Search Results (1,252)

This study characterizes the genomic identity, functional efficacy, and computational biophysics of FNL62-AMP, a novel antimicrobial peptide isolated from a phylogenomically distinct, newly identified Brevibacillus species. Production kinetics revealed a late-exponential phase onset of antibacterial activity with sustained potency against methicillin-resistant Staphylococcus aureus (MRSA). LC-MS/MS analysis identified the peptide sequence as NH₂-LLLLFR-COOH. FNL62-AMP demonstrated excellent formulation resilience, retaining full anti-MRSA activity under high thermal stress (80 °C for 6 h) and showing robust resistance to generic trypsin and proteinase K proteolysis. Formulative co-incubation assays demonstrated charge-dependent compatibility, where nonionic Triton X-100 preserved baseline efficacy while ionic surfactants induced antagonism. In vitro time-kill kinetics, scanning electron microscopy, and SYTOX Green assays confirmed rapid, concentration-dependent bactericidal action driven by immediate membrane permeabilization. Molecular dynamics simulations successfully captured the spontaneous self-assembly of 64 FNL62-AMP monomers into a stable macro-aggregate. This consolidation process was quantitatively characterized by a simultaneous contraction in the radius of gyration (R_g), a sharp drop in solvent-accessible surface area (SASA), and a transitional plateau in mean squared displacement (MSD). Ultimately, the high thermal stability, structural resilience, and predictable surfactant compatibility of FNL62-AMP propose ways to be developed for lead optimization and druggability. Full article

Chagas disease control relies on chemical interventions, currently compromised by insecticide resistance. Triatoma virus (TrV) emerges as a biological candidate, requiring standardized methodologies to purify, quantify, and relate viral doses to biological effects in triatomines. We established a comprehensive protocol for the quantitative study of TrV using Rhodnius prolixus as a model, combining physical purification via sucrose gradients and absolute quantification by qPCR targeting the TrVgp1 gene to link viral load with host survival. Primers were validated, and a plasmid standard curve was constructed for absolute quantification. Four isolation methods from Triatoma infestans macerates were compared, including an optimized discontinuous gradient protocol (EGM). High (6 × ${10}^6$ viral genome copies/µL) and low (2.47 × ${10}^5$ viral genome copies/µL) doses of EGM-purified TrV were evaluated in oral infections of R. prolixus over 16 days post-inoculation (dpi). The EGM protocol achieved the highest yields, around ${10}^9$ virus genome copies/µL of purified viral stock. Intestinal viral replication was dose-dependent, exhibiting distinct kinetic phases between low (3–7 dpi) and high (9–12 dpi) inoculum cohorts. Only the high dose significantly reduced host survival. In conclusion, this protocol allows high-yield TrV purification and absolute quantification in R. prolixus, establishing a robust dose–response foundation to assess triatomine susceptibility for integrated biological control programs. Full article

Background: Sustaining progress toward polio eradication requires not only effective vaccination but also a resilient laboratory network capable of timely poliovirus detection, confirmation, and genetic characterization. In the WHO African region, the African polio laboratory network provides essential virological support for eradication efforts; however, persistent circulating Vaccine-derived Polioviruses (cVDPVs) outbreaks and increasing demands of genomic surveillance continue to challenge laboratory capacity. Despite its critical role, evidence describing the operational performance, adaptive capacity, and evolution of regional polio laboratory network remains limited. This study evaluates the performance and operational experience of the African polio laboratory network in 2025, highlighting contributions to poliovirus detection, genomic surveillance, quality assurance, and outbreak response, while sharing lessons to inform regional public health systems. Methods: A retrospective secondary data analysis was conducted using laboratory surveillance and outbreak databases, supplemented by reviews of programmatic reports. Data were cleaned and harmonized prior to analysis. Descriptive analyses were performed to assess laboratory workload, timeliness indicators, genomic capacity, quality assurance performance, and operational challenges. Qualitative review of programmatic documents was conducted to identify contextual factors influencing performance. Results: In 2025, 77,230 Acute Flaccid Paralysis (AFP) specimens were analyzed across 16 laboratories. Ninety-two percent of specimens met the timeliness target for virus isolation, and 94% met the target for PCR-ITD. Genomic sequencing confirmed 20 cVDPV outbreaks in 10 countries. The establishment of new sequencing laboratories in Uganda and Nigeria reduced turnaround times, and a 2025 expansion plan aimed to build sequencing capacity in 12 additional countries. All laboratories assessed in 2024 for virus isolation, PCR-ITD, and environmental surveillance exceeded quality assurance accreditation thresholds and were rated “Pass”. The pilot implementation of Direct Detection Nanopore Sequencing (DDNS) techniques is expected to further strengthen genomic surveillance. Challenges remain, including stock out of essential supplies, uneven workloads, and infrastructure gaps. Conclusions: The African polio laboratory network has demonstrated sustained capacity, adaptability, and innovation in supporting polio eradication activities in the WHO African region. This study provides evidence on the importance of strengthening laboratory systems, expanding genomic capacity, and maintaining quality assurance mechanisms to support the final phase of polio eradication and broader public health surveillance. Full article

