Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

Spatiotemporal heterogeneity and long-term impact of meteorological, environmental, and socio-economic factors on scrub typhus in China from 2006 to 2018.

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.

KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population.

Killer-cell immunoglobulin-like receptors 2DL4 (KIR2DL4) and the human leukocyte antigen class I-G (HLA-G) display vital parts in immune responses against hepatitis C virus (HCV) infection. We select four potentially functional single nucleotide polymorphisms (SNPs) of KIR/HLA to explore the associations between KIR2DL4/HLA-G genetic variants and HCV infection results. In the present case-control study, a total of 2225 HCV-infected high-risk subjects, including 1778 paid blood donors (PBD) and 447 drug users were consecutively recruited before treatment from 2011 to 2018. KIR2DL4-rs660773, KIR2DL4-rs660437, HLA-G-rs9380142, and HLA-G-rs1707 SNPs were sorted as genotypes in the subdivided groups, involving 1095 uninfected controls subjects, 432 spontaneous HCV clearance subjects and 698 HCV persistent infection subjects. After genotyping experiments using the TaqMan-MGB assay, modified logistic regression was used to calculate the correlation among the SNPs and HCV infection. The SNPs were functionally annotated using bioinformatics analysis. Following adjusting by age, sex, alanine aminotransferase, aspartate aminotransferase, IFNL3-rs12979860, IFNL3-rs8099917, and the infection route, the logistic regression analysis discovered that KIR2DL4-rs660773 and HLA-G-rs9380142 were correlated with vulnerability to HCV infection (all p < 0.05). In a locus-dosage way, compared with subjects carrying the rs9380142-AA or rs660773-AA genotypes, subjects with rs9380142-AG or rs660773-AG/GG (all p < 0.05) were more vulnerable to HCV infection; the overall impact of their risk genotypes (rs9380142-AGrs660773-AG/GG) was correlated with an elevated incidence of HCV infection (ptrend < 0.001). In the Haplotype analysis, patients with haplotype AG were more likely to contract HCV compared to those with the highest common AA haplotype (p = 0.002) were higher in susceptibility to infect HCV. The SNPinfo web server estimated that rs660773 is a transcription factor binding site, whereas rs9380142 is a potential microRNA-binding site. In two Chinese high-risk population (PBD and drug uesrs), KIR2DL4 rs660773-G and HLA-G rs9380142-G alleles polymorphisms are related to HCV susceptibility. KIR2DL4/HLA-G pathway genes might affect the innate immune responses by regulating KIR2DL4/HLA-G transcription and translation play a potential role in HCV infection.

Frequency and polymorphism of acetylcholinesterase gene involved in the organophosphate resistance of Musca domestica in Guizhou Province, China.

Organophosphate (OP) resistance has been prevalent in Musca domestica populations worldwide since 1960s. Previous studies have demonstrated that point mutations of the acetylcholinesterase gene (Ace) are one of the important molecular mechanisms underlying OP resistance. However, few studies have investigated the molecular mechanisms of OP resistance in the past 10 years in China. In this study, we investigated the status of OP resistance and genetic diversity of Ace in the field populations of houseflies in Guizhou Province of China. The bioassays showed that the houseflies had 142-304-fold resistance to dichlorvos (DDVP) and 122-364-fold resistance to temephos, compared to the susceptible houseflies. Five nonsynonymous mutations (Y226F, V260L, G342A/V, F407Y) in Ace were detected among the 7 field populations, with an average frequency of 5.4%, 55%, 68%, 32%, and 94%, respectively, of which the Y226F mutation had not been reported previously. Eleven combinations of triple mutations (at positions 260, 342, and 407) were observed, of which the combination 260L/V+342A/V+407Y was predominant. The ZY and AS populations showed greatest diversity of allelic combination and the other five populations showed different distributions among different regions. These results indicate that the resistance to OPs is prevalent among the housefly populations and target-site insensitivity is the main cause of resistance in Guizhou Province. The difference in distribution and the allelic diversity of Ace in field populations may be due to the complexity and variability of insecticide application. It is necessary to monitor resistance to insecticides and conduct management of houseflies in Guizhou Province.

Epidemiology and Genomic characteristics of arenavirus in rodents from the southeast coast of P.R. China.

