Frontiers in Cellular and Infection Microbiology最新文献

Background: Tuberculosis (TB) remains a major global health challenge, with an estimated 10 million new cases and 1.4 million deaths annually. Identifying patients who would benefit from comprehensive pharmacist intervention services is critical for optimizing pharmacist intervention benefit outcomes and resource allocation. We developed a machine learning model to predict pharmacist intervention group assignment at hospital admission using clinical parameters.

Methods: We conducted a retrospective analysis of 467 TB patients from a tertiary care hospital. The prediction model was trained exclusively on clinical variables to predict pharmacist intervention group assignment (binary classification: intervention group = 1, control group = 0). To address limited sample size, we implemented data augmentation using multi-neighbor interpolation, expanding the dataset to 1,999 samples (328.1% increase). We developed an extensive feature engineering pipeline generating 122 optimized features and employed Optuna-based hyperparameter optimization (250 trials) with a multi-level ensemble architecture comprising 43 base models. Separately, we analyzed publicly available GEO datasets to provide biological interpretation and mechanistic insights, but these transcriptomic data were not used as model features.

Results: The ultimate ensemble model achieved accuracy of 92.25% (95% CI: 89.1-95.4%) and AUC-ROC of 96.96% (95% CI: 94.8-99.1%) in predicting pharmacist intervention group assignment, demonstrating the substantial impact of the optimization strategies employed. Analysis of GEO datasets identified 150 significantly differentially expressed genes (FDR < 0.05) and revealed enrichment in immune response and inflammation pathways, providing supportive biological context for the clinical prediction model.

Conclusions: Our study demonstrates that comprehensive machine learning optimization can achieve strong predictive performance for identifying patients who would benefit from pharmacist intervention. The clinical prediction model, trained exclusively on clinical variables, provides a robust framework for personalized TB treatment resource allocation. Supportive transcriptomic analyses provide biological context but are not used in model prediction. The model's accuracy (92.25%) and discriminative ability (AUC 96.96%) suggest potential for clinical implementation.

Various studies suggest that host gender is a disease-determining factor in schistosomiasis. Men have a higher prevalence in endemic areas and show a greater degree of liver damage in chronic infection with Schistosoma mansoni. It is currently unclear whether this is only due to socioeconomic causes, such as the working environment and behavior. It was recently suggested that molecular biological differences in the infected host could also contribute to the disease. Current studies in model systems suggest that hormonal influences affect liver metabolism during infection with S. mansoni. In particular, a metabolic recycling process in the cell, known as autophagy, could be altered in a sex-specific manner and influence the course of the disease. It is suspected that the differences in metabolism in the liver of S. mansoni-infected hosts could contribute to cell stress and thus to organ damage on the molecular level. This article summarizes and discusses known and new aspects of the gender-specific influence on liver metabolism in S. mansoni infection.

Background: Hypercapnic acidosis (HCA) is a hallmark of acute hypercapnic respiratory failure, often triggered by respiratory infections. Its role in lung injury remains controversial, with both protective and detrimental effects reported. However, the specific impact on pulmonary immune responses to lung infections remain poorly understood. To investigate the impact of HCA on alveolar response during infection, we developed an in vitro model combining human alveolar epithelial cells (type I and II) and macrophage-like THP-1 cells.

Methods: The co-culture and monocultures were infected with Pseudomonas aeruginosa or Streptococcus pneumoniae under normocapnic or HCA conditions. At 1 hour and 24 hours post-infection, we assessed inflammatory cytokine expression (IL-1β, CCL2, IL-8), tight junction protein levels (occludin, ZO-1) and bacterial survival.

Results: HCA modulated inflammation in pathogen-specific manner: IL-1β induction by S. pneumoniae was mainly CO₂-driven, while P. aeruginosa triggered strong IL-1β regardless of CO₂. Tight junction proteins were upregulated at 1 hour under HCA, particularly with macrophages, but occludin declined at 24 hours, potentially impairing epithelial repair. While extracellular bacterial loads were unaffected by CO₂, HCA promoted intracellular replication of P. aeruginosa in macrophages, without affecting intracellular survival in epithelial cells or overall bacterial burden in S. pneumoniae-infected cultures.

Conclusions: HCA condition differentially influence host responses depending on the infectious pathogen, compromising the barrier function and prolonging lung inflammation with differences according to time culture, which could benefit bacterial persistence.

Background: Serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) predicts antiviral response in adults with chronic hepatitis B (CHB); however, its prognostic performance against conventional biomarkers in children remains underexplored. This study aimed to characterize the kinetics of pgRNA and hepatitis B surface antigen (HBsAg) and evaluate their predictive value for treatment outcomes in children with CHB.

Methods: Sixty-five hepatitis B e antigen (HBeAg)-positive children with CHB who received ≥ 96 weeks of nucleos(t)ide analogue (NA) therapy were included. Serum viral biomarkers were measured at baseline, weeks 12, 48, and 96. Treatment outcomes were HBeAg seroconversion and HBsAg loss (Defined as HBsAg <100 IU/mL or seroclearance).

