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Traditional herbal extracts are attracting attention in the context of animal disease control because of their low side effects, diverse bioactive compounds, and low antimicrobial resistance risk. However, the underlying mechanisms remain inadequately understood. To characterize the multifaceted biological activities that underlie their therapeutic potential, this study systematically evaluated the antiviral and complex immunomodulatory properties of three distinct herbal combinations (designated Extracts A, B, and C) in vitro . The antiviral activities of the extracts were tested against bovine rotavirus and bovine coronavirus, two major pathogens of neonatal calf diarrhea, and their regulation of inflammatory mediators was assessed in a murine macrophage model (RAW 264.7 cells) stimulated with lipopolysaccharide from Escherichia coli by measuring nitric oxide production and the gene expression of inflammation related enzymes. Immunomodulatory effects were investigated by analyzing the gene expression of T helper cell-associated cytokines in both RAW 264.7 cells and bovine peripheral blood mononuclear cells (PBMCs). All three extracts exhibited inhibitory activity against both viruses and reduced the expression of specific inflammatory mediators. Furthermore, the extracts demonstrated complex immunomodulatory effects in bovine PBMCs, with Extract C promoting T helper 1 and T helper 17 responses while suppressing the regulatory T-cell transcription factor Forkhead Box P3. In conclusion, this in vitro study demonstrates that these herbal extracts possess antiviral and immunomodulatory potential, providing a basis for future studies to determine their relevance in viral infections associated with calf diarrhea.

We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3 . MSL-7 improves glucose tolerance and β-cell function of hIAPP + mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb . These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation. Islet amyloid polypeptide (IAPP) deposition is associated with islet cell loss in diabetes. Here the authors show that a small molecule autophagy enhancer reduces IAPP accumulation in vitro, and also improves glucose tolerance in hIAPP + mice fed high-fat diet, accompanied by reduced hIAPP accumulation, in vivo.

The circulation of carbapenemase-producing Escherichia coli (CPEC) in our society is a serious concern for vulnerable patients in nosocomial environments. However, the genomic epidemiology of the circulation of CPEC bacteria among companion animals remains largely unknown. In this study, epidemiological analysis was conducted using complete genome identification of CPEC ST410 isolates obtained from companion animals. To estimate the genomic distance and relatedness of the isolates, a total of 37 whole-genome datasets of E. coli ST410 strains were downloaded and comparatively analysed. As a result of the analysis, the genomic structure of the chromosomes and plasmids was identified, revealing the genomic positions of multiple resistance and virulence genes. The isolates in this study were grouped into the subclade H24/RxC, with fimH24 , and substituted quinolone resistance-determining regions (QRDRs) and multiple beta-lactamases, including extended-spectrum β-lactamase (ESBL) and carbapenemase. In addition, the in silico comparison of the whole-genome datasets revealed unidentified ST410 H24/Rx subgroups, including either high pathogenicity islands (HPIs) or H21 serotypes. Considering the genetic variations and resistance gene dissemination of the isolates carried by companion animals, future approaches for preventive measurement must include the “One Health” perspective for public health in our society.

Background Carbapenemase-producing Klebsiella pneumoniae (CPKP) is one of the most dangerous multidrug-resistant (MDR) pathogens in human health due to its widespread circulation in the nosocomial environment. CPKP carried by companion dogs, which are close to human beings, should be considered a common threat to public health. However, CPKP dissemination through companion animals is still under consideration of major diagnosis and surveillance systems. Methods Two CPKP isolates which were genotyped to harbor bla NDM-5 -encoding IncX3 plasmids, were subjected to the whole-genome study. Whole bacterial DNA was isolated, sequenced, and assembled with Oxford Nanopore long reads and corrected with short reads from the Illumina NovaSeq 6000 platform. The whole-genome structure and positions of antimicrobial resistance (AMR) genes were identified and visualized using CGView. Worldwide datasets were downloaded from the NCBI GenBank database for whole-genome comparative analysis. The whole-genome phylogenetic analysis was constructed using the identified whole-chromosome SNP sites from K. pneumoniae HS11286. Results As a result of the whole-genome identification, 4 heterogenous plasmids and a single chromosome were identified, each carrying various AMR genes. Multiple novel structures were identified from the AMR genes, coupled with mobile gene elements (MGE). The comparative whole-genome epidemiology revealed that ST378 K. pneumoniae is a novel type of CPKP, carrying a higher prevalence of AMR genes. Conclusions The characterized whole-genome analysis of this study shows the emergence of a novel type of CPKP strain carrying various AMR genes with variated genomic structures. The presented data in this study show the necessity to develop additional surveillance programs and control measures for a novel type of CPKP strain.

