Search Results (338)

Background/Objectives: Gallstone disease is a prevalent digestive disorder worldwide, with incidence increasingly linked to obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that intestinal microbial communities and their bioactive compounds play a central role in pathogenesis. Here, we aimed to clarify whether diet-related microbial alterations and circulating metabolites contribute to gallstone formation. Methods: We integrated dietary inflammatory index (DII) evaluation, genetic analyses of large-scale cohorts, and a cholesterol gallstone mouse model induced by a lithogenic diet (LD). Serum and fecal samples were subjected to metabolomic and metagenomic profiling, followed by multi-omics integration to identify links between microbial taxa, metabolites, and gallstone risk. Results: Higher DII scores were associated with increased gallstone risk. Genetic evidence supported bile acid and amino acid metabolism as potential mediating pathways, with Akkermansia muciniphila linked to decreased N-acetylarginine levels and CAG-448 showing an inverse association with glycodeoxycholate (GDCA). In LD-fed mice, shotgun metagenomics revealed enrichment of lithogenic taxa such as Bacteroides stercorirosoris and Enterocloster, whereas protective taxa, including Akkermansia muciniphila and CAG-448, were markedly depleted. Untargeted metabolomics confirmed elevations of GDCA and N-acetylarginine together with broader bile acid imbalance, amino acid stress, and long-chain acylcarnitine accumulation. Correlation analyses further showed that protective taxa were inversely associated with risk metabolites, whereas gallstone-enriched microbes displayed the opposite pattern. Conclusions: This study provides evidence consistent with a contributory role of gut microbiota–metabolite dysregulation in gallstone pathogenesis. Specific taxa (A. muciniphila, CAG-448) and metabolites (GDCA, N-acetylarginine) may serve as potential biomarkers or targets for microbiota- and diet-based prevention strategies. Full article

The HN pig, indigenous to Henan Province, is distinguished by its reduced lean meat yield and slower growth rates relative to commercial foreign breeds. To address these limitations, three hybrid combinations were generated through the crossbreeding of Huainan sows with Yorkshire, Landrace, and Berkshire sires. In this study, extensive transcriptomic and metabolomic analyses of the LD muscle were carried out for the first time, and carcass and meat quality characteristics were compared between hybrid and HN pigs. Slaughter and muscle quality assessments revealed that the lean meat percentage of LH and YH was significantly lower than that of HN, with YH exhibiting the lowest intramuscular fat level, indicating that this breed possesses enhanced lean meat production efficiency. Transcriptomic profiling revealed markedly increased expression of SLIT2, CH25H, NR4A2, NR4A1, FOSB, CRABP2, GDF10, and MRAP2 in all three hybrid groups compared to HN. Gene Ontology enrichment analysis identified that the skeletal muscle cell differentiation (GO:0035914) and transforming growth factor beta receptor signaling pathway (GO:0007179) were exclusively enriched in the YH vs. HN comparison. Non-targeted metabolomic analysis identified 31, 36, and 12 DAMs in BH vs. HN, LH vs. HN, and YH vs. HN comparisons, with pyruvate metabolism being the sole pathway common to all groups. An integrated multi-omics analysis revealed significant correlations between phytosphingosine levels and DEGs across all three comparisons. In summary, these results indicate that crossbreeding substantially improves lean meat yield in HN pigs while providing novel molecular insights into the underlying genetic and metabolic mechanisms. Full article

Lipid droplets (LDs) are cellular dynamic organelles involved in lipid storage and maintaining lipid balance. They contain many proteins on their surface that significantly affect their functions and behaviors. Thus, it becomes crucial to characterize the LD proteome using appropriate “omics” technologies that may contribute to an accurate understanding of the LD roles in human diseases. Indeed, LDs and their associated proteins are involved in several pathologies related to dysfunctional lipid metabolism, such as hyperlipidemia, obesity, metabolic syndrome, and cardiovascular diseases (CVDs). This review aims to provide an overview of “omics” studies focused on characterizing the LD proteome in the cardiovascular field, offering additional insight into the involvement of LDs in the development and progression of heart complications, as well as defining potential targets useful for diagnostic, preventive, and therapeutic approaches for patients. Full article

