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1.
Microbiol Spectr ; : e0374823, 2024 May 23.
Article En | MEDLINE | ID: mdl-38780256

The lasso peptide microcin J25 (MccJ25) possesses strong antibacterial properties and is considered a potential effective component of bacterial disease treatment drugs and safe food preservatives. Although MccJ25 can be heterologously expressed in Bacillus subtilis as we have previously reported, its regulation and accumulation are yet to be understood. Here, we investigated the expression level and stability of MccJ25 in B. subtilis strains with disruption in peptidase genes pepA, pepF, and pepT. Oligoendopeptidase F (PepF) was found to be involved in reduction of the production of MccJ25 by degradation of its precursor peptide. In the pepF mutant, the MccJ25 reached a concentration of 1.68 µM after a cultivation time exceeding 60 hours, while the wild-type strain exhibited a concentration of only 0.14 µM. Moreover, the production of MccJ25 in B. subtilis downregulated the genes associated with sporulation, and this may contribute to its accumulation. Finally, this study provides a strategy to improve the stability and production of MccJ25 in B. subtilis. IMPORTANCE: MccJ25 displays significant antibacterial activity, a well-defined mode of action, exceptional safety, and remarkable stability. Hence, it presents itself as a compelling candidate for an optimal antibacterial or anti-endotoxin medication. The successful establishment of exogenous production of MccJ25 in Bacillus subtilis provides a strategy for reducing its production cost and diversifying its utilization. In this study, we have provided evidence indicating that both peptidase PepF and sporulation are significant factors that limit the expression of MccJ25 in B. subtilis. The ΔpepF and ΔsigF mutants of B. subtilis express MccJ25 with higher production yield and enhanced stability. To sum up, this study developed several better engineered strains of B. subtilis, which greatly reduced the consumption of MccJ25 during the nutrient depletion stage of the host strain, improved its production, and elucidated factors that may be involved in reducing MccJ25 accumulation in B. subtilis.

2.
J Biol Chem ; : 107395, 2024 May 18.
Article En | MEDLINE | ID: mdl-38768812

B2 haplotype MHC has been extensively reported to confer resistance to various avian diseases. But its peptide-binding motif is unknown and the presenting peptide is rarely identified. Here, we identified the peptide-binding motif of B2 haplotype MHC Ⅰ molecules (X-A/V/I/L/P/S/G-X-X-X-X-X-X-V/I/L) in vitro using Random Peptide Library-based MHC-Ⅰ LC-MS/MS analysis. To further clarify the structure basis of the peptide binding motif, we determined the crystal structure of the BF2*02:01-PB2552-560 complex at 1.9 Šresolution. We found that BF2*02:01 had a relatively wide antigen-binding groove, and the structural characterization of pockets of BF2*02:01 was consistent with the characterization of peptide-binding motif. The wider features of the peptide-binding motif and increased number of peptides bound by BF2*02:01 than BF2*04:01 might resolve the puzzles for the presence of potential H9N2 resistance in B2 chickens. Afterwards, we explored the H9N2 AIV-induced cellular immune response in B2 haplotype chickens in vivo. We found that ratio of CD8+ T cell and kinetic expression of cytotoxicity genes including Granzyme K, IFN-γ, NK lysin, and PARP in PBMCs were significantly increased in defending against H9N2 AIV infection. Especially, we selected 411 epitopes as candidate epitopes based on the peptide-binding motif and further identified four CD8+ T-cell epitopes on H9N2 AIV including NS198-106, PB2552-560, NP182-190, and NP455-463 via ELI-spot IFN-γ detections after stimulating memory lymphocytes with peptides. More importantly, these epitopes were found to be conserved in H7N9 AIV and H9N2 AIV. These findings provide direction for developing effective T cell epitope vaccines using well-conserved internal viral antigens in chickens.

3.
Emerg Microbes Infect ; 13(1): 2343907, 2024 Dec.
Article En | MEDLINE | ID: mdl-38738553

Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.


