Shigellosis is a serious public health issue in many developing countries. The current gold standard for Shigella detection remains bacterial culture, yet it is constrained by cumbersome steps and long incubation time. CRISPR detection system has excellent performance in the diagnosis of infectious diseases. However, the conventional CRISPR-based detection platform's high sensitivity comes at the cost of dependence on nucleic acid extraction and amplification, and it faces the limitation of being unable to distinguish live or dead bacteria in the sample. Herein, we combined the robust binding specificity of aptamers with the powerful signal amplification of CRISPR/Cas12a trans-cleavage to establish a novel platform for the highly sensitive and specific detection of live S. flexneri, without requiring nucleic acid extraction or amplification. The results demonstrated that the optimal conditions for the CRISPR/Cas12a detection system were as follows: a Cas12a concentration of 50 nM, NEBuffer r2.1 as the reaction buffer, and a Cas12a:crRNA concentration ratio of 1:1. Additionally, the optimal conditions for the displacement reaction between bacteria and aptamer blocker hybridization double-stranded were determined as follows: Tris-HCl buffer (pH 8.0) with an incubation time of 1 h at room temperature. Under the aforementioned conditions, our aptamer-based CRISPR/Cas12a system demonstrates enhanced sensitivity and specificity in samples compared to qPCR method, while additionally enabling determination of bacterial viability status. It can detect live S. flexneri as low as 225 CFU/mL within 1.5 h. In conclusion, the viable S. flexneri detection platform developed in our study provides a rapid detection technical approach for surveillance and control of bacillary dysentery and other bacterial infections.

Fine particulate matter (PM2.5) and ozone (O3) are key air pollutants linked to a higher risk of cardiovascular diseases. However, the effects of combined PM2.5 and O3 exposure on cardiovascular health remain unclear. In this study, C57BL/6 J mice were exposed to PM2.5 suspension (6 mg/kg body weight) and/or O3 (1.00 ppm) for 8 weeks, resulting in abnormal myocardial enzyme profiles. Sirius Red and Masson's trichrome staining confirmed myocardial fibrosis and collagen deposition in the mice. Further experiments demonstrated that PM2.5 and O3 subchronic co-exposure increased cardiac inflammatory factors, phosphorylation of p38, ERK1/2, and JNK, as well as cardiomyocyte apoptosis. Subsequently, an atherosclerosis model was established using ApoE-/- mice, which were exposed to PM2.5 suspension (6 mg/kg b.w.) and O3 (1.00 ppm) for 8 consecutive weeks. During this period, the mice were treated with quercetin, a flavonoid antioxidant derived from plants. Our findings demonstrated that PM2.5 and O3 co-exposure promoted the progression of atherosclerosis. In contrast, administration of quercetin in PM2.5- and O3-exposed ApoE-/- mice significantly reduced cardiac enzyme markers, myocardial fibrosis, collagen deposition, cardiomyocyte apoptosis, and activation of the MAPK signaling pathway. Omics results revealed that quercetin primarily exerted its protective effects in atherosclerotic mice by modulating phosphatidylcholine, phosphatidylethanolamine, as well as the inflammatory signaling pathways. In summary, subchronic exposure to PM2.5 and O3 contributes to cardiac injury and accelerates the progression of atherosclerosis in mice and this detrimental effect can be mitigated by the administration of quercetin. Our study presents novel strategies aimed at mitigating the cardiovascular health impacts of air pollution.

Pet dogs provide well-documented physical and mental health benefits to humans through close interactions. However, the potential role of pet dogs as reservoirs of antibiotic resistance genes (ARGs) and the impact on shaping the gut microbiomes of their owners remains poorly characterized. The growing dual challenges of global antimicrobial resistance and widespread pet ownership underscore the importance of understanding human-animal resistome interactions crucial for One Health solutions. Consequently, this study conducted a metagenomic analysis of pet dogs, dog owners, and non-dog owners to investigate the effects of dogs on the microbiota composition, ARGs profiles, and mobile genetic elements (MGEs) of the human gut. The results indicated that pet dogs exhibited significantly higher gut abundance of both ARGs and ESKAPE pathogens (Enterococcus faecium and Acinetobacter baumannii) compared to humans. Moreover, the abundance of aminoglycoside resistance genes aac(6’)-Im and aac(6’)-Ie-aph(2’’)-Ia, tetracycline resistance genes tetO and tet40 were was significantly higher in dog owners than in non-dog owners. Enterobacteriaceae were identified as shared core ARG hosts in both dog and human guts. Collectively, our results indicate that cohabitation with pet dogs is associated with a shared gut resistome, reflecting correlated patterns of ARGs and resistant microbes. These findings emphasize the necessity of monitoring antibiotic resistance in companion animals, while maintaining the benefits of human-dog relationships.