The macroH2A variants mH2A1 and mH2A2 are structurally similar but not identical. Our previous study demonstrated that mH2A1 is reloaded during cell-cycle progression, but whether mH2A2 follows similar dynamics has remained unclear. Here, we used native ChIP-seq in synchronized Huh-7 cells to profile both variants at G1/S and G2/M. Although mH2A1- and mH2A2-enriched domains overlapped extensively, mH2A2 domains were largely stable across the cell cycle, in sharp contrast to the dynamic reloading of mH2A1. Only a small subset of mH2A2 domains showed phase-specific deposition or displacement. Among these, G1/S-unique mH2A2 domains were preferentially located in the active A compartment and coincided with reduced chromatin accessibility at binding sites for cell-cycle regulators. These G1/S-unique domains co-localize with genes involved in mitotic progression within the same A compartment, suggesting potential regulatory roles in both chromatin organization and transcriptional regulation. These findings refine the classical view of macroH2A variants as static repressive marks: mH2A2 is not entirely static, but its cell-cycle dynamics are far more restricted than those of its paralog mH2A1, occurring only at a small subset of genomic loci, with a regulatory logic distinct from that of mH2A1. Full article

For decades, beef cattle producers have safely used steroidal implants as a low-cost, highly effective growth technology, delivering improvements in average daily gain (10 to 30%) and feed efficiency (5 to 15%) compared with non-implanted cattle. These improvements stem from increased skeletal muscle hypertrophy resulting from exposure to steroidal implants. This literature review investigates the history of commercially available estrogens, androgens, and progestins, as well as the release rates of steroidal implants and carrier technologies within the context of U.S. beef production. It also examines the genomic and non-genomic mechanisms of action of these growth-promoting technologies, along with the physiological responses across successive production phases from suckling to harvest, which highlight how these tools modify growth trajectories and metabolic rates in beef cattle. Presenting up-to-date implant administration strategies that align implant potency, active ingredients, and duration of effectiveness with various production stages to optimize weight gain while preserving carcass quality and marbling. Full article

Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have improved outcomes across squamous cell carcinomas (SCCs) of the head and neck, lung, esophagus, and skin, yet durable responses remain confined to a subset of patients in every subtype. Objective response rates vary substantially across SCCs despite overlapping genomic alterations, comparable tumor mutational burden, and high PD-L1 expression, indicating that tumor-intrinsic biomarkers alone do not explain this variability. Growing evidence points to the tumor immune microenvironment, and in particular the myeloid compartment, as a critical determinant of immunotherapy responsiveness. In this review, we synthesize current evidence on myeloid-mediated immune regulation across SCC subtypes, focusing on tumor-associated macrophages, myeloid-derived suppressor cells/tumor-associated neutrophils, and dendritic cells, and the mechanisms by which these populations impair antigen presentation, restrict T cell infiltration, and sustain immunologically “cold” tumor states. We further examine therapeutic strategies aimed at reprogramming rather than simply depleting suppressive myeloid populations, including radiation therapy, STING agonism, and myeloid-targeted agents (CSF1R, PI3Kγ, and CXCR2 inhibition), each of which has shown encouraging preclinical and early clinical activity in combination with ICI. Collectively, this evidence supports a model in which the myeloid compartment functions as an actionable, convergent determinant of ICI resistance across SCC subtypes, rather than merely a passive biomarker. We propose that through the integration of spatial and single-cell profiling of myeloid states with clinical history it will be possible to predict response to immune checkpoint therapy and personalize myeloid-directed combination strategies, though the specific biomarkers needed to match individual patients to a given myeloid-targeted approach remain to be defined. We further discuss the toxicity considerations associated with both immune checkpoint blockade and radiation-based combination approaches, the early-phase status of most myeloid-targeted agents currently in clinical development, and the extent to which mechanistic insight, derived predominantly from HNSCC, generalizes to squamous cell carcinomas arising at other anatomic sites. Full article

