Search Results (6,328)

The indiscriminate use of antibiotics in food-producing animals serves as a major catalyst for the emergence of antibiotic-resistant infections. This study aimed to assess the genetic diversity and antibiotic resistance of Enterobacterales in animal-derived foods. A total of 905 animal-derived food samples, including meat, dairy, poultry, fish, and environmental sources, were collected from various locations in Pakistan. Isolates were confirmed through selective subculturing, morphological, biochemical, and MALDI-TOF analysis, followed by antibiotic susceptibility testing. Subsequently, PCR-based detection of antibiotic resistance genes and virulence-associated genes. Overall, a total of 263 (29.06%) Enterobacterales were identified, as follows: 58.55% (154/263) E. coli, 6.84% (18/263) K. pneumoniae, 21.29% (56/263) P. mirabilis, and 13.30% (35/263) Salmonella spp. Isolates showed a varying resistance pattern against different studied antibiotics, e.g., beta-lactams and inhibitors, ciprofloxacin, and tetracycline, while colistin and tigecycline remained most effective. All the isolates displayed an array of antibiotic resistance and virulence-associated genes. Particularly significant (<0.05) co-existence of bla_NDM and mcr-1 was observed among the Enterobacterales isolated from various animal-derived foods. This study underscores the need to monitor Enterobacterales in animal-derived foods, especially in developing countries, to curb the spread of resistant pathogens and ensure effective food safety measures. Full article

Selenium nanoparticles (SeNPs) show great potential for sustainable agriculture, but their green synthesis and practical application still need further optimization. This study established a green synthesis method for SeNPs using lyophilized rose (Rosa rugosa Thunb.) powder as both a reducing and stabilizing agent to reduce sodium selenite (Na₂SeO₃), key parameters, including template concentration, Na₂SeO₃/VC ratio, and reaction temperature were systematically optimized. This process yielded stable, spherical SeNPs with optimal properties, exhibiting a diameter of 90 nm and a zeta potential of −35 mV. Structural characterization confirmed that selenium forms chelation complexes through carboxyl and hydroxyl oxygen-binding sites. The SeNPs exhibited exceptional stability (retained 426 days at 25 °C) and pH tolerance (pH 4–10), though divalent cations (Ca²⁺) triggered aggregation. In agricultural application tests, 5 mg/L SeNPs increased tomato plant biomass by 84% and antioxidant capacity by 152% compared to controls, and the biosynthesis pathways of salicylic acid and jasmonic acid were upregulated. Moreover, the SeNPs exhibited strong concentration-dependent antifungal activity against several major pathogens. Among these pathogens, tomato gray mold (Botrytis cinerea) was the most sensitive, as evidenced by its low EC₅₀ (4.86 mg/L) and sustained high inhibition rates, which remained substantial even at 1 mg/L and reached 94% at 10 mg/L. These findings highlight SeNPs as a friendly alternative for minimizing agrochemical use in sustainable agriculture. Full article

Cancer remains one of the leading causes of mortality worldwide and continues to pose significant therapeutic challenges despite decades of research. Conventional treatments such as chemotherapy and radiotherapy often lack selectivity, damaging both malignant and healthy tissues and resulting in severe side effects. Photodynamic therapy (PDT) has emerged as a promising non-invasive alternative that selectively eradicates cancer cells or pathogens using a photosensitizer (PS), light, and oxygen. PDT induces necrosis or apoptosis in cancer cells by locally generating cytotoxic reactive oxygen species through targeted laser irradiation. However, its clinical efficacy is limited by factors such as tumor hypoxia, poor PS delivery efficiency, and light attenuation within biological tissues. Recent advances in liposomal nanoplatforms have shown considerable potential in overcoming these barriers. Liposomes can co-deliver PS, therapeutic agents, and oxygen, thereby enhancing PDT outcomes. This review outlines the fundamental principles of PDT and the physicochemical properties of liposomes. It then explores two major strategies for improving PDT efficacy using liposomes: PS-drug co-delivery and oxygen delivery to mitigate tumor hypoxia for synergistic therapeutic effects. Finally, current limitations and future perspectives of liposome-based nanomedicine in photodynamic cancer therapy are discussed. Overall, this review provides a foundation for advancing liposome-based strategies toward clinical implementation in photodynamic cancer treatment. Full article

