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The transmission and prevalence of Hand, Foot and Mouth Disease (HFMD) are affected by a variety of natural and socio-economic environmental factors. This study aims to quantitatively investigate the non-stationary and spatially varying associations between various environmental factors and HFMD risk. We collected HFMD surveillance cases and a series of relevant environmental data from 2013 to 2021 in Xi'an, Northwest China. By controlling the spatial and temporal mixture effects of HFMD, we constructed a Bayesian spatiotemporal mapping model and characterized the impacts of different driving factors into global linear, non-stationary and spatially varying effects. The results showed that the impact of meteorological conditions on HFMD risk varies in both type and magnitude above certain thresholds (temperature: 30 °C, precipitation: 70 mm, solar radiation: 13000 kJ/m2, pressure: 945 hPa, humidity: 69%). Air pollutants (PM2.5, PM10, NO2) showed an inverted U-shaped relationship with the risk of HFMD, while other air pollutants (O3, SO2) showed nonlinear fluctuations. Moreover, the driving effect of increasing temperature on HFMD was significant in the 3-year period, while the inhibitory effect of increasing precipitation appeared evident in the 5-year period. In addition, the proportion of urban/suburban/rural area had a strong influence on HFMD, indicating that the incidence of HFMD firstly increased and then decreased during the rapid urbanization process. The influence of population density on HFMD was not only limited by spatial location, but also varied between high and low intervals. Higher road density inhibited the risk of HFMD, but higher night light index promoted the occurrence of HFMD. Our findings further demonstrated that both ecological and socioeconomic environmental factors can pose multiple driving effects on increasing the spatiotemporal risk of HFMD, which is of great significance for effectively responding to the changes in HFMD epidemic outbreaks.

Exposure to carbon disulfide (CS2) is a recognized risk factor in the pathogenesis of Parkinson’s disease, yet the underlying mechanisms of deleterious effects on mitochondrial integrity have remained elusive. Here, through establishing CS2 exposure models in rat and SH-SY5Y cells, we demonstrated that highly expressed α-synuclein (α-Syn) is transferred to mitochondria via membrane proteins such as Tom20 and leads to mitochondrial dysfunction and mitochondrial oxidative stress, which ultimately causes neuronal injury. We first found significant mitochondrial damage and oxidative stress in CS2-exposed rat midbrain and SH-SY5Y cells and showed that mitochondrial oxidative stress was the main factor of mitochondrial damage by Mitoquinone intervention. Further experiments revealed that CS2 exposure led to the accumulation of α-Syn in mitochondria and that α-Syn co-immunoprecipitated with mitochondrial membrane proteins. Finally, the use of an α-Syn inhibitor (ELN484228) and small interfering RNA (siRNA) effectively mitigated the accumulation of α-Syn in neurons, as well as the inhibition of mitochondrial membrane potential, caused by CS2 exposure. In conclusion, our study identifies the translocation of α-Syn to mitochondria and the impairment of mitochondrial function, which has important implications for the broader understanding and treatment of neurodegenerative diseases associated with environmental toxins.

IntroductionThis study characterized Vibrio alginolyticus isolated from seafood and freshwater products in China (2020).Methods and ResultsIn total, 122 (95.31%) V. alginolyticus isolates were resistant to at least 1 antibiotic category, and 2 (1.56%) isolates were resistant to at least 3 antibiotic categories and belong to multi-drug resistance (MDR) isolates. A high prevalence rate was observed to be blaCARB (98.04%) encoding beta-lactam resistance, followed by tet (97.06%) encoding tetracycline resistance and fos (4.90%) encoding resistance to fosfomycin. Among the 57 V. alginolyticus isolates, the commonest virulence genes were type III secretion system translocated gene vopD, vopB, and vcrH (54.4%, 31/57), type III secretion system regulated gene tyeA (54.39%), followed by vscI and vscF (50.88%) encoded type III secretion system inner rod protein and needle protein, respectively. Multilocus sequence typing (MLST) showed considerable genetic diversity, with 34 distinct sequence types (STs) identified among 55 isolates. ST421 (n = 5), ST166 (n = 4), ST523 (n = 3), ST516 (n = 3), and ST507 (n = 3) were dominant STs among 55 V. alginolyticus isolates.DiscussionThese findings highlight the widespread occurrence of V. alginolyticus in both freshwater and seafood products, underscoring the critical need for vigilant monitoring of these bacteria. Such measures are essential for ensuring effective food safety management and safeguarding public health.

Abstract Background Imported cerebral malaria (CM) cases in non-endemic areas are often misdiagnosed, which delays treatment. Post-malaria neurological syndrome (PMNS) after recovery from severe malaria can also complicate diagnosis. Case We report an imported malaria case from West Africa with two sequential episodes with neurological syndromes within about a month. The first episode was diagnosed as CM with microscopy-positive Plasmodium falciparum infection. The second episode, occurring a month after the recovery from the first CM episode, was consistent with PMNS, since malaria parasites were not detected by microscopy in peripheral blood smears. However, this diagnosis was complicated by the detection of Plasmodium vivax in peripheral blood by PCR, suggesting a potential cause of the second episode by P. vivax. Conclusion This study suggests that PMNS often occurs after severe falciparum malaria. Concurrent P. vivax infection with pathogenic biomass being predominantly extravascular further complicates accurate diagnosis.