Severe hand, foot, and mouth disease (HFMD) poses a risk of serious multi-organ complications in children. While renal dysfunction has been observed in some cases, detailed investigations on kidney injury and molecular mechanisms remain limited. Coxsackievirus A6 (CVA6) has emerged as a major pathogen responsible for HFMD. To reveal the underlying pathways of CVA6-associated renal injury, we enrolled 90 children diagnosed with CVA6 infection and 45 healthy children. The levels of uric acid (UA), creatinine (CREA) and UREA in the serum were measured. We found that serum levels of UA, CREA, and UREA were significantly elevated in CVA6-infected children compared to healthy children. Subsequently, a previously established mouse model of CVA6 infection was used to assess urinary retention, kidney inflammation, and histopathological changes. Consistent with the clinical findings, infected mice exhibited increased CREA, UREA, and UA levels, urinary retention, and renal inflammation. Electron microscopy revealed glomerular atrophy and basement membrane thickening in CVA6-infected mice, accompanied by reduced expression of VEGF, Occludin, and VE-cadherin. Furthermore, complement deposition was also observed in glomeruli and renal tubules. Finally, CVA6 infection significantly increased phospho-p38 levels in mouse kidneys. To investigate the role of the p38-MAPK signaling pathway in CVA6-induced renal injury, we treated the CVA6-infected mice with PD169316, a specific inhibitor of p38/MAPK signaling pathway, and observed that the kidney injury in the treated group was alleviated. Overall, our findings highlight a critical role for the p38 phosphorylation in CVA6-induced renal injury, and provide new insights into the management of severe HFMD-associated kidney complications.

OBJECTIVES:The excessive use of antibiotics has driven β-lactam resistance in Escherichia coli, with the two-component system (TCS) playing a key role in regulating virulence and resistance genes. The EnvZ/OmpR TCS, involving the histidine kinase EnvZ and regulator OmpR, influences porin genes ompC and ompF. The authors' previous work suggested that EnvZ may regulate β-lactam antibiotic resistance, but the mechanism remains unclear. This study aimed to explore how EnvZ regulates β-lactam antibiotic resistance and virulence mechanisms in E. coli. METHODS:An envZ deletion mutant (ΔenvZ) was constructed from an imipenem-resistant E. coli strain (Sx181-128). Phenotypic assays evaluated antibiotic susceptibility, environmental tolerance, adhesion and motility. RNA sequencing (RNA-seq) compared transcriptional profiles between Sx181-128 and ΔenvZ. RESULTS:The envZ deletion mutant exhibited a 2-fold increase in susceptibility to six β-lactam antibiotics (cefoxitin, meropenem, imipenem, cefepime, amoxicillin and aztreonam) compared with the resistant strain Sx181-128, along with compromised tolerance especially under hypertonic condition. RNA-seq analysis revealed 338 differentially expressed genes (116 up-regulated, 222 down-regulated), primarily associated with porins, transporters, amino sugar and nucleotide sugar metabolism and flagellar assembly. Mechanistically, envZ deletion increased membrane permeability by dysregulating ompC and ompF expression, enhancing β-lactam antibiotic uptake. Additionally, ΔenvZ displayed increased adhesion to HeLa cells, bacterial motility and biofilm-forming capacity, suggesting a dual role for EnvZ in modulating both antibiotic resistance and virulence. CONCLUSIONS:EnvZ regulates β-lactam resistance by modulating porin expression and membrane permeability, while also influencing virulence traits like adhesion and motility. These findings highlight TCS-mediated resistance mechanisms and offer potential targets for novel antimicrobials or vaccines against E. coli.