Climate change is expected to alter the distribution of many threatened mammals, yet national-scale identification of climate refugia and conservation priorities remains limited for South Korea. This study aimed to map current hotspots and future refugia for 10 endangered mammal species and evaluate conservation implications under SSP climate scenarios. We compiled occurrence records from nationwide field surveys and protected-area monitoring and fitted ten species distribution models (GLM, GAM, GBM, CTA, ANN, SRE, FDA, MARS, RF, and MaxEnt) using biomod2 with climatic, topographic, and anthropogenic predictors at 1 km resolution. A weighted ensemble model achieved strong predictive performance (mean AUC = 0.840). Current richness hotspots were concentrated along the Baekdudaegan mountain range, and several national parks emerged as core multi-species areas. Variable-importance analysis indicated that topographic constraints (elevation and slope) dominated for most species, consistent with mountain-dependent habitat use. Future projections showed relatively stable richness patterns under SSP2–4.5 but pronounced contractions under SSP5–8.5 by the 2070s, with persistent high-suitability areas converging in the northern Baekdudaegan. The resulting suitability and richness layers provide spatial decision-support for protected-area strengthening, connectivity-oriented management, and targeted monitoring to support national climate-adaptation planning.

Climate change poses an unprecedented threat to global biodiversity, with birds serving as critical indicators of ecosystem responses. This study assessed the impacts of climate change on 29 endangered bird species in South Korea, a critical stopover region within the East Asian-Australasian Flyway (EAAF). Using Random Forest models, we predicted current (2010 baseline) and future species distributions under two climate scenarios (SSP2-4.5 and SSP5-8.5) for four time periods (2030s, 2050s, 2070s, and 2090s). Model performance was robust, with a mean AUC of 0.844 ± 0.122 across all species and 72.4% of species achieving AUC ≥ 0.80. Elevation emerged as the most influential predictor for 44.8% of species, followed by precipitation of the driest month (17.2%) and distance to water bodies (10.3%). Current species richness patterns showed spatial heterogeneity, with higher concentrations along coastal wetlands, particularly in the western and southern coasts and Jeju Island. Under SSP2-4.5, species richness patterns remained relatively stable through 2090, while SSP5-8.5 projected more dramatic shifts, particularly after 2070. Coastal regions and national parks exhibited differential responses, with some areas showing increases and others experiencing declines in species richness. High-elevation national parks, including Mt. Hallasan, Mt. Seoraksan, and Mt. Odaesan, demonstrated potential to serve as climate refugia, maintaining relatively stable species richness under both scenarios. Our spatial analysis at municipality and national park levels identified priority conservation areas and emphasized the need for climate refugium identification, habitat connectivity along elevational gradients, and adaptive management strategies. The findings provide actionable guidance for science-based conservation planning and contribute to international efforts to protect migratory birds along the EAAF. Urgent conservation measures are needed to safeguard coastal wetlands and establish ecological corridors to facilitate species range shifts under changing climatic conditions.