Conventional non-partitioned Landslide Susceptibility Mapping (LSM), which neglects geospatial heterogeneity, often has limitations in accurately capturing local risk patterns. To address this challenge, this study investigated the effectiveness of localized modeling in the environmentally diverse state of Oregon, USA, by comparing ecoregion-based local models with the non-partitioned model. We partitioned Oregon into seven distinct units using the U.S. Environmental Protection Agency (EPA) Level III Ecoregions and developed one global and seven local models with the eXtreme Gradient Boosting (XGBoost) algorithm. A comprehensive evaluation framework, including the Area Under the Curve (AUC), Landslide Density (LD), and the Total Deviation Index (TDI), was used to compare the models. The results demonstrated the clear superiority of the partitioned strategy. Moreover, different ecoregions were found to have distinct dominant landslide conditioning factors, revealing strong spatial non-stationarity. Although all models generated high AUC values (>0.93), LD analysis showed that the local models were significantly more efficient at identifying high-risk zones. This advantage was particularly pronounced in critical, landslide-prone western areas; for instance, in the Willamette–Georgia–Puget Lowland, the local model’s LD value in the ‘very high’ susceptibility class was over 3.5 times that of the global model. High TDI values (some >35%) further confirmed fundamental spatial discrepancies between the risk maps obtained by the two strategies. This research substantiated that, in geographically complex terrains, partitioned modeling is an effective approach for more accurate and reliable LSM, providing a scientific basis for developing targeted regional disaster mitigation policies. Full article

Skeletal muscle, the largest organ within the animal body, consists of multiple muscle fiber types. The distribution of these fiber types significantly impacts both athletic performance and the quality of meat. Growing evidence has demonstrated that transfer RNA (tRNA)-derived small RNAs (tsRNAs) are not merely byproducts of tRNA metabolism but also participate in multiple cellular metabolic processes. However, the role of tsRNAs in skeletal muscle fiber type transition remains elusive. In this study, a total of 403 differentially expressed tsRNAs were identified through small RNA sequencing in psoas major muscle (PM) and latissimus dorsi muscle (LD), among which 220 tsRNAs including tRF-Lys-TTT-012 were upregulated in psoas major muscle. Functional studies in C2C12 and PK15 cells demonstrated that it inhibited the proliferative capacity of C2C12 cells while promoting myogenic differentiation, increased the proportion of slow muscle fibers after differentiation, and drove muscle fiber type transition toward slow fibers. Additionally, tRF-Lys-TTT-012 enhanced mitochondrial number and function, potentially linking to the promotion of slow fiber characteristics. Collectively, tRF-Lys-TTT-012 may serve as a promising marker for slow muscle fibers and uncover a novel potential target for skeletal muscle fiber type transition toward the slow fiber phenotype. Full article

Citrobacter braakii is an emerging opportunistic pathogen of escalating clinical significance in animal hosts, though its pathogenic mechanisms remain poorly characterized. This study isolated a C. braakii strain (SCGY-1L) from diseased Siniperca chuatsi and confirmed its identity through integrated morphological, physiological, and molecular analyses. Comprehensive genomic sequencing revealed a 5.75 Mb genome comprising one circular chromosome and two plasmids. A Circos plot was constructed to visualize the genomic architecture of strain SCGY-1L, revealing 5482 protein-coding genes, 25 tRNA genes, and 86 rRNA genes. Additionally, 738 virulence-associated genes and 366 antibiotic resistance determinants were annotated, elucidating multidrug-resistant phenotypes including insensitivity to erythromycin and penicillin. Pathogenicity assessment established an LD₅₀ of 1.28 × 10⁶ CFU/mL in infected hosts, with histopathological analysis showing significant hemorrhage and necrosis in target organs (liver, spleen, kidney). Host transcriptome profiling generated 41.21 Gb of high-quality clean data, identifying 2201 differentially expressed genes post-infection (1568 up-regulated; 633 down-regulated). These were significantly enriched in phagocytosis, cytokine-mediated signaling, and inflammatory regulation pathways. These molecular insights establish C. braakii’s mechanistic framework for pathogenesis and host adaptation, providing critical targets for diagnostics and therapeutics against emerging Citrobacter infections. Full article

