Search Results (9,139)

Drug-resistant Klebsiella pneumoniae is a serious clinical problem, and bacteriophages are being investigated again as antibacterial agents. This study describes the phenotypic characterization and a preliminary in vivo evaluation of vB_Kpn_NIIPB-V0006, a bacteriophage isolated locally on a drug-resistant clinical K. pneumoniae strain. The genome of the phage was not sequenced. It has therefore not been screened for lysogeny-associated, toxin, virulence or antimicrobial resistance genes, and the results below describe what the phage does, not whether it is suitable for therapy. We assessed plaque morphology, specific lytic activity, titer, host range on a limited non-target panel, particle morphology, adsorption, one-step growth, chloroform exposure, the frequency of phage-resistant host variants, endotoxin reduction, short-term safety in mice and antibacterial effect in guinea pigs. The phage lysed the target strain, with an Appelman activity of 10⁻⁸ and a titer of 1.7 × 10¹¹ PFU/mL. Processing with 1-octanol lowered endotoxin content from 1200 to 12 EU/mL and preserved 80% of infective activity. Mice given the preparation intraperitoneally showed no mortality and no visible acute toxicity over 14 days. In guinea pigs with systemic K. pneumoniae infection, survival was the primary outcome: 0.5 mL three times daily gave 6/6 survivors against 1/6 in untreated controls (p = 0.015). Splenic bacterial burden, a secondary outcome, was also lower in that group (2.64 against 4.41 log₁₀ CFU/g). Two features of the design bias this second comparison in favor of treatment, since survivors and non-survivors were sampled at different times, and phage being carried over into the plating step is likely to have lowered colony counts. The 1.77 log₁₀ difference should therefore be read as an upper bound. The phage merits further study, but whole-genome sequencing, confirmation of the host species, host-range testing against diverse clinical isolates and a controlled comparison with antibiotic treatment are all needed before any therapeutic claim can be made. Full article

Network Digital Twins (NDTs) require accurate, structured, and timely data from heterogeneous communication networks. However, many existing approaches assume that this information is already available and do not address the operational path needed to convert raw observations into deployable twin artifacts. This paper presents DANA, a lifecycle-aware data acquisition and transformation system for dedicated network devices and general-purpose systems hosting virtualized or containerized functions. Its key technical contribution is a unified workflow that coordinates centralized and distributed acquisition through a common, state-aware normalization layer. Each observation is associated with source, temporal, scenario, and lifecycle metadata, enabling the system to preserve the structural baseline used to construct the twin while processing runtime monitoring information separately. The normalized representation is decoupled from deployment-specific descriptor generation, while data and control exchanges follow a publish/subscribe communication model. The system is evaluated in two complementary controlled laboratory scenarios. The centralized workflow demonstrates accurate topology reconstruction and high agreement in network reachability, whereas the distributed workflow validates the complete path from host-level acquisition and normalization to descriptor generation and twin instantiation. Complementary local microbenchmarks characterize MQTT transport, fixed-load resource use, and stop/recovery event propagation to a test consumer while preserving the structural baseline. These results support the feasibility of the proposed workflow in the studied environments; large-scale operation and full synchronization of deployed NDTs require further experimental validation. Full article

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), arises from complex interactions among genetic susceptibility, immune dysregulation, environmental factors, and the gut microbiome. Bacterial dysbiosis has been extensively studied, whereas the gut virome—comprising eukaryotic viruses and bacteriophages—remains less understood. Viruses can affect the intestinal barrier directly by infecting epithelial and immune cells, or indirectly by reshaping bacterial communities and host immunity. However, current evidence is dominated by cross-sectional associations and animal models, and whether virome alterations drive or result from intestinal inflammation remains unresolved. In this review, we provide a focused overview of intestinal barrier components relevant to IBD, synthesize human and animal evidence on IBD-associated viruses, and distinguish direct viral effects, microbiota-mediated effects, and bidirectional virus–microbiota interactions. We highlight bacteriophage–bacteria interactions as a central and potentially causal axis, discuss UC- and CD-specific differences, and outline causality gaps, search methodology, and emerging therapeutic strategies. Finally, we propose key unresolved questions and future research directions. Full article