Results: Patients initiating treatment before age 7 years had a significantly higher cumulative incidence of HBeAg seroconversion (73.5% vs. 48.4%) and HBsAg loss (50.0% vs. 9.7%) compared to older children (p < 0.05). Week 12 HBV pgRNA decline was an independent predictor of HBeAg seroconversion (area under the curve [AUC] = 0.793, 95% confidence interval [CI]: 0.686-0.900), outperforming HBV DNA and HBsAg kinetics. For predicting HBsAg loss, the week 12 HBsAg decline was an independent predictor (AUC = 0.762, 95% CI: 0.632-0.893), and its integration with patient age further improved predictive accuracy (AUC = 0.879, 95% CI: 0.796-0.962).

Conclusions: Early pgRNA kinetics more accurately predict HBeAg seroconversion, whereas HBsAg dynamics forecast HBsAg loss more effectively, particularly when combined with patient age. This complementary monitoring strategy provides a clinically applicable tool for optimizing personalized management in children with CHB.

Thyroid dysfunction is a common endocrine disease among women of childbearing age, which seriously affects reproductive health. From an immunological perspective, this in-depth analysis clarifies the complex relationship between thyroid function and female reproduction. We studied the hypothalamic-pituitary-gonadal axis regulation by thyroid hormones through direct and indirect mechanisms, including metabolic mediators such as prolactin and leptin. Recent studies have shown that inflammatory cytokines (IL-1α, IL-1β, IL-6, IFN-γ, and TNF-α) severely disrupt the production pathways of thyroid hormones, establishing an essential link between immune activation and reproductive problems. Since the placenta serves as an active immune interface affected by thyroid activity, there are significant physiological obstacles (including increased iodine clearance and elevated deiodinase activity), immunological challenges (such as altered cytokine profiles), and pathological barriers to optimal thyroid adaptation during pregnancy. This literature review indicates that thyroid problems substantially affect reproductive outcomes by altering the immune response at the maternal-fetal interface, influencing placental development, trophoblast invasion, and vascular remodeling. This review addresses a notable research deficiency through a modern perspective on thyroid dysfunction and reproductive issues, especially inflammatory cytokines related to preeclampsia. We believe that thyroid dysfunction can alter the expression of specific angiogenic factors (including sFlt-1, PlGF, and VEGF) and modify the immune cell profile at the maternal-fetal interface (particularly NK cells, macrophages, and T regulatory cells), creating a new framework for understanding and addressing thyroid-related reproductive diseases through targeted immunomodulatory strategies.

Introduction: Shewanella species (Shewanella spp.) were emerging and rare pathogens. Very few studies had focused on Shewanella spp. infection due to its low incidence. A retrospective analysis summarizing clinical and laboratory characteristics of Shewanella spp. infection at a tertiary hospital in Hefei City was conducted to learn more about the rare bacterium.

Methods: A total of 36 patients with Shewanella spp. infection from October 2019 to February 2025 were included. The data of all patients were collected by reviewing electronic records.

Results: Among 36 isolated strains, 77.8% were Shewanella algae and 22.2% were Shewanella putrefaciens. Abdominal pain was the most common clinical symptom. Intrahepatic stone and cholangitis was the main diagnosed disease. According to the type of main diagnosed disease, they were divided into two groups: hepatobiliary disease group and non-hepatobiliary disease group. The laboratory results were analyzed, and it was revealed that the laboratory characteristics of anemia, neutrophilia, leukocytosis, and so on were common. Serum coagulation tests results showed that it was significantly higher than the normal value, and all other serum biochemical and coagulation tests results were mostly normal. For microorganism culture, co-infection microorganisms were obtained. Shewanella spp. were usually susceptible to aminoglycoside, quinolone, cephalosporin, carbapenems, and compound antibiotics. All patients were treated with antibiotics, and there were one or more types of antibiotics to use, all of whom had effective treatment outcomes.

Discussion: Shewanella spp. infections were very limited. The study might improve the attention and awareness of the rare bacterial infection.

Objectives: Although Diphtheria-Tetanus-acellular Pertussis (DTaP) vaccines have been used in the U.S. for decades and have extensive safety records, a comprehensive post-marketing assessment for all available types is still needed. This study leveraged the Vaccine Adverse Event Reporting System (VAERS) database to evaluate adverse events following immunization (AEFI) and analyze potential associations with vaccine administration.

Methods: We extracted all reports of adverse events (AEs) following DTaP vaccination from the VAERS database for the period 1990 to May 2025. Our analysis included descriptive statistics to summarize patient demographics and clinical features, and disproportionality methods to identify potential safety signals.

Results: During the study period, the VAERS database documented 57,341 children under 7 years who received DTaP vaccines, corresponding to 57,368 administered doses and 193,955 adverse event (AE) reports. AE reporting was more frequent in males (52.46%) than females (45.07%), with more than half of the cases (50.44%) involving children under 2 years old. The most common clinical outcomes were recovery (62.53%) and hospitalization (10.29%). Most AEs (89.61%) occurred within 0-30 days after vaccination, with a median onset time of 1.0 days. Infanrix (37.95%) and Daptacel (25.04%) were the most frequently reported vaccine types. Disproportionality analysis detected 158 positive AE signals across 24 system organ classes (SOCs). Among all SAEs, pyrexia (ROR = 1.01) was the most frequently reported, followed by convulsion (ROR = 1.82) and vomiting (ROR = 1.05). The most common signals for non-SAEs included injection site erythema (ROR = 3.79), injection site swelling (ROR = 3.00), and erythema (ROR = 3.03).