Background: A COVID-19 outbreak in the rural areas of Shijiazhuang City was attributed to the complex interactions among vaccination, host, and non-pharmaceutical interventions (NPIs). Herein, we investigated the epidemiological characteristics of all reported symptomatic cases by picking Shijiazhuang City, Hebei Province in Northern China as research objective. In addition, we established an age-group mathematical model to perform the optimal fitting and to investigate the dynamical profiles under three scenarios. Methods: All reported symptomatic cases of Shijiazhuang epidemic (January 2-February 3, 2021) were investigated in our study. The cases were classified by gender, age group and location, the distributions were analyzed by epidemiological characteristics. Furthermore, the reported data from Health Commission of Hebei Province was also analyzed by using an age-group mathematical model by two phases and three scenarios. Results: Shijiazhuang epidemic caused by SARS-CoV-2 wild strain was recorded with the peak 84 cases out of 868 reported symptomatic cases on January 11, 2021, which was implemented with strong NPIs by local government and referred as baseline situation in this study. The research results showed that R0 under baseline situation ranged from 4.47 to 7.72, and Rt of Gaocheng Distinct took 3.72 with 95% confidence interval from 3.23 to 4.35 on January 9, the declining tendencies of Rt under baseline situation were kept till February 3, the value of Rt reached below 1 on January 19 and remained low value up to February 3 for Gaocheng District and Shijiazhuang City during Shijiazhuang epidemic. This indicated Shijiazhuang epidemic was under control on January 19. However, if the strong NPIs were kept, but remote isolation operated on January 11 was not implemented as of February 9, then the scale of Shijiazhuang epidemic reached 9,482 cases from age group who were 60 years old and over out of 31,017 symptomatic cases. The investigation also revealed that Shijiazhuang epidemic reached 132,648 symptomatic cases for age group who were 60 years old and over (short for G2) under risk-based strategies (Scenario A), 58,048 symptomatic cases for G2 under late quarantine strategies (Scenario B) and 207,124 symptomatic cases for G2 under late quarantine double risk strategies (Scenario C), and that the corresponding transmission tendencies of Rt for three scenarios were consistently controlled on Jan 29, 2021. Compared with baseline situation, the dates for controlling Rt below 1 under three scenarios were delayed 10 days. Conclusions: Shijiazhuang epidemic was the first COVID-19 outbreak in the rural areas in Hebei Province of Northern China. The targeted interventions adopted in early 2021 were effective to halt the transmission due to the implementation of a strict and village-wide closure. However we found that age group profile and NPIs played critical rules to successfully contain Shijiazhuang epidemic, which should be considered by public health policies in rural areas of mainland China during the dynamic zero-COVID policy.

Objective Campylobacter species are the main causes of foodborne illness worldwide, posing significant threats to public health. This study aimed to investigate the antibiotic resistance and genomic characterization of C. jejuni/C.coli from retail chickens in Beijing. Methods Antimicrobial susceptibility testing was conducted on 126 C. jejuni/C. coli isolated from retail chickens in Beijing, following CLSI protocols. Whole genomes of all isolates were sequenced using the Illumina platform. Results More C. coli (83.82%) showed multi-drug resistance than C. jejuni (8.62%). Genomic analysis demonstrated 42 sequence types (STs) and 12 clonal complexes (CCs), from which CC828 and CC52 were dominant. cdtA, cdtB and cdtC encoding cytotoxic protein were present spontaneously in most C. jejuni but not found in any C. coli isolates. The abundances of antibiotic resistance genes (ARGs) and virulence genes (VGs) in C. jejuni and C. coli were significantly different, with ARGs numbered in C. coli and VGs in C. jejuni. Conclusions High prevalence of multi-drug resistance C. coli and C. jejuni isolated from Beijing chickens were challenging clinical antibiotic usages in the treatment of Campylobacter infection. The surveillance of particular C. jejuni and C. coli STs correlated with higher resistance and virulence needs to be strengthened in the future.

Health risks associated with acrylamide (ACR) or high-fat diet (HFD) exposure alone have been widely concerned in recent years. In a realistic situation, ACR and HFD are generally co-existence, and both are risk factors for the development of neurological diseases. The purpose of the present study was to investigate the combined effects of ACR and HFD on the motor nerve function. As a result, neurobehavioral tests and Nissl staining disclosed that long-term HFD exacerbated motor dysfunction and the damage of spinal cord motor neurons in ACR-exposed mice. Co-exposure of ACR and HFD resulted in morphological changes in neuronal mitochondria of the spinal cord, a significantly reduced mitochondrial subunits NDUFS1, UQCRC2, and MTCO1, released the mitochondrial DNA (mtDNA) into the cytoplasm, and promoted the production of reactive oxygen species (ROS). Combined exposure of HFD and ACR activated the calpain/CDK5/Drp1 axis and caused the mitochondrial excessive division, ultimately increasing MLKL-mediated necroptosis in spinal cord motor neurons. Meanwhile, HFD significantly exacerbated ACR-induced activation of NFkB, NLRP3 inflammasome, and cGAS-STING pathway. Taken together, our findings demonstrated that combined exposure of ACR and HFD aggravated the damage of spinal cord motor neurons via neuroinflammation and necroptosis signaling pathway, pointing to additive effects in mice than the individual stress effects.

Abstract Background During 2021-2022, mainland China experienced multiple times of local COVID-19 outbreaks in several cities, including Yangzhou, Xi’an etc., and the Chinese government persistently adopted the zero-COVID policy in combating with the local outbreaks. Methods We develop a mathematical model with pulse population-wide nucleic acid screening, part of the zero-COVID policy, to reveal its role in controlling the spread of COVID-19. We calibrate the model by fitting the COVID-19 epidemic data of the local outbreaks in Yangzhou and Xi’an, China. Sensitivity analysis is conducted to investigate the impact of population-wide nucleic acid screening on controlling the outbreak of COVID-19. Results Without the screening, the cumulative number of confirmed cases increases by $$77.7\%$$ 77.7 % and $$62.2\%$$ 62.2 % in Yangzhou and Xi’an, respectively. Meanwhile, the screening program helps to shorten the lockdown period for more than one month when we aim at controlling the cases into zero. Considering its role in mitigating the epidemics, we observe a paradox phenomenon of the screening rate in avoiding the runs on medical resource. That is, the screening will aggravate the runs on medical resource when the screening rate is small, while it helps to relieve the runs on medical resource if the screening rate is high enough. We also conclude that the screening has limited effects on mitigating the epidemics if the outbreak is in a high epidemic level or there has already been runs on medical resources. Alternatively, a smaller screening population per time with a higher screening frequency may be a better program to avoid the runs on medical resources. Conclusions The population-wide nucleic acid screening strategy plays an important role in quickly controlling and stopping the local outbreaks under the zero-COVID policy. However, it has limited impacts and even increase the potential risk of the runs on medical resource for containing the large scale outbreaks.

Previously, we reported that the mammalian lysine monomethylase SET7 impairs the transcriptional activity of hypoxia-inducible factor (HIF), and set7-deficient zebrafish exhibit enhanced tolerance to hypoxia stress. Megalobrama amblycephala, an extensively farmed endemic species in China, is highly sensitive to hypoxia stress, which has posed a serious threat to its intensive and large-scale culture. Therefore, it is meaningful to identify key candidate genes related to the hypoxia tolerance trait in Megalobrama amblycephala. In this study, we found that set7 is highly conserved across species. The luciferase reporter assay showed that Megalobrama amblycephala set7 inhibits the transcriptional activity of hif-1αa/b and hif-2αa/b. Furthermore, using the fluorescent glucose analog 2-NBDG, we observed that overexpression of Megalobrama amblycephala set7 inhibited glucose uptake in EPC cells under hypoxic conditions. Our findings may provide clues to understand the function of Megalobrama amblycephala set7 in the hypoxia signaling pathway, and provide a potential target for genetic breeding of hypoxia tolerant species.