Viral dynamics of acute HIV infection and HIV rebound following suspension of antiretroviral therapy may be qualitatively similar but must differ given, for one, the development of adaptive immune responses. Understanding the differences between acute HIV infection and viral rebound dynamics in pediatric populations may provide insights into the mechanisms of viral control with potential implications for vaccine design and the development of effective targeted therapeutics for infants and children. Mathematical models have been a crucial tool to elucidate the complex processes driving viral infections within the host. Traditionally, acute HIV infection has been modeled with the standard model of viral dynamics, initially developed to explore viral decay during treatment, while viral rebound has necessitated extensions of that standard model to incorporate explicit immune responses. Previous efforts to fit these models to viral load data have underscored differences between the two infection stages, such as increased viral clearance rate and increased death rate of infected cells during rebound. However, these findings have been predicated on viral load measurements from disparate adult individuals. In this study, we aim to bridge this gap, in infants, by comparing the dynamics of acute infection and viral rebound within the same individuals by leveraging an infant non-human primate Simian/Human Immunodeficiency Virus (SHIV) infection model. Ten infant Rhesus macaques (RMs) orally challenged with SHIV.C.CH505.375H.dCT were given ART at 8 weeks post-infection. These infants were monitored for up to 60 weeks post-infection to ensure full suppression, then underwent analytic treatment interruption (ATI), resulting in viral rebound. We use the HIV standard viral dynamics model fit to viral load measurements in a nonlinear mixed effects framework to identify primary mechanisms distinguishing acute and rebound infection dynamics. We find that the primary difference between acute infection and viral rebound is the increased death rate of infected cells during the rebound phase. These findings allow us to formulate hypotheses about the effects of adaptive immune responses. Specifically, we propose that delayed viral rebound is characterized by a stronger CD8+ T-cell response. Our analysis provides evidence to support this notion and helps elucidate the observed outcomes. Full article

We examine how developer origin, citizenship-perspective instructions, and English versus Mandarin presentation shape sentiment scores from large language models (LLMs) for nationality-matched actions. Across two experiments using the same eleven-model panel, we collected 4,065,600 response records: 2,032,800 for the main corpus and 2,032,800 for the earlier corpus. Each corpus contains 26,400 bilingual stimulus rows, comprising 13,200 nationality-matched pairs across 22 event categories, two intended polarities, and three temporal frames, evaluated under seven conditions. Inference about developer origin uses ten models from the United States (US) and China and a nine-developer sensitivity analysis. In the main experiment, the English baseline developer-origin gap is $+0.698$ score points (exact model-label permutation $p=0.175$; developer-level $p=0.238$). Citizenship-perspective instructions produce language-averaged attribution changes of $+5.20$ points for the US persona and $-5.76$ for the China persona. All ten models shift in the requested direction in both English persona conditions; nine do so in each Mandarin condition. Mandarin changes absolute scoring, especially for positive-design items, while its average factorial effect on the paired attribution contrast is small and uncertain. The temporal origin interaction is also uncertain ($-0.142$ points; $p=0.587$), despite polarity-dependent temporal patterns. Non-numeric returns account for $0.064\%$ of main-experiment responses and occur only among hosted models. The experiments converge on substantial average persona steering and modest, uncertain baseline origin differences, with model-specific exceptions. Corpus content, persona wording, and collection period vary together, and reuse of the panel adds no independent origin units. The findings identify explicit perspective instructions as a consequential part of the scoring protocol within this fixed panel. The audit concerns nationality-matched generic scenarios and does not establish equivalence between origin groups or the absence of broader geopolitical bias. Full article

Olive knot disease, caused by Pseudomonas savastanoi pv. savastanoi, is a significant economic threat to olive cultivation in Mediterranean regions. This study focused on the polyphasic characterization of fifty-five P. savastanoi (Psav) isolates from various hosts (olive, oleander, myrtle, and jasmine) isolated in Crete, employing phenotypic, molecular, and copper resistance analyses. Biochemical profiling using LOPAT and API20 NE tests confirmed 100% similarity between olive, jasmine and oleander isolates and the type strain CFBP1670^T. Molecular characterization (BOX- and iaaL-PCR) revealed limited genetic variation among most isolates, with minor variations in myrtle, oleander, and Spanish broom strains. Multilocus sequence analysis further supported the close genetic relatedness of the Cretan isolates, while revealing limited internal differentiation. Copper resistance assays showed that most isolates were moderately sensitive (0.4 mM), while one oleander and one jasmine isolate were resistant (≥0.8 mM). In vitro evaluation of copper formulations showed that copper hydroxide, Bordeaux mixture, and tribasic copper sulfate effectively inhibited Psav growth, while copper oxide and copper oxychloride were largely ineffective. Finally, the copper resistance genes copA, copB, copD, copR, copS, and cusA were identified in all tested isolates regardless of their individual copper sensitivity levels, whereas copC, cusB, and cusC were not detected. This suggests that phenotypic variations in copper sensitivity likely stem from differences in gene expression rather than the mere presence or absence of these specific genes. These findings enhance the understanding of Psav diversity and provide a robust framework for optimizing sustainable management strategies for olive knot disease in Crete. Full article

