Search Results (1,043)

Background: Cervical cancer poses a threat to the health of women globally. Adolescent girls are the primary target population for HPV vaccination, and guardians’ attitude towards the HPV vaccine plays a significant role in determining the vaccination status among adolescent girls. Objectives: This study aimed to explore the factors influencing guardians’ HPV vaccine acceptance for their girls and provide clues for the development of health intervention strategies. Methods: Combining the health belief model as a theoretical framework, a questionnaire-based survey was conducted. A total of 2157 adolescent girls and their guardians were recruited. The multivariable logistic model was applied to explore associated factors. Results: The guardians had a high HPV vaccine acceptance rate (86.7%) for their girls, and they demonstrated a relatively good level of awareness regarding HPV and HPV vaccines. Factors influencing guardians’ HPV vaccine acceptance for girls included guardians’ education background (OR = 0.57, 95%CI = 0.37–0.87), family income (OR = 1.94, 95%CI = 1.14–3.32), risk of HPV infection (OR = 3.15, 95%CI = 1.40–7.10) or importance of the HPV vaccine for their girls (OR = 6.70, 95%CI = 1.61–27.83), vaccination status surrounding them (OR = 2.03, 95%CI = 1.41–2.92), awareness of negative information about HPV vaccines (OR = 0.59, 95%CI = 0.43–0.82), and recommendations from medical staff (OR = 2.32, 95%CI = 1.65–3.25). Also, guardians preferred to get digital information on vaccines via government or CDC platforms, WeChat platforms, and medical knowledge platforms. Conclusions: Though HPV vaccine willingness was high among Chinese guardians, they preferred to vaccinate their daughters at the age of 17–18 years, later than WHO’s recommended optimal age period (9–14 years old), coupled with safety concerns. Future work should be conducted based on these findings to explore digital intervention effects on girls’ vaccination compliance. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

To investigate the effect of Botrytis cinerea infection severity on the flavor characteristics of Petit Manseng noble rot wine, this study analyzed wines produced from Petit Manseng grapes grown in the eastern foothills of Helan Mountain, Ningxia, China. The grapes were categorized into three groups based on infection status: uninfected, mildly infected, and severely infected with Botrytis cinerea. Headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) and an electronic nose were employed to detect and analyze the aroma components of wines under the three infection conditions. Additionally, trained sensory panelists conducted sensory evaluations of the wine aromas. The results revealed that wines made from severely infected grapes exhibited the richest and most complex aroma profiles. A total of 70 volatile compounds were identified, comprising 32 esters, 17 alcohols, 5 acids, 8 aldehydes and ketones, 4 terpenes, and 4 other compounds. Among these, esters and alcohols accounted for the highest contents. Key aroma-active compounds included isoamyl acetate, ethyl decanoate, phenethyl acetate, ethyl laurate, hexanoic acid, linalool, decanoic acid, citronellol, ethyl hexanoate, and methyl octanoate. Sensory evaluation indicated that the “floral aroma”, “pineapple/banana aroma”, “honey aroma”, and “overall aroma intensity” were most pronounced in the severely infected group. These findings provide theoretical support for the harvesting of severely Botrytis cinerea-infected Petit Manseng grapes and the production of high-quality noble rot wine in this region. Full article

The focal “hot spot” neuropathologies in COVID-19 infection are revealing footprints of a hidden underlying collapse of a novel ultrafast ultradian Piezo2 signaling system within the nervous system. Paradoxically, the same initiating pathophysiology may underpin the systemic findings in COVID-19 infection, namely the multiorgan SARS-CoV-2 infection-induced vascular pathologies and brain–body-wide systemic pro-inflammatory signaling, depending on the concentration and exposure to infecting SARS-CoV-2 viruses. This common initiating microdamage is suggested to be the primary damage or the acquired channelopathy of the Piezo2 ion channel, leading to a principal gateway to pathophysiology. This Piezo2 channelopathy-induced neural switch could not only explain the initiation of disrupted cell–cell interactions, metabolic failure, microglial dysfunction, mitochondrial injury, glutamatergic synapse loss, inflammation and neurological states with the central involvement of the hippocampus and the medulla, but also the initiating pathophysiology without SARS-CoV-2 viral intracellular entry into neurons as well. Therefore, the impairment of the proposed Piezo2-induced quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling seems to be the principal and critical underlying COVID-19 infection-induced primary damage along the brain axes, depending on the loci of SARS-CoV-2 viral infection and intracellular entry. Moreover, this initiating Piezo2 channelopathy may also explain resultant autonomic dysregulation involving the medulla, hippocampus and heart rate regulation, not to mention sleep disturbance with altered rapid eye movement sleep and cognitive deficit in the short term, and even as a consequence of long COVID. The current opinion piece aims to promote future angles of science and research in order to further elucidate the not entirely known initiating pathophysiology of SARS-CoV-2 infection. Full article