Insufficient oxygen in the water (hypoxia) is one of the limiting factors for high-density culture in modern aquaculture. Hypoxia tolerance in fish has been reported to be related to the hypoxia-inducible factor (HIF)-α-mediated hypoxia signaling pathway. The well-defined function of the von Hippel-Lindau (VHL) tumor suppressor gene VHL is to mediate proteasomal degradation of hydroxylated HIF-α proteins, resulting in the downregulation of hypoxia signaling pathway. However, whether VHL has an impact on hypoxia tolerance is still elusive. In this study, we find that vhl+/- zebrafish have no gross defects in development, growth, reproduction, and movement. In addition, vhl+/- zebrafish also have normal vasculature. However, under hypoxia, vhl+/- zebrafish are more resistant to hypoxia treatment compared with their wildtype siblings. Further assays indicate that the number of erythrocytes is increased and the expression of hypoxia-responsive genes is enhanced in vhl+/- zebrafish compared with their wildtype siblings. These data indicate that loss of one copy of vhl in zebrafish facilitates hypoxia tolerance, revealing a function of vhl in hypoxia tolerance.

In recent years, the development and iteration of information technology have prompted the financial industry to transform and upgrade to financial technology (FinTech), which has received emerging attention from the global financial industry. While the FinTech industry is growing rapidly around the world, however, few studies have foucusd on the shortage of talent and difficulties in recruiting talent. First, this paper clarifies the shortage of FinTech talent through expert interviews and a questionnaire survey of 112 financial industry enterprises in Shanghai, China. Following, based on role theory, we construct a talent capability evaluation index system using 5 primary and 17 secondary indicators. Based on the exploration above, a gray optimization model is designed to support talent recruitment strategy for FinTech enterprises. The results indicate that Chinese FinTech talent should have composite abilities with outstanding professional technical skills and learning abilities, innovation and teamwork ability, project experience, and international vision. This study provides methodological guidelines for global FinTech talent evaluation and recruitment strategies and broadens the application of role theory and gray clustering theory.

Oxygen (O2) profoundly influences the physiological processes of aerobic organisms through a range of mechanisms. Recently, increasing evidence has revealed the relationship between viral infection and oxygen levels. However, due to a lack of feasible methods and in vivo models, how oxygen directly affects antiviral capability remains largely unknown. In contrast to terrestrial animals, fish live in water for life, where oxygen levels change more frequently than on land in areas with similar altitude. Therefore, fish appear to be ideal organisms for elucidating the effect of oxygen levels on antiviral responses. In this study, we report that zebrafish under low oxygen conditions are more susceptible to SVCV infection. Further assays indicate that low oxygen tension not only suppresses SVCV-induced IFN activation but also promotes SVCV replication in both zebrafish cell lines and zebrafish. This study provides novel insights into the effect of oxygen on antiviral responses and virus replication.

Summary: Exposure to carbon disulfide (CS2) has been associated with an increased incidence of parkinsonism in workers, but the mechanism underlying this association remains unclear. Using a rat model, we investigated the effects of chronic CS2 exposure on parkinsonian pathology. Our results showed that CS2 exposure leads to significant motor impairment and neuronal damage, including loss of dopaminergic neurons and degeneration of the substantia nigra pars compacta (SNpc). The immunoassays revealed that exposure to CS2 induces aggregation of α-synuclein and phosphorylated α-synuclein, as well as activation of necroptosis in the SNpc. Furthermore, in vitro and in vivo experiments demonstrated that the interaction between α-synuclein and the necrosome complex (RIP1, RIP3, and MLKL) is responsible for the loss of neuronal cells after CS2 exposure. Taken together, our results demonstrate that CS2-mediated α-synuclein aggregation can induce dopaminergic neuron damage and parkinsonian behavior through interaction with the necrosome complex.

The prediction system EpiSIX was used to study the COVID-19 epidemic in mainland China between November 2022 and January 2023, based on reported data from December 9, 2022, to January 30, 2023, released by The Chinese Center for Disease Control and Prevention on February 1, 2023. Three kinds of reported data were used for model fitting: the daily numbers of positive nucleic acid tests and deaths, and the daily number of hospital beds taken by COVID-19 patients. It was estimated that the overall infection rate was 87.54% and the overall case fatality rate was 0.078%–0.116% (median 0.100%). Assuming that a new COVID-19 epidemic outbreak would start in March or April of 2023, induced by a slightly more infectious mutant strain, we predicted a possible large rebound between September and October 2023, with a peak demand of between 800,000 and 900,000 inpatient beds. If no such new outbreak was induced by other variants, then the current COVID-19 epidemic course in mainland China would remain under control until the end of 2023. However, it is suggested that the necessary medical resources be prepared to manage possible COVID-19 epidemic emergencies in the near future, especially for the period between September and October 2023.

Abstract Background Parasite diversity and population structure influence malaria control measures. Malaria transmission at international borders affects indigenous residents and migrants, defying management efforts and resulting in malaria re-introduction. Here we aimed to determine the extent and distribution of genetic variations in Plasmodium vivax populations and the complexity of infections along the China–Myanmar border. Methods We collected clinical P. vivax samples from local and migrant malaria patients from Laiza and Myitsone, Kachin State, Myanmar, respectively. We characterized the polymorphisms in two P. vivax merozoite surface protein markers, Pvmsp-3α and Pvmsp-3β, by PCR-restriction fragment length polymorphism (PCR–RFLP) analysis. We sought to determine whether these genetic markers could differentiate these two neighboring parasite populations. Results PCR revealed three major size variants for Pvmsp-3α and four for Pvmsp-3β among the 370 and 378 samples, respectively. PCR–RFLP resolved 26 fragment-size alleles by digesting Pvmsp-3α with Alu I and Hha I and 28 alleles by digesting Pvmsp-3β with Pst I. PCR–RFLP analysis of Pvmsp-3α found that infections in migrant laborers from Myitsone bore more alleles than did infections in residents of Laiza, while such difference was not evident from genotyping Pvmsp-3β. Infections originating from these two places contained distinct but overlapping subpopulations of P. vivax. Infections from Myitsone had a higher multiplicity of infection as judged by the size of the Pvmsp-3α amplicons and alleles after Alu I/Hha I digestion. Conclusions Migrant laborers from Myitsone and indigenous residents from Laiza harbored overlapping but genetically distinct P. vivax parasite populations. The results suggested a more diverse P. vivax population in Myitsone than in the border town of Laiza. PCR–RFLP of Pvmsp-3α offers a convenient method to determine the complexity of P. vivax infections and differentiate parasite populations.

