Antibiotic resistance genes (ARGs) in airborne dust represent an emerging concern for public health, particularly in indoor environments where human exposure is prolonged. While external environmental pressures are known to shape the abundance and diversity of microorganisms in indoor dust, their role in ARG dynamics remains underexplored. This study assessed the temporal and spatial patterns of airborne ARGs in indoor dust across four Nordic cities (Aarhus, Bergen, Reykjavik, and Uppsala) using electrostatic dust collectors (EDCs) in the same households at two time points: 2012 and 2022. Shotgun metagenomic sequencing was performed to profile ARGs. National antibiotic consumption data were obtained from the European Surveillance of Antimicrobial Consumption (ESAC-Net), outdoor air pollution data (PM2.5 and PM10) from the Copernicus Atmosphere Monitoring Service (CAMS), and meteorological parameters from the NASA POWER database. Beta diversity analysis revealed city-specific differences in ARG composition (PERMANOVA, R2 = 0.18, P = 0.03), but no consistent temporal shift over the 10-year period. Macrolide, tetracycline, and aminoglycoside resistance genes were among the most abundant and persistent classes. A previously undetected macrolide resistance sequence was identified across all cities in 2022. Although national antibiotic consumption declined, cross-sectional correlations between national antibiotic consumption and ARG abundance strengthened from 2012 (Spearman's ρ = 0.25) to 2022 (ρ = 0.37), suggesting sustained ARG presence despite reduced antibiotic consumption. Several ARG classes showed associations with outdoor particulate matter, and these relationships were influenced by local meteorological conditions. For example, higher absolute humidity was associated with a weaker relationship between PM and polymyxin resistance genes, whereas stronger wind speeds were associated with stronger relationships between PM and Sulfonamide resistance genes. These findings highlight the complex environmental interplay between antibiotic consumption, air pollution, meteorological factors, and ARG dynamics in indoor air, emphasizing the need for integrated environmental and AMR surveillance, especially in the context of climate change.

Antibiotic resistance genes (ARGs), as emerging environmental contaminants, have become a global environmental health concern due to their distribution and dissemination across urbanization gradients. This study systematically investigated the diversity, abundance patterns, and driving mechanisms of 173 ARGs, 30 mobile genetic elements (MGEs), and 120 virulence factor genes (VFGs) along a typical urbanization gradient (urban, suburban, and ecological zones) using soil samples collected from Baoding city center to Baiyangdian Lake periphery. High-throughput sequencing and quantitative PCR analyses revealed that suburban areas exhibited significantly higher total relative abundance of ARGs compared to urban and ecological zones (p < 0.05), particularly for aminoglycoside-, fluoroquinolone-, Macrolide-Lincosamide-Streptogramin B-, and multidrug-resistance genes. Suburban soils also showed elevated levels of VFGs associated with Klebsiella pneumoniae, Salmonella enterica, and Escherichia coli (p < 0.05). Notably, significant associations between ARGs and VFGs were observed, with both demonstrating high loads in suburban areas, suggesting these transitional zones may serve as "incubators" for resistant pathogens. Correlation analyses suggest that both biotic (MGEs, microbial communities) and abiotic factors (urbanization, heavy metals, soil properties) may contribute to ARGs and VFGs dissemination, with MGEs appearing to play a central role. Structural equation modeling indicates that urbanization could influence ARGs and VFGs assembly, potentially by altering soil properties, heavy metals, and microbial communities. MGE-mediated horizontal transfer might facilitate ARGs spread, whereas heavy metals and specific microbial taxa may be associated with VFG distribution patterns. These findings provide critical scientific insights into the transmission dynamics of resistance genes during urbanization and offer strategic guidance for developing targeted environmental management policies to mitigate resistance dissemination.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoma with a poor prognosis. The human T-lymphotropic virus 1 (HTLV-1) is associated with immunodeficiency and increased extranodal involvement in patients with diffuse large B-cell lymphoma (DLBCL). We report on a 47-year-old woman with spastic paraparesis and hepatitis B who was diagnosed with the acute form of ATLL. The clinical picture reveals peripheral generalized lymphadenopathy and splenomegaly. Findings on a hematologic exam indicated leukocytosis with lymphocytosis. A bone marrow biopsy/aspiration confirmed 50% T-cell lymphoid infiltration. Biochemistry results revealed hypercalcemia and a high lactate dehydrogenase value. Results of a CT scan indicated abdominal and thoracic adenopathy as well as moderate splenomegaly. A supraclavicular lymph node biopsy established a DLBCL diagnosis. The final diagnosis was composite lymphoma, DLBCL, and ATLL. The CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate [Oncovin], and prednisone) regimen was chosen due to the patient's ECOG performance status. Multiple infectious complications were diagnosed during chemotherapy-induced secondary aplasia. A complete remission, confirmed via PET-CT imaging, was obtained. After 1 month, a skin tumor on the upper right thigh was discovered and biopsied, and the histopathological exam and immunochemistry findings indicated Epstein-Barr virus-DLBCL lymphoma. The association of 2 aggressive lymphomas in a single HTLV-1 carrier is a rare report, and the evolution was severe, complicated by opportunistic infections, and unfavorable.