Preliminary evidence suggests that patients with Enterococcus faecalis bacteremia and infective endocarditis, particularly those without an identifiable source, may have an increased prevalence of colorectal neoplasia. Whether systematic colonoscopy should be recommended in this population remains unresolved. EnteroColonus is a multicenter, prospective, observational matched cohort study that will recruit adults aged 50 years or older with E. faecalis bacteremia and/or infective endocarditis from 22 Spanish centers, together with asymptomatic controls undergoing colorectal cancer screening. Cases will be stratified into E. faecalis bacteremia/endocarditis of unknown origin (EFBEUO) and with suspected source (EFBESS). The original planned sample size initially was 414 participants: 276 cases and 138 matched controls. Under the amended protocol, the current confirmatory sample-size target is 165 participants (110 cases and 55 matched controls; 2:1 case-to-control allocation). Core procedures include colonoscopy, histopathology, clinical and microbiological phenotyping of colonic samples, fecal microbiome profiling by shotgun metagenomics, detection of E. faecalis genetic material in colorectal biopsy specimens using 16S sequencing and species-specific qPCR, and whole-genome, SNP, and phylogenetic analyses of clinical isolates. Secondary endpoints include microbiome profiles, biopsy positivity for E. faecalis, genomic traits of bloodstream isolates, mortality, relapse/recurrence, and development of a colorectal neoplasia risk score. This protocol is designed to clarify which patients with E. faecalis bloodstream infection might benefit from systematic colonoscopy evaluation and to explore host–microbe mechanisms underlying the observed association with colorectal neoplasia. Full article

Viral therapy requires effective control of intracellular viral replication while limiting harmful host responses that may contribute to disease progression and complications. Thymoquinone (TQ), a major bioactive constituent of Nigella sativa, has potential antiviral and host-protective properties, but its therapeutic implications are limited by poor aqueous solubility, chemical instability, and variable tissue exposure. This review critically explores TQ nanoformulations (Nano-TQ) as a promising strategy to overcome these limitations and enable dual antiviral therapy through improved intracellular delivery and modulation of virus-associated host injury. Research published between 2000 and 2026 is evaluated, with emphasis on TQ-specific antiviral activity, nanoformulation platforms, intracellular trafficking, virus-informed delivery, host complications, and translational development. Current evidence indicates that nanoformulation can improve the pharmaceutical and pharmacokinetic properties of TQ and may facilitate delivery to disease-relevant tissues. However, direct evidence that Nano-TQ can achieve functionally relevant intracellular delivery, selectively engage virus-related targets, or provide superior antiviral efficacy over free TQ remains limited. We therefore propose that the key translational benchmark should be a reproducible therapeutic advantage coupled to intracellular TQ exposure, target engagement, and reduced infectious viral output rather than improved bioavailability alone. Future studies should integrate virus-specific infection models, PK–PD relationships, and safety assessments to progress Nano-TQ toward a clinically relevant dual-action antiviral nanomedicine. Full article

Adjuvant chemotherapy is a cornerstone of curative treatment for solid tumours; however, its benefit is frequently limited by poor tolerability and low treatment completion rates after surgery. Importantly, tolerability decreases from neoadjuvant to adjuvant regimens, a phenomenon particularly evident in gastrointestinal malignancies and observed in breast cancer, despite the latter generally involving less extensive surgery. Moreover, the mechanisms underlying this reduced tolerability remain a conundrum in clinical practice. This narrative review explores the discrepancy between neoadjuvant and adjuvant chemotherapy tolerability in gastrointestinal and breast cancers, focusing on potential biological and pharmacological determinants. Clinical and translational evidence is analysed, including treatment completion, dose intensity, and toxicity profiles in perioperative settings (i.e., any chemotherapy around the time of surgery, e.g., preoperative, intraoperative, and immediately postoperative chemotherapy), with emphasis on conventional cytotoxic regimens. Across tumour types, neoadjuvant chemotherapy is consistently associated with higher completion rates and greater dose intensity than adjuvant treatments. Although postoperative morbidity, nutritional impairment, sarcopenia, organ dysfunction and delayed recovery contribute to reduced tolerance and may prevent the initiation or completion of postoperative chemotherapy, particularly in gastrointestinal cancers, these factors may not fully account for the observed differences across treatment settings. We therefore discuss additional pharmacokinetic and tumour-related hypotheses as complementary explanations requiring clinical validation. Emerging evidence indicates that tumour burden and surgical resection may modify systemic drug handling, including pharmacokinetics and tissue distribution. The removal of a tumour could decrease the sequestration of drugs and change the interactions between the host and the drugs, which might narrow the therapeutic index after surgery. Consequently, the tolerability of adjuvant chemotherapy could be linked to both postoperative vulnerability and potential biological changes resulting from tumour removal. Optimising treatment sequencing will require integration of pharmacological, physiological, and tumour-specific factors to develop personalised strategies that balance treatment efficacy and quality of life. Full article

