Search Results (5,377)

Tripartite interaction among arbuscular mycorrhizal fungi (AMF), small grain cereals—including wheat, barley, oats, and rye—and pathogenic organisms constitute a highly complex ecological system with major implications for plant health, productivity and resilience. AMF colonization increases nutrient acquisition, particularly phosphorus and nitrogen, while concurrently priming host defense mechanisms that increase resistance to a broad spectrum of pathogens. These benefits, however, are strongly context-dependent and modulated by AMF species composition, host genotype, soil characteristics, and environmental conditions. AMF activate resistance pathways and modulate the rhizosphere microbiome, underscoring their central role in shaping plant–pathogen dynamics. Importantly, the relevance of these interactions extend beyond crop protection and yield stability to encompass food security and sustainability goals aligned with the One Health framework, which recognizes the interconnectedness of plant, environmental, and human health. Field implementation of AMF-based strategies has the potential to reduce reliance on chemical fertilizers and pesticides, thereby promoting sustainable cereal production, restoring soil biodiversity, and enhancing ecosystem services, with downstream benefits for human nutrition and environmental safety. This review integrates current knowledge on AMF–cereal–pathogen interactions, synthesizing mechanistic advances and applied perspectives while identifying critical knowledge gaps that must be addressed to effectively deploy AMF in resilient and sustainable agroecosystems within a One Health context. Full article

Bacterial spot disease in peaches, also known as bacterial shot hole disease, with Xan-thomonas arboricola pv. pruni (Xap) as the causal agent, poses a significant threat to peach yield and quality due to its long latency period, rapid onset, and difficulty in control. This article presents the first systematic review of research on the peach bacterial spot pathogen, Xap, comprehensively integrating the latest advances in disease distribution, pathogen identification, integrated control strategies, and mechanisms of pathogenesis and host resistance, thereby forming a complete and up-to-date knowledge framework. The aim is to provide a reference for the control of peach bacterial spot disease and to promote the sustainable and rapid development of the peach industry. Full article

The escalating crisis of antimicrobial resistance (AMR) and the stagnating antibiotic pipeline have renewed interest in bacteriophage therapy. While natural phages offer specificity and low toxicity, their narrow host range, bacterial resistance, and safety concerns limit clinical use. To overcome these hurdles, phages are being engineered using biotechnology. This review outlines the history of phage therapy and systematically summarizes advances in engineered phage preparation, including genetic modification, chemical conjugation, and physical encapsulation. We highlight the application of engineered phages against multidrug-resistant infections, gastrointestinal diseases through gut microbiome modulation, and as targeted delivery vehicles or immune adjuvants in cancer therapy. While significant advances have been made, several critical challenges remain, particularly in regulatory approval, large-scale manufacturing, and ensuring long-term safety. We conclude that engineered phages, as customizable and precise biological tools, are poised to advance precision phage medicine, offering a transformative solution to AMR and fostering convergence across synthetic biology, medicine, and environmental science. Full article