Vibrio vulnificus, a foodborne pathogen, has a high mortality rate. Despite its relevance to public health, the identification of virulence genes associated with the pathogenicity of currently known clinical isolates of V. vulnificus is incomplete and its synergistic pathogenesis remains unclear. Here, we integrate whole genome sequencing (WGS), genome-wide association studies (GWAS), and genome-wide epistasis studies (GWES), along with phenotype characterization to investigate the pathogenesis and survival strategies of V. vulnificus. GWAS and GWES identified a total of six genes (purH, gmr, yiaV, dsbD, ramA, and wbpA) associated with the pathogenicity of clinical isolates related to nucleotide/amino acid transport and metabolism, cell membrane biogenesis, signal transduction mechanisms, and protein turnover. Of these, five were newly discovered potential specific virulence genes of V. vulnificus in this study. Furthermore, GWES combined with phenotype experiments indicated that V. vulnificus isolates were clustered into two ecological groups (EGs) that shared distinct biotic and abiotic factors, and ecological strategies. Our study reveals pathogenic mechanisms and their evolution in V. vulnificus to provide a solid foundation for designing new vaccines and therapeutic targets.

The World Health Organization (WHO) declared monkeypox as a public health emergency of international concern (PHEIC) on July 23, 2022, their highest level of alert. This raised concerns about the management of the global monkeypox outbreak, as well as the scientific analysis and accurate prediction of the future course of the epidemic. This study used EpiSIX (an analysis and prediction system for epidemics based on a general SEIR model) to analyze the monkeypox epidemic and to forecast the major tendencies based on data from the USA CDC (https://www.cdc.gov) and the WHO (https://www.who.int/health-topics/monkeypox). The global outbreak of monkeypox started in the UK on May 2, 2022, which marked the beginning of an epidemic wave. As of October 28, 2022, the cumulative number of reported cases worldwide was 77,115, with 36 deaths. EpiSIX simulations predict that the global monkeypox epidemic will enter a low epidemic status on March 1, 2023 with the cumulative number of confirmed cases ranging from 85,000 to 124,000, and the total number of deaths ranging from 60 to 87. Our analysis revealed that the basic reproduction number (R0) of monkeypox virus (MPXV) is near to 3.1 and the percentage of asymptomatic individuals is 13.1 %–14.5 %, both of which are similar to the data for SARS. The vaccination efficiency against susceptibility (VEs) of individuals who have had monkeypox is ∼ 79 %, and the vaccination efficiency against infectiousness (VEi) of individuals who have had monkeypox is ∼ 76 %–82 %. The mean incubation period for monkeypox is 8 days. In total, 94.7 % of infected individuals develop symptoms within 20 days and recover within 2 weeks after the confirmation of symptoms. Simulation results using EpiSIX showed that ring vaccination was remarkably effective against monkeypox. Our findings confirmed that a 20-day isolation for close contacts is necessary.

Abstract Background This study compared the bacterial spectrum and antibiotic susceptibility of uropathogens in older and younger patients with urinary stones to provide appropriate antibiotic management. Methods We retrospectively reviewed urinary tract infection patients with urolithiasis, presented to Xiangya Hospital from March 2014 to April 2021. Patients were divided into older and younger groups according to 60 years of age. The bacterial spectrum and drug sensitivity of uropathogens were compared. Results A total of 542 strains of uropathogens (177 in older and 365 in younger groups) were isolated from 507 patients. E. coli (41.8% vs 43.6%) remains the most common pathogen, followed by E. faecalis (6.2% vs 9.6%) in older and younger groups, respectively. Particularly, K. pneumoniae was significantly more frequent in older (9.6%) than in younger group (4.7%, P

Abstract Background Urothelial bladder cancer (BC) is one of the most prevalent malignancies with high mortality and high recurrence rate. Angiogenesis, tumor growth and metastasis of multiple cancers are partly modulated by CC chemokines. However, we know little about the function of distinct CC chemokines in BC. Methods ONCOMINE, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan–Meier plotter, cBioPortal, GeneMANIA, and TIMER were used for analyzing differential expression, prognostic value, protein–protein interaction, genetic alteration and immune cell infiltration of CC chemokines in BC patients based on bioinformatics. Results The results showed that transcriptional levels of CCL2/3/4/5/14/19/21/23 in BC patients were significantly reduced. A significant relation was observed between the expression of CCL2/11/14/18/19/21/23/24/26 and the pathological stage of BC patients. BC patients with high expression levels of CCL1, CCL2, CCL3, CCL4, CCL5, CCL8, CCL13, CCL15, CCL17, CCL18, CCL19, CCL22, CCL25, CCL27 were associated with a significantly better prognosis. Moreover, we found that differentially expressed CC chemokines are primarily correlated with cytokine activity, chemokines receptor binding, chemotaxis, immune cell migration. Further, there were significant correlations among the expression of CC chemokines and the infiltration of several types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Conclusions This study is an analysis to the potential role of CC chemokines in the therapeutic targets and prognostic biomarkers of BC, which gives a novel insight into the relationship between CC chemokines and BC.