The cohesin complex is a highly conserved, ring-shaped protein assembly that plays fundamental roles in chromosome biology. Originally identified as the molecular glue that holds sister chromatids together from DNA replication until cell division, cohesin has since been recognized as a pleiotropic regulator of genome organization, gene expression, DNA repair, and cell fate determination. In embryonic stem cells (ESCs), cohesin’s functions extend beyond canonical sister chromatid cohesion to include the maintenance of three-dimensional (3D) chromatin architecture through DNA loop extrusion, regulation of pluripotency-associated transcriptional programs, and facilitation of homologous recombination-mediated DNA repair during the prolonged S phase. Recent discoveries have revealed that meiosis-specific cohesin components, particularly the α-kleisin subunit REC8 and its interacting partner STAG3, are expressed and functionally active in mitotic ESC chromosomes, where they contribute to chromosomal organization and sister chromatid cohesion in concert with mitotic RAD21-containing cohesin. Furthermore, the interplay between cohesin and condensin complexes at shared genomic binding sites has emerged as a critical determinant of chromosome topology, with cohesin depletion leading to aberrant condensin accumulation and chromosome hypercompaction. Importantly, perturbations in cohesin function not only impair ESC self-renewal but also direct lineage-specific differentiation, linking cohesin to stem cell fate determination. Germline mutations in cohesin and its regulators underlie a spectrum of developmental disorders termed cohesinopathies, while somatic mutations are frequently observed in various cancers. This review provides a comprehensive overview of the diverse roles of cohesin in chromosome structure, cell cycle regulation, and stem cell biology, with particular emphasis on recent findings in ESCs that illuminate the complex interplay between mitotic and meiotic cohesin complexes. Full article

Melatonin is an important stress-protective agent in plant growth. Methyltransferase (ASMT) is an important enzyme in the concluding phase of melatonin production in plants. In this study, we performed the genome-wide identification and functional investigation of the ASMT gene family in hexaploid wheat and 14 other plants. ASMT genes in 15 plants were identified by using HMM scanning against the proteomes derived from a single representative reference genome for each species. They were classified into three subfamilies I-III by constructing four types of phylogenetic trees (Neighbour-joining with p-distance model, Neighbour-joining with JTT model, Maximum likelihood, and Bayesian inference). Based on exon–intron structure and domain diagrams, a conserved structural pattern characterized by successive intron phases 1 and 0 (the “1-0” pattern) was found in ASMT genes during evolution. Collinear events analysis indicated that polyploidization and tandem duplication synergistically promote the expansion of T. aestivum ASMT members. Cis-acting element analysis revealed that numerous stress- and hormone-responsive motifs (such as ABRE and LTR) were present in ASMTs of wheat, suggesting a role for ASMTs in adaptive signal transduction. Transcriptome analysis revealed that specific T. aestivum ASMT genes were strongly responsive to stress; for instance, II_TraesCS2B02G041200 and II_TraesCS2B02G606200 were strongly upregulated under drought and salt stress, respectively. To independently confirm the stress responsiveness of these candidates in a different genetic background, we performed quantitative real-time PCR (qRT-PCR) on selected genes under drought and salt treatments. The result showed that the expression trends of transcriptome and qRT-PCR were almost the same, identifying these ASMT genes as strong stress-responsive candidates under drought and salt treatments. In this study, we performed identification, classification, evolution analysis and expression pattern analysis of ASMTs in wheat and 14 other plants. Our study will provide a framework for the targeted genetic improvement of melatonin-mediated stress resistance. Full article

