Search Results (21,273)

Salmonella remains one of the most critical zoonotic pathogens in the poultry sector, linked to animal disease, foodborne illness, and the global crisis of antimicrobial resistance (AMR). Poultry acts as a major reservoir, enabling Salmonella transmission from hatchery to retail products through horizontal, vertical, and environmental routes. Despite the use of biosecurity, vaccination, antibiotics, and chemical decontamination, effective and sustainable control across the poultry value chain remains difficult, particularly in the face of rising multidrug-resistant strains and growing consumer concerns over chemical residues. Bacteriophages (phages), viruses that selectively infect and lyse bacteria, have emerged as a promising biological alternative for Salmonella control. Although many studies have reported the effectiveness of phages against bacterial species, including Salmonella, in the poultry industry, reports on their full potential to combat antimicrobial-resistant Salmonella across the entire poultry value chain remain limited. Therefore, this review synthesizes current evidence on the application of phages throughout the poultry value chain, including on-farm interventions, processing plant decontamination, and food packaging and storage. Findings from the reviewed articles indicate over a 90% reduction in Salmonella spp. in poultry farms and post-harvest meat, along with lower mortality in phage-treated groups compared to untreated groups; however, these outcomes depend on several factors (e.g., phage strains, concentrations, application methods, and environmental conditions). Laboratory, pilot, and field studies consistently demonstrate that phage preparations, especially when formulated as cocktails or combined with complementary interventions, can achieve substantial reductions in Salmonella, including antibiotic-resistant serovars, in live birds, eggs, poultry environments, and meat products. Unlike antibiotics and chemical sanitizers, phages act with high specificity, preserving beneficial microbiota and maintaining the sensory and nutritional quality of poultry products. Their safety has been supported by toxicological and genomic assessments, and several phage-based products have obtained regulatory approval, including Generally Recognized as Safe (GRAS) status for food applications in the United States. By integrating efficacy, safety, regulatory, and practical deployment data, this review highlights bacteriophages as a scientifically validated and One Health–aligned tool capable of reducing Salmonella transmission from farm to fork across the poultry value chain, thereby laying the foundation for their future adoption in the poultry industry. Phage-based interventions offer a sustainable pathway to enhance food safety, limit antimicrobial resistance (AMR) dissemination, and strengthen consumer confidence in poultry products. However, the major limitation is the emergence of phage-resistant bacterial strains, as well as the potential involvement of some phages in the transfer of resistance and virulence genes, which could raise public concern. Nevertheless, the use of phage cocktails and whole-genome sequencing, involving tools such as ResFinder and virulence finder, can facilitate the selection of safe phages for application. Full article

Antisense oligonucleotides (ASOs) are a class of nucleic acid therapeutics that modulate gene expression through diverse mechanisms. Since their initial demonstration in inhibiting viral genes, advances in medicinal chemistry, pharmacology, and delivery have enabled robust and durable target engagement across multiple tissues. Chemical modifications to the backbone, ribose, and nucleobases have improved nuclease resistance, binding affinity, and pharmacokinetics, while conjugation and delivery technologies have expanded tissue accessibility. Beyond classical RNase H–mediated RNA degradation, ASOs regulate gene expression via splicing modulation, microRNA inhibition, transcriptional activation, and translation modulation, supporting both gene silencing and upregulation strategies. Multiple ASO drugs are now approved, particularly for genetic diseases, with many more in clinical development. This review outlines the evolution of antisense technology, key chemical and delivery innovations, ASO pharmacokinetics and intracellular trafficking, the mechanisms underlying gene regulation, and current clinical applications and future opportunities. Full article