Cattle Diseases , Orthomyxoviridae Infections , Phylogeny , Thogotovirus , Animals , China/epidemiology , Cattle , Thogotovirus/genetics , Thogotovirus/classification , Thogotovirus/isolation & purification , Thogotovirus/immunology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae Infections/transmission , Seroepidemiologic Studies , Swine , Cattle Diseases/epidemiology , Cattle Diseases/virology , Cattle Diseases/transmission , Goats , Swine Diseases/virology , Swine Diseases/epidemiology , Antibodies, Viral/blood , Humans , Deltainfluenzavirus
4.
Mult Scler Relat Disord ; 87: 105683, 2024 May 11.
Article En | MEDLINE | ID: mdl-38761695

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear. METHODS: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined. RESULTS: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities. CONCLUSIONS: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan.

5.
Front Endocrinol (Lausanne) ; 15: 1359210, 2024.
Article En | MEDLINE | ID: mdl-38596217

Introduction: Infertility affects 8-12% of couples worldwide, with 15-30% classified as unexplained infertility (UI). Thyroid autoimmunity (TAI), the most common autoimmune disorder in women of reproductive age, may impact fertility and pregnancy outcomes. However, the underlying mechanism is unclear. This study focuses on intrauterine insemination (IUI) and its potential association with TAI in UI patients. It is the first meta-analysis following a comprehensive literature review to improve result accuracy and reliability. Methods: Retrospective cohort study analyzing 225 women with unexplained infertility, encompassing 542 cycles of IUI treatment. Participants were categorized into TAI+ group (N=47, N= 120 cycles) and TAI- group (N=178, N= 422 cycles). Additionally, a systematic review and meta-analyses following PRISMA guidelines were conducted, incorporating this study and two others up to June 2023, totaling 3428 IUI cycles. Results: Analysis revealed no significant difference in independent variables affecting reproductive outcomes. However, comparison based on TAI status showed significantly lower clinical pregnancy rates (OR: 0.43, P= 0.028, 95%CI: 0.20-0.93) and live birth rate (OR: 0.20, P= 0.014, 95%CI: 0.05 ~ 0.71) were significantly lower than TAI- group. There was no significant difference in pregnancy rate between the two groups (OR: 0.61, P= 0.135, 95%CI: 0.32-1.17). However, the meta-analysis combining these findings across studies did not show statistically significant differences in clinical pregnancy rates (OR:0.77, P=0.18, 95%CI: 0.53-1.13) or live birth rates (OR: 0.68, P=0.64, 95%CI: 0.13-3.47) between the TAI+ and TAI- groups. Discussion: Our retrospective cohort study found an association between TAI and reduced reproductive outcomes in women undergoing IUI for unexplained infertility. However, the meta-analysis incorporating other studies did not yield statistically significant associations. Caution is required in interpreting the relationship between thyroid autoimmunity and reproductive outcomes. Future studies should consider a broader population and a more rigorous study design to validate these findings. Clinicians dealing with women with unexplained infertility and TAI should be aware of the complexity of this field and the limitations of available evidence.


Infertility , Pregnancy Outcome , Pregnancy , Humans , Female , Pregnancy Outcome/epidemiology , Retrospective Studies , Thyroid Gland , Autoimmunity , Cohort Studies , Reproducibility of Results , Infertility/therapy , Insemination
6.
Virol Sin ; 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38679333

