Fungal infections pose a significant health burden in Denmark. Increasing global antifungal use and emerging antifungal resistance underscore the need for ongoing characterization of national prescribing trends to inform antifungal stewardship. Danish Health Data Bank Medstat site was accessed to assess total antifungal dispensing in Denmark from 1996 to 2025 across primary care, secondary care (hospitals), and over-the-counter sectors for both topical and systemic antifungals. Over the 30-year period, national antifungal dispensing patterns shifted substantially, with increased dispensing of azole/corticosteroid combination products in primary care (mean annual change of 0.065 g or ml per 1000 inhabitants/day), and persistent predominance of miconazole in secondary care and over-the-counter settings. Systemic prescribing was dominated by oral terbinafine in primary care and fluconazole in secondary care. Oral terbinafine dispensing in primary care was highest in 2009, while fluconazole dispensing peaked in 2013 in secondary care. Following peaks between 2009 and 2013, dispensing of several systemic antifungals subsequently declined, suggesting evolving prescribing patterns over time. Continued increases in azole/corticosteroid dispensing raises concerns regarding antifungal stewardship. Shifts in systemic antifungal dispensing for terbinafine and fluconazole may reflect changes in demographics, disease incidence (e.g., cancer), treatment guidelines, and clinical practice.

Cyclin-dependent kinase 9 (CDK9), the kinase associated with positive transcription elongation factor b (P-TEFb), enhances transcription elongation by phosphorylating RNA polymerase II and transcription elongation factors. The critical function of P-TEFb is in mediating networks of transcription that are induced by cytokines. More specifically, P-TEFb is involved in STAT3 signaling induced by IL-6 and TNF-inducible NF-κB activation. Within these signaling cascades, the pathways become hyperactivated due to abnormal CDK9 activity, which in turn increases inflammation and causes tissue damage. Pharmacological research has recently made great strides, and new CDK9 inhibitors are being considered as potential treatment options for regulating abnormal inflammatory responses. The efficacy of these inhibitors in reducing inflammation and symptom severity has been demonstrated in preclinical studies of inflammatory diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, and atherosclerosis. The advancement of next-generation CDK9 inhibitors with improved selectivity and diminished off-target effects provides considerable promise for the treatment of many inflammatory disorders.

Maqueda-Cabrera and Cuéllar-Cruz reported dose-dependent activity of the organometallic compound N-(2-hydroxyethyl)ferroceneselenoamide (FE1) against Nakaseomyces glabratus in a Galleria mellonella infection model. FE1 at 20 mg/kg produced complete larval protection and reduced fungal burden relative to fluconazole tested at the same dose. These findings are promising but remain preliminary because only the reference strain CBS138 was evaluated and the compound's mechanism of action is unknown. Further work should test geographically and genetically diverse clinical isolates, azole- and echinocandin-resistant phenotypes, and other clinically important opportunistic yeasts. Mechanistic studies should examine fungal stress-response pathways, resistance evolution, toxicity, pharmacokinetics/pharmacodynamics, and larval immune responses. G. mellonella is best positioned as a pre-screening or intermediate-screening experimental model rather than a direct predictor of clinical efficacy. A staged programme that links reproducible invertebrate endpoints to mammalian validation and WHO fungal-priority objectives could clarify whether FE1 merits further development as an antifungal candidate.