Conclusions: This post-marketing surveillance indicates that most reported AEs were non-serious and occurred within 30 days following vaccination. These findings support the known safety profile of DTaP vaccines and highlight identifiable timing patterns of AEs, which may help inform monitoring strategies and benefit-risk assessments after immunization.

Introduction: Pseudorabies virus (PRV), a significant pathogen of swine, causes substantial economic losses, and even poses an emergent public health concern due to its zoonotic potential. The continuous evolution of PRV has undermined the effectiveness of current vaccines and antiviral drugs. Consequently, there is an urgent need to develop novel strategies to curb its spread.

Methods: The inhibitory effect of garcinone C on PRV replication was assessed in vivo and in vitro. To determine the stage of antiviral action, treatments were administered at different time points: pre-treatment, co-treatment, and post-infection. RNA sequencing was performed, and differentially expressed genes (DEGs) were identified.

Results: In the study, we found that garcinone C inhibited PRV replication in a concentration- and timedependent manner in vitro. The antiviral activity of garcinone C was specific to post-infection administration and did not extend to pre-treatment and cotreatment conditions. Transcriptomic analysis identified DEGs between garcinone C- and vehicle-treated cells after PRV infection. KEGG pathway enrichment analysis of the DEGs indicated that the antiviral effect of garcinone C was primarily associated with the PI3K-Akt signaling pathway, potentially through the downregulation of the host epidermal growth factor. Furthermore, garcinone C suppressed the production of key inflammatory cytokines such as IL-6, IL-8, and TNF-a during PRV infection. Oral administration of garcinone C conferred protection in PRVinfected mice, leading to attenuated weight loss, an improved survival rate, as well as reduced pathological changes and viral loads in tissues.

Discussion: Collectively, our findings identify garcinone C as a promising therapeutic candidate against PRV and elucidate its underlying molecular mechanism.

Calf diarrhea is a common gastrointestinal disease that usually occurs within one month of birth. The disease causes the greatest economic losses to the cattle industry. Currently, a variety of diagnostic methods have been developed for calf diarrhea infections. However, existing methods are still unsatisfactory in terms of sensitivity, specificity, simplicity, cost, and speed.To provide a more sensitive, specific, simpler, and faster detection method, we recently developed an RPA-CRISPR/Cas12a assay that can detect BVDV, BCoV, BRV, and ETEC infections in cattle on-site. Testing for each pathogen is performed in a single test tube, without the need to open the tube in the middle, and can be completed in under 50 minutes.The RPA-CRISPR/Cas12a assay can detect BVDV, BCoV, BRV, and ETEC at concentrations of at least 10 copies/μL. The RPA-CRISPR/Cas12a assay does not produce false-positive results due to the presence of other pathogens. The sensitivity of BCoV, BRV, and ETEC in the RPA-CRISPR/Cas12a quadruple assay is equivalent to that of single qPCR. The sensitivity of BVDV in the quadruple assay is slightly lower than that of the single qPCR method.Due to its sensitivity, specificity, simplicity, and rapidity, the RPA-CRISPR/Cas12a assay is more practical for on-site detection of cattle diarrhea pathogens than any existing detection method.

Introduction: Leptospirosis is a zoonotic disease caused by Leptospira interrogans and represents a major public health and veterinary concern. The persistence of the pathogen is closely associated with biofilm formation, yet targeted therapeutics are currently unavailable. The GroEL chaperonin, a conserved protein involved in biofilm formation and immunogenicity, was investigated as a potential therapeutic target.

Methods: A structure-based virtual screening approach was performed using a library of 543,503 natural compounds from the Life Chemicals database. Top-ranked ligands were evaluated using molecular docking and physicochemical and pharmacokinetic property analyses. Density functional theory calculations were performed to assess electronic stability, followed by molecular dynamics simulations to evaluate ligand-protein complex stability. Principal component analysis and MM-PBSA binding free energy calculations were subsequently applied to characterize conformational dynamics and binding affinity.

Results: Five compounds (F3385-2019, F1243-0200, F3139-0927, F2801-0179, and F1864-0208) exhibited strong binding affinities toward GroEL, with docking energies ranging from -10.34 to -8.26 kcal/mol. All shortlisted compounds complied with Lipinski's Rule of Five and demonstrated favorable pharmacokinetic properties. Molecular dynamics simulations and MM-PBSA analyses indicated stable ligand-protein interactions. Among the candidates, F1864-0208 and F1243-0200 emerged as the most stable and promising leads, whereas the remaining compounds showed moderate inhibition.

Discussion: This study provides computational evidence supporting GroEL as a viable drug target in L. interrogans. The identified natural compounds may represent promising scaffolds for the development of novel anti-leptospiral agents. Further in vitro and in vivo studies are required to validate their therapeutic efficacy and safety.