ABSTRACT Sequence type 88 (ST88) methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as an important pathogen that causes infections in humans, especially when it has strong biofilm production and multidrug resistance (MDR). However, knowledge of the determinants of resistance or virulence and genomic characteristics of ST88 MRSA from China is still limited. In this study, we employed the antimicrobial resistance (AMR), biofilm formation, and genomic characteristics of ST88 MRSA collected from various foods in China and estimated the worldwide divergence of ST88 MRSA with publicly available ST88 genomes. All ST88 isolates studied were identified as having resistance genes, while 50% (41/82) harbored MDR genes. All isolates carried core virulence genes related to immune modulation, adherence, secreted enzymes, and hemolysin. In addition, all 20 Chinese ST88 isolates showed biofilm production capacity, three strongly so. Bayesian phylogenetic analysis showed that Chinese ST88 clones formed an independent MRSA lineage, with two subclades associated with acquisition of type IVc staphylococcal cassette chromosome mec (SCCmec) elements. In contrast, all African ST88 strains were subtyped as SCCmecIVa, where the African clades were mixed with a few European and American isolates, suggesting potential transmission from Africa to these regions. In summary, our results revealed the evolution of ST88 MRSA in humans, animals, and foods in Africa and Asia. The food-associated ST88 genomes in this study will remedy the lack of food-associated ST88 isolates, and the study in general will extend the discussion of the potential exchanges of ST88 between humans and foods or food animals. IMPORTANCE ST88 MRSA has frequently been detected in humans, animals, and foods mainly in Africa and Asia. It can colonize and cause mild to severe infections in humans, especially children. Several studies from African countries have described its genotypic characteristics but, limited information is available on the evolution and characterization of ST88 MRSA in Asia, especially China. Meanwhile, the molecular history of its global spread remains largely unclear. In this study, we analyzed the genomic evolution of global ST88 MRSA strains in detail and identified key genetic changes associated with specific hosts or regions. Our results suggested geographical differentiation between ST88 MRSA’s evolution in Africa and its evolution in Asia, with a more recent clonal evolution in China. The introduction of ST88 MRSA in China was aligned with the acquisition of SCCmecIVc elements, specific virulent prophages, and AMR genes.

Non-typhoidal Salmonella (NTS) is a major cause of human salmonellosis globally. Food animals are major NTS reservoirs. An increase in antimicrobial resistance (AMR) in foodborne NTS has led to clinical treatment failures. Here, to examine the prevalence and perform characterization of foodborne NTS with AMR in China, we tested the antimicrobial susceptibility of 1,256 NTS isolates cultured from retail foods in 2020 in China. The antimicrobial susceptibility of 26 antimicrobial agents representing 12 classes was evaluated with the broth-microdilution method; the presence of ten mcr genes was screened with multi-PCR. The complete closed genomes of mcr -gene-carrying isolates were generated by hybrid assembly through whole genome sequencing on both the PacBio and Illumina platforms. Genomic features and genetic environments of the mcr-1 gene were analysed. The overall drug resistance rate was 92.28%, and the multi-drug resistance (MDR) rate was 76.53%. A total of 341 AMR profiles were determined, and resistance was highest to nalidixic acid (63.38%). Among 887 NTS isolates with MDR, 232 showed co-resistance to cefotaxime and ciprofloxacin, and 25 were resistant to ten classes of antimicrobial agents. The resistance of NTS isolated from different regions varied. Isolates from raw chicken sources most frequently showed resistance. Four NTS carried the mcr-1 gene and represented four different serotypes. Four mcr-1 gene-bearing plasmids from the four Salmonella isolates were classified into two replicon types (IncI2 and IncHI2A). Two mcr-1 genes in IncI2 type plasmids were found to be located between a PAP2 family protein-encoding gene and a relaxase-encoding gene, whereas the other two mcr-1 gene structures in IncHI2A type plasmids showed variations in the presence of insertion sequences. Our data demonstrated severe AMR among foodborne NTS isolated from food in China, thus highlighting the importance of antimicrobial susceptibility surveillance to decrease the spread of AMR, particularly to critical drugs in human medicine.

Understanding the tensile strength properties and damage evolution mechanism in fissured rock is very important to fundamental research and engineering design. The effects of flaw dip angle on the tensile strength, macroscopic crack propagation and failure mode of symmetrical Brazilian discs of rock-like materials were investigated. A parallel bonding model was proposed to examine the damage of pre-flawed discs under splitting the load. The microscopic parameters of particles and bonds in the model that can characterize rock-like materials’ mechanical and deformation properties were obtained by calibrating against the laboratory test results. The crack development, energy evolution and damage characteristics of Brazil discs containing a single pre-existing flaw were studied at the microscopic scale. The results show that the flaw significantly weakens the strength of the Brazilian disc, and both the peak load and the initial cracking load decrease with increasing flaw angle. The failure modes of the rock-like specimens are mainly divided into three types: wing crack penetration damage mode, tensile-shear penetration damage mode and radial penetration failure mode. Except for the flaw dip angle 0°, the wing cracks generally sprouted at the tip of the pre-flaw, and the wing cracks at both tips of the pre-flaw are centrosymmetric. Crack coalescence was concentrated in the post-peak stage. Based on the particle flow code (PFC) energy partitions, the damage variables characterized by dissipation energy were proposed. The disc specimen’s pre-peak damage variables and peak damage variables decreased with increasing flaw angle, and the damage was concentrated in the post-peak phase.

Objective To investigate the distribution of virulence genes and pathotypes of diarrheogenic Escherichia coli(DEC) from commercial pig farms, providing reference data for prevention and control of foodborne diseases caused by the bacteria from the pork production industry. Methods The virulence genes of Escherichia coli(E. coli), isolated from 12 pig farms, were detected by multiplex real-time quantitative polymerase chain reaction(PCR). Results Among 985 E. coli isolated from pig farms, DEC accounted for 28.83%(284/985), including 225 enteroaggregative E. coli (EAEC, 22.84%, 225/985), 14 enterotoxigenic E. coli (ETEC, 1.42%, 14/985), 12 enteropathogenic E. coli (EPEC, 1.22%, 12/985), 10 enterohemorrhagic E. coli (EHEC, 1.02%, 10/985), 9 enteroinvasive E. coli (EIEC, 0.91%, 9/985), 13 hybrid EHEC-ETEC(1.32%, 13/985), and 1 hybrid EPEC-ETEC(0.10%, 1/985). Among all those strains, one from the nose swab of a breeder had the same EHEC-ETEC virulence genotype as those positive samples detected in pig nose swab and feces. It was also found that the contamination rate of DEC in early fattening stage was significantly higher than that in late fattening stage(χ2=1.10, P

