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Frequent outbreaks of dengue are considered to be associated with an increased risk for endemicity of the disease. The occurrence of a large number of indigenous dengue cases in consecutive years indicates the possibility of a changing dengue epidemic pattern in Guangdong, China. To have a clear understanding of the current dengue epidemic, a retrospective study of epidemiological profile, serological response, and virological features of dengue infections from 2005-2011 was conducted. Case data were collected from the National Notifiable Infectious Diseases Reporting Network. Serum samples were collected and prepared for serological verification and etiological confirmation. Incidence, temporal and spatial distribution, and the clinical manifestation of dengue infections were analyzed. Pearson's Chi-Square test was used to compare incidences between different age groups. A seroprevalence survey was implemented in local healthy inhabitants to obtain the overall positive rate for the specific immunoglobulin (Ig) G antibody against dengue virus (DENV). The overall annual incidence rate was 1.87/100000. A significant difference was found in age-specific incidence (Pearson's Chi-Square value 498.008, P<0.001). Children under 5 years of age had the lowest incidence of 0.28/100000. The vast majority of cases presented with a mild manifestation typical to dengue fever. The overall seroprevalence of dengue IgG antibody in local populations was 2.43% (range 0.28%-5.42%). DENV-1 was the predominant serotype in circulation through the years, while all 4 serotypes were identified in indigenous patients from different outbreak localities since 2009. A gradual change in the epidemic pattern of dengue infection has been observed in recent years in Guangdong. With the endemic nature of dengue infections, the transition from a monotypic to a multitypic circulation of dengue virus in the last several years will have an important bearing on the prevention and control of dengue in the province and in the neighboring districts.

Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible.

Salmonella 4,[5],12:i:- has been regarded as the predominant pandemic serotype causing diarrheal diseases globally, while multidrug resistance (MDR) constitutes great public health concerns. This study provided a detailed and comprehensive genome-scale analysis of this important Salmonella serovar in the past decade in Guangdong, China. Our results revealed the complexity of two distinct transmission modes, namely global transmission and local expansion, circulating in Guangdong over a decade. Using phylogeography models, the origin of Salmonella 4,[5],12:i:- was predicted from two aspects, year and country, that is, Salmonella 4,[5],12:i:- emerged in 1983, and was introduced from the UK, and subsequently differentiated into the local endemic lineage circa 1991. Additionally, based on the pan-genome analysis, it was found that the gene accumulation rate in local endemic BAPS 1 lineage was higher than in other lineages, and the horizontal transmission of MDR IncHI2 plasmid associated with high resistance played a major role, which showed the potential threat to public health.

BackgroundInformation on geographical accessibility to maternal healthcare (MHC) and coverage of maternal health service utilisation at high spatial resolution in Nepal are important for evidence-based health planning.MethodsBased on the Nepal Health Facility Registry dataset in 2022, we measured the geographical accessibility to MHC facilities across Nepal. Using data from 2022 Nepal Demographic and Health Survey and other sources, we assessed the relationships between geographical accessibility and the utilisation of the three major healthcare services (ie, four or more antenatal care (ANC) visits, institutional delivery and postnatal care (PNC) check-up), by applying Bayesian geostatistical models. High-resolution maps on coverage of the above services were produced.ResultsThe geographical accessibility showed high in the central and southern Terai belt but low in the northern mountains, with average travel-mode adjusted travel time for ANC, institutional delivery and PNC 26.74, 40.72 and 29.09 min, respectively. Negative correlations were found between geographical accessibility with four or more ANC visits (OR 0.76, 95% Bayesian credible interval, BCI 0.65 to 0.90), institutional delivery (OR 0.76, 95% BCI 0.64 to 0.90) and PNC check-up (OR 0.87, 95% BCI 0.76 to 0.99), respectively. Population-weighted coverages for four or more ANC visits, institutional delivery and PNC check-up were estimated 83.25% (95% BCI 80.43% to 85.35%), 84.26% (95% BCI 81.30% to 86.08%) and 73.19% (95% BCI 69.43% to 76.09%), respectively, across Nepal. The northern mountains and southeastern Terai showed low coverage for the three healthcare services, while the central, eastern and western hilly regions exhibited good coverage.ConclusionGeographical accessibility is important in utilisation of maternal health services in Nepal. The high-resolution maps enable an evidence-based assessment for better health planning.