Improving growth while preserving breed-defining characteristics is a central challenge in indigenous livestock breeding. We addressed this issue in Jining Grey goats using low-depth whole-genome sequencing and a conservative multi-evidence marker-prioritization framework. The discovery cohort included 70 performance-graded goats at 3 months (n = 37) and 6 months (n = 33; mean depth, 2.07×), and 47 seven-day-old goats from the same project were used for exploratory early-life trend analysis (mean depth, 2.10×). After site-level filtering, phasing, and within-cohort imputation, masking-based assessment of 120,000 genotype cells yielded 94.38% exact genotype concordance and a hard-dosage correlation of 0.919. Performance grading captured consistent differences in body weight and body-size traits, but the small 3-month Conventional group required conservative interpretation. Selective-sweep analyses highlighted breed-background regions, including signals near KIT, whereas GWAS and superior-genotype comparisons prioritized candidate growth loci, including chr10:78518687 for six-month chest girth and literature-supported genes involved in muscle growth and developmental regulation. Overlap and permutation analyses indicated limited physical overlap between growth-prioritized loci and major selective-sweep regions. A 99-SNP candidate panel showed exploratory prediction potential (maximum cross-validated r ≈ 0.47), whereas seven-day analyses showed only nominal trends without FDR significance. These findings provide a preliminary marker resource for future Jining Grey goat breeding and conservation, pending external validation, denser genotyping, and functional confirmation. Full article

Replication and transcription share the DNA template and must be coordinated to preserve genome integrity. Although temporally organized across the cell cycle, essential transcriptional programs—encoding replication machinery, canonical histones, and DNA repair factors—operate concurrently with DNA synthesis during S phase. Transcription–replication conflicts (TRCs) therefore constitute a recurrent endogenous source of replication stress (RS), particularly under hypertranscriptional or chromatin-constrained conditions. A frequent outcome of TRCs is the formation of R-loops–RNA:DNA hybrids that can stall or collapse replication forks, leading to DNA damage. This review summarizes current evidence supporting a broader involvement of ERCC6/CSB at the transcription–replication interface beyond its established role in transcription-coupled repair. We discuss how ERCC6 participates in RNA polymerase II processing, chromatin remodeling, R-loop metabolism, replication fork protection, and repair pathway engagement following RS, operating through both its ATPase domain and intrinsically disordered regions. Conversely, in homologous recombination-deficient contexts, ERCC6 may favor mutagenic restart mechanisms, including break-induced replication; and recent evidence indicates that ERCC6 status influences cellular fate and the genomic distribution of stress-induced mutations, linking transcription-coupled repair with transcription-dependent mutagenesis. These observations support a model in which ERCC6 coordinates transcription-associated repair with RS responses, shaping genome maintenance and mutational outcomes, with implications for cancer and therapeutic strategies. Full article

The geographic range and outbreak intensity of vector-borne viral infections are increasing as climate, land use, urbanization, and human mobility reshape vector ecology and human exposure. Despite their growing importance to public health, effective antiviral and preventive options remain limited for many emerging and reemerging vector-borne viruses due to viral genetic diversity, rapid evolutionary capacity, sporadic outbreak patterns, and economic constraints. While these viruses differ in taxonomy, genome organization, vector specificity, tissue tropism, and clinical manifestations, they exploit a shared vulnerability in host antiviral defense, particularly the timing of innate antiviral immunity to support viral replication, immune evasion, inflammatory dysregulation, and disease progression. Rather than simply suppressing antiviral defense, vector-borne viruses can delay early viral nucleic acid sensing, attenuate interferon induction or responsiveness, and extend the initial phase for viral replication. As viral burden increases and infected tissues undergo stress or damage, delayed immune activation can shift toward excessive inflammatory amplification, contributing to disease-specific pathology. In this study, we examine this temporal rewiring of innate antiviral immunity in representative vector-borne viruses such as dengue virus, chikungunya virus, and severe fever with thrombocytopenia syndrome virus and propose that understanding these conserved host dependencies may lead to broader, stage-specific, adaptable antiviral strategies that complement conventional virus-directed approaches. Full article