IntroductionModeling on infectious diseases is significant to facilitate public health policymaking. There are two main mathematical methods that can be used for the simulation of the epidemic and prediction of optimal early warning timing: the logistic differential equation (LDE) model and the more complex generalized logistic differential equation (GLDE) model. This study aimed to compare and analyze these two models.MethodsWe collected data on (coronavirus disease 2019) COVID-19 and four other infectious diseases and classified the data into four categories: different transmission routes, different epidemic intensities, different time scales, and different regions, using R2 to compare and analyze the goodness-of-fit of LDE and GLDE models.ResultsBoth models fitted the epidemic curves well, and all results were statistically significant. The R2 test value of COVID-19 was 0.924 (p < 0.001) fitted by the GLDE model and 0.916 (p < 0.001) fitted by the LDE model. The R2 test value varied between 0.793 and 0.966 fitted by the GLDE model and varied between 0.594 and 0.922 fitted by the LDE model for diseases with different transmission routes. The R2 test values varied between 0.853 and 0.939 fitted by the GLDE model and varied from 0.687 to 0.769 fitted by the LDE model for diseases with different prevalence intensities. The R2 test value varied between 0.706 and 0.917 fitted by the GLDE model and varied between 0.410 and 0.898 fitted by the LDE model for diseases with different time scales. The GLDE model also performed better with nation-level data with the R2 test values between 0.897 and 0.970 vs. 0.731 and 0.953 that fitted by the LDE model. Both models could characterize the patterns of the epidemics well and calculate the acceleration weeks.ConclusionThe GLDE model provides more accurate goodness-of-fit to the data than the LDE model. The GLDE model is able to handle asymmetric data by introducing shape parameters that allow it to fit data with various distributions. The LDE model provides an earlier epidemic acceleration week than the GLDE model. We conclude that the GLDE model is more advantageous in asymmetric infectious disease data simulation.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi'an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi'an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics.

The Changi NEWater Project Phase 2 purifies the secondary effluent of an urban sewage treatment plant using a two-stage microfiltration membrane (MF) and reverse osmosis (RO) process to produce NEWater for industrial use and to supplement drinking water sources. The total recovery rate of the system was 73.5%. The turbidity removal rate of the MF unit was 93.4% and the silt density index (SDI) value of MF product water was stable below 3. The performance of the pretreatment unit met the design standards. After reverse osmosis treatment, the total organic carbon removal rate was 99.4% and the desalination rate was greater than 99%. The quality of the NEWater was superior to the drinking-water standards of Singapore and the World Health Organization. Because of its advanced automatic control system, the Changi NEWater Project Phase 2 required a staff of only 15 operation and management personnel. The total operational cost was between 0.08 and 0.15 $/m³, of which energy consumption, chemical consumption, maintenance costs, and labor costs accounted for 62.9%, 20.2%, 7.3% and 9.6%, respectively. The energy consumption was between 0.6 and 0.8 ​kWh/m³. The Changi NEWater Project Phase 2 represents a milestone in water cycle engineering practice because of its excellent process design, superior product water quality, high degree of automatic control, and low operational energy consumption.

The Greater Mekong Subregion (GMS) is the epicenter of antimalarial drug resistance. We determined in vitro susceptibilities to 11 drugs of culture-adapted Plasmodium falciparum isolates from adjacent areas (Laiza and Muse) along the China–Myanmar border. Parasites from this region were highly resistant to chloroquine and pyrimethamine but relatively sensitive to other antimalarial drugs. Consistently, the Dd2-like pfcrt mutations were fixed or almost fixed in both parasite populations, and new mutations mediating piperaquine resistance were not identified. Similarly, several mutations related to pfdhfr and pfdhps were also highly prevalent. Despite their geographical proximity, malaria parasites from Laiza showed significantly higher in vitro resistance to artemisinin derivatives, naphthoquine, pyronaridine, lumefantrine, and pyrimethamine than parasites from Muse. Likewise, the pfdhfr N51I, pfdhps A581G, pfmrp1 H785N, and pfk13 F446I mutations were significantly more frequent in Laiza than in Muse (p < 0.05). For the pfmdr1 mutations, Y184F was found only in Laiza (70%), whereas F1226Y was identified only in Muse (31.8%). Parasite isolates from Laiza showed a median RSA value of 5.0%, significantly higher than the 2.4% in Muse. Altogether, P. falciparum parasite populations from neighboring regions in the GMS may diverge substantially in their resistance to several antimalarial drugs. This information about different parasite populations will guide antimalarial treatment policies to effectively manage drug resistance during malaria elimination.

In this study, the static response of the preliminary pilot tunnels excavation to the ground, and the dynamic response of the group cavern system under seismic excitation under the use of the construction of a metro station based on the Pile-Beam-Arch approach are investigated through numerical calculation. The results suggest that the excavation sequences of “top first and then bottom” and “middle first and then both sides” can generate the minimum ground settlement. When the pilot tunnels were excavated, the horizontal PGA (peak ground acceleration) amplification coefficient tends to increase with significant nonlinear characteristics under the excitation of EI Centro wave with a horizontal acceleration of 0.15 g, and the horizontal PGA amplification coefficient reaches the maximum at the ground surface. The effect of horizontal acceleration around the upper pilot tunnels increases. Under the static load, the maximum principal stress of the lining structure after the completion of the pilot tunnels is largely concentrated at the foot of the arch of the pilot tunnel, and the maximum principal stress value is 1.124 MPa. The maximum principal stress is primarily concentrated at the foot of the arch and the foot of the upper and lower guide tunnel under seismic excitation, and the maximum principal stress value is 1.424 MPa. This study reveals that a reasonable excavation sequence can be employed when the pilot tunnels are being excavated to control the settlement. Furthermore, the support of the arch and footing of the pilot tunnels should be enhanced during the seismic design.

Due to soil disturbance during the construction of metro stations, the initial stress of the stratum is modified, leading to ground settlement within a particular range, fracturing the surrounding buildings and even causing significant ground deformation and building collapse. This paper employed the Pile-Beam-Arch method to assemble the Daguanying Station of Beijing Metro Line 7 as the engineering background. The numerical calculation method was used to study the regulations of ground settlement and structural deformation throughout the construction stage. Meanwhile, the effect of surface loading was taken into account and surface settlement control strategies were suggested. Finally, the Stochastic medium theory was used to predict surface settlement. It was evident from the study’s findings that the pilot tunnels excavation and the arches installation accounted for 67% and 23.1% of the total surface settlement, respectively, and produced the most surface settlement. Surface settlement can be significantly reduced by utilizing grouting reinforcement technology and the pilot tunnels excavation approach of “upper first, then lower and side first, then middle”. The structure was much less stressed during the pre-construction stage, with the maximum principal stress ranging from 1 to 5 MPa; after construction was finalized, the maximum principal stress reached 14.203 MPa, concentrating mostly in the middle column part, which was the consequence of the combined action of the upper load and the lower soil uplift. Additionally, there was a linear relationship between the surface load and ground settlement. The bottom slab and the middle column were situated where the structure’s most unfavorable components were concentrated. The conclusions of the surface settlement prediction demonstrated that there were discrepancies between the theoretical calculation and the simulated; thus, the prediction results were more conservative. The study results can serve as a reference for construction sites.