Prostate cancer remains a major therapeutic challenge, particularly after progression to castration-resistant disease, where persistent androgen receptor signaling, metabolic adaptation, immune escape, and treatment resistance jointly limit clinical benefit. Regulated cell death (RCD) is increasingly recognized not only as an endpoint of tumor cell elimination but also as a dynamic regulator of prostate cancer progression, therapeutic vulnerability, and tumor–immune interactions. In this review, we propose an immunometabolic framework in which androgen receptor signaling, lipid and redox metabolic reprogramming, oxidative stress, and therapeutic pressure converge to shape the susceptibility of prostate cancer cells to distinct RCD modalities. We focus on autophagy and ferroptosis as two extensively studied and translationally relevant pathways, while also discussing emerging roles of necroptosis, pyroptosis, and cuproptosis. Particular attention is given to how RCD-associated signals, including damage-associated molecular patterns, inflammatory mediators, and lipid peroxidation products, may remodel the tumor immune microenvironment and influence the transition between immune-cold and immune-inflamed phenotypes. We further summarize RCD-targeted therapeutic strategies, including ferroptosis induction, autophagy inhibition, nanodrug delivery systems, rational combination therapy, and biomarker-guided patient stratification. Finally, we discuss key translational barriers, including context-dependent biological effects, limited clinical validation, tumor heterogeneity, adaptive resistance, and insufficient predictive biomarkers. By integrating cell death biology with metabolic reprogramming, immune remodeling, and therapeutic resistance, this review highlights RCD as a promising but context-dependent therapeutic vulnerability in advanced prostate cancer. Full article

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disorder characterized by increased pulmonary vascular resistance and vascular remodeling. Genetic polymorphisms, epigenetic modifications, and ion channel dysregulation are increasingly recognized as key contributors to disease pathogenesis. Anoctamin-1 (ANO1/TMEM16A), a calcium-activated chloride channel, plays a critical role in vascular tone regulation. Objective: This study aimed to investigate the association between ANO1 gene polymorphisms (rs7127129 and rs2509153), promoter methylation status, and serum chloride levels in patients with idiopathic pulmonary arterial hypertension (IPAH), congenital heart disease (CHD), and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 106 IPAH patients, 40 CHD patients, and 30 CTEPH patients, together with 125 healthy controls, were included. The control group had a comparable age distribution, with a balanced sex ratio, whereas females predominated in all three PH groups. Genotyping was performed using TaqMan-based real-time PCR. Promoter methylation was analyzed using bisulfite conversion followed by quantitative real-time PCR. Serum chloride levels were measured using an ion-selective electrode method. Results: No significant association was observed between rs7127129 and rs2509153 polymorphisms and IPAH or CTEPH (p > 0.05). However, rs7127129 showed a significant association with CHD (p < 0.05). After excluding hypertensive patients, both polymorphisms remained significantly associated with CHD. Serum chloride levels differed significantly among groups (p < 0.001), with higher levels observed particularly in the CTEPH and CHD groups compared to controls, while IPAH patients exhibited intermediate but still elevated levels relative to controls. In contrast, promoter methylation levels were significantly lower in all patient groups compared to controls. An inverse relationship between chloride levels and methylation status was observed. Conclusions: ANO1 polymorphisms are not major determinants of IPAH or CTEPH but may contribute to CHD susceptibility. Increased serum chloride levels, together with decreased promoter methylation, suggest a potential mechanistic link between ion channel dysregulation and epigenetic alterations in pulmonary hypertension. Further large-scale and functional studies are warranted. Full article

The einkorn wheat group, comprising ancient diploid species (2n = 14, AA), including Triticum monococcum, Triticum boeoticum, and Triticum urartu, represents a valuable source of genetic variation for improving disease resistance in wheat. To develop a practical platform for introgressing powdery mildew resistance into bread wheat, we screened 21 einkorn accessions with Blumeria graminis f. sp. tritici (Bgt) race E09 and identified seven resistant donors. Because direct hybridization between diploid einkorn (AA) and hexaploid wheat (AABBDD) is constrained by genomic divergence and poor cross-compatibility, we crossed resistant einkorn accessions with susceptible durum wheat and induced chromosome doubling in the F₁ hybrids to generate synthetic durum–einkorn amphiploids. Nine amphiploids were obtained. Chromosome counts and genomic in situ hybridization confirmed the expected genomic constitution (AABBAA) in most lines, with limited variation in chromosome number in two amphiploids. Phenotyping against Bgt race E09 showed that three amphiploids retained high resistance, four showed moderate resistance, and two were moderately susceptible. Marker analysis identified five einkorn accessions contain known Pm genes such as Pm60, Pm60b, and PmNCA6/Pm37, as well as their derived amphipliods. Two einkorn accessions and their derived amphiploids may harbor novel Pm genes. Field evaluation of the agronomic traits of these amphiploids indicated some improvement in tillering, spike length, and seed weight. Moreover, these amphiploids had better seed-setting rates in crosses and backcrosses with common wheat. These synthetic durum–einkorn amphiploids thus offer a new bridging platform for transferring alien genes from diploid einkorn to hexaploid common wheat, providing valuable genetic resources for wheat-breeding programs. Full article