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

The objective of this study was to investigate the inhibitory effect of chlorogenin 3-O-β-chacotrioside derivatives against H5N1 subtype of the highly pathogenic avian influenza (HPAI) viruses and its molecular mechanism. A series of novel small molecule pentacyclic triterpene derivatives were designed and synthesized and their antiviral activities on HPAI H5N1 viruses were detected. The results displayed that the derivatives UA-Nu-ph-5, XC-27-1 and XC-27-2 strongly inhibited wild-type A/Duck/Guangdong/212/2004 H5N1 viruses with the IC50 values of 15.59 ± 2.4 μM, 16.83 ± 1.45 μM, and 12.45 ± 2.27 μM, respectively, and had the selectivity index (SI) > 3, which was consistent with the efficacy against A/Thailand/kan353/2004 pseudo-typed viruses. Four dealt patterns were compared via PRNT. The prevention dealt pattern showed the strongest inhibitory effects than other patterns, suggesting that these derivatives act on the entry process at the early stages of H5N1 viral infection, providing protection for cells against infection. Further studies through hemagglutinin inhibition (HI) and neuraminidase inhibitory (NAI) assay confirmed that these derivatives inhibited H5N1 virus replication by interfering with the viral hemagglutinin function. The derivatives could recognize specifically HA protein with binding affinity constant KD values of 2.57 × 10−4 M and 3.67 × 10−4 M. In addition, through site-directed mutagenesis combined with a pseudovirion system, we identified that the high-affinity docking sites underlying interaction were closely associated with amino acid residues I391 and T395 of HA. However, the potential binding sites of the derivatives with HA did not locate at HA1 sialic acids receptor binding domain (RBD). Taken together, these study data manifested that chlorogenin 3-O-β-chacotrioside derivatives generated antiviral effect against HPAI H5N1 viruses by targeting the hemagglutinin fusion machinery.

Abstract The first highly pathogenic (HP) influenza A/H7N9 was reported in Guangdong in January 2017. To investigate the emergence and spread of HP A/H7N9 in Guangdong province, we sequenced 297 viruses (58 HP A/H7N9, 19 low pathogenic (LP) A/H7N9, and 220 A/H9N2) during 2016–2017. Our analysis showed that during the fifth wave, three A/H7N9 lineages were co-circulating in Guangdong: the local LP Pearl River Delta (PRD) lineage (13%), the newly imported LP Yangtze River Delta (YRD) lineage (23%), and the HP YRD lineage (64%). Previously circulating YRD-lineage LP during the third wave evolved to the YRD-lineage HP A/H7N9 in Guangdong. All YRD-lineage LP detected during the fifth wave most likely originated from newly imported viruses into Guangdong. Genotype comparison of HP A/H7N9 suggests limited outward spread of HP A/H7N9 to other provinces. The distribution of HP A/H7N9 cleavage site variants on live poultry markets differed from that found in humans, suggesting a V1-type cleavage site may facilitate human infections.