A library of quinoline-based thiourea hybrids 1-41 was synthesized via a single-step reaction scheme. All compounds were evaluated for their inhibitory potential against α-amylase, α-glucosidase, AChE, and BChE enzymes as well as for DPPH radical scavenging activity. Among forty-one compounds, 27-31 and 33-37 showed excellent inhibition against α-amylase (IC50 = 18.36-28.21 µM) and α-glucosidase (IC50 = 17.77-29.31 µM) compared to the standard acarbose (IC50 = 16.98 ± 0.12, 14.19 ± 0.06 µM). Moreover, compounds 27, 28, 30, 31, 34, 35, and 37 inhibited AChE (IC50 = 5.60-14.97 µM) and BChE (IC50 = 6.99-15.70 µM) with greater potency than the standard donepezil chloride (IC50 = 1.49 ± 0.13, 2.39 ± 0.06 µM). Kinetic analyses were conducted for the most active compounds to elucidate their modes of enzyme inhibition. Furthermore, molecular docking studies were conducted to explore ligand binding interactions within the enzyme active site. All synthesized derivatives were further evaluated for their DPPH radical scavenging activity, among which compounds 27, 28, 30, 31, 34, and 35 exhibited significant to moderate antioxidant potential (SC50 = 23.92-34.73 µM) compared with the reference standard ascorbic acid (SC50 = 18.28 ± 0.15 µM). Among this library, compound 31, with a difluoro group on the phenyl ring, was identified as the most potent inhibitor against all enzymes. Thus, this study suggests that the reported compounds hold the potential to be further advanced as lead anti-Alzheimer and anti-diabetic agents.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is associated with progressive hepatic alterations, including steatosis and fibrosis, which may affect liver mechanical properties. Shear wave elastography (SWE) is a non-invasive imaging technique that enables quantitative assessment of tissue stiffness; however, its application in diabetic animal models remains limited. This study aimed to evaluate liver elasticity using SWE in a high-fat diet (HFD) and streptozotocin (STZ)-induced rat model of T2DM, using histopathological examination as the reference standard. Methods: Twenty-four rats were randomly allocated to either a control group (n = 12) or a diabetic group (n = 12). Diabetes was induced using HFD feeding followed by low-dose STZ administration. Liver elasticity was assessed in vivo using SWE at two examination sessions. Shear wave velocity measurements were obtained from eight liver regions of interest and expressed in meters per second (m/s). Following euthanasia, liver tissues were subjected to histopathological evaluation using hematoxylin and eosin, Masson's trichrome, and periodic acid-Schiff staining. Results: Diabetic rats demonstrated marked histopathological alterations, including macrovesicular and microvesicular steatosis, hepatocellular vacuolization, increased collagen deposition, and glycogen depletion. Collagen deposition was significantly greater in diabetic animals, while glycogen content was significantly reduced (3.70 ± 1.05 vs. 26.87 ± 2.87; p < 0.05). SWE revealed consistently higher liver shear wave velocities in diabetic rats compared with controls at both examination sessions. Although liver stiffness increased over time in both groups, these changes did not reach statistical significance. Conclusions: HFD/STZ-induced diabetes was associated with increased liver stiffness and histopathological evidence of hepatic injury and fibrosis. SWE may represent a feasible non-invasive approach for assessing diabetes-related changes in liver mechanical properties.

Burial is a prevalent approach for disposing of human and animal carcass. Carcass decomposition is a key natural disturbance that reshapes microbial communities and modulates biogeochemical cycles. Animal intestines serve as critical natural reservoirs of antibiotic resistance genes (ARGs), and carcass decomposition concurrently remodels intestinal bacterial assemblages and resistome profiles. Most previous studies have characterized microbial succession in surface-exposed carcasses, yet the coordinated temporal shifts of intestinal microbiota, resistomes, and horizontal gene transfer (HGT) signatures within buried carcasses remain underexplored. We established a buried rat carcass model and performed metagenomic sequencing to characterize temporal dynamics of intestinal bacteria, ARGs, mobile genetic elements (MGEs), and HGT events. Bacterial communities underwent directional succession accompanied by reduced α-diversity and stage-specific β-diversity. Proteobacteria gradually outcompeted Firmicutes and Bacteroidetes to become dominant taxa. The resistome followed regular temporal changes: tetracycline and macrolide-lincosamide-streptogramin (MLS) ARGs prevailed in early decomposition, while multidrug, β-lactam, polymyxin, and quinolone ARGs accumulated in mid-late stages, with ARG richness peaking on day 28. Approximately 83% of temporally dynamic ARG subtypes were positively correlated with decomposition duration. Procrustes analysis (R[2] = 0.859) revealed strong correlations between bacterial succession and resistome dynamics, with Proteobacteria as potential multidrug-resistant hosts and major HGT donors. This study identifies a correlative cascade of microbial succession that drives MGE functional shift, which in turn increased HGT potential and ultimately leads to resistome accumulation in buried carcass intestinal habitats. These findings expand the theoretical framework of disturbance-driven microbial-resistome co-succession and offer insights into drivers of antibiotic resistance propagation in terrestrial cadaver systems.IMPORTANCEAnimal carcass burial is a ubiquitous natural terrestrial disturbance, and carcass intestinal contents represent a major endogenous reservoir of environmental antibiotic resistance genes (ARGs). Although extensive research has characterized microbial succession of exposed carcasses, the co-occurrence patterns of gut microbiome and resistome together with associated horizontal gene transfer (HGT) under buried conditions remain underexplored. Using metagenomic profiling of decomposing rat intestinal feces, this study explores a potential correlative cascade spanning bacterial succession, mobile genetic element (MGE) functional shifts, increased HGT potential, and gradual ARG enrichment. Our findings expand the ecological data set focused on subsurface buried carcass habitats and advance mechanistic knowledge of coupled microbiome-resistome succession driven by postmortem decomposition.