Psoriasis vulgaris is a chronic immune-mediated inflammatory disease in which treatment response is assessed using clinical indices such as the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), despite their limited ability to capture systemic inflammation and underlying immunological activity. This narrative review aims to summarize current evidence on inflammatory biomarkers for monitoring treatment response and to evaluate their potential clinical utility. A structured, non-systematic literature search was performed in April–May 2026 across PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov, focusing primarily on literature published during the preceding 10 years, with selected earlier studies being retained when directly relevant. Emerging data indicate that multiple biomarker domains may reflect therapeutic outcomes, including cytokines and chemokines, acute-phase proteins, complete-blood-count (CBC)-derived inflammatory indices, genetic markers, micro(mi)RNAs, metabolomic and lipidomic profiles, and tissue-based markers. These biomarkers may serve as severity-associated, baseline-predictive, pharmacodynamic, or prognostic markers, and these roles should not be interpreted interchangeably. Nevertheless, discrepancies between biomarker dynamics and clinical improvement occur, reflecting the partial dissociation between local and systemic inflammation, disease heterogeneity, and differences in response kinetics. Although inflammatory biomarkers provide a biologically grounded framework for assessing treatment response, their clinical implementation remains limited. Further large-scale, standardized studies are required to validate candidate markers and support the development of integrated, multi-omics approaches for personalized management. Full article

The aim of this study was to determine the association between matrix metalloproteinase (MMP1, MMP2, and MMP3) gene variations and susceptibility to Peyronie’s disease, and to investigate their effects on disease progression. This cross-sectional case–control study included a total of 182 individuals—91 patients with Peyronie’s disease and 91 healthy controls. Peripheral venous blood samples (5 mL) were collected, and genomic DNA was isolated using standard spin-column extraction kits. The promoter regions of MMP1, MMP2, and MMP3 were amplified via polymerase chain reaction (PCR), and genotyping was performed using restriction fragment length polymorphism (RFLP) assays with specific restriction endonucleases. All genotyping procedures were conducted in a blinded fashion. Hardy–Weinberg equilibrium analysis (HWE), binary logistic regression with rigorous multiplicity adjustments (Bonferroni-adjusted p-values), and non-parametric Kruskal–Wallis/Mann–Whitney tests with Dunn–Bonferroni post hoc comparisons were utilized. The frequency of the 2G allele for MMP1 (−1607 1G/2G) was significantly higher in the patient group (0.4830) compared to the control group (0.2360; p < 0.05). Similarly, significant differences in allele frequencies were observed for MMP2 (−735 C/T) and MMP3 (−1171 5A/6A) between the cohorts (p < 0.05). HWE analysis confirmed that all investigated variations were in equilibrium in both groups (all p > 0.05). Logistic regression analysis showed that the MMP1 1G/1G genotype was associated with lower odds of Peyronie’s disease (OR: 0.250, p < 0.001), while the 1G/2G (OR: 2.032, p = 0.023) and 2G/2G (OR: 3.509, p = 0.005) genotypes were significantly associated with increased odds. Temporally, carriers of the MMP1 2G/2G genotype presented predominantly in the acute phase, exhibiting a significantly shorter median symptom duration (6.00 months, IQR: 3.00–9.00) compared to 1G/1G carriers (12.00 months, IQR: 5.25–36.00; p = 0.016, adj p = 0.048). For MMP2 (−735 C/T), the CC genotype was associated with higher odds of Peyronie’s disease (OR: 3.049, p < 0.001), while the TT genotype was associated with lower odds (OR: 0.278, p = 0.002). Furthermore, penile plaques were detected in 90% of patients with the CC genotype (p < 0.001). Patients with the CC genotype presented with a median symptom duration of 6.00 months (IQR: 3.00–12.00), whereas TT carriers exhibited a significantly longer duration (24.00 months, IQR: 4.00–48.00; p = 0.002, adj p = 0.006). Regarding MMP3 (−1171 5A/6A), the 5A/5A (OR: 3.930, p = 0.002) and 5A/6A (OR: 2.050, p = 0.022) genotypes were significantly associated with increased odds of the disease, while the 6A/6A genotype showed an inverse association (OR: 0.226, p < 0.001). Patients carrying the 5A allele presented characteristically in the acute phase, with a median symptom duration of 6.00 months (5A/5A) or 4.00 months (5A/6A), which was significantly extended to a median of 24.00 months (IQR: 7.50–54.00) in the 6A/6A genotype (p < 0.001, adj p < 0.001). The findings indicate robust statistical associations between the MMP1 2G, MMP2 C, and MMP3 5A alleles and increased susceptibility to Peyronie’s disease, as well as distinct correlations with compressed symptom durations, acute-phase characteristics, and plaque presence. Because this study relied on peripheral blood DNA genotyping without direct tissue expression quantification in a cross-sectional design, these genetic variations reflect strong exploratory associations rather than direct causal evidence. These markers highlight significant prognostic potential that warrants validation in larger, prospective, longitudinal cohorts. Full article