OBJECTIVE:To perform genomic analysis on plasmid-mediated quinolone-resistance (PMQR) in Shigella. METHODS:We assembled a global collection of 8325 PMQR-positive Shigella isolates (1998-2025) and subjected them to comprehensive genomic analysis. RESULTS:Geographically, the isolates spanned 37 countries, with the majority sourced from the United States (47.02%) and the United Kingdom (32.28%). Eight distinct PMQR genes-aac(6')-Ib-cr, oqxAB, qepA, qnrA, qnrB, qnrD, qnrS, and qnrVC-were identified in the Shigella analysed. qnrS was the most predominant PMQR gene (62.05%), followed by qnrB (38.76%). One hundred and eight sequence types were identified among the PMQR-positive Shigella isolates, with ST152 predominating (59.51%). Notably, multiple antibiotic resistance genes (ARGs) were universal in PMQR-positive Shigella, with aph(6)-Id (5825 out of 8325), tet(B) (2398 out of 8325), and blaTEM-1 (2232 out of 8325) the most prevalent. PMQR-positive Shigella from developed countries displayed a significant decreasing trend in the abundance of ARGs and collection year and displayed the opposite trend in the abundance of virulence factors between developed and developing countries (P < .001). Correlation analysis demonstrated that mobile genetic elements constitute principal vectors for the spread of PMQR genes. The abundance of plasmid replicons positively correlated with the abundance of ARGs (P < .001), demonstrating the spread of plasmid-driven ARGs in PMQR-positive Shigella. In addition, high genetic similarity among geographically dispersed PMQR-positive Shigella isolates implies intercountry dissemination. CONCLUSIONS:These findings elucidate PMQR-positive Shigella genomic characteristics and transmission dynamics, necessitating global surveillance reinforcement against this antimicrobial resistance threat.

BACKGROUND:Enterovirus 71 (EV71) is the main causative agent of severe hand, foot, and mouth disease (HFMD) in children. Dysregulation of microRNAs (miRNAs) has been associated with HFMD progression, but the underlying regulatory mechanisms remain incompletely characterized. METHODS:Rhabdomyosarcoma cells (RD) and human glioblastoma astrocytoma cells (U87-MG) were infected with EV71 at varying multiplicities of infection. In vivo, 5-day-old C57BL/6 mice, with C57 mice treated with STM2457 were intraperitoneally injected with a lethal dose of EV71. Molecular analyses included Western blotting, co-immunoprecipitation, and RNA immunoprecipitation. Clinical blood samples from HFMD patients were used for validation. RESULTS:In this study, we found that EV71 infection increased METTL3 expression and m6A methylation levels in the flanking regions of pri-miR-146a, promoting miR-146a maturation, which in turn suppresses TRAF6 and IRAK1 expression and inhibits IFN-I production, affecting the progression of EV71-induced HFMD. Co-immunoprecipitation and immunofluorescence assays demonstrated interaction between METTL3 and DGCR8, as well as nuclear co-localization of METTL3 with DGCR8. Furthermore, this regulatory mechanism was also confirmed through the intraperitoneal injection of STM2457 (a METTL3 inhibitor) to intervene in EV71 infection. Finally, detection conducted on clinical blood samples of HFMD demonstrated the specificity of IRAK1 in detecting severe HFMD. CONCLUSION:These findings will not only aid in understanding the mechanisms by which EV71 infection impacts the host immune system but also provide a scientific basis for identifying early diagnostic biomarkers and developing new therapeutic strategies.

OBJECTIVES:Shigella is the pathogen of bacterial dysentery. With the widespread use of antibiotics, the burden of antibiotic resistance in Shigella has become increasingly pronounced. METHODS:In this study, the cfa gene of ampicillin-resistant strain (Res) was knocked out and back-complemented strains were constructed. The susceptibility of Res and Δcfa strains to ampicillin was compared, and the molecular regulatory mechanisms of cfa gene on antibiotic resistance in Shigella were explored by screening the differentially expressed mRNAs, proteins, and metabolites of the two groups. In addition, we examined differences between the two groups in growth, biofilm formation, environmental stress (including temperature, pH, salt, oxidative stress, and carbon and nitrogen sources), and cytotoxicity. RESULTS:The sensitivity of Δcfa to ampicillin was increased 32-fold compared to the Res strain (64 µg/mL vs. 2 µg/mL). Compared to the Res strain, the Δcfa mutant exhibited a 16-fold increase in susceptibility to amoxicillin, penicillin and aztreonam, a 4-fold increase in susceptibility to cefotaxime, and a 2-fold increase in susceptibility to cefazolin, ceftazidime, ceftriaxone and tetracycline. The MICs of Δcfa-pcfa complemented strain was elevated to 4, 32, and 16 µg/mL for ampicillin, penicillin, and amoxicillin, respectively. The differential metabolites of the two groups were significantly enriched in the cysteine and methionine metabolic pathways (P < 0.05). Under no antibiotic stress, Δcfa grew faster than the Res strain and had greater biofilm formation capacity and environmental stress adaptation, but there was no significant difference in the virulence effect of the culture supernatant on Vero cell between the two groups. CONCLUSIONS:The cfa gene orchestrates sulfur metabolism and coordinates the cysteine-methionine biosynthetic pathway in bacteria. The cfa gene not only mediates penicillin antibiotics resistance mechanisms in Shigella sonnei but also modulates critical physiological processes.