This study examines the genetic diversity and population structure of silver carp (Hypophthalmichthys molitrix), an ecologically and economically important freshwater species. Samples were collected from 17 sites along the Yangtze River, including LCH, LCS, LJHK, and LXZX, as well as one population from the United States (SV). Restriction-site associated DNA sequencing (RAD-seq) generated 759,453 high-quality single-nucleotide polymorphisms (SNPs) for population genomic analyses, including genetic differentiation (F_ST), population structure, and linkage disequilibrium (LD) decay. Genetic variation was primarily found within populations (78.05%), with 21.94% among populations. Most sites exhibited low genetic differentiation (F_ST < 0.05), suggesting high admixture along the river, although a few sites displayed elevated values (F_ST > 0.15). Rapid LD decay in LCH, LCS, and LJZ indicated frequent recombination and moderate to large effective population sizes. These patterns reflect the influence of geographic and ecological factors on population structure. Conservation strategies should maintain genetic connectivity while protecting distinct genetic resources. Populations with high differentiation, such as LXZX and LWZ, warrant targeted management to preserve unique genetic diversity. Full article

Analysis of selection signatures in the genomes of farm animals enables the detection of genomic regions affected by selection and contributes to the identification of genes underlying adaptive and productive traits. This research aimed to identify loci under selection pressure and to detect candidate genes in Dzhalgin Merino sheep by performing a comparative genomic analysis with the related Australian Merino and Rambouillet breeds. A total of 293 animals were included in the analysis, comprising Dzhalgin Merino (n = 53), Australian Merino (n = 50), Australian Industry Merino (n = 88), and Rambouillet (n = 102). Whole-genome SNP genotyping data for Dzhalgin Merino were generated within this study, while data for Australian Merino, Australian Industry Merino, and Rambouillet were obtained from the SheepHapMap project. For the purposes of analysis, Australian Merino and Australian Industry Merino were combined into a single group (n = 138). To enhance the reliability of the results, three independent methods were employed to detect selection signatures: the fixation index (FST), analysis of linkage disequilibrium variation (varLD), and the cross-population number of segregating sites by length (xp-nSL). The study showed that Dzhalgin Merino have unique genetic signatures potentially associated with adaptation and productivity, which opens up new opportunities for their selection. The identified genes can become the basis for developing new breeding programs aimed at improving both the productive qualities and the adaptive abilities of the breed. Further research should be aimed at a detailed investigation of gene structure within loci under selection pressure and at clarifying the mechanisms by which these genes influence animal phenotypes. A total of 185 genes were identified within genomic regions exhibiting selection signatures. Among these, particular attention was given to EPHA6, MLLT3, ROBO1, KIAA0753, MED31, SLC13A5, and ELAVL4, which are involved in biological processes such as growth, development, and reproduction. The identified genes represent potential targets for breeding programs aimed at increasing productivity and adaptive capacity of the breed. Full article

Background: It has recently been proposed that the retina plays an important modulatory role in the control of motor function that is usually attributed exclusively to the function of the nigro-striatal dopamine (NSD) system. Indeed, it has been proposed further that Parkinson’s disease (PD) begins in and progresses from the retina and may be effectively treated from there. While previous intraocular work has employed intravitreal (IVIT) administration of toxins to induce experimental PD, the first study series reported here examines the effect of IVIT haloperidol on motor performance while the second study examines the effect of IVIT haloperidol on the unilateral rotation model of PD, both in a circadian context. Methods: Motor tests included open field performance and the latency to perform three motor tests after the IVIT injection of haloperidol with and without amphetamine pretreatment. In a second study, IVIT injections of the melatonin antagonist ML-23 or L-dopa were made after unilateral lesions of the NSD in rats that were placed in a rotometer examining spontaneous ipsilateral and contralateral turning. Results: IVIT haloperidol produced robust changes in several motor parameters during the light and dark phase of the LD cycle which were enhanced by amphetamine pretreatment. In the second study, while IVIT L-dopa had only a minor effect on spontaneous rotation during the light phase, IVIT haloperidol produced a robust effect upon ipsilateral turning. The reduction in spontaneous ipsilateral turning was seen after IVIT injections into the eye ipsilateral or contralateral to the hemisphere in which NSD destruction occurred. Reduced turning was seen during both the light and dark phases of the L/D cycle. Conclusions: These results illustrate that IVIT injections of DA and melatonin receptor antagonists can differentially alter motor function via the retina. This suggests that the retina may be a treatment target not only for PD but also for other DA- and melatonin-mediated disorders such as drug addiction, psychosis and schizophrenia. Full article