Metabolic dysfunction–associated steatotic liver disease (MASLD) is now the most common chronic liver disorder worldwide. Once started with hepatic steatosis, it can progress to metabolic dysfunction–associated steaohepatitis (MASH), cirrhosis, and even hepatocellular carcinoma. Insulin resistance is a major driver of hepatic lipogenesis in this disease context. Gut barrier dysfunction also contributes to the progression to MASH by allowing bacterial lipopolysaccharide (LPS) to breach into the hepatic tissues. Amphibian skin secretion peptides (ASSPs) are therefore of particular interest, given their combined metabolic and antimicrobial activities. Some ASSPs enhance glucose-stimulated insulin secretion and GLP-1 release, whereas others attenuate LPS-driven inflammatory signaling. This review introduces these ASSPs with a focus on their insulinotropic/incretinotropic and immunomodulatory activities. Also, in the latter part, pharmaceutical strategies to improve blood circulation time and structural stability would be discussed. Full article

The increasing resistance of agricultural pests and disease-vectoring arthropods to synthetic pesticides underscores the urgent need for novel and sustainable biocidal agents. This study evaluates, for the first time, the insect antifeedant and ixodicidal activities of essential oils derived from ten Amazonian Piper species and their major constituents. Antifeedant effects were assessed against Spodoptera littoralis, Myzus persicae, and Rhopalosiphum padi, whereas ixodicidal activity was tested on Hyalomma lusitanicum. Additionally, the effects of these oils on the plant-parasitic nematode Meloidogyne javanica were investigated. Essential oils from Piper mituense (51.6% apiol) and P. sancti-felicis (76.1% apiol) exhibited the highest bioactivity, achieving more than 75% feeding inhibition across all insect species and 100% tick mortality. P. mituense consistently demonstrated greater potency, suggesting possible synergistic interactions among its minor constituents. Principal component analysis linked apiol-rich chemotypes with broad-spectrum activity. In contrast, oils rich in oxygenated caryophyllene derivatives, particularly those from P. casapiense, showed strong selective antifeedant effects against R. padi. Pure apiol displayed activity across all assays, whereas no nematicidal effects were observed. Molecular docking analyses supported these findings, indicating that apiol can interact with acetylcholinesterase in addition to its known effect on cytochrome P450 targets. Overall, these results identify complementary Piper chemotypes with promising potential as dual-purpose biopesticides for integrated pest management strategies. Full article

Mycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia in children, yet little is known about the role of nasopharyngeal microbiota dysbiosis in susceptibility to infection and disease subtype. In this study, we performed 16S rRNA sequencing on nasopharyngeal samples from 102 pediatric MPP patients, 104 influenza A patients, and 103 healthy controls and compared the microbial diversity, composition, and functional profiles across groups. The MPP group exhibits an altered nasopharyngeal microbial composition, characterized by reduced microbial diversity and an increased relative abundance of genera including Mycoplasma, Pseudomonas, Acinetobacter, and Tannerella. Distinct microbiota profiles were identified for the MPP subtypes, with Mycoplasma more abundant in bronchopneumonia (BP) than in lobar pneumonia (LP). A microbial classifier based on the relative abundance of the nasopharyngeal microbiota was established to distinguish MPP patients from both influenza patients and healthy controls, with an area under the receiver operating characteristic curves of 0.978. Key microbial features associated with MPP included Mycoplasma, Mycobacterium, Aeromonas, and Acinetobacter. In addition, PICRUSt2-based functional predictions suggested alterations in amino acid metabolism and predicted functional pathways associated with bacterial infection and antimicrobial resistance in MPP patients. In conclusion, this study provides comprehensive insights into alterations in the nasopharyngeal microbiota in pediatric MPP. These findings highlight the potential role of dysbiosis in disease progression and suggest that changes in microbiota composition and functional profiles are associated with MPP infection. Full article