Hypoxia frequently triggers mass mortality events in pearl oysters during the summer months. Hypoxic preconditioning (HP), repeated exposure to sublethal low-oxygen conditions, has been proposed as a potential strategy to enhance stress resistance. Here, we investigated how HP affects hypoxia tolerance in the pearl oyster Pinctada fucata martensii, with emphasis on host apoptotic and immune regulation and the gut microbiota. Pearl oysters assigned to HP (experimental group, EG) and to a non-preconditioned control group (CG) were subjected to sustained hypoxic challenge (1.5 ± 0.1 mg/L DO for 15 days). HP significantly increased the expression of apoptosis- and immunity-related genes (MyD88, IκK, NF-κB) while suppressing JNK expression in gills after extended hypoxia (MyD88: EG 2.26 ± 0.65 vs. CG 0.96 ± 0.29, p < 0.05, ~2.3-fold increase; NF-κB: EG 1.50 ± 0.20 vs. CG 0.81 ± 0.31, p < 0.05, ~1.8-fold increase; IκK: EG 1.55 ± 0.38 vs. CG 0.65 ± 0.12, p < 0.05, ~4.0-fold increase; JNK: EG 0.49 ± 0.25 vs. CG 1.44 ± 0.51, p < 0.05, ~0.34-fold), consistent with a pre-activated yet controlled stress response. In parallel, HP markedly reshaped the intestinal microbial community under hypoxia, increasing alpha diversity (Ace, Chao, and Sobs indices) and enriching potentially beneficial bacterial phyla such as Planctomycetota, Nitrospirota, and Fusobacteriota, groups often linked to nutrient cycling and short-chain fatty acid production. Collectively, these results suggest that HP-enhanced hypoxia tolerance in P. f. martensii is associated with coordinated modulation of host apoptotic and immune signaling and concomitant shifts in gut microbiome diversity. These findings highlight the role of the host–microbiota axis in environmental acclimation and suggest that HP may be a practical tool for improving bivalve performance under hypoxic stress in aquaculture. Full article

Colorectal cancer (CRC) develops through both conventional adenoma–carcinoma and serrated neoplasia pathways, yet noninvasive screening still under-detects the advanced precursor lesions that enable true cancer prevention. Stool-based screening reduces CRC mortality, but its preventive impact remains constrained by limited detection of advanced precancerous lesions (APLs), including advanced adenomas and sessile serrated lesions. Next-generation multitarget stool DNA assays (mt-sDNA; e.g., Cologuard Plus) have established high sensitivity for CRC and specificity approaching 94%, leaving improved APL detection as the principal opportunity for innovation. This review presents a consensus framework for a multi-omic stool screening paradigm that integrates host epigenetic markers (DNA methylation) with gut microbiome features using artificial intelligence (AI). Multi-omics capture complementary layers of early tumor biology: epithelial shedding and field effects reflected in host methylation signals together with luminal ecological and inflammatory changes represented by microbial features. Evidence from cross-cohort microbiome studies indicates that microbial signatures provide an additive—rather than standalone—axis of information for CRC and its precursor lesions. Because microbiome-based models are highly susceptible to batch effects arising from collection devices, extraction chemistry, sequencing platforms, and bioinformatic pipelines, practical mitigation strategies are outlined, including harmonized pre-analytics, batch-aware study design, leakage-resistant validation, and computational harmonization. A translational roadmap linking analytical validity, locked-model development, and prospective colonoscopy-verified clinical validation is proposed, aligned with TRIPOD + AI, STARD, PROBAST-AI, SPIRIT-AI, CONSORT-AI, and DECIDE-AI reporting standards. Scenario modeling using BLUE-C prevalence estimates suggests that improving APL sensitivity from approximately 43% to 55–65% at ~94% specificity could translate to detecting roughly 13–23 additional advanced precancerous lesions per 1000 individuals screened, highlighting the potential prevention impact of a multi-omic approach. This framework aims to guide developers and clinical investigators toward next-generation stool tests capable of materially improving precursor-lesion detection while maintaining clinically acceptable specificity. Full article

