rate of 1.65 × 10(-3) per site per year. The Chinese 1E rubella virus isolates were grouped into either cluster 1 or cluster 2, which likely originated in 1997 and 2006, respectively. Cluster 1 viruses were found in all provinces examined in this study and had a mutation rate of 1.90 × 10(-3) per site per year. The effective number of infections remained constant until 2007, and along with the introduction of rubella vaccine into the national immunization program, although the circulation of cluster 1 viruses has not been interrupted, some viral lineages have disappeared, and the epidemic started a decline that led to a decrease in the effective population size. Cluster 2 viruses were found only in Hainan Province, likely because of importation.

Hsa_circ_0072008 regulates cell proliferation, migration, and invasion in cervical squamous cell carcinoma via miR-1305/helicase, lymphoid specific (HELLS) axis.

Cervical squamous cell carcinoma (CESC) is one of the most common cancers in women. Recent studies have proved that circular RNAs (circRNAs) could regulate the progress of CESC, but the mechanism is still indistinct. In this work, we explored the roles of circ_0072008 in CESC. The expression levels of circ_0072008, microRNA-1305 (miR-1305) and mRNA of HELLS (helicase, lymphoid specific) were detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) in CESC tissues. Meanwhile, the level of HELLS was quantified by western blot analysis. Besides, the cell functions were examined by colony formation assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, flow cytometry assay and western blot. Furthermore, the interaction between miR-1305 and circ_0072008 or HELLS was detected by dual-luciferase reporter assay. The function of circ_0072008 in CESC has also been further verified in vivo by xenograft model experiments. The levels of circ_0072008 and HELLS were upregulated, and the miR-1305 level was decreased in CESC tissues in contrast to that in normal tissues. For functional analysis, silencing circ_0072008 inhibited cell proliferation and cell migration, whereas enhanced cell apoptosis in CESC cells. In mechanism, circ_0072008 acted as a miR-1305 sponge to regulate the level of HELLS. Moreover, miR-1305 was confirmed to repress the progression of CESC cells by suppressing HELLS. Meanwhile, knockdown of circ_0072008 inhibited CESC cells growth in vivo. In conclusion, circ_0072008 facilitated CESC cell proliferation, migration, and invasion through increasing HELLS expression by regulating miR-1305, which also offered an underlying targeted therapy for CESC treatment.

The adsorption characteristics of Cu(II) and Zn(II) on the sediments at the mouth of a typical urban polluted river in Dianchi Lake: taking Xinhe as an example.

This study is to determine the spatial distribution characteristics of Cu and Zn adsorption on the sediments of the estuary of Dianchi Lake, as well as the composite adsorption law of Cu and Zn on combinations of sediment organic matter, metal oxides, and organic-inorganic composites. The relationship between the adsorption contribution of each component of the substance. A static adsorption experiment was applied to the sediments in the estuary of Dianchi Lake. The relationship between adsorption capacity and sediment composition was analyzed through correlation analysis and redundant analysis. The results show that along the direction of the river flow and the vertical depth, the adsorption capacity presents a relatively obvious spatial distribution law; the change trend of sediment component content is not the same as the change trend of Cu and Zn adsorption capacity. The change trend of the sediment component content is not the same as the change trend of the adsorption amount of Cu and Zn, and the compound effect between the components affects the adsorption amount. The adsorption of Cu by the four groups of sediments after different treatments is more in line with the Freundlich isotherm adsorption model; When adsorbing Zn, the untreated and removed organic matter and iron-aluminum oxide group are in good agreement with the Freundlich model, while the organic matter-removed group and the iron-aluminum oxide removal group are more consistent with the Langmuir isotherm adsorption model; The adsorption contribution rate of organic-inorganic composites in sediments is not a simple addition of organic matter and iron-aluminum oxides, but a more complex quantitative relationship.

miR­802 inhibits the epithelial­mesenchymal transition, migration and invasion of cervical cancer by regulating BTF3.