Thirteen mandarin and hybrid cultivars grafted onto the commercial rootstocks Rangpur Lime and Swingle Citrumelo were comparatively assessed for vegetative growth, fruit physicochemical attributes, and field incidence and severity of Altenaria Brown Spot (ABS) and Huanglongbing (HLB). The experiment was conducted from January 2015 to December 2018 under a randomized block design, with ten replicates per scion–rootstock combination. Plant height, canopy volume, fruit mass, juice yield, acidity, soluble solids, and disease assessments were performed. RL induced greater vegetative growth but was associated with higher HLB severity, particularly in the Dekopon IAC 2009 and TM × LP 358 varieties. SC resulted in less vigorous trees but improved fruit quality, with higher acidity and soluble solids. Regarding ABS, the Loose Jacket IAC 515 and Muscia varieties showed high susceptibility, while Ortanique IAC 554 and Rainha BRS exhibited tolerance to both ABS and HLB. These findings suggest that although RL promotes vigorous growth, it may increase disease susceptibility, whereas SC is associated with reduced disease severity and improved fruit quality. Ortanique IAC 554 and Rainha BRS showed consistently low severity of ABS and HLB, combined with stable vegetative development and fruit quality, underscoring the importance of rootstock choice for guiding cultivar deployment in orchards under high disease pressure. Full article

Background/Objectives: Ventilator-associated pneumonia (VAP) remains a major complication in patients requiring prolonged mechanical ventilation. The effect of tracheostomy on VAP risk remains controversial, particularly when differences in duration of mechanical ventilation are considered. This study evaluated the association between tracheostomy, VAP occurrence, and clinical outcomes in mechanically ventilated ICU patients. Methods: We conducted a retrospective matched exposed–unexposed cohort study in a tertiary-care ICU in Mexico City. Patients undergoing tracheostomy were compared with an age- and sex-matched subcohort of intubated patients receiving invasive mechanical ventilation for ≥48 h. VAP incidence was assessed using cumulative incidence, incidence density, and multivariable generalized linear models. Results: A total of 218 patients were included (55 tracheostomized and 163 intubated). VAP incidence density was similar between groups (31.5 vs. 30.3 per 1000 ventilator-days; RR 1.04, 95% CI 0.7–1.7), whereas cumulative incidence was higher among tracheostomized patients (61.8% vs. 22.7%; RR 2.7, 95% CI 1.9–3.9). Broad-spectrum antibiotics, mechanical ventilation ≥ 5 days, chronic pulmonary disease, and ICU stay remained associated with VAP occurrence in an exploratory multivariable model. Gram-negative microorganisms predominated, and antimicrobial resistance was more frequent among tracheostomized patients. Conclusions: Tracheostomy was associated with higher cumulative incidence of VAP, but a similar incidence density compared with endotracheal intubation. The crude association between tracheostomy and VAP disappeared after adjustment for confounding factors, suggesting that prolonged mechanical ventilation and ICU exposure are more important determinants of VAP risk than tracheostomy itself. Full article

Grapevine downy mildew, caused by the oomycete pathogen Plasmopara viticola (P. viticola), is one of the most devastating diseases threatening the global grape industry. The pathogen invades host plants through stomata, triggering a series of highly coordinated physiological disorders and biochemical defense events. This review systematically summarizes the dynamic changes in morphological structures (stomatal characteristics), physiological functions (photosynthesis, membrane system integrity, and carbon metabolism), and multi-level biochemical defense systems (reactive oxygen species (ROS) scavenging enzyme system, phenylpropanoid metabolic pathway, pathogenesis-related proteins, and phenolic compounds) in grapevines following infection. It focuses on analyzing the differences in the timing, intensity, and metabolic reprogramming of defense responses between resistant and susceptible cultivars, pointing out that the essence of disease resistance lies in early pathogen recognition and rapid defense induction. The conflicting conclusions regarding indicators such as soluble sugars, peroxidase (POD), and superoxide dismutase (SOD) are discussed from the perspectives of experimental systems, cultivar genetic backgrounds, and pathogen physiological race differences. Furthermore, the known physiological and biochemical alterations are linked to upstream signaling pathways, including salicylic acid and jasmonic acid (SA/JA), calcium signaling, and mitogen-activated protein kinase (MAPK) cascades. Recent advances in revealing resistance mechanisms in the omics era are also introduced. Finally, future research directions are proposed, including constructing multi-indicator dynamic evaluation models, verifying key gene functions using gene editing, exploring the potential of epigenetic regulation, and developing integrated control strategies combined with microbiome research. This review aims to provide theoretical support for grapevine downy mildew resistance breeding and sustainable disease management. Full article