In contrast to honeybees, the Australian stingless bee Tetragonula carbonaria appears to be robust against microbial pathogens. Streptomyces sp. 127Q, isolated from T. carbonaria, inhibited the growth of Lysinibacillus sphaericus, which is the only microorganism reported to affect T. carbonaria. The antimicrobials were purified from Streptomyces sp. 127Q by bioassay-guided isolation using ethyl acetate extraction and Diaion HP20 chromatography, followed by reverse phase HPLC fractionation. The antimicrobial compounds were identified by high-resolution mass spectrometry, UV-Vis-spectroscopy, nuclear magnetic resonance spectroscopy, and genome mining as new members of the trioxacarcin/gutingimycin family having a 1,2-dihydroxyanthraquinone aromatic core structure. A closely related gutingimycin with a 1,2-dihydroxyanthraquinone moiety was previously observed in a crystallisation experiment of trioxacarcin A with an oligonucleotide. Streptomyces sp. 127Q produces a wide range of trioxacarcins/gutingimycins. At the onset of trioxacarcins production, Streptomyces sp. 127Q appeared to rapidly convert trioxacarcin epoxides with water, guanine, and nicotinic acid. The 1,2-dihydroxyanthraquinone trioxacarcins, trioxacarcin 692 and trioxacarcin 780, inhibited L. sphaericus with minimal inhibitory concentrations (MICs) of 37.5 μM and 75 μM, respectively. The MIC against Escherichia coli and Staphylococcus aureus was 75 μM and 150 μM, respectively. In the photoantimicrobial screening, the MIC for trioxacarcin 692 against E. coli and S. aureus decreased by 8-fold, and for trioxacarcin 780 by 4-fold. Following light pretreatment, trioxacarcin 692 (9.4 μM) inhibited E. coli and S. aureus at concentrations comparable to those of the established antibiotics ciprofloxacin and vancomycin. Neisseria gonorrhoeae was only inhibited at an MIC of ca. 18.8 μM after light preincubation. The 1,2-dihydroxyanthraquinone trioxacarcins constitute powerful antimicrobial compounds belonging to the trioxacarcin/gutingimycin family. Full article

Ovarian cancer exhibits clinical heterogeneity; reliable prognostic stratification remains challenging despite extensive biomarker research. We performed an integrative analysis of transcriptomic and proteomic data to identify prognostically distinct molecular clusters in ovarian cancer. Using The Cancer Genome Atlas dataset, RNA sequencing and reverse–phase protein array data from 146 overlapping samples were analyzed. Genes (n = 150) and proteins (n = 67) showing nominal associations with overall survival (p < 0.05) were integrated; k–means clustering identified two patient clusters with highly significant differences in survival (p = 8.59 × 10⁻¹⁵). The SAR2 and ACTN4 genes and their corresponding protein expression levels showed high correlations among the significant genes and proteins (correlation coefficients > 0.80). Gene set enrichment analysis revealed that genes regulated by the PAX2 and BCL6 transcription factors were significantly enriched. The identified clusters were validated across six independent public transcriptomic datasets comprising 617 patients; consistent survival separation was observed between the patient clusters (p < 0.05). Clustering based on immunohistochemistry–derived expression profiles of nine proteins in an independent patient cohort demonstrated a significant difference in survival (p = 0.04). Integrative analysis of multi–omics data provided robust prognostic stratification in ovarian cancer while capturing the underlying molecular and biological features. Full article