Glaciers cover a substantial portion of the world and are home to various biological populations. The Himalayas constitute the largest glaciated region outside the poles; hence, they are regarded as "The Third Pole" of the World. There are around 84 glaciers in the Teesta basin (Sikkim Himalaya). There is substantially less data available on the microbial diversity embedded in the glacial ice core samples of the Sikkim Himalaya, as well as their physico-chemistry and potential geomorphological hazards related to their retreat or decrease in snow-line cover. The present study aims to evaluate the microbial diversity in the glacier ice core region and the study area; therefore, two glaciers in the Sikkim Himalaya were chosen: Frey-Peak and Rathong Glacier. The bacterial diversity analysis reveals the prevalence of various phyla, including Pseudomonadota, Actinomycetota, Bacillota, and Bacteroidota. The random forest model reveals the significant contributions of various elements, including Na, Mg, K, Ca, and Zn, to the alpha diversity of the studied glaciers. Among physicochemical parameters, pH was found to contribute the most in shaping bacterial diversity. Cluster of Orthologous Groups (COG) analysis underscored a predominance of genes associated with amino acids (23.5%), carbohydrates (18.93%), lipids (10.88%), energy (17.26%), coenzymes (9.38%), and ion transport/metabolism (14.71%). KEGG (Kyoto Encyclopedia of Genes and Genomes) Orthology (KO) analysis revealed the presence of 4,915 to 96,954 genes. Interestingly, the metagenomic analysis revealed the presence of specific species of Bradyrhizobium, Beijerinckia, Burkholderia, and Corynebacterium, which are associated with nitrogen metabolism, suggesting their potential involvement in biogeochemical processes. Additionally, a total of 59 to 419 bacterial genes related to sulphur metabolism were deduced through the KEGG functional analysis. The study detected the presence of various antibiotic resistance genes corresponding to different classes of antibiotics, including aminoglycoside, tetracycline, fluoroquinolone, macrolide, and erythromycin. Network analysis reveals that antibiotic resistance genes primarily interact with the phyla Pseudomonadota, Bacillota, and Actinomycetota. The melting of glaciers, a significant effect of climate change, may release contaminants, antibiotic resistance genes, and pathogenic bacteria into free-flowing rivers, potentially impacting human health.

Hyperthermia-mediated drug delivery offers a promising strategy to enhance the efficacy of chemotherapy while minimizing systemic toxicity. Thermosensitive liposomes (TSLs) release their therapeutic payload in response to elevated temperature, enabling targeted delivery to tumor tissues. Here we introduce a hybrid multiscale model based on a Krogh cylinder approach to describe temperature-sensitive liposome transport and drug release in tumor tissue. Spatial transport of liposomes and released drug in the vascular and interstitial domains is described by one-dimensional (1D) transport equations, while intracellular drug internalization is represented by local compartmental (0D) kinetics. The model incorporates key physiological processes including blood flow, passive transvascular diffusion of liposomes, interstitial diffusion of released drug, and cellular uptake via receptor binding and internalization. The temperature field is calculated using the Pennes' bioheat equation, and its effects on physiological parameters-such as permeability, diffusivity, and blood velocity-are incorporated via temperature-dependent functions. A sensitivity analysis was performed to identify dominant transport parameters. Microvascular permeability, tissue diffusivity and Krogh cylinder radius were identified as the most influential parameters affecting drug delivery. Simulation results revealed that a 30-min preheating phase prior to drug administration significantly enhances treatment efficacy, increasing internalized doxorubicin concentrations by 29.4% while maintaining a low probability (5%) of tissue necrosis. This compact and computationally efficient model provides an effective framework for designing and optimizing hyperthermia-assisted chemotherapy. Its computational efficiency and physiological detail make it specifically suitable for use in treatment planning and real-time therapeutic decision-making in solid tumors.