The healing issue is a central, not completely understood, problem in pharmacology, approached by many concepts. One of the most well-known is Robert’s and Szabo’s concept of cytoprotection, which holds innate cell (epithelial (Robert), endothelial (Szabo)) integrity, protection/maintenance/reestablishing in the stomach to be translated to other organ therapy (cytoprotection→organoprotection) via cytoprotection agent’s effect. Thereby, we defend stable gastric pentadecapeptide BPC 157 therapy, efficacy, pleiotropic beneficial effects along with high safety (LD1 not achieved) against Józwiak and collaborators’ review speculating its negative impact, speculation of angiogenesis toward tumorogenesis, increased NO and eNOS, toward damaging free radicals formation, and neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease). Contrarily, in wound healing and general healing capabilities as reviewed, as a cytoprotective agent, and native cytoprotection mediator, BPC 157 controls angiogenesis and the NO-system healing functions, and counteracts the pathological presentation of neurodegenerative diseases in acknowledged animal models (i.e., Parkinson’s disease and Alzheimer’s disease), and presents prominent anti-tumor potential, in vivo and in vitro. BPC 157 resolved cornea transparency maintenance, cornea healing “angiogenic privilege” (vs. angiogenesis/neovascularization/tumorogenesis), does not produce corneal neovascularization, but rather opposes it, and per Folkman’s concept, it demonstrates anti-tumor effect in vivo and in vitro. BPC 157 exhibits a distinctive effect on NO-level (increase vs. decrease), always combined with counteraction of free radicals formation, and in mice and rats, BPC 157 therapy counteracts Parkinson’s disease-like and Alzheimer’s disease-like disturbances. Thus, BPC 157 therapy means targeting angiogenesis and NO’s cytotoxic and damaging actions, but maintaining, promoting, or recovering their essential protective functions. Full article