BACKGROUND: Wenzhou virus (WENV), a member of the Mammarenavirus genus in the Arenaviridae family, has been detected in wild rodents from eight provinces in China, including Zhejiang, Shandong, Hainan, Xinjiang, Hunan, Guangdong, Yunnan, and Jiangxi provinces, and some countries from Southeast Asia. The IgG-antibodies of WENV have been detected in both healthy populations and patients with unknown fever and respiratory symptoms. However, the potential harmfulness of WENV to humans has been underestimated due to mild symptoms after infection, similar to respiratory diseases. Thus, it is imperative to enhance the surveillance of WENV in wild rodents, particularly Rattus norvegicus, and continuously monitor its prevalence. RESULTS: From 2017 to 2021, a total of 390 wild rodents were collected from six provinces in the eastern and southern coastal areas, containing nine species of rats. Samples of each tissue were collected, and PCR amplified for identification. Four R. norvegicus samples were detected to be WENV-positive. No genomic sequence of WENV was detected in Rattus flavipectus, Rattus losea, Suncus murinus, Apodemus agrarius, Mus musculus, Microtus fortis, Micromys minutus, and Niviventer niviventer from Jiangsu, Zhejiang, Fujian, Hainan, Guangdong and Guangxi provinces. Three genomic sequences were identified to be WENV by phylogenetic analysis. The full-length sequences of HAIKOU-40 were amplified in R. norvegicus from Hainan, which showed a close relationship to Wufeng/ WFS, sharing 84.5-89.4% homology at the nucleotide level and 91.6-98.9% homology at the amino acid level. Phylogenetic analysis revealed that HAIKOU-40 formed an Asia-specific cluster with all WENVs and Loie River mammarenavirus (LORV), provisionally named Asian ancestry. This cluster has diverged earlier from the remaining mammarenavirus. The sequences obtained in Xiamen, Fujian province showed more than 90% nucleotide identities with WENV, which may be a strain of WENV. Additionally, the sequence of Wuxi-87 which was a positive sequence detected in Wuxi, Jiangsu province exhibited 83% nucleotide identity with Lassa virus (LASV). Further efforts will be made to isolate and identify this virus strain, verify the relationship between Wuxi-87 and LASV, and confirm whether R. norvegicus is a new host of LASV. CONCLUSIONS: In this study, we conducted a systematic examination of the prevalence of WENV among rodents on the southeast coast of China. Additionally, we characterized the genome of a newly discovered WENV strain, that confirmed the role of R. norvegicus in the transmission of WENV. This highlights the importance of investigating the prevalence of WENV in both wild rodents and humans.

Epidemiologic changes of infectious diseases in the post-SARS era in China, 2004-2018.

OBJECTIVES: To outline 44 major infectious diseases in the post-SARS (severe acute respiratory syndrome) in China and describe their long-term trends and changes by age, sex, epidemic season, and province. BACKGROUND: After the outbreak of severe acute respiratory syndrome (SARS) in 2003, with the change of infectious disease prevention and control system and the improvement of residents' quality of life, the incidence and mortality of infectious diseases have undergone major changes. METHODS: The data of 44 major infectious diseases in China from 2004 to 2018 were obtained from the monthly analysis report of the China Information System for Disease Control and Prevention (CISDCP) and the Public Health Science Data Center. Joinpoint r regression models were used to examine trends in incidence and mortality for 44 major and important infectious diseases from 2004 to 2018. RESULTS: From 2004 to 2018, 20,105, 500, 772 patients (10, 306, 546, 523 males and 9, 798, 954, 249 females) were diagnosed with 44 major infectious diseases. The overall incidence of 44 infectious diseases increased significantly from 294.6 per 100,000 people in 2004 to 479.1 per 100,000 people in 2010, with 7.9% APC (95% CI 5.2% -10.7%, P < 0.001), then slowed, and then increased to 561.2 per 100,000 people in 2018, with 1.5% APC (-0.1%-3.2%, P = 0.070). The overall mortality rose significantly, from 0.49 to 1.13 per 100,000 people between 2004 and 2011, with an APC increase of 11.6% (7.7% -15.6%, P < 0.001), and then remained stable until 2018. Among these, the prevalence of vaccine-preventable diseases and gastrointestinal & enteroviral diseases remained high and increased year by year. Patients with zoonotic diseases have the greatest risk of death, while patients with sexually transmitted and blood-borne diseases have the greatest number of deaths. Incidence rates vary considerably across geographic regions. Western China has a disproportionate burden of infectious diseases compared with eastern regions. CONCLUSIONS: After the event of SARS in 2003, infectious disease preventing and controlling model has undergone major changes in China, and certain achievements have been made in this field. Although overall morbidity and case fatality rates are still rising, they have leveled off. In reducing the disproportionate disease burden in the western region, expanding vaccination programs, preventing further increases in rates of sexually transmitted diseases, renewing efforts for emerging and persistent infectious diseases, and addressing seasonal and unpredictable outbreaks (such as the COVID-19 pandemic), there are still remain many challenges.