Background Salmonella enterica includes the major serovars associated with human salmonellosis. In this study, 1764 clinical Salmonella enterica isolates from diarrhea outpatients were collected from fifteen cities in Guangdong province, China, between 2007 and 2012. These isolates represent all of the Salmonella isolates collected from the province during that period. Methods The isolates were characterized by serovar determination, antimicrobial susceptibility tests and PFGE fingerprint typing. Results The serovar distribution results demonstrated that Salmonella Typhimurium (n = 523, 29.65%) and Salmonella 4,5,12:i:- (n = 244, 13.83%) are the most common serovars causing infant salmonellosis, whereas Salmonella Enteritidis (n = 257, 14.57%) mainly causes human salmonellosis in adults. The serovar shift from Salmonella Enteritidis to Salmonella Typhimurium occurred in 2008. Antimicrobial susceptibility data showed a high burden of multidrug resistance (MDR) (n = 1128, 56.58%), and a 20%-30% increase in the number of isolates resistant to ciprofloxacin (n = 142, 8.05%) and third-generation cephalosporins (n = 88, 4.99%) from 2007–2012. Only 9.97% of isolates (n = 176) were fully susceptible to all agents tested. A high burden of MDR was observed in Salmonella Typhimurium and Salmonella 4,5,12:i:- for all age groups, and a reduced susceptibility to third-generation cephalosporins and quinolones occurred particularly in infants (≤6 years). The dominant PFGE patterns were JPXX01.GD0004, JEGX01.GD0006-7 and JNGX01.GD0006-7. ACSSuT was the predominant MDR profile in the Salmonella Typhimurium & 4,5,12:i:- complexes, while ASSuT-Nal and ASSu-Nal were the major MDR profiles in Salmonella Enteritidis. The predominant PFGE patterns of the Salmonella Typhimurium & 4,5,12:i:- complexes and Salmonella Stanley were most prevalent in infants (≤6 years). However, no obvious relationship was observed between these PFGE profiles and geographic location. Conclusions These data reveal the serovar distribution of isolates recovered from diarrhea patients, the characteristics of resistant strains and fingerprint typing in Guangdong from 2007 to 2012. These results highlight a serovar shift and a worrying percentage of MDR strains with increasing resistance to quinolones and third-generation cephalosporins. Thus, continued surveillance of Salmonella and their MDR profiles using combined molecular tools and efforts to control the rapid increase in antimicrobial resistance among Salmonella in Guangdong are needed.

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a global threat to the human population. Identifying animal species susceptible to infection with the SARS-CoV-2/ HCoV-19 pathogen is essential for controlling the outbreak and for testing valid prophylactics or therapeutics based on animal model studies. Here, different aged Chinese tree shrews (adult group, 1 year old; old group, 5-6 years old), which are close relatives to primates, were infected with SARS-CoV2. X-ray, viral shedding, laboratory, and histological analyses were performed on different days postinoculation (dpi). Results showed that Chinese tree shrews could be infected by SARS-CoV-2. Lung infiltrates were visible in X-ray radiographs in most infected animals. Viral RNA was consistently detected in lung tissues from infected animals at 3, 5, and 7 dpi, along with alterations in related parameters from routine blood tests and serum biochemistry, including increased levels of aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Histological analysis of lung tissues from animals at 3 dpi (adult group) and 7 dpi (old group) showed thickened alveolar septa and interstitial hemorrhage. Several differences were found between the two different aged groups in regard to viral shedding peak. Our results indicate that Chinese tree shrews have the potential to be used as animal models for SARS-CoV-2 infection.

Quantifying the effects of coal mining subsidence on soil quality is critical for developing sustainable strategies in the local agriculture. The objective of this study was to assess the effects of slope position because of coal mining on soil quality using principal component analysis. Soil samples were collected from five positions in the subsided farmland: Top slope position (1), upper slope position (2), middle slope position (3), lower slope position (4), and bottom position (5). Samples from an adjacent non-subsided farmland (CK) were used as a reference. For each soil sample, 21 different physical, chemical and biological attributes were investigated. The principal components analysis (PCA) identified the bulk density (BD), salinity, organic matter (OM) content, urease enzymatic activity (UA), actinomycete quantities (AQ), polyphenol oxidase enzymatic activity (POA) and phosphatase enzymatic activity (PA) as the most sensitive indicators in a minimum data set (MDS) to assess the soil quality. The soil quality index (SQI) was highest for positions 5 (1.220), 4 (1.203), CK (1.101), 1 (1.093), 3 (1.080), and 2 (1.044). Positions 5 and 4 had higher SQI values but lower crop yields than CK, which suggests that higher SQI does not represent higher production, and other soil quality indicators, which were not investigated in this study, had stronger effects on the crop productivity. Overall, the slope position because of coal mining subsidence strongly affected the soil quality and crop yields.