The recent concurrent emergence of H5N1, H5N6, and H5N8 avian influenza viruses (AIVs) has caused significant avian mortality globally. Since 2020, frequent human-animal interactions have been documented. To gain insight into the novel H5 subtype AIVs (i.e., H5N1, H5N6 and H5N8), we conducted a comparative analysis on phylogenetic evolutionary and biological properties of H5 subtype AIVs strains isolated from China between January 2021 and September 2022. Phylogenetic analysis revealed that the 41 H5Nx strains belonged to clade 2.3.4.4b, with 13 related to H5N1, 19 to H5N6, and 9 to H5N8. The genetic relatedness analysis based on global 2.3.4.4b viruses showed that all the viruses described in this study was likely originated from H5N8, exhibiting a heterogeneous evolutionary history between H5N1 and H5N6 during 2015-2022 worldwide. In this context, we further estimated that H5N1, characterized by higher evolutionary rates in 2021-2022 and more sites under positive selection pressure in 2015-2022. The antigenic profiles of novel H5N1 and H5N6 exhibited notable variations. Further hemagglutination inhibition assay suggest that some A(H5N1) viruses may be antigenically distinct from the circulating H5N6 and H5N8 strains. Mammalian challenge assays demonstrated that the H5N8 virus (21GD001_H5N8) displayed the highest pathogenicity in mice, followed by the H5N1 virus (B1557_H5N1) and then the H5N6 virus (220086_H5N6), suggesting a heterogeneous virulence profile of H5 AIVs in the mammalian hosts. Based on the above results, we consider that A(H5N1) viruses have a higher risk of emergence in the future. Collectively, these findings unveil a new landscape of different evolutionary history and biological characteristics of novel H5 AIVs in clade 2.3.4.4b, contributing to a better understanding for designing more effective strategies for the prevention and control of novel H5 AIVs.

8.
Vet Microbiol ; 293: 110099, 2024 Jun.
Article En | MEDLINE | ID: mdl-38677125

Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.


CRISPR-Cas Systems , Encephalitis Virus, Japanese , RNA, Guide, CRISPR-Cas Systems , Virus Replication , Virus Replication/genetics , Encephalitis Virus, Japanese/genetics , Encephalitis Virus, Japanese/physiology , Humans , RNA, Guide, CRISPR-Cas Systems/genetics , Gene Library , Animals , Host-Pathogen Interactions/genetics , Encephalitis, Japanese/virology , Cell Line , HEK293 Cells , Clustered Regularly Interspaced Short Palindromic Repeats
9.
Lab Chip ; 24(10): 2712-2720, 2024 May 14.
Article En | MEDLINE | ID: mdl-38655620

A colorimetric biosensor was elaboratively designed for fast, sensitive and multiplex bacterial detection on a single microfluidic chip using immune magnetic nanobeads for specific bacterial separation, immune gold@platinum palladium nanoparticles for specific bacterial labeling, a finger-actuated mixer for efficient immunoreaction and two coaxial rotatable magnetic fields for magnetic nanobead capture (outer one) and magnet-actuated valve control (inner one). First, preloaded bacteria, nanobeads and nanozymes were mixed through a finger actuator to form nanobead-bacteria-nanozyme conjugates, which were captured by the outer magnetic field. After the inner magnetic field was rotated to successively wash the conjugates and push the H2O2-TMB substrate for resuspending these conjugates, colorless TMB was catalyzed into blue TMBox products, followed by color analysis using ImageJ software for bacterial determination. This simple biosensor enabled multiplex Salmonella detection as low as 9 CFU per sample in 45 min.


Biosensing Techniques , Lab-On-A-Chip Devices , Salmonella , Biosensing Techniques/instrumentation , Salmonella/isolation & purification , Colorimetry/instrumentation , Gold/chemistry , Microfluidic Analytical Techniques/instrumentation , Palladium/chemistry , Metal Nanoparticles/chemistry , Platinum/chemistry
10.
Diseases ; 12(3)2024 Mar 20.
Article En | MEDLINE | ID: mdl-38534984