Background: Degenerative lumbar spine disease is a prevalent cause of chronic low back pain that significantly impairs daily function and quality of life. While conservative management is the first line of treatment, many patients ultimately require instrumented lumbar spine surgery. However, postoperative outcomes vary considerably, with emerging evidence suggesting that preoperative psychological factors such as anxiety, depression, and pain catastrophizing may influence recovery. The SAP-LD (Scale for Anxiety and Pain in Lumbar Degeneration) study was designed to assess the prognostic role of these psychological and physical parameters in surgical outcomes. Methods: This prospective observational study enrolled 70 adult patients with degenerative lumbar spine pathology scheduled for instrumented surgical treatment at the University of Brescia and ASST Spedali Civili di Brescia between March and December 2024. Preoperative assessments included demographic, clinical, and radiologic data along with validated scales: the Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). Follow-up evaluations were performed at 45 days and at 6 months, and statistical analyses were conducted using correlation tests, ANOVA, and regression modeling. Results: The demographic analysis of the 70 enrolled patients shows a balanced gender distribution (38 females, 34 males) with a mean age of 61 years (range 23–81). The educational level distribution indicates that the majority of patients (44.29%) have a secondary education level, while 35.71% have a tertiary education level. Regarding employment status, 50% of the patients are retired or not working. Patients with clinically significant anxiety and/or depression showed higher levels of perceived pain, pain catastrophizing, and disability at baseline. These patients reported significantly worse scores on the Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS), and Oswestry Disability Index (ODI). The Oswestry Disability Index (ODI) demonstrates a clinically significant improvement (reduction) in disability between the preoperative period (t0) and the 45-day follow-up (t2), with the median decreasing from 39.00 to 13.00. However, there is a partial regression at the 6-month follow-up (t3), with the median increasing to 27.00. For the SF-36 Health Survey, the General Health subscale shows an improvement between t0 and t2 (median increasing from 55.00 to 60.00), followed by a slight decrease at t3 (median 55.00). Similar patterns are observed in most other subscales, with initial improvement followed by partial regression. The Pain Catastrophizing Scale (PCS) shows a substantial reduction in catastrophizing between t0 and t2 (median decreasing from 16.00 to 3.00), followed by an increase at t3 (median 11.00), though still below baseline levels. Pain intensity as measured by the Visual Analogue Scale (VAS) shows a significant reduction at t2 (median decreasing from 5.00 to 3.00), but increases again at t3 (median 6.00), even exceeding the preoperative level. For the Hospital Anxiety and Depression Scale (HADS), no significant differences were observed across time points, with values indicating mild symptoms throughout the study period. Correlation analyses confirmed that higher preoperative anxiety and depression scores were predictive of poorer postoperative outcomes. Specifically, higher HADS scores at baseline are associated with higher ODI scores (increased disability) at all time points (p = 0.002), higher VAS scores (increased pain) at all time points (p = 0.015), and lower scores on SF-36 subscales, particularly Emotional Well-being (p = 0.00023) and Social Functioning (p = 0.002). Higher PCS scores at baseline are associated with higher ODI scores at all time points (p = 0.001), higher VAS scores at all time points (p = 0.008), and lower scores on SF-36 subscales, particularly Pain (p = 0.00023) and Physical Functioning (p = 0.04254). The mixed linear models analysis confirms these findings, showing that the ODI score decreases significantly between t0 and t2 (p = 0.00023) and increases between t2 and t3, though this increase is not statistically significant (p = 0.079). For VAS scores, there is a significant decrease between t0 and t2 (p = 0.00023) and a significant increase between t2 and t3 (p = 0.04254). Patients with elevated preoperative HADS scores tended to have slower recovery trajectories and reported lower satisfaction levels. These findings reinforce the prognostic value of psychological assessments in spine surgery and suggest that targeted psychological interventions could improve patient outcomes. Conclusions: By identifying psychological predictors of postoperative recovery, this study underscores the importance of integrating preoperative psychological screening into routine clinical practice. The results suggest that a multidisciplinary approach, including both surgical and psychological care, could enhance long-term functional outcomes and quality of life for patients undergoing instrumented lumbar spine surgery. Full article

Tumor drug resistance exhibits substantial heterogeneity across cancer types, reflecting distinct molecular mechanisms in each malignancy. To characterize this complexity, we developed a pan-cancer transfer learning framework that integrates bulk RNA-seq data with a residual variational autoencoder (Res VAE) backbone. Five models were trained on the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, which includes drug response profiles for 72 chemotherapeutic agents. Among them, three models are specially designed by incorporating variational autoencoders and large pretrained models (LLMs): the LLM large VAE (VAE_LL), the LLM small VAE (VAE_LS), and the LLM distillation VAE (VAE_LD). Random Forest (RF) and eXtreme Gradient Boosting (XGB) were included as ensemble learning baselines. After internal cross-validation, the top four models (VAE_LL, VAE_LD, XGB, and RF) were applied to five representative TCGA cohorts comprising 1,836 patients. For each cancer type, resistance to nine clinically relevant first-line drugs was modeled, resulting in 180 drug–cancer prediction tasks. Among all models, VAE_LD achieved the best overall performance, with a mean AUC of 0.81 and an F1 score of 0.92 on the GDSC benchmark, and maintained strong predictive power in the clinical validation phase. Interpretation analyses identified tumor-specific resistance biomarkers with clinical significance. In lung adenocarcinoma, elevated expression of TFF1 was repeatedly associated with resistance to Gefitinib and correlated with poor patient prognosis, indicating its potential as a therapeutic target. In glioblastoma, OPALIN, LTF, IL2RA, and SLC17A7 were implicated in Temozolomide resistance through pathways related to epithelial differentiation and angiogenesis. In conclusion, the VAE_LD model offers a high-performing and interpretable approach for predicting drug resistance across multiple tumor types. It supports the identification of clinically actionable biomarkers and provides a robust framework for precision oncology applications. Full article