MicroRNA (miR)-802 has been discovered to be involved in the occurrence and development of numerous types of tumor; however, studies into the role of miR­802 in cervical cancer are limited. Therefore, the present study aimed to investigate the regulatory effects of miR­802 in cervical cancer cells. miR­802 expression levels in cervical cancer tissue and cells were analyzed using reverse transcription­quantitative (RT­q)PCR, a dual­reporter luciferase activity assay was used to identify the direct target gene of miR­802, and RT­qPCR and western blotting were performed to determine the relationship between miR­802 and basic transcription factor 3 (BTF3). Cell viability, and migration and invasion were analyzed using Cell Counting Kit­8 and Transwell assays, respectively. Finally, the expression levels of metastasis­associated proteins, N­cadherin and E­cadherin, were determined using RT­qPCR and western blotting. Decreased expression levels of miR­802 were found in cervical cancer tissues and cells, and the overexpression of miR­802 inhibited cell viability, migration and invasion. Moreover, miR­802 was discovered to directly target BTF3 to inhibit its expression. Notably, the overexpression miR­802 markedly reversed the promotive effect of BTF3 on cell viability, in addition to the migratory and invasive abilities of the cells. Simultaneously, the overexpression of miR­802 significantly suppressed epithelial­mesenchymal transition, and the expression levels of matrix metallopeptidase (MMP)2 and MMP9 in cells through regulating BTF3. In conclusion, the present study revealed that miR­802 may suppress cervical cancer progression by decreasing BTF3 expression levels, indicating that it may represent a potential therapeutic target for the treatment and prognosis of patients with cervical cancer.

Hollow Square RodLike Microtubes Composed of Anatase Nanocuboids with Coexposed {100}, {010}, and {001} Facets for Improved Photocatalytic Performance.

In this study, hollow square rodlike microtubes composed of anatase nanocuboids with coexposed {100}, {010}, and {001} facets were successfully synthesized via a mild hydrothermal treatment method in the presence of NH4F by using layered H2Ti3O7 ribbons as the precursor. The precursor H2Ti3O7 ribbons were prepared from H+/Na+ ion-exchanged Na2Ti3O7. The suspension solution of protonated H2Ti3O7 ribbons was adjusted to desired pH values (0.5-13.0) prior to hydrothermal treatment. The elongated direction of the microtubes is along the b axis, according to the profile of the H2Ti3O7 ribbons. The transformation from staggered [Ti3O7]2- sheets to hollow square rodlike microtubes contained the formation and recombination of the dispersed octahedral [Ti(OH)2(OH2)4]2+ monomers, the formation and growth of the initial anatase nuclei, and the reassembly of the anatase nanocuboids along the b-axis direction during the continuous hydrothermal process. The degradation rate of pH 0.5-TiO2 was the highest at 1.66 × 10-2 min-1, which was 1.3, 1.5, 2.0, 2.3, and 18.4 folds higher than that of pH 3.0-TiO2 (1.27 × 10-2 min-1), pH 7.0-TiO2 (1.11 × 10-2 min-1), pH 5.0-TiO2 (0.83 × 10-2 min-1), P25-TiO2 (0.73 × 10-2 min-1), and the blank sample (0.09 × 10-2 min-1), respectively. Compared with P25-TiO2 and the other anatase TiO2 samples, pH 0.5-TiO2 exhibited the best photocatalytic activity, which was mainly attributed to its larger proportion of {010} (or {100}) facets, smaller crystalline size, higher band gap, and larger specific surface area.

Tracking echovirus eleven outbreaks in Guangdong, China: a metatranscriptomic, phylogenetic, and epidemiological study.

In April 2019, a suspect cluster of enterovirus cases was reported in a neonatology department in Guangdong, China, resulting in five deaths. We aimed to investigate the pathogen profiles in fatal cases, the circulation and transmission pattern of the viruses by combining metatranscriptomic, phylogenetic, and epidemiological analyses. Metatranscriptomic sequencing was used to characterize the enteroviruses. Clinical and environmental surveillance in the local population was performed to understand the prevalence and genetic diversity of the viruses in the local population. The possible source(s), evolution, transmission, and recombination of the viruses were investigated by incorporating genomes from the current outbreak, from local retrospective surveillance, and from public databases. Metatranscriptomic analysis identified Echovirus 11 (E11) in three fatal cases. Seroprevalence of neutralization antibody to E11 was 35 to 44 per cent in 3-15 age groups of general population, and the viruses were associated with various clinical symptoms. From the viral phylogeny, nosocomial transmissions were identified and all E11 2019 outbreak strains were closely related with E11 strains circulating in local population 2017-19. Frequent recombination occurred among the 2019 Guangdong E11 outbreak strains and various genotypes in enterovirus B species. This study provides an example of combining advanced genetic technology and epidemiological surveillance in pathogen diagnosis, source(s), and transmission tracing during an infectious disease outbreak. The result highlights the hidden E11 circulation and the risk of viral transmission and infection in the young age population in China. Frequent recombination between Guangdong-like strains and other enterovirus genotypes also implies the prevalence of these emerging E11 strains.