Background: The post–coronavirus disease 2019 (COVID-19) pandemic resurgence of Mycoplasma pneumoniae (MP) infections, particularly in China, underscores the need to understand the drivers of disease severity.Purpose: This study aimed to evaluate the association between predominantly circulating MP strains and disease severity in Henan Province, central China.Methods: We integrated the clinical data of 3,060 pediatric patients and analyzed the epidemiological characteristics of MP pneumonia (MPP) in the Henan region in 2020–2024. Bronchoalveolar lavage fluid collected from 137 patients was analyzed using multilocus sequence typing and multilocus variable number tandem-repeat analysis to investigate the correlation between genotype and clinical outcome.Results: A significant post-COVID MPP outbreak was predicted in 2023. Genotyping revealed the cocirculation of 2 major genotypes: the prevalent ST3 (57.7%, severe ratio [31.6%]) and the less common but highly virulent ST14 (26.3%, severe ratio [72.2%]). Phylogenetic clustering confirmed ST14/3-5-6-2 as part of a broader hypervirulent lineage, common cluster label 14 (CCL14), which was significantly associated with disease severity (χ2=19.39; P<0.001). Patients infected with CCL14 strains exhibited a distinct hyperinflammatory profile marked by elevated D-dimer levels, complement C4 levels, and platelet count. The mutation ratio of macrolide resistance sites in the MP strains from Henan Province was approximately 75%.Conclusion: Our findings identified the CCL14 lineage as a key driver of disease severity in macrolide-resistant pediatric MPP in Henan Province, China. This under scores the importance of integrating molecular surveillance with clinical monitoring to mitigate disease burden.

Enterovirus A71 (EV-A71), a member of the genus Enterovirus within the family Picornaviridae , induces neuroinflammation; however, the underlying mechanisms remain incompletely understood. This study demonstrates that the C5a-C5aR1 axis plays a pivotal role in EV-A71-induced blood-brain barrier (BBB) disruption and neuroinflammation, primarily by regulating neutrophil migration. Using human brain specimens and a mouse model, we observed pronounced inflammatory cell infiltration in the brainstem and BBB disruption following EV-A71 infection. Immunofluorescence analysis revealed robust activation of the C5a-C5aR1 axis in fatal EV-A71 cases. Notably, C5aR1 knockout (KO) mice displayed reduced Evans blue extravasation and preserved tight junction protein expression after infection. Immunopathological examination of fatal human cases further confirmed perivascular neutrophil (CD177⁺) infiltration in the brainstem. Importantly, C5aR1 deficiency significantly attenuated neutrophil accumulation and neutrophil extracellular trap (NET) release. Given that peptidylarginine deiminase 4 (PAD4) is a key enzyme driving NET formation, we generated neutrophil-specific PAD4 knockout mice (PAD4 Ne-KO) by crossing S100A8-Cre and PAD4 fl/fl lines. As anticipated, neutrophil-specific PAD4 deletion or pharmacological NET blockade substantially ameliorated BBB injury and neuroinflammation following EV-A71 infection. Overall, our findings underscore a critical role for the C5a-C5aR1-neutrophil/NETs pathway in EV-A71 encephalitis pathogenesis and support its targeting as a therapeutic strategy for critically ill patients.