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly known as long-COVID—can persist for months. Recent studies have identified the emergence of diverse autoantibodies in COVID-19, including those targeting nuclear antigens, phospholipids, type I interferons, cytokines, endothelial components, and G-protein-coupled receptors. These autoantibodies are more frequently detected in patients with moderate to severe disease and have been implicated in immune dysregulation, vascular injury, and persistent symptoms. This review examines the underlying immunological mechanisms driving autoantibody production during SARS-CoV-2 infection—including molecular mimicry, epitope spreading, and bystander activation—and discusses their functional roles in acute and post-acute disease. We further explore the relevance of autoantibodies in maternal–fetal immunity and comorbid conditions such as autoimmunity and cancer, and we summarize current and emerging therapeutic strategies. A comprehensive understanding of SARS-CoV-2-induced autoantibodies may improve risk stratification, inform clinical management, and guide the development of targeted immunomodulatory therapies. Full article

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

Limited molecular data exist on zoonotic parasites Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in Angus calves from Guizhou, China. This study constitutes the first molecular epidemiological survey of these pathogens in this region. 817 fecal samples from Angus calves across 7 intensive beef farms (Bijie City). Nested PCR methods targeting SSU rRNA (Cryptosporidium spp.), gp60 (Cryptosporidium bovis subtyping), bg/gdh/tpi (G. duodenalis), and ITS (E. bieneusi) coupled with DNA sequencing were employed. DNA sequences were analyzed against the NCBI. database. Statistical differences were assessed via a generalized linear mixed-effects model. Cryptosporidium spp. prevalence 23.5% (192/817; 95% CI 28.1–34.6%), with C. bovis predominating 89.6% (172/192; 95% CI 84.4–93.5%) and six subtypes (XXVIa-XXVIf). Highest infection in 4–8-week-olds 29.9% (143/479; 95% CI 25.8–34.1%) (p < 0.01). G. duodenalis: 31.3% (256/817; 95% CI 28.1–34.6%) positive, overwhelmingly assemblage E 97.6% (6/256; 95% CI 0.9–5.0%), zoonotic assemblage A was marginal 0.7% (6/817; 95% CI 0.3–1.6%). Farm-level variation exceeded 10-fold (e.g., Gantang: 55.0% (55/100; 95% CI 44.7–65.0%) vs. Tieshi: 4.9% (5/102; 95% CI 1.6–11.1%). E. bieneusi: prevalence 19.7% (161/817; 95% CI 17.0–22.6%), exclusively zoonotic genotypes BEB4: 49.7% (80/161; 95% CI 41.7–57.7%); I: 40.4% (65/161; 95% CI 32.7–48.4%). Strong diarrhea association (p < 0.01) and site-specific patterns (e.g., Guanyindong: 39.2%). While Giardia exhibited the highest prevalence (31.3%) with minimal zoonotic risk, Enterocytozoon—despite lower prevalence (19.7%)—posed the greatest public health threat due to exclusive circulation of human-pathogenic genotypes (BEB4/I) and significant diarrhea association, highlighting divergent control priorities for these enteric parasites in Guizhou calves. Management/Public health impact: Dominant zoonotic E. bieneusi genotypes (BEB4/I) necessitate: 1. Targeted treatment of 4–8-week-old Angus calves. 2. Manure biofermentation (≥55 °C, 3 days), and 3. UV-disinfection (≥1 mJ/cm²) for karst water to disrupt transmission in this high-humidity region. Full article