Diphthamide-specific mono-ADP-ribosylating toxins form a structurally conserved but phylogenetically diverse family of AB-type bacterial toxins, with Pseudomonas exotoxin A (PE) serving as a prototypical member. Here, we expand the known diversity of PE-like toxins (PLTs) through comprehensive genome mining and phylogenetic, structural and sequence analyses of PE, Chx, and their Aeromonas and Vibrio cholerae homologues. Aeromonas toxins separate into two distinct groups: a PE-like cluster (AEI) and a cholix-like cluster (AEII), while a fourth cholix subgroup (ChxIV) is identified within V. cholerae, expanding the previously described ChxI–III classification. Although all newly identified toxins retain the core catalytic architecture and hallmark residues essential for ADP-ribosylation of eEF2, they differ in key functional motifs, including receptor-binding residues, furin cleavage loops, and C-terminal ER-retrieval signals, suggesting variation in host-cell uptake routes and intracellular trafficking. Signal peptides were present in all toxins but varied modestly between clusters, consistent with normal species-level Sec-pathway variation rather than divergent secretion mechanisms. Together, our findings provide a significantly expanded overview of PLT diversity and indicate that Aeromonas-derived toxins comprise at least two evolutionarily and mechanistically distinct groups. These insights offer a framework for future functional studies and highlight PLTs as emerging virulence factors in environmentally and clinically relevant bacteria. Full article

Cordyceps fumosorosea (Wise) is a prominent entomopathogenic fungus with a broad host spectrum. The specificity of its infection mechanisms across different hosts, especially among lepidopteran species, remains largely enigmatic. This study employed RNA sequencing (RNA-Seq) and Tandem Mass Tag (TMT) proteomics to elucidate the differential pathogenic behavior exhibited by a particular C. fumosorosea isolate when confronting Plutella xylostella and Spodoptera litura. Our analyses revealed 3342 and 2416 differentially expressed genes (DEGs) and 332 and 296 differentially expressed proteins (DEPs) in C. fumosorosea cultured on the cuticles of P. xylostella (PI) and S. litura (SI), respectively. Notably, gene clusters and proteins associated with metabolism, cellular processes, and organismal systems were predominantly upregulated in the strain cultivated on PI compared to that cultivated on SI. In the PI group, significantly enriched metabolic pathways included fatty acid metabolism, nitrogen metabolism, and the metabolism of glycine, serine, threonine, and phenylalanine. Conversely, in the SI group, the upregulated proteins were significantly enriched in pathways related to phenylalanine metabolism, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, and peroxisomal activities. These insights shed light on the reasons behind the distinct pathogenicity exhibited by a single C. fumosorosea against diverse hosts, offering prospects for the engineering of fungal strains with enhanced virulence. Full article

Little is known about the baseline health status of Australia’s native rodents. The resultant knowledge gaps are problematic for wildlife translocations, as assessing disease risk is integral to translocation planning and outcomes. A disease risk analysis was conducted for the conservation translocation of native rodents to Dirk Hartog Island, Western Australia. This analysis resulted in a recommendation for a multidisciplinary project to reduce knowledge gaps about the health status of Shark Bay mice (Pseudomys gouldii) and greater-stick-nest rats (Leporillus conditor). Between 2021 and 2022, 130 Shark Bay mice and 122 greater stick-nest rats were translocated to Dirk Hartog Island. Mucosal swabs, whole blood, faeces, and ectoparasites were collected from a subset of these individuals. Molecular testing for four infectious agents was performed, parasite burdens and haematological parameters were examined, and relationships between these variables, health metrics and post-translocation short-term survival were assessed. Necropsies with routine histological assessment on translocation mortalities were performed where feasible. Several indicators of non-infectious factors contributing to morbidity or mortality were found, highlighting the need to iteratively evaluate translocation strategies. There was also an apparent absence of some host-specific parasites, suggesting that active approaches to parasite conservation during translocations should be considered. Molecular evidence of herpesviruses, a paramyxovirus, Bartonella sp., Trypanosoma sp. and Mycoplasma spp. were detected among the translocated animals. Although not associated with morbidity or short-term mortality in this study, the disease potential of these agents is still present. Overall, these results contribute important new data on health baselines for both species, which will assist in informing future conservation planning. Full article