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick - borne zoonotic infectious disease. Severe SFTS cases exhibit an extremely high fatality rate, but there remain no effective clinical treatments.MethodsPropensity Score Matching (PSM) and logistic regression analysis were used to assess the efficacy, safety, and baseline factors influencing patient prognosis of tocilizumab in the treatment of SFTS.ResultsA total of 833 SFTS cases were included, of whom 171 received tocilizumab. After PSM, a higher recovery rate was observed in the tocilizumab group than in the control group (76.61% vs 67.70%, P = 0.039). However, the between-group difference in in-hospital mortality did not reach statistical significance after matching (16.96% vs 15.22%, P = 0.322). Regarding selected adverse events (AEs) such as co-infection, the between-group differences did not reach statistical significance; these represent observed differences in retrospectively recorded data and should not be interpreted as evidence of safety. Multivariable logistic regression showed that age ≥ 65 years, vasopressor therapy, platelet transfusion, and Ct value were associated with prognosis among tocilizumab-treated patients, with vasopressor use and platelet transfusion likely reflecting disease severity rather than independent causal determinants.ConclusionIn this retrospective cohort, after PSM, tocilizumab use was associated with a higher recovery rate in SFTS patients, although the between-group difference in in-hospital mortality did not reach statistical significance. Observed differences in selected AEs were based on retrospectively recorded data and should not be interpreted as evidence of safety. Given the exploratory nature, prospective studies are warranted.

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus harbored by fruit bats (Pteropodidae). The virus spreads through zoonotic spillover via intermediate animal hosts or contaminated environments, and through human-to-human transmission. Since its emergence in 1998, NiV has triggered recurrent outbreaks across South and Southeast Asia, with case-fatality rates of 40-75%. Two genotypes (NiV-M and NiV-B) differ in transmissibility and pathogenicity. WHO-listed as a priority pathogen, NiV has no approved vaccines or antiviral therapeutics. The virus gains entry into host cells through Ephrin-B2/B3 receptors, and evades innate immunity via non-structural proteins (V, W, C) and structural proteins. These evasion strategies disrupt multiple nodes in type I and II interferon (IFN-I/II) signaling pathways, including suppression of RIG-I/MAVS and inhibition of STAT1/STAT2 nuclear translocation, and dysregulation of NF-κB activation. Finally, these mechanisms facilitate viral replication and systemic dissemination. Infection also elicits adaptive immunity, including neutralizing antibodies against viral glycoproteins (G and F) and durable virus-specific CD4⁺ and CD8⁺ T-cell responses. Fatal outcomes correlate with high early viremia, delayed or insufficient antibody production, and dysregulated innate and adaptive immunity. In affected organs, particularly the brain, persistent cytokine storm driven predominantly by CXCL10 recruits inflammatory infiltrates and amplifies immunopathological damage. Current intervention strategies include vaccine candidates (ChAdOx1 Nipah B, mRNA-1215, HeV-sG) and antiviral approaches such as nucleoside analogs, monoclonal antibodies, and fusion inhibitors. This review comprehensively synthesizes current knowledge on NiV epidemiology, pathogenesis, and countermeasure development, providing a conceptual framework to interpret its exceptional virulence and prioritize targets for effective outbreak control.

Background Severe hand, foot, and mouth disease (HFMD) poses a substantial threat to pediatric health. Host genetic factors, particularly those involved in complement activation, influence susceptibility to HFMD; however, the contribution of complement gene polymorphisms to disease severity remains unclear. Methods A total of 189 HFMD patients caused by coxsackievirus A6 (CVA6) were enrolled from Henan Children’s Hospital; among them, 94 were classified as severe cases and 95 as mild cases. Genomic DNA was isolated from peripheral blood leukocytes using a modified phenol–chloroform extraction protocol. PCR-RFLP was used for genotyping. Logistic regression assessed SNP associations with severe HFMD risk. Results Significant associations were observed for the following genetic variants between patients with mild and severe disease: Complement 5 (C5) rs3761847 (GA vs. GG: OR = 2.547, 95% CI: 1.084–5.982); C3 rs2250656 (TC vs. TT: OR = 1.850, 95% CI: 1.021–3.351); and complement factor H (CFH) rs1065489 (TT vs. GG: OR = 2.804, 95% CI: 1.164–6.751; GT vs. GG: OR = 2.337, 95% CI: 1.085–5.033). ROC analysis showed that complement-related gene polymorphisms had clinical utility for predicting HFMD severity (AUC = 0.653, 95% CI: 0.575–0.730). Moreover, specific genotypes were associated with changes in laboratory parameters. Conclusion Our results suggest that C5, C3, and CFH variants influence susceptibility to severe CVA6-induced HFMD in Chinese Han children. Complement gene polymorphisms may help clinicians identify children at higher risk.