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

11.
Vet Microbiol ; 292: 110052, 2024 May.
Article En | MEDLINE | ID: mdl-38492531

H5N8 highly pathogenic avian influenza virus (HPAIV) has caused huge losses to the global poultry industry and critically threatens public health. Chickens are the important host for the transmission. However, the distribution of H5N8 avian influenza virus (AIV) in chicken and the infected cell types are limitedly studied. Therefore, in this study, we detected viral replication and infection by generating recombinant H5N8 AIV expressing an easily tracked mApple fluorescent reporter. The results showed that recombinant viruses passaged four times in chicken embryos successfully expressed mApple proteins detected by fluorescence microscopy and WB, which verified that the constructed recombinant viruses were stable. Compared to parental virus, although recombinant virus attenuated for replication in MDCK cells, it can still replicate effectively, and form visible plaques. Importantly, the experiments on infection of chicken PBMCs in vitro showed a strong correlation between mApple positivity rate and NP positivity rate (r = 0.7594, P =0.0176), demonstrating that mApple reporter could be used as an indicator to accurately reflect AIV infection. Then we infected monocytes/macrophages in PBMCs in vitro and detected the mApple positive percentage was 55.1%-80.4%, which confirmed the chicken primary monocytic/macrophages are important target cells for avian influenza virus infection. In chicken, compared with parental virus, the recombinant virus-infected chickens had lower viral titers in oropharyngeal cloacal and organs, but it can cause significant pathogenicity in chicken and the mortality rate was approximately 66%. In addition, the results of bioluminescent imaging showed that the fluorescence in the lungs was strongest at 5 days post-infection (DPI). Finally, we discovered the mApple positive expression in chicken lung immune cells (CD45+ cells), especially some T cells (CD4 and CD8 T cells) also carrying mApple, which indicates that the H5N8 AIV showed a tropism for immune cells including chicken T cells causing potentially aggressive against cellular immunity. We have provided a simple visualization for further exploration of H5N8 AIV infected chicken immune cells, which contributes to further understanding pathogenic mechanism of H5N8 AIV infection in chicken.


Communicable Diseases , Influenza A Virus, H5N8 Subtype , Influenza A virus , Influenza in Birds , Influenza, Human , Orthomyxoviridae Infections , Chick Embryo , Animals , Humans , Chickens/genetics , Genes, Reporter , Orthomyxoviridae Infections/veterinary , Influenza A virus/genetics , Communicable Diseases/veterinary
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 250-256, 2024 Feb.
Article Zh | MEDLINE | ID: mdl-38387930

To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival. METHODS: The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed. RESULTS: The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old (P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine (P =0.002), albumin≤30 g/L on d30 after transplantation (P =0.007), CMV-DNA positive (P =0.028), fungal infection before transplantation (P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD (P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation (P =0.008) and albumin≤30 g/L on d30 after transplantation (P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC (P =0.041). CONCLUSION: For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.


Cystitis, Hemorrhagic , Cystitis , Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Middle Aged , Retrospective Studies , Cystitis/etiology , Cystitis/drug therapy , Cystitis/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Risk Factors , Cytomegalovirus Infections/complications , Albumins/therapeutic use , DNA/therapeutic use , Graft vs Host Disease/complications
13.
Chronobiol Int ; 41(3): 447-455, 2024 03.
Article En | MEDLINE | ID: mdl-38320972

Women are disproportionally affected by psychological distress and lack of social support and are more vulnerable to the negative impact of chronotype on mental health. This study evaluates cross-sectional associations between chronotype and mental health, while assessing the mediating role of social support among women from diverse racial/ethnic backgrounds. Women from the American Heart Association Go Red for Women Research Network were included (N = 506, mean age = 37 ± 15.7, 61% racial/ethnic minority). Chronotype, depression, perceived stress, health-related quality of life, and social support were assessed at baseline using validated self-reported questionnaires. Linear regression and causal mediation analyses were performed. Depression and negative emotionality were higher among women with evening vs. morning/intermediate chronotypes (all p < 0.05). Multivariable analyses adjusted for sociodemographic and clinical confounders showed associations between evening chronotype and higher depression (p = 0.004) and negative emotionality (p = 0.010). However, these associations were no longer significant after adjusting for social support (depression: p = 0.12; negative emotionality: p = 0.18). Social support significantly mediated 44.6% and 45.8% of the total effect of chronotype on depression and negative emotionality, respectively. Social support represents a potential mechanism underlying the associations between eveningness and poor mental health. Chronotype and social support should be considered in interventions for the promotion of mental health in women.