Uranium occurrence and gangue mineralogy govern the choice of leaching process for sandstone-hosted uranium deposits. This study evaluates CO₂ + O₂ leaching of calcite-rich uranium ore from the Bayinqinggeli deposit in the northern Ordos Basin using mineralogical characterization, thin-section and agitated leaching experiments, and PHREEQC modeling. The dominant U–Si-bearing phase is interpreted as coffinite, although its mineralogical identification remains provisional in the absence of phase-specific structural and oxidation-state analyses. Thin-section observations revealed pronounced dissolution of exposed calcite and coffinite grains, but only minor surface corrosion of pyrite. Agitated leaching tests showed that increasing bicarbonate concentration improved uranium recovery, with diminishing gains above approximately 2 g/L. Calcite dissolution supplied bicarbonate, but equilibrium calculations indicated that the amount dissolved within a single pore-water volume was small relative to the calcite inventory. Thus, bicarbonate generation does not necessarily imply extensive liberation of encapsulated uranium minerals or a substantial increase in aquifer permeability. Pyrite oxidation may promote carbonate dissolution through acid generation, while also consuming oxygen and potentially producing pore-clogging precipitates. The results support further evaluation of CO₂ + O₂ recovery for this deposit. A modeled initial CO₂ dosage of 5 g/L produces approximately 2 g/L bicarbonate, and maintaining pressure in the surface processing circuit may limit CO₂ loss and calcite precipitation. These operating suggestions require validation under field flow and recirculation conditions. Full article

Breakthroughs in gene-editing technologies have brought pig-to-human xenotransplantation to the clinical forefront. Nevertheless, the micro-scale impacts of the complex pathophysiological milieu within recipients on grafts have long been overlooked by the academic community. Focusing on stromal vascular fraction (SVF) cells and preadipocytes widely present in donor organs, this study explores the potential mechanism underlying beige adipogenesis induced by post-operative anti-inflammatory drugs (e.g., dexamethasone) and surgical stress (norepinephrine), as well as its possible relationship with host immune system activation. The literature search and study-selection reporting were informed by PRISMA 2020. Five information sources were searched, and nine relevant studies on experimentally induced porcine adipose beiging, predominantly in vitro, were included in marker-specific meta-analyses. The meta-analysis showed a higher pooled expression of CD137, CIDEA, UCP3, PGC1α and DIO2 during experimentally induced porcine beige adipogenesis. To explore the structural plausibility of cross-species interaction, molecular docking analysis of the candidate protein CD137 was performed using AlphaFold 3. The predicted binding energies were −9.4 kcal/mol for porcine CD137–human CD137L and −9.0 kcal/mol for the human homologous complex. These computational predictions suggest a structurally plausible interaction, but the results do not demonstrate stronger biological binding, macrophage activation, or immune rejection. Overall, the findings support a hypothesis that porcine adipocyte beiging and CD137-related cross-species interactions may be relevant to xenograft immunometabolism; direct experimental validation in xenotransplantation models is required. Full article

During a parasitological survey of freshwater fishes from Khun Thale Swamp, Surat Thani Province, Thailand, a new species of opecoelid trematode, Dactylostomum brayi n. sp., was recovered from the intestine of the Asian redtail catfish Hemibagrus nemurus (Bagridae). Of the 1065 fishes examined, representing 33 species, 27 genera, and 16 families, the parasite was found exclusively in H. nemurus, with a prevalence of 27.27% and a mean intensity of 2.33 worms per infected host, suggesting a high degree of host specificity. The new species differs from all recognised freshwater congeners in the number of ventral sucker papillae, body proportions relative to the oral sucker, and the morphology of the reproductive organs. This represents the second record of Dactylostomum from Thailand, following specimens identified as Dactylostomum sp. by R. A. Bray from the same host and deposited in the Natural History Museum, London, in 1983. The present study also provides the first molecular characterisation (18S, ITS2, and 28S rRNA) for the genus Dactylostomum and reveals a close phylogenetic relationship with Dimerosaccus. These findings contribute to the taxonomy and distribution of Dactylostomum and provide a basis for future systematic and phylogenetic studies of this poorly known genus. Full article