Leptospirosis is a zoonotic disease caused by pathogenic Leptospira, prevalent in tropical/sub-tropical regions. This study aimed to clarify the prevailing leptospiral species, clinical features, and risk factors of leptospirosis in north-central Bangladesh in 2024. Venous blood and urine samples were collected from 117 patients with clinically suspected leptospirosis. Among these cases, 75 (64%) tested positive for Leptospira infection by IgM ELISA test and/or PCR. By phylogenetic analysis of the 16S rRNA gene, all the samples tested were classified into L. wolffii (pathogenic group P2), showing high sequence identity to those of the type strain Khorat-H2 (97–99%) and L. wolffii reported in Bangladesh previously. Confirmed leptospirosis patients were mostly male (93%), aged 15–60 years (93%), living in rural areas in low socioeconomic conditions. Variable symptoms were presented by patients, with jaundice (84%), nausea/vomiting (84%), and myalgia (67%) being common. Some patients showed severe symptoms involving the nervous system (disorientation and neck stiffness) and the respiratory tract (cough, shortness of breath, and hemoptysis). Major risk factors for leptospirosis were exposures to mud/wet soil, sanding water, heavy rain, working in a paddy field, and cattle. In conclusion, L. wolffii was revealed to be circulating endemically in north-central Bangladesh, since its first detection in 2018, associated with variable and severe clinical symptoms in humans. Full article

Black spot is currently one of the most widespread diseases affecting Yanbian Pingguoli pears (Pyrus pyrifolia cv. ‘Pingguoli’), resulting in significant economic losses for fruit farmers. It is mainly caused by infestation by the fungal group of Alternaria species. To date, no research has reported the presence of Alternaria species and the pathogen of black spot disease on Yanbian Pingguoli pears in China. This study isolated, identified, and performed molecular profiling of 124 Alternaria strains collected from 15 major growing areas of Yanbian Pingguoli pear (more than 5000 trees). Moreover, the study evaluated the ability of Artemisia capillaris essential oil (AcEO) to suppress the mycelial expansion of Alternaria pathogens and conducted comprehensive chemical profiling. Overall, 124 pathogenic fungi were identified as Alternaria tenuissima (67 isolates, 54.0%) and A. alternate (57 isolates, 46.0%). AcEO showed a strong inhibitory effect on the two Alternaria species, with a minimal inhibitory concentration (MIC) value equivalent to 5.0 μL/mL. Eucalyptol, 2,2-Dimethyl-3-methylenebicyclo [2.2.1] heptane, (-)-alcanfor, and β-copaene were identified as the predominant bioactive components of AcEO. AcEO demonstrated concentration-dependent inhibition of the mycelial growth of A. tenuissima and A. alternata. These findings position AcEO as a promising candidate for developing sustainable fungicides to combat Alternaria-induced crop losses. Full article

Salmonella is a major zoonotic pathogen and phage cocktails offer a novel strategy against its infections. This study aimed to characterize Salmonella phages and assess the efficacy of various phage combinations, both in vitro and in vivo. Three phages (PJN012, PJN042, PJN065) were isolated, showing stability across a broad range of temperatures and pH values, and lacking genes associated with lysogenicity, virulence, and antibiotic resistance. Combined with two known phages (PJN025, vB_SalS_JNS02), they formed cocktails tested for lytic activity against S. Enteritidis and S. Typhimurium. Phage cocktails (comprising 2–5 phages) that demonstrated efficacy in vitro were validated using Galleria mellonella models. For S. Enteritidis strain 015, prophylactic cocktail C18 increased larval survival to 90% at 48 h (vs. 3% control). For S. Typhimurium strain 024, phage cocktail 26 showed the best therapeutic effect when co-injected with the bacterium, with a survival rate of up to 85% at 96 h, compared to 30% in the positive control group. Biofilm assays showed cocktails inhibited formation more effectively (e.g., at 24 h, C14 and C17 reduced biofilm formation by 93.74% and 94.21%, respectively) than removed established ones. The cocktails depended on bacterial type, phage genera, combinations, and incubation time. Robust in vitro screening remains crucial for optimizing phage formulations despite potential in vivo discrepancies. Full article