Drug-resistant Plasmodium vivax malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. P. vivax resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (pvdhps), dihydrofolate reductase (pvdhfr), and GTP cyclohydrolase I (pvgch1) genes. This study aims to investigate the prevalence and spread of drug resistance markers in P. vivax populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute P. vivax infection. Samples with single-clone P. vivax infections were sequenced for pvdhps and pvdhfr genes and genotyped for 6 flanking microsatellite markers. Copy number variation in the pvgch1 gene was also examined. Polymorphisms were observed in six different codons of the pvdhps gene (382, 383, 512, 549, 553, and 571) and six different codons of the pvdhfr gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of pvdhfr gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of pvdhps gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the pvdhfr gene differentiated clinical samples from wild type and quadruple mutant genotypes (FST= 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of pvgch1 suggests that SP-resistant P. vivax may harbor alternative mechanisms to secure sufficient folate.

Deaths due to invasive fungal disease (IFD) have been increasing every year. Early and rapid detection is important to reduce the mortality rate associated with IFD. In this study, we explored a novel diagnostic method for detecting IFD, which involves the G Factor α subunit (GFαSub) from Limulus polyphemus. The GFαSub double-sandwich method was developed to detect (1,3)-β-D-glucans in human serum using purified GFαSub and horseradish peroxidase-labeled GFαSub. The GFαSub double-sandwich method and the G test were performed and compared. Using GFαSub sequence analysis, the expression plasmid pET30a-GFαSub252-668 was synthesized, and GFαSub252-668 was expressed and purified via isopropyl-β-d-thiogalactoside induction and nickel-nitrilotriacetic acid affinity. The optimization method was established via the orthogonal method. Using this method, the sera of 36 patients with IFD and 92 volunteers without IFD underwent detection, and the receiver operating characteristic curve of the GFαSub252-668 double-sandwich method was described. The sensitivity and specificity of the GFαSub252-668 double-sandwich method were 91.67 and 82.61%, respectively, and there was good correlation with the G test for the serum specimens of 36 patients with pulmonary IFD (R2 = 0.7592). In conclusion, our study suggests that the GFαSub252-668 double-sandwich method was satisfactory at detecting IFD cases. This method can be promoted and further developed as a novel method for diagnosing IFD.

ABSTRACT Staphylococcus aureus is a worldwide leading cause of numerous diseases ranging from food-poisoning to lethal infections. Methicillin-resistant S. aureus (MRSA) has been found capable of acquiring resistance to most antimicrobials. MRSA is ubiquitous and diverse even in terms of antimicrobial resistance (AMR) profiles, posing a challenge for treatment. Here, we present a comprehensive study of S. aureus in China, addressing epidemiology, phylogenetic reconstruction, genomic characterization, and identification of AMR profiles. The study analyzes 673 S. aureus isolates from food as well as from hospitalized and healthy individuals. The isolates have been collected over a 9-year period, between 2010 and 2018, from 27 provinces across China. By whole-genome sequencing, Bayesian divergence analysis, and supervised machine learning, we reconstructed the phylogeny of the isolates and compared them to references from other countries. We identified 72 sequence types (STs), of which, 29 were novel. We found 81 MRSA lineages by multilocus sequence type (MLST), spa, staphylococcal cassette chromosome mec element (SCCmec), and Panton-Valentine leukocidin (PVL) typing. In addition, novel variants of SCCmec type IV hosting extra metal and antimicrobial resistance genes, as well as a new SCCmec type, were found. New Bayesian dating of the split times of major clades showed that ST9, ST59, and ST239 in China and European countries fell in different branches, whereas this pattern was not observed for the ST398 clone. On the contrary, the clonal transmission of ST398 was more intermixed in regard to geographic origin. Finally, we identified genetic determinants of resistance to 10 antimicrobials, discriminating drug-resistant bacteria from susceptible strains in the cohort. Our results reveal the emergence of Chinese MRSA lineages enriched of AMR determinants that share similar genetic traits of antimicrobial resistance across human and food, hinting at a complex scenario of evolving transmission routes. IMPORTANCE Little information is available on the epidemiology and characterization of Staphylococcus aureus in China. The role of food is a cause of major concern: staphylococcal foodborne diseases affect thousands every year, and the presence of resistant Staphylococcus strains on raw retail meat products is well documented. We studied a large heterogeneous data set of S. aureus isolates from many provinces of China, isolated from food as well as from individuals. Our large whole-genome collection represents a unique catalogue that can be easily meta-analyzed and integrated with further studies and adds to the library of S. aureus sequences in the public domain in a currently underrepresented geographical region. The new Bayesian dating of the split times of major drug-resistant enriched clones is relevant in showing that Chinese and European methicillin-resistant S. aureus (MRSA) have evolved differently. Our machine learning approach, across a large number of antibiotics, shows novel determinants underlying resistance and reveals frequent resistant traits in specific clonal complexes, highlighting the importance of particular clonal complexes in China. Our findings substantially expand what is known of the evolution and genetic determinants of resistance in food-associated S. aureus in China and add crucial information for whole-genome sequencing (WGS)-based surveillance of S. aureus.

Background: Long non-coding RNA FGD5 antisense RNA 1 (FGD5-AS1), identified to be a carcinogenic lncRNA, exhibits a regulatory role in some malignancies including non-small cell lung cancer (NSCLC). The aim of the present research is to decipher the function and underlying mechanism of FGD5-AS1 in progression of NSCLC. Methods: Expression of FGD5-AS1, miR-493-5p and DEAD-box protein 5 (DDX5) in NSCLC tissues and cells was quantified utilizing qRT-PCR. Cell proliferation was assessed by CCK-8 method. Scratch healing test and Transwell assay were used for assaying cell migration and invasion. Expressions of DDX5 and epithelial-mesenchymal transition (EMT)-related proteins were examined by Western blot. Additionally, targeting relationships between FGD5-AS1 and miR-493-5p, miR-493-5p and DDX5 were verified by dual-luciferase reporter gene assay. Results: Expression of FGD5-AS1 in NSCLC tissues and cell lines was up-regulated. Expression of FGD5-AS1 was in association with enlarged tumor size and lymph node metastasis of the patients. Knockdown of FGD5-AS1 led to the inhibition of proliferation, migration, invasion and EMT of NSCLC cells. FGD5-AS1 directly targeted miR-493-5p, while DDX5 was the target of miR-493-5p in NSCLC cells. Additionally, FGD5-AS1 could positively regulate the expression of DDX5 via suppressing miR-493-5p. Conclusion: FGD5-AS1 facilitates the proliferation, migration, invasion and EMT of NSCLC cells by sponging miR-493-5p and up-regulating DDX5.