Perioperative neurocognitive disorder (PND) is a concern following anesthesia, particularly in individuals at risk for Alzheimer’s disease (AD). This study compared the cognitive and pathological effects of propofol and remimazolam in a mouse model with AD following surgery. Five-month-old male ApoE4-KI mice underwent abdominal surgery under either propofol (170 mg/kg) or remimazolam (85 mg/kg) anesthesia. Cognitive function was assessed using the Morris water maze and Y-maze, and neuronal apoptosis and amyloid-beta (Aβ) deposition in the CA3 and dentate gyrus (DG) of the hippocampus were evaluated preoperatively and at 2, 4, and 7 days postoperatively. Both groups showed similar postoperative cognitive functions, with increased relative escape latency at day 2 and decreased relative spontaneous alternation at days 4 and 7. However, the neuropathological analysis revealed that propofol-induced significantly more neuronal death in the CA3 (days 4 and 7) and DG (days 2, 4, and 7), and greater Aβ accumulation in the CA3 (days 2 and 4) and DG (days 2 and 7) compared to remimazolam (p < 0.05). Propofol was associated with more pronounced neuropathologic changes in the hippocampus compared to remimazolam. These findings suggest remimazolam may be a safer anesthetic for patients at risk for neurodegenerative disorders, as it is associated with less severe hippocampal pathology, which is characteristic of AD.

Infection of hepatitis B virus (HBV) increase the incidence of chronic liver disease and hepatocellular carcinoma (HCC). The hepatitis B viral x (HBx) protein encoded by the HBV genome contributes to the pathogenesis of HCC and thus, negative regulation of HBx is beneficial for the alleviation of the disease pathogenesis. MARCH5 is a mitochondrial E3 ubiquitin ligase and here, we show that high MARCH5 expression levels are correlated with improved survival in HCC patients. MARCH5 interacts with HBx protein mainly accumulated in mitochondria and targets it for degradation. The N-terminal RING domain of MARCH5 was required for the interaction with HBx, and MARCH5 H43W lacking E3 ligase activity failed to reduce HBx protein levels. High expression of HBx results in the formation of protein aggregates in semi-denaturing detergent agarose gels and MARCH5 mediates the elimination of protein aggregates through the proteasome pathway. HBx-induced ROS production, mitophagy, and cyclooxygenase-2 gene expression were suppressed in the presence of high MARCH5 expression. These results suggest MARCH5 as a target for alleviating HBV-mediated liver disease.

Proteus mirabilis is a commensal bacterium dwelling in the gastrointestinal (GI) tract of humans and animals. Although New Delhi metallo-[beta]-lactamase 1 (NDM-1) producing P. mirabilis is emerging as a threat, its epidemiology in our society remains largely unknown. LHPm1, the first P. mirabilis isolate harboring NDM-1, was detected from a companion dog that resides with a human owner. The whole-genome study revealed 20 different antimicrobial resistance (AMR) genes against various classes of antimicrobial agents, which corresponded to the MIC results. Genomic regions, including MDR genes, were identified with multiple variations and visualized in a comparative manner. In the whole-genome epidemiological analysis, multiple phylogroups were identified, revealing the genetic relationship of LHPm1 with other P. mirabilis strains carrying various AMR genes. These genetic findings offer comprehensive insights into NDM-1-producing P. mirabilis, underscoring the need for urgent control measures and surveillance programs using a \"one health approach\".

This study analyzed the spatial patterns of species composition and biodiversity according to elevation on Mt. Gyebangsan, a representative protected ecosystem and the national park in Korea. Based on existing vegetation survey data, differences in species composition heterogeneity according to elevation were verified using non-metric multidimensional scaling and multi-response permutation procedure analyses. Significant differences were identified using the Sørensen distance measure. Zeta (ζ)-diversity was analyzed based on the number of shared species among habitats to quantitatively interpret the structural characteristics of biodiversity along the altitudinal gradient. The analysis revealed that the understory species composition became increasingly distinct and alpha-diversity increased with elevation. High-elevation areas (A3, A4) experienced frequent physical disturbances, including wind damage and limited moisture, resulting in active canopy openings. Consequently, rhizomatous species, including Sasa borealis rapidly covered the ground, influencing the understory vegetation structure. ζ-Diversity analysis showed that the ζ-ratio in high-elevation regions sharply declined with increasing ζ-order, indicating limited species overlap among habitats and the dominance of deterministic processes. Thus, altitudinal gradients represent a key factor in shaping biodiversity, indicating that climatic variables directly affect understory distribution and species turnover. This study quantitatively assessed biodiversity and ecological heterogeneity within the national park, providing a scientific foundation for biodiversity conservation and management.