New insecticides for indoor residual spraying (IRS) are being developed to manage resistance. Chlorfenapyr (Sylando^® 240SC), a pro-insecticide, is metabolized by active mosquitoes into the toxic metabolite tralopyril. This mode of action requires adapted “free flying” bioassays (because chlorfenapyr is converted to its toxic metabolite tralopyril when mosquitoes are metabolically active). A miniature-experimental hut (MEH) assay was developed within the Ifakara Ambient Chamber Test (I-ACT) with a rabbit as a host to measure residual efficacy under controlled conditions. Sylando^® 240SC was compared with SumiShield^® 50WG (clothianidin) for 12-month residual efficacy against malaria and arbovirus vectors. Residual activity was assessed on mud, wood and concrete with two huts per substrate treated with Sylando^® 240SC, one with SumiShield^® 50WG, and one with untreated control. Five replicates of 20 mosquitoes per strain (malaria vectors: pyrethroid-susceptible Anopheles gambiae and -resistant An. arabiensis and An. funestus; culicines Aedes aegypti and Culex quinquefasciatus) were exposed overnight at one-week post spraying and monthly thereafter. Multivariable mixed-effect logistic regression with binomial errors and log link function assessed non-inferiority with a 7% margin on mosquito mortality as the primary outcome for malaria vectors. Both products induced delayed mortality, with higher effects on malaria vectors than culicines. Across all substrates and malaria species combined over the full 12 months of observation, Sylando^® 240SC was non-inferior to SumiShield^® 50WG on mortality measured at 72 h (76% vs. 67%, OR = 0.86, 95% CI: 0.77–0.97) and 168 h (89% vs. 82%, OR = 0.74, 95% CI: 0.63–0.87). Sylando^® 240SC performed comparably to SumiShield^® 50WG, supporting its use as an IRS additional option. The new I-ACT mini-experimental-hut assay provides a practical tool for evaluating pro-insecticides. The importance of free-flight evaluation methods for pro-insecticides is discussed. Full article

Potato virus Y (PVY), widely regarded as one of the world’s most important plant viruses, seriously threatens global potato production and food security. PVY deploys its proteins to interact with key host factors, thereby enabling viral replication, accumulation, and systemic infection. PVY also exhibits high genetic diversity and frequent recombination, which promote host adaptation and immune evasion. In response, potato plants perceive viral effectors through intracellular immune receptors and activate antiviral defenses. Over the past decade, significant progress has been made in elucidating PVY–host defense and counter-defense mechanisms. Here, we summarize the molecular basis of PVY pathogenicity and highlight recent advances in PVY resistance genes (e.g., Ry_sto and Ry_chc). Finally, we integrate emerging insights from plant virology and nucleotide-binding leucine-rich repeat (NLR) biology to discuss prospective, multi-pronged strategies for PVY management. Full article

Background/Objectives: The ocular surface is continuously exposed to microorganisms, and disruption of host–microbial balance may lead to infection or postoperative complications. Increasing antimicrobial resistance and biofilm formation have highlighted the need for alternative or complementary non-antibiotic strategies to control ocular surface microbial burden. Liposomal ozonated oil eyedrops have demonstrated antimicrobial and antibiofilm activity in preclinical and preliminary clinical studies. The aim of this study was to evaluate changes in ocular surface microbiological culture results before and after treatment with liposomal ozonated oil eyedrops in a real-world clinical setting. Methods: This was a prospective, observational, real-world pre–post study including 101 eyes from 101 patients undergoing ocular surface microbiological sampling in routine clinical practice. Two samples were obtained per patient: Sample I immediately before treatment and Sample II at the routine follow-up visit after short-course treatment with liposomal ozonated oil eyedrops (1 drop, four times daily, for 4 days). The interval between samples ranged from 3 to 5 days (median 3 days). Microbiological cultures were classified as positive or showing no growth. Paired changes in culture positivity were analyzed using McNemar’s exact test. Results: At baseline, 87 of 101 samples (86.1%) yielded positive cultures, while 14 (13.9%) showed no growth. Following treatment, culture positivity decreased to 11 of 101 samples (10.9%), with 90 samples (89.1%) showing no growth. Among baseline-positive samples, microbiological clearance was observed in 76 cases (87.4%). No cases converted from culture-negative to culture-positive at follow-up. The reduction in culture positivity after treatment was statistically significant (McNemar’s exact test, p < 0.001). Recent antibiotic exposure within 14 days prior to baseline sampling was reported in 8 patients (7.9%). Persistent positive cultures were observed in a minority of cases and were mainly associated with common ocular surface pathogens. Conclusions: In routine clinical practice, short-term treatment with liposomal ozonated oil eyedrops was associated with a significant reduction in ocular surface culture positivity over a short follow-up interval. Full article