Coxsackievirus B3 (CV-B3) infection causes inflammatory conditions such as viral myocarditis and meningitis, and incidence rates are rising annually. While children are more likely to be affected by severe manifestations, the molecular basis of this age-dependent susceptibility is poorly understood. In this study, we used young Balb/c mice at three developmental stages (7-, 14-, and 30-day-old mice) to investigate CV-B3 pathogenesis. Our findings revealed that 7-day-old mice exhibited substantial infection susceptibility and pathological severity compared to older mice. Critically, an age-dependent analysis showed a progressive decline in the expression of CV-B3-binding Coxsackievirus and Adenovirus Receptor (CAR) splice variants (CAR1 and CAR2) at both the transcriptional and translational levels as the mice matured from 7 to 30 days. These receptor isoforms demonstrated a direct correlation with viral replication efficiency in younger hosts. Concurrently, aging was associated with a rise in non-binding CAR variants (CAR3 and CAR4). During CV-B3 infection, the abundance of CAR1/CAR2 in young mice facilitated accelerated viral proliferation, coupled with the hyperactivation of the NLRP3 inflammasome and the expansion of IL-17-producing γδT cells (γδT17 cells). This cascade triggered excessive production of proinflammatory cytokines (IL-1β, IL-18, and IL-17), culminating in pronounced inflammatory infiltrates within cardiac and cerebral tissues. These findings establish NLRP3 inflammasome dysregulation as a critical determinant of CV-B3-induced tissue damage and provide novel insights into the heightened susceptibility to CV-B infection during early life and its associated severe disease rates. Full article

In Africa, Rift Valley Fever poses a substantial risk to animal health, and human cases occur after contact with infected animals or their tissues. RVF has re-emerged in Uganda after nearly five decades, with multiple outbreaks recorded since 2016. We investigated a unique RVF outbreak associated with an animal abortion storm of 30 events and human cases on a dairy farm in Mbarara District, Western Uganda, in February 2023. Genomic analysis was performed, comparing animal and human RVF viruses (RVFV) circulating in the region. A cluster of thirteen human RVF cases and nine PCR-positive animals could directly be linked with the abortion storm. Overall, during the year 2023, we confirmed 61 human RVFV cases across Uganda, 88.5% of which were reported to have had direct contact with livestock, and a high case fatality rate of 31%. We recommend implementing extensive health education programs in affected communities and using sustainable mosquito control strategies to limit transmission in livestock, coupled with initiating animal vaccination trials in Uganda. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

Virus infections in plants are a major threat to crop production and sustainable agriculture, which results in significant yield losses globally. The past decade has seen the development and deployment of sophisticated high-throughput omics technologies including genomics, transcriptomics, proteomics, and metabolomics, in order to try to understand the mechanisms underlying plant–virus interactions and implement strategies to ameliorate crop losses. In this review, we discuss the current state-of-the-art applications of such key omics techniques, their challenges, future, and combinatorial use (e.g., single cell and spatial omics coupled with super-resolution high-throughput imaging methods and artificial intelligence-based predictive models) to obtain new mechanistic insights into plant–virus interactions, which could be exploited for more effective plant disease management and monitoring. Full article

The increasing circulation of multi-drug-resistant pathogens, coupled with the sluggish development of new antibiotics, is weakening our capacity to combat human infections, resulting in elevated death tolls. To address this worldwide crisis, antimicrobial peptides (AMPs) are viewed as promising substitutes or adjuvants for combating bacterial infections caused by multidrug-resistant organisms. Here, the antimicrobial activity and structural characterization of a novel 13-amino acid cationic peptide named RKW (RKWILKWLRTWKK-NH2), designed based on known AMPs sequences and the identification of a key tryptophan-rich structural motif, were described. RKW displayed a broad-spectrum and potent antimicrobial and antibiofilm activity against Gram-positive and Gram-negative pathogens, including ESKAPE bacteria and fungi with minimal inhibitory concentrations (MBC) ranging from 5 µM to 20 μM. Structural results by fluorescence and Circular Dichroism (CD) spectroscopy revealed that the peptide was folded into a regular α-helical conformation in a membrane-like environment, remaining stable in a wide range of pH and temperature for at least 48 h of incubation. Furthermore, RKW showed low toxicity in vitro against mammalian fibroblast cells, indicating its potential as a promising candidate for the development of new antimicrobial or antiseptic strategies. Full article