Kasugamine (2,4-diamino-2,3,4,6-tetradeoxy-d-mannose, 1) is a rare multideoxy diamino-sugar forming the core skeleton of the commercial aminoglycoside antibiotic Kasugamycin (KSG, 2), an agricultural fungicide that has been used against rice blast disease for more than 60 years. Despite the reported biosynthetic gene cluster (BGC) for 2, the enzymatic logic leading to the formation of 1 remained unclear. Here, we report the biosynthetic mechanism of 1. Five enzymes─KsgQ, KsgB, KsgD, KsgR, and KsgC─can biochemically convert uridine diphosphate-N-acetyl-d-glucosamine (UDP-GlcNAc, 4) to generate the sugar donor 6, which is incorporated into 2, as confirmed by stable isotope-labeled feeding experiments. KsgB is characterized as the first enzyme catalyzing the deacetylation of uridine diphosphate-N-acetyl-d-mannosamine (UDP-ManNAc, 5), while KsgR represents the first UDP-sugar 3-dehydrase catalyzing the C-3 deoxygenation of the KsgD product (8) via the cofactors pyridoxal-5'-phosphate (PLP) and l-glutamic acid (l-Glu), and employs a ColD-like catalytic mechanism, as shown by crystallographic analysis, molecular docking, and site-directed mutagenesis. Our findings unravel the biosynthetic mysteries of 1, highlight the intriguing strategies for biosynthesizing diamino-sugars in nature, and provide some evidence for further completely uncovering the biosynthetic logic of 2.

Acinetobacter baumannii has emerged as one of the most challenging opportunistic pathogens in modern healthcare due to its remarkable ability to acquire and disseminate antimicrobial resistance determinants. Carbapenem-resistant A. baumannii (CRAB) is now recognized by the World Health Organization as a critical priority pathogen, highlighting the urgent need for improved diagnostic, surveillance, and therapeutic strategies. This review synthesizes current evidence on the relationship between phenotypic antimicrobial susceptibility patterns and underlying genetic determinants of resistance in A. baumannii. A structured literature search was conducted across major biomedical databases (PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library), supplemented by citation tracking and relevant institutional sources, focusing on studies published between 2016 and 2026. The analysis integrates findings from studies examining phenotypic antimicrobial susceptibility testing (AST) with molecular and genomic investigations of resistance mechanisms, including carbapenemases, aminoglycoside-modifying enzymes, efflux pumps, and resistance-associated genomic islands. Particular attention is given to the complex and sometimes discordant relationship between genotype and phenotype, where the presence of resistance genes does not always translate directly into phenotypic resistance due to regulatory mechanisms, gene expression variability, and genomic context. The review further discusses methodological differences in AST standards and genomic prediction approaches that may contribute to variability across studies. Collectively, the evidence supports a multidimensional interpretation of antimicrobial resistance in A. baumannii, emphasizing the necessity of integrating phenotypic and genotypic data for accurate diagnostics, surveillance, and clinical decision-making. This integrated perspective may contribute to improved understanding of resistance evolution and support the development of more effective strategies for managing multidrug-resistant A. baumannii infections.

Antibiotic resistance genes (ARGs) are prevalent in livestock environments due to antimicrobial use, yet their airborne dispersal into human-occupied indoor spaces remains poorly characterized. We investigated whether airborne ARGs disperse from livestock stables into farmers' homes and surrounding outdoor environments. Electrostatic dust collectors were deployed in paired pig and cow stables and their associated homes in Jutland, Denmark, to collect settled airborne dust. Pooled samples were analyzed using shotgun metagenomic sequencing. ARG dispersal patterns were assessed using FEAST source tracking and ecological similarity metrics, including shared ARG ratios and Jaccard indices. Pig production systems exhibited higher antibiotic use and stronger resistome continuity with farmers' homes than cow systems, reflected by greater FEAST contributions (P = 0.029) and Jaccard similarity (P = 0.029). Beta-diversity analysis supported higher compositional similarity between pig stables and homes (PERMANOVA R2 = 0.23, p = 0.052), whereas cow environments showed greater divergence (R2 = 0.41, P = 0.035). Across environments, tetracycline, macrolide-lincosamide-streptogramin B, and aminoglycoside resistance genes dominated, consistent with livestock-specific antibiotic use patterns. Supplementary indoor-outdoor comparisons across cow, pig, and chicken stables (from an independent 2024 sampling campaign not directly comparable to the 2008 EDC-based survey) revealed contrasting dispersal dynamics, with higher bacterial species spillover from cow stables but stronger ARG overlap from pig stables. Collectively, these findings are consistent with airborne ARG connectivity across occupational and environmental interfaces and support consideration of air as a potential pathway in One Health AMR surveillance.