Chronotype , Sleep , Humans , Female , Young Adult , Adult , Middle Aged , Circadian Rhythm , Mental Health , Cross-Sectional Studies , Ethnicity , American Heart Association , Quality of Life , Minority Groups , Surveys and Questionnaires , Social Support
14.
Virol Sin ; 39(2): 205-217, 2024 Apr.
Article En | MEDLINE | ID: mdl-38346538

Swine are regarded as "intermediate hosts" or "mixing vessels" of influenza viruses, capable of generating strains with pandemic potential. From 2020 to 2021, we conducted surveillance on swine H1N2 influenza (swH1N2) viruses in swine farms located in Guangdong, Yunnan, and Guizhou provinces in southern China, as well as Henan and Shandong provinces in northern China. We systematically analyzed the evolution and pathogenicity of swH1N2 isolates, and characterized their replication and transmission abilities. The isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1 (PB2, PB1, PA and NP genes), triple-reassortant swine (NS gene), Eurasian Avian-like (HA and M genes), and recent human H3N2 (NA gene) lineages. The NA, PB2, and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017 (H3N2). The HA gene of swH1N2 exhibits a high evolutionary rate. The five swH1N2 isolates replicate efficiently in human, canine, and swine cells, as well as in the turbinate, trachea, and lungs of mice. A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among them. Collectively, these current swH1N2 viruses possess zoonotic potential, highlighting the need for strengthened surveillance of swH1N2 viruses.


Evolution, Molecular , Influenza A Virus, H1N2 Subtype , Orthomyxoviridae Infections , Reassortant Viruses , Swine Diseases , Animals , Swine , Reassortant Viruses/genetics , Reassortant Viruses/pathogenicity , Reassortant Viruses/isolation & purification , China/epidemiology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/transmission , Orthomyxoviridae Infections/veterinary , Swine Diseases/virology , Swine Diseases/transmission , Influenza A Virus, H1N2 Subtype/genetics , Influenza A Virus, H1N2 Subtype/pathogenicity , Influenza A Virus, H1N2 Subtype/isolation & purification , Humans , Mice , Dogs , Phylogeny , Virus Replication , Public Health , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/virology , Influenza, Human/transmission , Mice, Inbred BALB C , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/pathogenicity , Influenza A Virus, H3N2 Subtype/isolation & purification , Virulence , Female
15.
J Med Virol ; 96(3): e29491, 2024 Mar.
Article En | MEDLINE | ID: mdl-38402626

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.


Antiviral Restriction Factors , Bunyaviridae Infections , Severe Fever with Thrombocytopenia Syndrome , Humans , Bunyaviridae Infections/immunology , Membrane Proteins/immunology , Phlebovirus , RNA-Binding Proteins/immunology , Severe Fever with Thrombocytopenia Syndrome/immunology , Viral Proteins/metabolism , Virus Internalization , Antiviral Restriction Factors/immunology
16.
Mol Biol Evol ; 41(2)2024 Feb 01.
Article En | MEDLINE | ID: mdl-38243850

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.


Lizards , Melanins , Animals , Melanins/genetics , Lizards/genetics , Zebrafish , Body Temperature Regulation/genetics , Skin Pigmentation/genetics , Color
17.
J Affect Disord ; 351: 250-258, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38280566