Background/Objectives: Cervical cancer is mainly driven by persistent infection with high-risk human papillomaviruses (HPV), particularly HPV16 and HPV18. Despite advances in cytology, HPV-DNA testing and vaccination, challenges remain in the triage of HPV-positive individuals, prognostic stratification and prediction of treatment response. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs, together with host genetic factors influencing ncRNA expression and emerging lncRNA-encoded peptides, are increasingly recognized as regulators of HPV-associated carcinogenesis. This review summarizes their biological and potential clinical relevance. Methods: A structured literature search was conducted in PubMed and Scopus. Eligible studies included experimental, clinical, observational, genomic and translational investigations on ncRNA dysregulation, circulating or exosomal ncRNAs, treatment-response signatures, host genetic variation and lncRNA-encoded peptides in HPV-associated cervical precancer and cancer. Results: HPV oncoproteins can reshape host ncRNA networks through transcriptional and epigenetic mechanisms. Several miRNAs, lncRNAs and circRNAs are involved in cell-cycle control, apoptosis, senescence, epithelial–mesenchymal transition, immune regulation, DNA repair and treatment resistance. Circulating, exosomal and urinary ncRNA signatures have shown diagnostic or prognostic potential in exploratory cohorts. Specific lncRNAs, including ENSG00000267838/lnc-LENG9-5 and lncRNA-EME1, have been associated with chemoradiotherapy response and radioresistance. The lncRNA-encoded peptide TUBORF represents a novel preclinical therapeutic candidate, while genetic variation may further modulate lncRNA function in HPV-related cervical cancer. Conclusions: ncRNAs are promising candidates for risk stratification, non-invasive diagnosis, treatment-response prediction and therapeutic development in HPV-associated cervical disease. However, evidence remains exploratory, requiring prospective multicentre validation and standardized workflows before clinical implementation. Full article

Plateau waters in Northern Sichuan, China, act as critical headwaters of the Yellow River. Microbial communities in water bodies and soil matrices within this region are increasingly pressured by intensive animal rearing; yet few studies have characterized microbial shifts across entire riverine niches. In this study, we employed next-generation sequencing based metagenomics to investigate microbial features, community structure and diversity, metabolic potentials, and antibiotic resistance genes (ARGs) in the Baihe River, a tributary in the source region of the Yellow River. Sampling locations covered the main stem and three tributaries of the Baihe River, spanning from its source, through upstream and downstream segments, to the convergence site with the main stem of the Yellow River. Results revealed that Pseudomonadota and Bacteroidota were the most abundant phyla. The relative abundance of most taxa at multiple taxonomic levels exhibited an increasing trend along the river continuum driven by rising total nitrogen (TN) and total phosphorus (TP) concentrations; however, a notable exception occurred at BH1 (the Baihe source), where the abundance of numerous taxa was markedly higher than in downstream samples. We detected abundant ARGs predominantly associated with antibiotic resistance. Furthermore, prevalent viruses affiliated with the phyla Uroviricota and Nucleocytoviricota, together with pathogenic bacteria, were identified as etiological agents of diverse infectious diseases. This study provides novel perspectives for managing aquatic contamination in plateau river ecosystems by linking environmental variables, microbial succession, and resistome distribution. Full article

Pathogenesis-related (PR) proteins are crucial for plant defense against pathogen infection. However, the specific role of thaumatin-like proteins (TLPs), which comprise the PR-5 family, in plant immune responses has not been thoroughly investigated. Filipendula ulmaria is a medicinal plant with valuable pharmacological properties, including antimicrobial, anti-inflammatory, gastroprotective, immunomodulatory, and anticancer activities. The structure of the TLP family and its role in the immune system of meadowsweet have not been studied so far. The goal of this study was to analyze in detail the TLP gene family in meadowsweet and explore its response to fungal infection. In the meadowsweet genome, we identified 27 putative TLP genes, examined their structure and location on chromosomes, analyzed cis-regulatory elements in the promoter regions, predicted the structure and physicochemical characteristics of the encoded proteins, and performed a phylogenetic analysis. We also studied the differential expression of TLP genes under Bipolaris sorokiniana infection. Of six differentially expressed genes, three genes were up-regulated 48 h post-infection, suggesting their involvement in defense response to the fungus. The results obtained shed light on the role of the TLP gene family in the immune system of F. ulmaria and form the foundation for the creation of disease-resistant crops in agriculture and the development of bio-based antimicrobials in medicine. Full article

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article