Edible and medicinal plants provide a treasure trove of natural phytochemicals for mining the next generation of green food preservatives. Herein, we evaluated antibacterial activities of 55–95% ethanol extracts from the edible rhizome of Rumex madaio (RmEEs). The 75% ethanol extract displayed the strongest antibacterial activity, and its purified fraction 2 (RmEE-F2) blocked the proliferation of common pathogens Staphylococcus aureus and Vibrio cholerae, with minimum inhibitory concentrations (MICs) of 391 μg/mL. RmEE-F2 (1 × MIC) altered the bacterial cell surface biophysical parameters and impaired cell structure, resulting in intracellular nucleic acid and protein leakage. It manifested bacteriostatic rates of 88.21–91.17% against S. aureus and V. cholerae in spiked fish (Carassius auratus) and shrimp (Penaeus vannamei) during storage at 4 °C for 24 h. Meanwhile, RmEE-F2 effectively rendered the pH rising and reduced lipid oxidation and protein degradation of C. auratus and P. vannamei meat samples at 4 °C for 6 days. Additionally, RmEE-F2 (< 781 µg/mL) showed non-cytotoxicity to human colon Caco-2, liver HepG-2, and lung A549 cell lines, and rescued V. cholerae and S. aureus-infected Caco-2 cellcells with enhanced viability of 14.31–16.60% (1 × MIC). Comparative transcriptomic analysis revealed down-regulated protein synthesis, cell wall and cell membrane synthesis, and or DNA replication and repair in the tested bacteria triggered by RmEE-F2. The major antibacterial compounds in RmEE-F2 included melibiose (9.86%), 3-(N, N-dimethylaminomethyl) indole (7.12%), and citric acid (6.07%). Overall, this study underscores the promising potential of RmEE-F2 for aquatic product green preservation. Full article

Basic helix-loop-helix (bHLH) transcription factors represent one of the largest transcriptional regulator families in cereal crops such as rice, maize, and wheat. They play crucial and diverse roles in regulating key agronomic traits and essential physiological processes. This review provides a systematic synthesis of the functionally characterized bHLH genes across the three major cereals, offering a comparative perspective on their roles in growth, development, and stress responses. We comprehensively summarize their documented functions, highlighting specific regulators such as TaPGS1 for grain size, rice ILI subfamily for leaf angle, OsbHLH004 for seed dormancy and maize “Ms23-Ms32-bHLH122-bHLH51” cascade for the anther development. Their conserved and species-specific functions in iron homeostasis (e.g., IRO2) and in responses to drought, cold, salinity, and pathogens are also detailed. Additionally, we discuss the underlying molecular mechanisms, including specific binding to E-box/G-box cis-elements, protein dimerization, and integration with hormone signaling pathways. By integrating the current knowledge, this review serves as a consolidated and up-to-date reference that highlights the strategic potential of bHLH transcription factors in molecular breeding programs for improving yield, quality, and stress tolerance in cereals. Full article

Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy, yet its molecular basis remains poorly understood. Numerous studies have analyzed RNA, protein, and microRNA alterations, but results are often inconsistent across subtypes and methodologies. To address this gap, we conducted a systematic review integrating transcriptomic, proteomic, and microRNA data from 117 human studies of FCD subtypes I–III. Differentially expressed factors were extracted, categorized by subtype, and analyzed using pathway enrichment and network approaches. Our integrative analysis revealed convergent dysregulation of neuroinflammatory, synaptic, cytoskeletal, and metabolic pathways across FCD subtypes. Consistently altered genes, including IL1B, TLR4, BDNF, HMGCR, and ROCK2, together with dysregulated microRNAs such as hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-132-3p, were linked to PI3K–Akt–mTOR, Toll-like receptor, and GABAergic signaling, emphasizing shared pathogenic mechanisms. Importantly, we identified overlapping transcript–protein patterns and subtype-specific molecular profiles that may refine diagnosis and inform therapeutic strategies. This review provides the first cross-omics molecular framework of FCD, demonstrating how convergent pathways unify heterogeneous findings and offering a roadmap for biomarker discovery and targeted interventions. Full article