Coxsackievirus A6 (CVA6) is a nonenveloped, single-stranded RNA virus linked to neurological complications. Emerging evidence suggests neutrophil pyroptosis drives inflammation. However, the role of neutrophil pyroptosis in CVA6 pathogenesis remains unexplored. Ten-day-old wild-type (WT), Caspase-1 KO, and GSDMD KO mice were infected with a lethal dose of CVA6. For in vivo and in vitro studies, we used the caspase-1 inhibitor belnacasan, disulfiram, and anti-Ly6G antibody. We also generated neutrophil-specific PAD4-knockout mice (PAD4 Ne-KO) by deleting Padi4 under the S100A8 promoter. Post-infection, clinical scores, survival, and body weight were monitored. Brain tissues and bone marrow-derived neutrophils (BMDNs) were collected for analysis. Key methods included qPCR, Western blotting, histology/immunofluorescence, flow cytometry, and TEM to assess pyroptosis, inflammation, and immune cell infiltration. Findings were further validated using blood samples from HFMD patients. In this study, we investigated how the Caspase-1/GSDMD pathway mediates neutrophil extracellular trap (NET) release and drives CVA6-induced neuroinflammation. CVA6 infection increased neutrophil numbers in mouse brain and peripheral blood, along with elevated MPO-DNA—a NET marker. In BMDNs, degranulation and NET formation occurred by 24 hpi, accompanied by Caspase-1/GSDMD activation. Caspase-1 knockout prolonged survival and reduced GSDMD-N expression in brain neutrophils; pharmacological Caspase-1 inhibition decreased mature IL-1β and IL-18 in brain tissue and suppressed CVA6 replication in BMDNs. Together, in vitro and in vivo data indicate that Caspase-1/GSDMD activation and NETosis critically contribute to CVA6-induced brain injury. This was confirmed by GSDMD knockout or disulfiram-mediated GSDMD inhibition, both of which markedly reduced NET release and neuropathology. Notably, global neutrophil depletion worsened infection—suggesting a protective role—whereas neutrophil-specific PAD4 knockout improved survival. Clinically, GSDMD expression showed a significant positive correlation with NETosis markers in patient samples from CVA6-infected individuals. These findings enhance understanding of enteroviral pathogenesis, identify GSDMD as a promising therapeutic target, and provide a novel framework for developing precision interventions that reduce excessive inflammation without impairing essential host defenses.

Severe fever with thrombocytopenia syndrome (SFTS) is a newly discovered tick-borne disease caused by SFTS virus (SFTSV) infection. Patients present with high fever, thrombocytopenia, and multiple organ dysfunction, with a high mortality rate and a lack of specific treatment, all of which indicate that research on the deterioration mechanism and treatment of this disease is urgent. Currently, multiple studies have indicated that cytokine storm is one of the core factors contributing to the deterioration of the disease. SFTSV inhibits the host's type I interferon response through its non-structural protein NSs, thereby promoting immune evasion and viral replication. Extensive viral stimulation leads to dysfunction and abnormal polarization of immune cells (including monocytes, macrophages, dendritic cells, T cells, and B cells), triggering the massive release of pro-inflammatory factors(such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β)), anti-inflammatory factors (such as interleukin-10 (IL-10)), and chemokines(such as interferon-gamma inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8)). This cytokine storm exacerbates the imbalance between pro-inflammatory and anti-inflammatory factors, as well as immune paralysis, leading to vascular endothelial damage, microthrombosis, and ultimately, multi-organ failure, which determines the clinical outcome. Simultaneously, specific cytokines and immune cell phenotypes can serve as biomarkers for disease severity and prognosis. In terms of treatment, this article further summarizes the intervention strategies targeting the aforementioned immune links, including intravenous immunoglobulin (IVIG), tocilizumab (targeting the IL-6 receptor), inhibitors of Janus kinase (JAK) and nuclear factor-kappa B (NF-κB) signaling pathways, interferon, neutralizing antibodies, and other immunotherapy methods. By analyzing the dynamic changes and mechanisms of cytokine storm in the course of SFTS, and summarizing current potential immunotherapy methods, this article aims to provide a theoretical framework for the future treatment of SFTS.