Impact of outdoor air pollution on the incidence of pertussis in China: a time-series study.

BACKGROUND: The increasing number of pertussis cases worldwide over the past two decades has challenged healthcare workers, and the role of environmental factors and climate change cannot be ignored. The incidence of pertussis has increased dramatically in mainland China since 2015, developing into a serious public health problem. The association of meteorological factors on pertussis has attracted attention, but few studies have examined the impact of air pollutants on this respiratory disease. METHODS: In this study, we analyzed the relationship between outdoor air pollution and the pertussis incidence. The study period was from January 2013 to December 2018, and monthly air pollutant data and the monthly incidence of patients in 31 provinces of China were collected. Distributed lag nonlinear model (DLNM) analysis was used to estimate the associations between six air pollutants and monthly pertussis incidence in China. RESULTS: We found a correlation between elevated pertussis incidence and short-term high monthly CO2 and O3 exposure, with a 10 µg/m3 increase in NO2 and O3 being significantly associated with increased pertussis incidence, with RR values of 1.78 (95% CI: 1.29-2.46) and 1.51 (95% CI: 1.16-1.97) at a lag of 0 months, respectively. Moreover, PM2.5 and SO2 also played key roles in the risk of pertussis surged. These associations remain significant after adjusting for long-term trend, seasonality and collinearity. CONCLUSIONS: Overall, these data reinforce the evidence of a link between incidence and climate identified in regional and local studies. These findings also further support the hypothesis that air pollution is responsible for the global resurgence of pertussis. Based on this we suggest that public health workers should be encouraged to consider the risks of the environment when focusing on pertussis prevention and control.

ROS-mediated TCA cycle is greatly related to the UV resistance of Bacillus thuringiensis.

Bacillus thuringiensis (Bt) is a popular and environment-friendly biopesticide. However, similar to other microbial pesticides, Bt is limited by ultraviolet (UV) radiation during its application, which greatly reduces its toxicity and persistence. To further know the mechanism of Bt against UV radiation, metabolomic profiles between Bt LLP29 and its UV-resistant mutant LLP29-M19 were compared, analyzed, and annotated in this study, and then a total of 61 metabolites with different abundances were detected. With P < 0.05 as the standard, a total of 12 metabolic pathways were enriched, including the TCA cycle. According to the result of RT-qPCR, the expression levels of the TCA cycle key genes in Bt LL29-M19, such as icd1 citZ, citB, sdhA, sdhB, sdhC, fumA, and mdh, were found down-regulated for 85.58%, 37.02%, 70.87%, 85.97%, 76.33%, 83.15%, 87.28%, and 35.77% than those in Bt LLP29. It was consistent with the down-regulation trend of the TCA cycle key enzymes activity in Bt LLP29-M19. Consistently, the enzyme activities of ICDH, SDH, and PDH in LLP29-M19 were detected 86.28%, 43.93%, and 83.03% lower than those in Bt LLP29. It was revealed that the reduced TCA cycle was required for Bt UV radiation resistance, which was also demonstrated by the addition of inhibitors furfural and malonic acid, respectively. Based on the result of RT-qPCR, the gene transcription levels of the main reactive oxygen species (ROS) generation pathways were down-regulated, such as EMP, however, the activity of the main degrading enzymes was up-regulated, which showed the reduction of ROS generation rate was a way for the TCA cycle to regulate the anti-ultraviolet resistance of Bt. All of these provide solid evidence for reprogramming metabolomics to strengthen Bt UV radiation resistance.

Molecular detection of spotted fever group rickettsiae in hedgehogs (Erinaceus amurensis) and hedgehog-attached ticks in Xuyi County, Southeast China.