Background: Dominantly acting variants in TUBB2B have primarily been associated with cortical dysplasia complex with other brain malformations 7 (CDCBM7), a disorder in which cortical brain abnormalities are typically linked to developmental delay/intellectual disability (DD/ID) and seizures. While the majority of TUBB2B pathogenic variants have been linked to isolated CDCBM7, only one family with CDCBM7 and congenital fibrosis of the extraocular muscles (CFEOM) has been reported so far. We describe a second individual with a severe phenotype of CFEOM combined with CDCBM7 carrying a pathogenic TUBB2B missense variant previously reported in two individuals with isolated CDCBM7. Methods: A trio-based WGS analysis was performed. The structural impact of the identified substitution was assessed by using the UCSF Chimera (v.1.17.3) software and PyMOL docking plugin DockingPie tool. Results: WGS analysis identified a de novo missense TUBB2B variant (p.Ile202Thr, NM_178012.5), previously associated with isolated CDCBM7. Structural analysis and docking simulations revealed that Ile202 contributes to establishing a proper hydrophobic environment required to stabilize GTP/GDP in the β-tubulin pocket. p.Ile202Thr was predicted to disrupt these interactions. Conclusions: Our findings broaden the mutational spectrum of TUBB2B-related CFEOM, targeting a different functional domain of the protein, and further document the occurrence of phenotypic heterogeneity. We also highlight the limitations of exome sequencing in accurately mapping TUBB2B coding exons due to its high sequence homology with TUBB2A and suggest targeted or genome analyses when clinical suspicion is strong. Full article

In Abidjan, the treatment of pig waste is becoming a priority given the continued growth of pig farms, which readily reuse manure as organic fertilizer. This study evaluated the effectiveness of anaerobic digestion for simultaneous biogas production and pathogen reduction from pig farm residues. Two 1600 L biodigesters were installed at pig farms in Port Bouët (PBk) and Abobo (Ab). They were fed with pig manure and water (1:4 ratio) and monitored over 56 days. The total biogas production was 22.63 m³ and 16.31 m³ for the PBk and Ab digesters, respectively, with peak production occurring between days 14 and 28. Following biofilter treatment, the methane content increased to 80–82%, yielding potential energy outputs of 2.32–3.29 kWh/d, with optimal production occurring at a pH of 7.28–7.76. The COD, BOD₅, organic acid, and total nitrogen levels decreased progressively in the biodigesters, while the mineral element content remained almost unchanged. Complete elimination was achieved for most of the bacteria tested (E. coli, Enterococcus, Salmonella, etc.). However, Bacillus and Clostridium were able to persist, albeit with significant reductions of between 3.11 and 5.79 log₁₀. Anaerobic digestion is an effective method of combining waste treatment and energy recovery. It eliminates major pathogens while producing valuable biogas. This makes it a sustainable waste management solution for urban agricultural systems. Full article

Pseudorabies virus (PRV), a major swine pathogen, causes severe neurological, respiratory, and reproductive disorders, resulting in substantial economic losses to the global swine industry. Previous studies have shown that the gD glycoprotein of PRV has an effective protective effect. In this study, we constructed a plasmid DNA vaccine (pVAX1-GD-Fc) encoding a gD protein fused with pig IgG Fc and evaluated the adjuvant effects of porcine cGAS, the universal STING complex mimic (UniSTING), or IFN-α in mice. The mice were immunized three times (days 0, 14, and 21) with pVAX1-GD-Fc in the presence or absence of an adjuvant, followed by lethal challenge with PRV-HLJ8 3 days after the final immunization. The results revealed that the pVAX1-GD-Fc group exhibited 20% mortality (1/5 mice) on day 7 postchallenge, and all adjuvanted groups achieved 100% survival during the 14-day observation period. Flow cytometric analysis of splenocytes one week after the second immunization revealed significantly greater CD8+ T cell proportions in the adjuvant groups than in both the mock and pVAX1-GD-Fc-only control groups (p < 0.01). Furthermore, T cell proliferation assays demonstrated a significantly increased stimulation index in the adjuvant-treated mice, confirming enhanced cellular immunity. These findings demonstrate that cGAS, UniSTING, and IFN-α can serve as effective vaccine adjuvants to rapidly enhance cellular immune responses to PRV, highlighting their potential application in veterinary vaccines. Full article