Studies have shown that swertiamarin (STM) has multiple biological activities, but its anti-tumour effects and molecular mechanisms are still unclear. The present research aimed to validate the STM’s impacts on the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and to study its potential mechanism. Two HCC cell lines were treated with STM. Tumour growth was observed by the mouse tumour xenografts model. HCC cell lines stably expressing T-cell lymphomas 1 (FRAT1) were generated by lentivirusmediated overexpression. Cell viability, proliferation, migration, and invasion were observed using Cell Counting Kit-8 (CCK8), the xCELLigence Real-Time Cell Analyzer system (RTCA), and transwell analysis, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to observe the expression of FRAT1 and proteins related to the Wnt/β-catenin signalling pathway. Tumour growth was inhibited by STM in vivo. STM suppressed the proliferation, migration, and invasion of HCC cells. STM negatively regulated FRAT1 expression, whereas overexpressed FRAT1 blocked the anti-tumour function of STM. The results revealed that STM suppressed the FRAT1/Wnt/β-catenin signalling pathway. The findings of this study provide new insights into investigation of therapeutic strategies against HCC.

Objectives Interleukin-37 (IL-37) has been identified as a potent inhibitor of the immune response. This study aimed to examine IL-37 expression in patients with chronic active hepatitis B (CAHB), and explore its possible regulatory role during inflammation. Methods Peripheral blood mononuclear cells (PBMCs) were collected from control (n = 20) and CAHB patients (n = 30) before and after treatment with entecavir (EVT) for 24 weeks. The PBMCs were cultured with lipopolysaccharide and IL-37 expression was determined by real-time polymerase chain reaction and flow cytometry. The mRNA and protein concentrations of IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in PBMCs were also measured. Results Levels of IL-37, IL-1β, IL-6, and TNF-α were significantly increased in the supernatant of PBMCs from patients with CAHB. IL-37 significantly reduced the expression of IL-1β, IL-6, and TNF-α. EVT resulted in regression of intraocular inflammation in patients with CAHB, associated with decreased production of IL-37. Conclusion These results suggest that increased expression of IL-37 was associated with the suppression of the inflammatory response in patients with CAHB. Furthermore, EVT treatment of CAHB was also correlated with downregulation of IL-37, indicating that EVT may partially alleviate the immune response by modulating IL-37 production.

Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007–2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of IC50s. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resistance genetic background. Furthermore, network analysis of drug resistance genes indicated that certain haplotypes associated multidrug resistance persisted in these years, albeit there were year-to-year fluctuations of the predominant haplotypes. Keywords: Drug resistance, Plasmodium falciparum, Mutation, In vitro assay, China-Myanmar border

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobin E (HbE, β26 Glu-Lys) are two common red cell disorders in Southeast Asia. G6PD deficiency produces hemolytic anemia, which can be triggered by certain drugs or infections. HbE is asymptomatic or is manifested as microcytic, minimally hemolytic anemia. The association between G6PD deficiency and HbE is little understood. This study aimed to investigate G6PD deficiency and HbE in a Kachin ethnic group in the China-Myanmar border area. G6PD enzyme activity was measured using a quantitative G6PD assay, G6PD variants genotyped by the SNaPshot assay, and an HbE gene mutation identified by an amplification refractory mutation system and subsequently confirmed by using a reverse dot blot hybridization assay from 100 unrelated individuals in the study area. G6PD enzyme activity ranged from 0.4 to 24.7 U/g Hb, and six males had severe G6PD deficiency (1.2-4.5 U/g Hb). Among the 24 G6PD-deficient subjects, 22 (92%) had the Mahidol 487G>A mutation (12 male hemizygotes, one female homozygote, and nine female heterozygotes), while the G6PD genotypes in two female subjects were unknown. HbE was identified in 39 subjects (20 males and 19 females), including 15 HbEE (seven males and eight females) and 24 HbAE (13 males and 11 females). Twenty-three subjects co-inherited both G6PD deficiency and HbE (22 with HbAE and one with HbEE). Whereas mean Hb levels were not significantly different between the HbA and HbE groups, G6PD-deficient males had significantly lower Hb levels than G6PD-normal males (P < 0.05, t-test). However, it is noteworthy that two G6PD-deficient hemizygous males with HbAE were severely anemic with Hb levels below 50 g/L. This study revealed high prevalence of co-inheritance of G6PD deficiency with HbAE in the Kachin ethnicity, and a potential interaction of the G6PD Mahidol 487G>A and HbAE in males leading to severe anemia. The presence of 6% males with severe G6PD deficiency raised a major concern in the use of primaquine for radical cure of vivax malaria.

Petroleum depletion and climate change have inspired research on bio-based polymers and CO2 capture. Tung-oil-based polyols were applied to partially replace polyether-type polyols from petroleum for sustainable polyurethane. Tung-oil-based polyurethane (TBPU), was prepared via a two-step polycondensation, that is, bulk prepolymerization and chain extension reaction. The graphene oxide (GO) was prepared via Hummer’s method. Then, TBPU was composited with the GO at different ratios to form a TBPU/GO hybrid film. The GO/TBPU films were characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), thermal gravimetric analysis (TGA) and scanning electron microscope (SEM), followed by the measurement of mechanical properties and gas permeability. The results showed that the addition of tung-oil-based polyols enhanced the glass transition temperature and thermal stability of TBPU. The mechanical properties of the hybrid film were significantly improved, and the tensile strength and elongation at break were twice as high as those of the bulk TBPU film. When the GO content was higher than 2.0%, a brittle fracture appeared in the cross section of hybrid film. The increase of GO content in hybrid films improved the selectivity of CO2/N2 separation. When the GO content was higher than 0.35%, the resulting GO agglomeration constrained the gas separation and permeation properties.