Tick-borne diseases like Rickettsia, Anaplasma and Ehrlichia are widespread infectious zoonoses that threaten the health of both humans and animals worldwide. Ticks and their hosts, such as hedgehogs, can play a crucial role in transmitting tick-borne diseases and the cycle of Rickettsia. To investigate the presence and identity of Rickettsia in hedgehogs and hedgehog-attached ticks in Xuyi County, Southeast China, 114 ticks were collected from 45 hedgehogs captured totally. Via morphological and molecular methods, all these ticks were identified as two species: Haemaphysalis flava (110/114, 96.5%) and Haemaphysalis longicornis (4/114, 3.5%). Rickettsia spp. were genotypically characterized by PCR targeting rrs, gltA, ompA, ompB, and sca4 gene fragments. The prevalence of spotted fever group rickettsiae (SFGR) infection found in hedgehogs and ticks was 17.8% (8/45) and 78.1% (89/114), respectively. Phylogenetic analyses demonstrated that those Rickettsia spp. belong to two species: Rickettsia heilongjiangensis (R. heilongjiangensis XY-1) and a potential new species, Candidatus Rickettsia xuyiensis XY-2. The present study gave the first evidence of R. heilongjiangensis and Candidatus R. xuyiensis in ticks and hedgehogs of Southeast China. Our findings suggest that hedgehogs might be involved in the natural transmission cycle of Rickettsia species.

The polymorphism and geographical distribution of knockdown resistance of adult Anopheles sinensis populations in eastern China.

BACKGROUND: Anopheles sinensis is one of the major malaria vectors in China and other southeast Asian countries, including Vietnam, Cambodia, Thailand. Vector control is considered to be the critical measure for malaria control, while the increasing prevalence of insecticide resistance caused by long-term use of insecticides, especially pyrethroids, is threatening the successful control of An. sinensis. In order to understand the underlying resistance mechanisms involved and molecular basis, the principal malaria vector, An. sinensis from Jiangsu and Anhui provinces, Southeast China, was investigated. METHODS: The adult Anopheles mosquitoes were sampled from multiple sites across Jiangsu and Anhui provinces, and sufficient mosquitoes collected from eleven sites for insecticide susceptibility bioassays. The DIIS4-DIIS6 region of the para-type sodium channel gene was amplified and sequenced, then multiple PCR and Taqman assays were used to assess the frequencies of kdr mutations at the target gene. RESULTS: In the present study, most of the adult An. sinensis populations were pyrethroids resistant, which indicated the presence of kdr resistance mutations in the para-type sodium channel gene. Sequence analyses demonstrated the kdr mutation existed at codon 1014 in Jiangsu and Anhui provinces. In adult An. sinensis, three mutant types (TTT L1014F, TTC L1014F, and TGT L1014C) of kdr alleles were detected, while no wild type (TTG L1014) was observed. The TTC L1014F mutation was first reported in Anhui province. CONCLUSIONS: The highly polymorphic kdr alleles were observed in all the adult An. sinensis populations, which suggested that in-depth studies are required for carrying on insecticide resistance monitoring and specific resistance mechanisms studying into establish effective long-term malaria vector control program in eastern China.

Correction to: The polymorphism and geographical distribution of knockdown resistance of adult Anopheles sinensis populations in eastern China.

Please be advised that since publication of the original article [1] the authors have flagged that they omitted to provide the up-to-date version of Fig. 1 and, as such, the wrong version of Fig. 1 is present in the article.

Group A Rotaviruses in Chinese Bats: Genetic Composition, Serology, and Evidence for Bat-to-Human Transmission and Reassortment.

Bats are natural reservoirs for many pathogenic viruses, and increasing evidence supports the notion that bats can also harbor group A rotaviruses (RVAs), important causative agents of diarrhea in children and young animals. Currently, 8 RVA strains possessing completely novel genotype constellations or genotypes possibly originating from other mammals have been identified from African and Chinese bats. However, all the data were mainly based on detection of RVA RNA, present only during acute infections, which does not permit assessment of the true exposure of a bat population to RVA. To systematically investigate the genetic diversity of RVAs, 547 bat anal swabs or gut samples along with 448 bat sera were collected from five South Chinese provinces. Specific reverse transcription-PCR (RT-PCR) screening found four RVA strains. Strain GLRL1 possessed a completely novel genotype constellation, whereas the other three possessed a constellation consistent with the MSLH14-like genotype, a newly characterized group of viruses widely prevalent in Chinese insectivorous bats. Among the latter, strain LZHP2 provided strong evidence of cross-species transmission of RVAs from bats to humans, whereas strains YSSK5 and BSTM70 were likely reassortants between typical MSLH14-like RVAs and human RVAs. RVA-specific antibodies were detected in 10.7% (48/448) of bat sera by an indirect immunofluorescence assay (IIFA). Bats in Guangxi and Yunnan had a higher RVA-specific antibody prevalence than those from Fujian and Zhejiang provinces. These observations provide evidence for cross-species transmission of MSLH14-like bat RVAs to humans, highlighting the impact of bats as reservoirs of RVAs on public health.IMPORTANCE Bat viruses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola, Hendra, and Nipah viruses, are important pathogens causing outbreaks of severe emerging infectious diseases. However, little is known about bat viruses capable of causing gastroenteritis in humans, even though 8 group A viruses (RVAs) have been identified from bats so far. In this study, another 4 RVA strains were identified, with one providing strong evidence for zoonotic transmission from bats to humans. Serological investigation has also indicated that RVA infection in bats is far more prevalent than expected based on the detection of viral RNA.