This study investigated the prevalence, genetic diversity, antimicrobial resistance, and virulence characteristics of Campylobacter spp. isolated from retail chicken carcasses in Beijing, China. Overall, Campylobacter was detected in 55.88% of samples, with significantly higher contamination in wet markets compared to supermarkets. A total of 106 non-duplicated isolates were obtained, including 59 C. jejuni and 47 C. coli, exhibiting high genetic diversity with 78 sequence types (STs) and 15 novel STs identified. Antimicrobial susceptibility testing revealed universal resistance to fluoroquinolones and high resistance to tetracycline, while multidrug resistance was prevalent, particularly in C. coli. Genotypic analysis identified 34 resistance genes and 4 point mutations, showing generally strong genotype-phenotype correlation, although notable discrepancies were observed, especially for florfenicol and azithromycin. The health risks to humans posed by tetracycline and macrolide-lincosamide-streptomycin (MLS)-associated antibiotic resistance genes (ARGs) should be given priority attention. Virulence profiling demonstrated that C. jejuni harbored significantly more virulence-associated genes than C. coli, including genes linked to Guillain-Barré syndrome, indicating a substantial potential public health risk from contaminated poultry.

Yak grazing systems are fundamental to pastoralist livelihoods on the Qinghai-Tibet Plateau (QTP), and their safe and sustainable development is essential for regional socioeconomic stability. Diarrhea is a multifactorial disease that severely impairs calf growth and may lead to mortality. In this study, we integrated second- and third-generation metagenomic sequencing with untargeted metabolomics to elucidate the underlying mechanisms and associated biosafety risks in yak calves with diarrhea. The results revealed significant gut microbiota dysbiosis in affected calves, characterized by reduced α-diversity and disrupted metabolism of arachidonic acid (AA) and its derivatives. Analysis of 1799 high-quality metagenome-assembled genomes (MAGs; ≥50% completeness and ≤5% contamination) showed a markedly increased relative abundance of Escherichia coli (16.4%) in diarrheal feces, far exceeding that observed in healthy controls. Eight assembled E. coli strains served as major reservoirs of antibiotic resistance genes (ARGs), contributing to high fecal abundances of resistance genes associated with MLS antibiotics (22.1%), bacitracin (21.7%), and β-lactams (19.9%), along with abundant mobile genetic elements (MGEs), including tnpA (21.1%) and IS91 (13.0%). Viral profiling identified E. coli as a key host for bacteriophages belonging to the families Chimeraviridae, Straboviridae, and Suoliviridae. These phages carried ARGs and MGEs that matched those detected in E. coli, potentially facilitating the dissemination of resistance through horizontal gene transfer. StrainPhlAn analysis further demonstrated that multidrug-resistant E. coli strains are widespread even among healthy calves, indicating the presence of a hidden resistome with potential for inter-individual transmission. These findings provide important theoretical guidance for managing yak calf diarrhea and offer valuable references for improving livestock production safety and mitigating antimicrobial resistance on the QTP.