The Mabi Block is located in the southern Qinshui Basin, representing an underexplored region with high-rank coal seams that host significant Coalbed Methane (CBM) potential. Despite extensive CBM development in the nearby Anze and Zheng Zhuang blocks, the geological and geophysical controls on Coalbed Methane enrichment in Mabi remain insufficiently constrained. This study integrates the core data (63 samples) of isothermal adsorption tests, well-logging data from (13 wells), and 3D seismic attributes to systematically evaluate the key controlling factors, such as burial depth, roof and floor lithology, and sealing capacity, in the horizons of the No.3# and No.15# coal seams. Lithology is characterized using natural gamma ray (GR), acoustic (AC), deep resistivity (RD), compensated neutron log (CNL), and seismic wave impedance inversion. Coal quality parameters, ash content, and the Langmuir volume (V_L) are correlated with gas content, and structural controls are mapped using curvature, fault interpretation, and burial depth analysis. The results show that thick mudstone and limestone roofs, moderate burial depth (1100–1350 m), synclinal structural lows, and thicker coal seams (6–9 m) collectively enhance methane preservation. The ash content (%) exhibits a moderate negative correlation with the Langmuir volume (R² = 0.4) and gas content. Structural curvature (syncline) and fault intensity strongly govern lateral sealing integrity, where anticline zones and faulted regions display notable degassing. This integrated assessment contributes to a refined CBM optimization model for the Mabi Block and guides targeted future drilling, reservoir evaluation, and production optimization. Full article

Recent findings suggest that the gut microbiome significantly influences cancer outcomes, including responses to immune checkpoint inhibitor (ICI) treatments. Although early research focused on gut bacteria, it is now understood that the microbiome includes a bacteriome, virome, and mycobiome, all of which can modulate host immunity. Some commensal bacteria enhance anti-tumor immune responses and improve ICI efficacy, as demonstrated in both mice and patients. Fecal microbiota transplants (FMT) from patients responding to ICI have successfully reversed resistance in certain non-responders. In addition to bacteria, gut fungi and viruses are gaining attention as further factors influencing ICI effectiveness and toxicity. Recent multi-omics studies across cancer cohorts show that fungal and viral populations in the gut vary between ICI responders and non-responders. Commensal fungi may shape anti-cancer immunity by inducing inflammatory or tolerogenic pathways, while viral components can stimulate innate immune sensors that promote tumor surveillance. On the other hand, gut dysbiosis marked by expansion of pathobionts (including opportunistic fungi) and reduction in beneficial microbes is linked to serious immune-related adverse events (irAEs) such as ICI-induced colitis. This review discusses the multi-kingdom gut microbiome–bacteria, fungi, and viruses–and their interactions with the immune system in cancer therapy. We emphasize known mechanisms linking these microbes to anti-tumor immunity, overview human studies associating gut microbiome profiles with ICI outcomes and explore strategies to modulate the microbiome to enhance ICI efficacy while reducing toxicity. Understanding and utilizing the gut mycobiome and virome in conjunction with the bacteriome could pave the way for new biomarkers and therapeutic adjuvants in cancer immunotherapy. Full article