Enterovirus 71 (EV71) is the principal pathogen linked to severe hand, foot, and mouth disease (HFMD), with its pathogenesis remaining poorly understood. Here, we found that EV71 infection dramatically increases the expression of NEAT1, resulting in the formation of paraspeckles. Notably, NEAT1 specifically enhances IFN-β transcription via the DDX60-IRF7 pathway, thereby promoting host resistance to EV71. Further experiments indicated that NEAT1 serves as a positive feedback for DDX60 signaling. In detail, NEAT1 facilitates the relocation of the paraspeckle protein SFPQ to the paraspeckle. This action alleviates SFPQ's transcriptional repression on DDX60 and MDA5, which collaborate to promote IFN-β transcription. Subsequently, we noted a comparable regulation of NEAT1 in vivo. Importantly, our case-control study found that lower NEAT1-2 expression in peripheral blood leukocytes during early HFMD stages correlates with disease severity. Our findings suggest that NEAT1 serves as an intrinsic anti-EV71 molecule, with reduced levels potentially indicating a poor prognosis.

Climate change has increased the frequency of extreme temperature and humidity events. Although the association between temperature and hand‒foot‒mouth disease (HFMD) is well-established, evidence regarding the synergistic amplification of risk driven by compound temperature‒humidity events remain limited. This study aims to investigate the temperature‒humidity synergistic effects on the HFMD risk and burden across China based on daily HFMD surveillance records and meteorological data from 302 cities during the period 2011–2019. Temperature‒humidity interactions are evaluated using generalized additive models (GAMs). Bivariate compound events are defined based on multiple temperature‒humidity percentile combinations. Exposure‒lag‒response relationships between temperature‒humidity compound events and HFMD risk are quantified using distributed lag nonlinear models (DLNMs) to identify high-risk thresholds with extreme characteristics. The HFMD burden is assessed through attributable case calculations. In over 18 million cases, we identified substantial synergistic effects between high temperature and humidity (S = 1.328, 95% CI: 1.286–1.370). Concurrent exposure above the 70th temperature percentile and 80th humidity percentile constituted high-risk conditions for HFMD (RR: 1.298, 95% CI: 1.222–1.379) at the national level, yet specific thresholds and associated risks exhibited spatial heterogeneity across regions. Subgroup analysis further identified preschool children and regions with economic disadvantages as vulnerable populations. The frequency of high HFMD risk compound events increased by 24% during 2017–2019 compared with 2011–2013. We identified 464,823 HFMD cases attributable to high-risk compound events across China, with the burden increasing most substantially in Northeast and North China. These findings provide a scientific basis for developing climate-adaptive early-warning systems and targeted interventions.

Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, n = 42; severe, n = 43) and healthy controls (n = 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several amino acids were significantly different between the three groups. Pathway analysis revealed that arginine, proline, and tryptophan metabolism are implicated in the pathogenesis of HFMD. A similar arginine depletion was observed in the brain tissues of CVA6-infected mice. Importantly, L-arginine supplementation improved the survival rate of CVA6-infected mice, inhibited virus multiplication, and reduced pathological autophagy associated with mTOR-autophagy pathway in the brain. Collectively, arginine, as the hub amino acid metabolite of the mammalian target of rapamycin (mTOR) signaling pathway affecting autophagy, plays an important role in the pathogenesis of severe HFMD. L-arginine supplementation may serve as a potential therapeutic option for critical patients with HFMD.

>Preterm birth(PTB),defined as a live birth occurring before 37 weeks of gestation,is associated with numerous adverse outcomes.These include poor growth,respiratory disorders,heightened susceptibility to infections because of low body weights,underdeveloped body functions,and low immunity.Such complications considerably affect infant health,pose life-threatening risks,and impose substantial social and economic burdens.

Infectious mononucleosis (IM), is mainly caused by the primary infection with Epstein-Barr virus (EBV). Generally, most patients with IM are deemed to have a favorable prognosis, yet a small proportion of children will need hospitalization. This study aimed to explore the epidemiological features of IM among hospitalized children in Henan Province from 2014 to 2023 and forecast monthly IM hospitalizations in 2024. We conducted a retrospective analysis of all inpatients with IM in Henan Children’s Hospital and the Third Affiliated Hospital of Zhengzhou University from January 2014 to December 2023. Demographic information, clinical diagnosis, and admission time were meticulously analyzed. Wavelet analysis and SARIMA model were employed to identify disease periodicity and forecast hospitalization with IM, respectively. There were 7,269 IM inpatients, which accounted for 0.70