S3T-Net: A novel electroencephalogram signals-oriented emotion recognition model.

In this paper, a novel skipping spatial-spectral-temporal network (S3T-Net) is developed to handle intra-individual differences in electroencephalogram (EEG) signals for accurate, robust, and generalized emotion recognition. In particular, aiming at the 4D features extracted from the raw EEG signals, a multi-branch architecture is proposed to learn spatial-spectral cross-domain representations, which benefits enhancing the model generalization ability. Time dependency among different spatial-spectral features is further captured via a bi-directional long-short term memory module, which employs an attention mechanism to integrate context information. Moreover, a skip-change unit is designed to add another auxiliary pathway for updating model parameters, which alleviates the vanishing gradient problem in complex spatial-temporal network. Evaluation results show that the proposed S3T-Net outperforms other advanced models in terms of the emotion recognition accuracy, which yields an performance improvement of 0.23% , 0.13%, and 0.43% as compared to the sub-optimal model in three test scenes, respectively. In addition, the effectiveness and superiority of the key components of S3T-Net are demonstrated from various experiments. As a reliable and competent emotion recognition model, the proposed S3T-Net contributes to the development of intelligent sentiment analysis in human-computer interaction (HCI) realm.

Engineering extracellular vesicles mimetics for targeted chemotherapy of drug-resistant ovary cancer.

Aim: To develop nanocarriers for targeting the delivery of chemotherapeutics to overcome multidrug-resistant ovarian cancer. Materials & methods: Doxorubicin-loaded nanovesicles were obtained through serial extrusion, followed by loading of P-glycoprotein siRNA and folic acid. The targeting ability and anticancer efficacy of the nanovesicles were evaluated. Results: The doxorubicin-loaded nanovesicles showed a high production yield. The presence of P-glycoprotein siRNA and folic acid resulted in reversed drug resistance and tumor targeting. This nanoplatform tremendously inhibited the viability of multidrug-resistant ovarian cancer cells, which was able to target tumor tissue and suppress tumor growth without adverse effects. Conclusion: These bioengineered nanovesicles could serve as novel extracellular vesicles mimetics for chemotherapeutics delivery to overcome multidrug resistance.

When treating cancer affecting the ovaries, which is an organ in the female reproductive system, two challenges that arise are the inefficient delivery of chemotherapeutic drugs and the development of drug resistance inside the tumor. In this study, very small nano-scale particles called nanovesicles, which contain a chemotherapeutic drug called doxorubicin, were developed in an attempt to overcome both of these concerns. These nanovesicles were secreted by a healthy cell from an ovary, isolated and loaded with doxorubicin. These nanovesicles were also loaded with siRNA, which, in this case, prevents the synthesis of a protein in ovarian tumor cells called P-glycoprotein. This protein is responsible for pumping chemotherapy drugs back out of tumor cells, so preventing its synthesis was intended to counter chemotherapeutic resistance. The targeting ability of the nanovesicle was also enhanced with folic acid, as folic acid receptors are present on the surface of these tumor cells in higher numbers. These nanovesicles were readily and specifically taken up by ovarian tumor cells in mice with induced ovarian cancer. This reversed drug resistance and enhanced the toxic effects of doxorubicin on the tumor cells, which, in turn, increased tumor cell death and prevented tumor cell migration. No obvious adverse effect was found in mice treated with the nanovesicle system compared with the free chemotherapy drug with critical systematic toxicity. This research provides new avenues for ovarian cancer treatment, with combined therapies of siRNAs and chemotherapeutic drugs, targeted to tumor cells specifically, within nanovesicles.

Urea Cycle of Bacillus thuringiensis Affects Its Survival under UV Stress.