Background: The health and viability of captive elephants, which are central to off-site conservation efforts and health management in Thailand, is threatened by emerging infectious diseases. This is partly due to genetic differences in immune-related genes, especially in the major histocompatibility complex (MHC) and, among these, loci such as DQA play a crucial role in immune surveillance. Data pertaining to MHC polymorphisms in elephants are scarce, and thus this study investigated such polymorphisms and selection signatures in a partial fragment of exon 2 of the MHC Class II DQA gene. Methods: The approach we used targeted next-generation sequencing and diversity analyses of individuals from three captive elephant camps in Northern Thailand. Results: Eight alleles containing 11 SNPs were identified in the exon 2 fragment, encompassing both silent and missense mutations, some of which may influence immune function. Notably, the allele Elma-DQA*TH3, which is identical to Loaf-DQA*01 and Elma-DQA*01, previously reported as the most common alleles in Loxodonta and Elephas, was found at low frequencies. This shift may reflect local selective pressures that shape MHC allele distributions. Evidence of mixed selection (both positive and balancing) was detected in the partial fragment of DQA exon 2, suggesting a dynamic interplay between evolutionary forces. Positive selection likely reflects an adaptation to emerging or locally prevalent pathogens, whereas balancing selection maintains allelic diversity over time to enable a broad immunological response. Conclusions: Our findings reveal immunogenetic variations in captive Thai elephants, and provides insights into host–pathogen interactions that inform conservation and health strategies with the aim of improving disease resilience. Full article

The genus Orthoflavivirus (family Flaviviridae) comprises several important pathogens that are widespread across the globe, often co-circulating in many regions. In Austria, the closely related mosquito-borne West Nile (WN) and Usutu (USU) viruses have been detected since the early 2000s. Orthoflavivirus-neutralizing antibodies primarily target the major envelope protein E. However, due to their antigenic relationship, recurring contacts with different orthoflaviviruses can lead to the induction of broadly cross-reactive E-specific antibodies. These can pose a problem in the diagnosis and differentiation of orthoflavivirus infections. Therefore, we established immunological assays based on the non-structural protein 1 (NS1) to differentiate infections caused by WN and USU viruses. The NS1 protein is secreted during acute infection, and NS1-specific antibodies have been reported to be less cross-reactive than those against E. Using sera from individuals with a confirmed WN or USU virus infection, it was possible to distinguish between the two virus infections with high accuracy, specifically when IgM and IgG results were combined. Full article

Objectives: Antimicrobial resistance is a major global health threat. This study aimed to assess the impact of antimicrobial-resistant bacterial pneumonia on in-hospital mortality and length of hospital stay in Spain using a large, nationally representative cohort. Methods: A retrospective cohort study that used data from Spain’s Registry of Specialized Health Care Activity (RAE-CMBD) between 2017 and 2022. Hospitalized adults with bacterial pneumonia were included. Hospitalization episodes with bacterial antimicrobial resistance, defined according to ICD-10-CM codes for antimicrobial resistance (Z16.1, Z16.2), were analyzed versus hospitalization episodes without these codes. Multivariate logistic regression models, adjusted for potential confounders (e.g., age, comorbidity, intensive care unit admission) and sensitivity analyses (Poisson regression and propensity score matching test), were performed. Results: Of the 116,901 eligible hospitalizations, 6017 (5.15%) involved antimicrobial-resistant bacteria. Patients with antimicrobial-resistant bacterial pneumonia were older (median 75 vs. 72 years), had greater comorbidity (Elixhauser–van Walraven index: 8 vs. 5), and were more frequently admitted to the intensive care unit (22% vs. 14%). Crude in-hospital mortality was higher in the antimicrobial resistance group (18.46% vs. 10.05%, p < 0.0001), with an adjusted odds ratio of 1.47 (95% confidence interval, 1.36–1.58), p < 0.0001. Length of hospital stay was prolonged in antimicrobial resistance patients (median 14 vs. 8 days; adjusted incident rate ratio of 1.46; 95% confidence interval of 1.41 to 1.50). The most prevalent antimicrobial resistant pathogens were Staphylococcus aureus and Gram-negative bacilli (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli). Conclusions: Antimicrobial resistance is associated with longer hospital stays and an up to 50% higher risk of mortality. Despite the implementation of control policies in place over the past decade, policymakers must strengthen AMR surveillance and ensure adequate resource allocation. Clinicians, in turn, must reinforce antimicrobial stewardship and incorporate rapid diagnostic tools to minimize the impact of antimicrobial resistance on patient outcomes. Full article