Epidemiological serosurvey of poliovirus in Guangdong, China: A cross-sectional study.

A cross-sectional study for poliovirus seroprevalence in Guangdong was carried out in 2014, just before a change in polio vaccine commenced in 2015. The aim of the study was to test whether polio immunity level was high enough to satisfy the polio vaccine switch. A total of 6339 people were tested for poliovirus neutralization antibodies (NA). Overall NA seropositivity for PV1, PV2 and PV3 were 95.2%, 94.9% and 88.7%, and the respective geometric mean titer (GMT) were 82.9, 55.8, and 26.3, respectively. There were statistically significant differences in the positive rates and GMT of the 3 serotypes and PV3 had relatively lower positive rates and GMT. The highest seropositivity and GMT were observed in the 1-9 year-old age group. The positive rates of NA and GMT for PV1, PV2 and PV3 in the western region of Guangdong were lower than those of other three regions. The results of this study showed that the population of Guangdong province had a high polio immunity level, a stable base for a polio vaccine switch.

[The Complete Sequence Analysis of 18 Strains of Coxsackievirus A6 in Guangdong Province of China].

In this study, we examined the complete genome of coxsackievirus A6 (CVA6) from hand, foot, and mouth disease in Guangdong Province from 2013,and explored the genetic similarities and differences in epidemic and non-epidemic stains of CVA6.Eighteen strains of CVA6 were included in complete genome sequencing, and the sequences were subject to phylogenetic analysis,sequence alignment analysis and genetic recombination analysis using the software DNASTAR6.0,MEGA5.2and SimPlot3.5.1.The results showed that the complete genome of 18 Guangdong CVA6strains ranged from 7390bp to 7392bp.No insertions or deletions were detected in the coding region. There were several insertions and deletions in 5'UTR and 3'UTR.Phylogenetic analysis indicated that the nucleotide and amino acid sequence identity between the 18 complete genomes were 90.5%-99.6% and 97.5%-99.9%,respectively.The strains isolated in2013 could be further divided into two clusters, III and IV, while the strains isolated in 2011 were only present in the IV cluster. Genetic recombination analysis revealed that the Guangdong representative strain of CVA6,GD870/2013,had gene recombination in the P2 and P3regions,while the GD839/2013 strain did not show obvious genetic recombination. Genome-wide analysis of CVA6 revealed that there are two possible transmitted chains, III and IV, in epidemic strains from Guangdong Province in 2013.The transmitted chain Ⅲ originated from the strain with genetic recombination in the P2 and P3regions,whichwas completely different from the chain IV. Transmission of chain IV of CVA6 was only observed in the nonepidemic 2011 strain.

[Epidemiology Characteristics and Pathogen Surveillance of Hand, Foot and Mouth Disease in Guangdong Province, China, 2008～2015].