Bacillus thuringiensis (Bt) is widely used to produce biological pesticides. However, its persistence is limited because of ultraviolet (UV) rays. In our previous study, we found that exogenous intermediates of the urea cycle were beneficial to Bt for survival under UV stress. To further explore the effect of the urea cycle on the resistance mechanism of Bt, the rocF/argG gene, encoding arginase and argininosuccinate synthase, respectively, were knocked out and recovered in this study. After the target genes were removed, respectively, the urea cycle in the tested Bt was inhibited to varying degrees. The UV stress test showed that the urea cycle disorder could reduce the resistance of Bt under UV stress. Meanwhile, the antioxidant enzyme activities of Bt were also decreased to varying degrees due to the knockout of the target genes. All of these results revealed that the urea cycle can metabolically regulate the stress resistance of Bt.

An immunochromatographic test for serological diagnosis of scrub typhus.

A fluorescent immunochromatographic test (FM-ICT) was developed for rapid detection of anti-Orientia tsutsugamushi antibodies in serum samples. The FM-ICT was constructed based on the dual-antigen sandwich method. Truncated 56 kDa outer membrane protein of O. tsutsugamushi strain SJ, was expressed in E. coli and mixed with those of Ptan and Gillam strains. A thin line of the protein mixture was precisely sprayed across a nitrocellulose membrane making this the "Test" line. Polyclonal antibodies (pAbs) to O.tsutsugamushi were sprayed in another line across the membrane making this the "Control" line. Fluorescent microspheres conjugated 56 kDa proteins reacting with sample serum will be captured on the "Test" line if the sample contains antibodies to O.tsutsugamushi. Several experimental parameters were optimized. After optimizing the reaction procedure, the results are visible, within 6 min, with the naked eye under ultraviolet light. The limit of detection (LOD) was determined to be 7.63 ng/mL with prepared polyclonal antibodies. No cross-reaction was observed with sera samples from other febrile diseases. In clinical evaluations, the strips showed 94.92% sensitivity (106/112) and 93.75% specificity (56/60). The FM-ICT we developed will provide a new tool for on-site diagnosis of scrub typhus.

Epidemic Characteristics and Meteorological Risk Factors of Hemorrhagic Fever With Renal Syndrome in 151 Cities in China From 2015 to 2021: Retrospective Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China.

Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.

Potential novel Colpodella spp. (phylum Apicomplexa) and high prevalence of Colpodella spp. in goat-attached Haemaphysalis longicornis ticks in Shandong province, China.

Tick-borne Apicomplexan parasites pose a significant threat to both public health and animal husbandry. Identifying potential pathogenic parasites and gathering their epidemiological data are essential for prospectively preventing and controlling infections. In the present study, genomic DNA of ticks collected from two goat flocks (Goatflock1 and Goatflock2) and one dog group (Doggroup) were extracted and the 18S rRNA gene of Babesia/Theileria/Colpodella spp. was amplified by PCR and sequenced. Phylogenetic analysis was conducted based on the obtained sequences. The differences in pathogen positive rates between ticks of different groups were statistically analyzed using the Chi-square or continuity-adjusted Chi-square test. As a result, two pathogenic Theileria (T.) luwenshuni genotypes, one novel pathogenic Colpodella sp. HLJ genotype, and two potential novel Colpodella spp. (referred to as Colpodella sp. struthionis and Colpodella sp. yiyuansis in this study) were identified in the Haemaphysalis (H.) longicornis ticks. Ticks of Goatflock2 had a significantly higher positive rate of Colpodella spp. than those from Goatflock1 (χ2=92.10; P = 8.2 × 10-22) and Doggroup (χ2=42.34; P = 7.7 × 10-11), and a significantly higher positive rate of T. luwenshuni than Doggroup (χ2=5.38; P = 0.02). However, the positive rates of T. luwenshuni between Goatflock1 and Goatflock2 were not significantly different (χ2=2.02; P = 0.16), and so as the positive rates of both pathogens between Goatflock1 and Doggroup groups (P > 0.05). For either Colpodella spp. or T. luwenshuni, no significant difference was found in prevalence between male and female ticks. These findings underscore the potential importance of Colpodella spp. in domestic animal-attached ticks, as our study revealed two novel Colpodella spp. and identified Colpodella spp. in H. longicornis for the first time. The study also sheds light on goats' potential roles in the transmission of Colpodella spp. to ticks and provides crucial epidemiological data of pathogenic Theileria and Colpodella. These data may help physicians, veterinarians, and public health officers prepare suitable detection and treatment methods and develop prevention and control strategies.

Decoding the RNA viromes in shrew lungs along the eastern coast of China.

Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.