A dearth of knowledge exists on identifying the begomoviruses and distributing cassava mosaic viruses across key cassava-growing regions of Sierra Leone. The study aimed to identify and map the distribution of cassava mosaic disease (CMD)-associated viruses in farmers’ fields in Sierra Leone. Cassava (Manihot esculenta Crantz) leaf samples were collected in 109 smallholder farms during a geo-referenced survey conducted from 10th May to 5th June 2024. Molecular diagnostics were carried out to identify the viral strains associated with CMD. Findings revealed that infection by stem cutting was more predominant in the south, east, north, and northwest regions than in the west region. In contrast, infection by whitefly was predominant in the west, north, and northwest regions. PCR screening of 426 samples coupled with sequence analysis revealed the presence of African cassava mosaic-like (ACMV-like) viruses, and East African cassava mosaic-like (EACMV-like) viruses as single infections at 78.1% and 1.3%, respectively. Co-infections of ACMV-like and EACMV-like viruses were detected in 20.6% of the tested samples. In addition, 70.6% of the samples positive for EACMV-like virus (single and mixed infections) were found to be positive for East African cassava mosaic Cameroon virus (EACMCMV). The ACMV and co-infection of ACMV and EACMV viruses were present in all regions, while EACMCV was detected in all regions except the western area. The results indicate more prevalence of the EACMCMV variant in Sierra Leone. This study suggests utilization of participatory surveillance and good agronomic practices to manage CMD in Sierra Leone. Full article

This article reviews the multifaceted roles of itaconate in immune regulation and inflammatory metabolism. Itaconic acid is a dicarboxylic acid with anti-inflammatory, antioxidant, and anti-tumor properties. It is initially produced by the heating decomposition of citric acid and is closely related to the tricarboxylic acid cycle. In immune regulation, itaconate regulates macrophage function through a variety of mechanisms, including metabolic reprogramming, polarization regulation, inhibition of cytokine production, and regulation of oxidative stress. It can also affect the function of T cells and B cells. In terms of inflammatory metabolism, itaconate can regulate the production of inflammatory factors, inhibit the activity of succinate dehydrogenase, and affect cellular energy metabolism and lipid metabolism. Its mechanism of action involves the inhibition of succinate dehydrogenase, covalent modification of proteins, influence on epigenetic modification, and playing a role through the G protein-coupled receptor OXGR1 (Oxoglutarate Receptor 1). Itaconic acid derivatives have shown good effects in anti-inflammation and anti-oxidation and have broad application prospects in clinical treatment, including the treatment of inflammatory diseases, anti-tumor and anti-microbial infection. However, the long-term safety and side effects of itaconic acid as a therapeutic agent still need to be further studied. Future studies will further explore the synthesis and function of itaconic acid in different cell types, its physiological effects in non-inflammatory conditions, and its potential application in clinical treatment in order to develop new therapeutic strategies and improve the treatment effect of chronic inflammatory and metabolism-related diseases. Full article

Respiratory syncytial virus (RSV) is a major human respiratory pathogen, particularly affecting infants, the elderly, and immunocompromised individuals. RSV exists in both spherical and filamentous forms, with the filamentous morphology associated with enhanced infectivity and cell-to-cell spread. Here, we demonstrate that RhoA, a small GTPase involved in cytoskeletal regulation, is essential for filamentous RSV morphogenesis through its role in organizing lipid raft microdomains. Rhosin, a selective RhoA inhibitor developed through structure-guided screening, disrupts GEF–RhoA interactions to block RhoA activation. The pharmacological inhibition of RhoA with Rhosin significantly reduced filamentous virion formation, disrupted RSV fusion (F) protein colocalization with lipid rafts, and diminished cell-to-cell fusion, without affecting overall viral replication. Scanning electron microscopy revealed that Rhosin-treated infected HEp-2 cells exhibited fewer and shorter filamentous projections compared to the extensive filament formation seen in untreated cells. β-galactosidase-based fusion assays confirmed that reduced filamentation corresponded with decreased cell-to-cell fusion. The biophysical separation of RSV spherical and filamentous particles by sucrose gradient velocity sedimentation, coupled with fluorescence and transmission electron microscopy, showed that Rhosin treatment shifted virion morphology toward spherical forms. This suggests that RhoA activity is critical for filamentous virion assembly, which may enhance viral spread. Immunofluorescence microscopy using lipid raft-selective dyes (DiIC₁₆) and fusion protein-specific antibodies revealed the strong co-localization of RSV proteins with lipid rafts. Importantly, the pharmacological inhibition of RhoA with Rhosin disrupted F protein partitioning into raft domains, underscoring the requirement for intact lipid rafts in assembly. These findings highlight a novel role for host RhoA signaling in regulating viral assembly through raft microdomain organization, offering a potential target for host-directed antiviral intervention aimed at altering RSV structural phenotypes and limiting pathogenesis. Full article