Colorectal cancer (CRC), characterized by epidermal growth factor receptor (EGFR) overexpression, is often associated with poor prognosis and limited therapeutic response to conventional chemotherapy. In this study, we developed EGFR-targeted extracellular vesicles (EGFR-tEVs) by transiently engineering donor cells to display the GE11 peptide, aiming to enhance the precision of doxorubicin (Dox) delivery. The physicochemical properties of EGFR-tEVs were characterized using TEM, NTA, and Western blot. In vitro, EGFR-tEV-Dox exhibited increased cellular uptake in EGFR-overexpressing HCT-116 cells, leading to the activation of the p53-Bax-cleaved PARP1 apoptotic pathway. Notably, while Dox treatment induced p53 in normal colon fibroblasts (CCD18-Co), it did not trigger significant Bax activation or PARP1 cleavage, suggesting a preference for survival-related signaling in non-malignant cells. In a xenograft mouse model, EGFR-tEVs + Dox administration resulted in a 33.1% reduction in tumor volume and an 82.8% decrease in Ki-67 expression compared to the control group. These results indicate that transient receptor-mediated targeting enhances functional drug delivery to malignant tissues while minimizing pro-apoptotic induction in normal cells. Our findings suggest that EGFR-tEVs + Dox represents a balanced therapeutic strategy that improves antitumor efficacy with a favorable safety profile for EGFR-positive colorectal cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases relies primarily on DNA-damaging agents whose efficacy depends on sustained cytotoxic exposure. Whether brief treatment can induce durable transcriptional remodeling remains unclear. Mithramycin A (MA) is a GC-rich DNA-binding agent with transcriptional regulatory activity involving chromatin-associated pathways. Here, we investigated the molecular and functional consequences of a single 90-min HIPEC-mimetic MA exposure in colorectal cancer models. RNA sequencing revealed extensive and coordinated transcriptional remodeling, affecting a substantial fraction of expressed genes and producing a response qualitatively distinct from mitomycin C. MA selectively suppressed key chromatin-associated regulatory factors, including DNMT1, JARID2, and HDAC4, while coordinately activating canonical cyclin-dependent kinase inhibitors CDKN1A, CDKN1C, and CDKN2C. Gene set enrichment analysis demonstrated enrichment of G2/M checkpoint pathways and suppression of oncogenic gene networks. These molecular changes translated into sustained inhibition of clonogenic growth and activation of caspase-dependent apoptosis following drug washout, with hyperthermia potentiating apoptotic signaling. Collectively, these findings indicate that brief MA exposure induces selective modulation of chromatin regulators and durable transcriptional reorganization, supporting modulation of chromatin regulatory networks as a potential therapeutic strategy for HIPEC-based colorectal cancer therapy.

Diabetic retinopathy (DR), recognized as a progressive neurovascular and microvascular complication of diabetes, remains one of the leading causes of visual disability worldwide, within the context of a sustained increase in ophthalmic diseases and retinal vascular disorders that compromise vision. This study aimed to characterize the progression of diabetic retinopathy in a streptozotocin (STZ)-induced Wistar rat model. A single dose of 65 mg/kg body weight was administered, with follow-up periods at 2, 4, 8, and 10 weeks, compared to healthy controls. STZ-induced rats exhibited reduced weight gain compared to the control group. They also showed markedly variable hyperglycemia, with glucose concentrations ranging from 250 to 530 mg/dL. Histological analysis of retinal tissue at week 4 revealed early signs of vascular compromise, including early indications of a microenvironment conducive to neovascularization and edema. By week 8, retinal damage had progressed to hemorrhage, persistent edema, and layer-specific vascular disruption. At week 10, intensified neovascularization and exacerbated edema indicated advanced microvascular deterioration. Immunofluorescence analysis demonstrated a temporal accumulation of CD8[+] T cells in the retina, correlating with photoreceptor degeneration. The coordinated dynamics of CD4[+] and CD8[+] T cells suggested transient immune activation during STZ-induced retinal degeneration. Gene expression profiling revealed a proinflammatory and pro-oxidative retinal microenvironment, characterized by the overexpression of angiogenic pathways and proliferative signals. Simultaneously, the antioxidant response appeared partially impaired. Collectively, these findings provide mechanistic perspective on the multifactorial nature of diabetic retinopathy. Oxidative stress, inflammation, and angiogenesis converge to disrupt retinal homeostasis. This experimental model may serve as a reliable platform for future studies aimed at elucidating disease pathophysiology, identifying novel therapeutic targets, and evaluating emerging ophthalmic antidiabetic interventions.