BACKGROUND: The relationship between chronotype and anxiety, depression, and insomnia was inconsistent. We aimed to assess the association between chronotype and mental health and the potential moderating effect of age and socioeconomic status (SES). METHODS: A multi-stage sampling cross-sectional study with 12,544 adults was conducted. Chronotype, anxiety, depression, and insomnia were investigated by 5-item Morning and Evening, 7-item Generalized Anxiety Disorder, 9-item Patient Health, and the 7-item Insomnia Severity Index Questionnaires. Logistic regression was conducted. RESULTS: The predominant chronotype was morning chronotype (69.2 %), followed by 27.6 % intermediate and 3.2 % evening chronotype. The prevalence of anxiety, depression, and insomnia was 0.7 %, 1.9 %, and 9.6 %, respectively. Compared with intermediate chronotype, morning chronotype participants had a lower risk of anxiety (OR = 0.28,95%CI:0.18-0.44), depression (OR = 0.54,95%CI:0.41-0.72) and insomnia (OR = 0.67,95%CI:0.58-0.77), while evening chronotype participants had a higher risk of depression (OR = 1.98,95%CI:1.06-3.71) but not anxiety or insomnia. Interactions between chronotype with age and SES on insomnia (Pinteraction < 0.05) were found. A more profound association between morning chronotype and insomnia was observed in <65 years participants (OR = 0.59,95%CI:0.50-0.71) and those with monthly household income ≥10,000yuan (OR = 0.21,95%CI:0.12-0.35), compared with their counterparts. LIMITATIONS: The cross-sectional design limited causal conclusions. Only adults were included; the findings could not be generalized to children. CONCLUSIONS: The morning chronotype might be protective for anxiety, depression, and insomnia, while the evening chronotype might be a risk factor for depression. Future studies are needed to assess the efficacy of chronotype-focused intervention for mental health. Insomnia prevention efforts should pay more attention to the elderly and those with lower incomes.


Sleep Initiation and Maintenance Disorders , Adult , Child , Humans , Aged , Sleep Initiation and Maintenance Disorders/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Depression/psychology , Chronotype , Anxiety/epidemiology , Anxiety Disorders , China/epidemiology , Surveys and Questionnaires , Sleep , Circadian Rhythm
18.
PLoS One ; 19(1): e0296190, 2024.
Article En | MEDLINE | ID: mdl-38215179

Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20-54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54-0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention.


Endometriosis , Vitamin D Deficiency , Humans , Female , United States/epidemiology , Vitamin D , Calcifediol , Endometriosis/complications , Nutrition Surveys , Cross-Sectional Studies , Vitamins
20.
Sleep Health ; 10(1): 65-68, 2024 Feb.
Article En | MEDLINE | ID: mdl-38007300

OBJECTIVES: To evaluate associations between psychosocial factors and sleep characteristics commonly linked to cardiovascular disease risk among racially/ethnically diverse women. METHODS: Women from the AHA Go Red for Women cohort (N = 506, 61% racial/ethnic minority, 37 ± 16years) were assessed using self-reported questionnaires. Logistic regression models were adjusted for age, race, ethnicity, education, and insurance. RESULTS: Women with depression had ∼3-fold higher odds of short sleep (95%CI=1.69-4.61), 2-fold higher odds of poor sleep quality and obstructive sleep apnea risk (95%CI=1.42-3.70 and 1.34-4.24), 4-fold higher odds of insomnia (95%CI=2.42-6.59), and greater likelihood of having an evening chronotype (OR:2.62, 95%CI=1.41-4.89). Low social support was associated with insomnia (OR:1.79, 95%CI=1.18-2.71) and evening chronotype (OR:2.38, 95%CI=1.35-4.19). Caregiving was associated with short sleep (OR:1.73, 95%CI=1.08-2.77) and obstructive sleep apnea risk (OR:2.46, 95%CI=1.43-4.22). CONCLUSIONS: Depression, caregiver strain, and low social support are significantly associated with poor sleep and evening chronotype, highlighting a potential mechanism linking these psychosocial factors to cardiovascular disease risk.


Cardiovascular Diseases , Sleep Apnea, Obstructive , Sleep Initiation and Maintenance Disorders , United States/epidemiology , Humans , Female , Ethnicity , Sleep Initiation and Maintenance Disorders/epidemiology , Cardiovascular Diseases/epidemiology , Chronotype , American Heart Association , Minority Groups , Sleep , Sleep Apnea, Obstructive/epidemiology
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