To understand the epidemiological etiology characteristics of hand, foot and mouth disease(HFMD)in Guangdong province, and to explore the risk change trend of the whole province. By using the descriptive epidemiological methods, the whole province's incidence trend, population distribution and pathogenic form of HFMD were analyzed with the HFMD surveillance data,population data and geographic information of Guangdong province from 2008 to 2015.The analysis results show: A total of 2,133,722 cases of HFMD, including 5,066 severe cases and 259 death cases were reported in Guangdong province from 2008 to 2015.All the cities of Guangdong had HFMD cases, especially the Pearl River Delta Regions, which were on high-risk areas. There were two peaks every year, with the main peak of incidence occurred in spring and summer, and the sub peak occurred in autumn.Most cases were children aged<5years old, the proportion of this group in overall infections, the severe and death cases were 90.58%,95.93%and 97.30%,respectively,while the proportion for the children less than 3years old were 77.32% and 81.85%,respectively. The incidence of this disease among men was higher than that of women. Dynamic changes were presented between different years and seasons:CV-A16 was more popular in 2009,and enterovirus that none EV-A71 and none CV-A16 were predominant strains in 2013 and 2015.Especially in 2015,the proportion of other EV ranged as high as 71.97%.Besides,EV-A71 was the absolute predominance pathogen within death cases and was important pathogen in severe cases. This study suggests that HFMD epidemiology and laboratory monitoring in Guangdong Province should be strengthened, and provides scientific data support for further improvement of HFMD prevention and control strategies in Guangdong Province.

Isolation and Characterization of a Highly Mutated Chinese Isolate of Enterovirus B84 from a Patient with Acute Flaccid Paralysis.

Enterovirus B84 (EV-B84) is a newly identified serotype within the species Enterovirus B (EV-B). To date, only ten nucleotide sequences of EV-B84 are published and only one full-length genome sequence (the prototype strain) is available in the GenBank database. Here, a highly mutated EV-B84 (strain AFP452/GD/CHN/2004) was recovered from a patient with acute flaccid paralysis in the Guangdong province of China in 2004 making this the first report of EV-B84 in China. Sequence comparison and phylogenetic dendrogram analysis revealed high variation from the global EV-B84 strains (African and Indian strains) and frequent intertypic recombination in the non-structural protein region, suggesting high genetic diversity in EV-B84. The Chinese EV-B84 strain, apparently evolving independently of the other ten strains, strongly suggests that the EV-B84 strain has been circulating for many years. However, the extremely low isolation rate suggests that it is not a prevalent EV serotype in China or worldwide. This study provides valuable information about the molecular epidemiology of EV-B84 in China, and will be helpful in future studies to understand the association of EV-B84 with neurological disorders; it also helps expand the number of whole virus genome sequences of EV-B84 in the GenBank database.

The Epidemiological Study of Coxsackievirus A6 revealing Hand, Foot and Mouth Disease Epidemic patterns in Guangdong, China.

Enterovirus A71 (EVA71) and Coxsackievirus A16 (CVA16) are regarded as the two major causative pathogens in hand, foot and mouth disease (HFMD) epidemics. However, CVA6, previously largely ignored, became the predominant pathogen in China in 2013. In this study, we describe the epidemiological trends of CVA6 during the annual HFMD outbreaks from 2008 to 2013 in Guangdong, China. The study results show that CVA6 has been one of three major causative agents of HFMD epidemics since 2009. The periodic rotation and dominance of the three pathogens, EVA71, CVA16 and CVA6, may have contributed to the continuously increasing HFMD epidemics. Moreover, phylogenetic analysis of the VP1 gene shows that major circulating CVA6 strains collected from 2009 to 2013 are distinct from the earlier strains collected before 2009. In conclusion, the discovery from this research investigating epidemiological trends of CVA6 from 2008 to 2013 explains the possible pattern of the continuous HFMD epidemic in China. The etiological change pattern also highlights the need for improvement for pathogen surveillance and vaccine strategies for HFMD control in China.

Whole genomic sequence and replication kinetics of a new enterovirus C96 isolated from Guangdong, China with a different cell tropism.

Enterovirus 96 (EV-C96) is a newly described serotype within the enterovirus C (EV-C) species, and its biological and pathological characters are largely unknown. In this study, we sequenced the whole genome of a novel EV-C96 strain that was isolated in 2011 from a patient with acute flaccid paralysis (AFP) in Guangdong province, China and characterized the properties of its infection. Sequence analysis revealed the close relationship between the EV-C96 strains isolated from the Guangdong and Shandong provinces of China, and suggested that recombination events occurred both between these EV-C96 strains and with other EV-C viruses. Moreover, the virus replication kinetics showed EV-C96 Guangdong strain replicated at a high rate in RD cells and presented a different cell tropism to other strains isolated from Shandong recently. These findings gave further insight into the evolutionary processes and extensive biodiversity of EV-C96.

Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.

The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China.