Pine wilt disease, caused by the pine wood nematode Bursaphelenchus xylophilus (Steiner & Bührer) Nickle, poses a major threat to pine forests worldwide. While avermectin-based pesticides are currently used for pine wilt disease management, alternative approaches are needed to mitigate the risk of resistance. This study evaluated the nematicidal activity of 24 synthetic alkyloxyalkanols (ROR′OH) against B. xylophilus. The compounds were synthesized by the etherification of diols with 1-bromoalkanes and tested in a microplate bioassay. Mortality was measured after 24 h, and LD₅₀ values were calculated. Several compounds, including 2-(1-decyloxyl)-1-ethanol (C10OC2OH) and 8-(1-hexyloxy)-1-octanol (C6OC8OH), showed potent nematicidal effects, with LD₅₀ values of less than 50 ppm. Structure–activity relationship analysis revealed that compounds with chains containing an even number of carbons in both the alkyl and alkyloxy groups tended to exhibit increased activity. Clustering analysis confirmed that carbon parity significantly affected efficacy (Mann–Whitney U = 15, p < 0.001). Compared with previously reported plant-derived compounds, several of these alkyloxyalkanols demonstrated superior potency. The results suggest that odd–even carbon chain parity, a known physicochemical phenomenon of n-alkanes, may underlie variations in nematicidal activity. These findings provide insight into the design of novel nematicides targeting B. xylophilus. Full article

Pet owners have become more aware of how their pet’s nutrition can influence the pet’s life expectancy, wellness, and energy. Evaluating the new ingredients claiming better pet health for nutrient contributions requires significant investment and targeted animal commitment while current research aims to find alternative approaches. Research on pet foods in universities is overseen by the Institutional Animal Care and Use Committee, which has restrictions on the use of vertebrates in testing but places no restrictions on the use of insects. The research reported here studied three species of beetles (Coleoptera: Dermestidae), Trogoderma variabile (Ballion), Trogoderma inclusum (LeConte), and Dermestes maculatus (DeGeer) as potential model organisms to evaluate pet food nutrient bioavailability. The larvae of all three species were fed a balanced pet food diet under various laboratory conditions to determine their protein efficiency ratios (PERs) over a 144 h period. Results suggested that D. maculatus larvae reared at 27 °C, 60–65% R.H. (relative humidity), and a photoperiod of 16:8 L:D were the most efficient at converting ingested protein into weight gain with an average protein efficiency ratio (PER) of 1.439. Further experiments were conducted using only D. maculatus larvae with shorter time windows of 48 h and 24 h. The 24 h feeding time was successful and yielded an average PER of 2.476. These findings suggest that D. maculatus larvae may be a useful model organism for pet food bioavailability studies. Full article

In the last decades, extracts of Viscum album L., commonly known as European mistletoe, have attracted increasing interest for their immunomodulatory, anti-inflammatory and antioxidant activities. Nowadays, they are mainly used in complementary cancer treatments. A targeted LC-MRM-MS was selected to determine the chemical composition and the activities of a V. album homeopathic mother tincture (MT#39998). Results showed a complex chemical composition, which was compared with that of other similar extracts. The LC-MRM-MS data were confirmed and complemented by HPLC analysis. Viscotoxins content was evaluated because of their cytotoxicity. MT#39998 was tested for its cytotoxic and antioxidant effect, before and after viscotoxins removal. The composition of MT#39998 in viscotoxins was similar to that of other products already present in the market and its safety was confirmed by estimation of LD₅₀ based on in vitro IC₅₀ values (LD₅₀ was >2 g/kg). The aim of this study is to report a case study on a plant extract. The study was based on the chemical composition, including the metabolome, and on the pharmacological data, including toxicity and antioxidant activities, to validate the current utilization. Full article