The rapid spread of antibiotic resistance through plasmid-mediated conjugation remains a primary global health concern. Despite its critical role in horizontal gene transfer, no approved drugs currently target this process, leaving a critical therapeutic gap. Integration Host Factor (IHF), a DNA-binding protein essential for plasmid replication and mobilization, emerges as a promising yet underexplored target for anti-conjugation strategies. This work aimed to develop a predictive computational model and identify small molecules that disrupt IHF function, thereby reducing plasmid transfer and limiting resistance gene dissemination. A curated dataset of 65 compounds with reported anti-plasmid activity was analyzed using a 3D-QSAR model based on algebraic descriptors computed with QuBiLS-MIDAS. The model was validated through leave-one-out cross-validation (Q² = 0.82), Tropsha’s criteria, and Y-scrambling. Representative compounds were selected via pharmacophore clustering and evaluated through molecular docking at both the DNA-binding site and a predicted allosteric pocket of IHF. The most promising complexes underwent 200 ns molecular dynamics simulations to assess stability and interaction patterns. The QSAR model demonstrated strong predictive performance (R² = 0.90). Docking simulations revealed more favorable binding energies at the allosteric site (up to −12.15 kcal/mol) compared to the DNA-binding site. Molecular dynamics confirmed the stability of these interactions, with allosteric complexes showing lower RMSD fluctuations and consistent binding energy profiles. Dynamic cross-correlation analysis revealed that allosteric ligand binding induces conformational changes in key catalytic residues, including Pro65, Pro61, and Leu66. These alterations may compromise DNA recognition and disrupt the initiation of replication. To our knowledge, this is the first computational study proposing allosteric inhibition of IHF as an anti-conjugation strategy. These findings provide a foundation for experimental validation and the development of novel agents to prevent horizontal gene transfer, offering a promising approach to restoring antibiotic efficacy against multidrug-resistant pathogens. Full article

Cervical cancer has a high incidence and mortality, and is one of the leading causes of cancer-related deaths among women worldwide. The infection with high-risk subtypes of the human papillomavirus (HPV) represents a crucial factor in the development of precancerous lesions. HPV oncoproteins target multiple host factors to promote uncontrolled cellular proliferation, genomic instability, profound metabolic reprogramming, resistance to apoptosis and immune evasion. Thus, cervical carcinogenesis involves metabolic reprogramming in patient cells, such as enhanced aerobic glycolysis, and altered glutamine, lipid and mitochondrial metabolism, which collectively support the bioenergetic and biosynthetic demands of cancer cells. Cancer cells also activate several mechanisms to adapt and survive under hypoxic/anoxic conditions. The mechanisms underlying cervical carcinogenesis often involve non-coding RNAs. This review aims at summarizing the mechanisms and factors involved in the development and progression of cervical cancer following HPV infection, and offers an overview of the available therapies that have been developed for this disease. Full article

Introduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017–2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 ± 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory. Full article

Beta-2-microglobulin (B2M) is a key component protein in the processing and presentation of major histocompatibility complex (MHC)-I antigens and plays an important role in the immune system regulation. Previous studies have shown that B2M is significantly overexpressed in the intestinal tissues of sheep that are resistant to E. coli F17b infection (defined by milder clinical symptoms post-challenge) compared to those that are susceptible (exhibiting severe diarrhea). Based on this finding, this study aimed to investigate whether B2M influences the adhesion of E. coli F17b to sheep intestinal epithelial cells (IECs) and to assess its role in regulating IEC proliferation and migration. We tested this by overexpressing and knocking down B2M in IECs, and then measured bacterial adhesion through colony counts and fimbrial gene expression (RT-qPCR). Moreover, cell health was assessed using proliferation (CCK-8 and EdU) and migration (scratch) assays. The results showed that upregulation of B2M expression inhibited E. coli F17b adhesion and promoted IEC proliferation and migration. Silencing B2M increased bacterial adhesion and impaired cell function. In summary, B2M helps protect sheep IECs from E. coli F17b by strengthening the epithelial barrier through improved cell growth, proliferation, and migration. These findings elucidate part of the host defense mechanism against E. coli F17b, providing a basis for further research. Full article

Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut–lung axis and improve respiratory innate immunity in a mouse model of Streptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) were orally administered to Swiss mice prior to pneumococcal challenge. The resistance to the infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads, prevented bacteremia, and attenuated lung injury. This protective effect was associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. Conclusions: These findings demonstrate a strict strain-dependent effect among porcine L. salivarius isolates and identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innate immunity through the gut–lung axis. This work supports further studies of LAFF998 as an immunobiotic strategy for the prevention of respiratory infections in pigs. Full article