Search Results (371)

Population aging and widespread sedentary lifestyles have increased the prevalence of chronic non-communicable diseases, many of which are linked to progressive disruptions of cellular homeostasis. Autophagy, a conserved cellular degradation and recycling pathway, plays a central role in maintaining metabolic flexibility, proteostasis, and organ function. However, aging and physical inactivity impair autophagic regulation, thereby contributing to the development of sarcopenia, cardiovascular diseases, metabolic disorders, and neurodegenerative diseases. Physical exercise is a non-pharmacological intervention that can restore autophagic activity and confer systemic health benefits in multiple preclinical and clinical contexts. Increasing evidence indicates that these benefits are mediated not only by local tissue adaptations but also by complex inter-organ communication. Central to this process are exercise-induced bioactive factors, collectively termed exerkines, including myokines, cardiokines, adipokines, hepatokines, osteokines, and circulating miRNAs. Rather than acting independently, exerkines form an integrated signaling network that fine-tunes autophagic flux across multiple tissues. Exerkine-mediated regulation of autophagy involves key pathways such as AMPK/mTOR, FoxO, SIRT1, ULK1, and TFEB, thereby coordinating energy metabolism, mitochondrial quality control, inflammation, and protein turnover in skeletal muscle, heart, liver, adipose tissue, bone, and the central nervous system. This review summarizes current evidence on representative exerkines and their roles in autophagy-dependent inter-organ crosstalk, highlighting the exercise–exerkine–autophagy axis as a promising target for preventing and managing chronic diseases. Full article

Background/Objectives: Breast cancer is a heterogeneous and complex disease with significant individual differences in molecular immunophenotype, biological behavior, histopathological morphology, and response to chemotherapy. The presence of tumor-infiltrating lymphocytes (TILs) has gained considerable attention due to growing evidence of their involvement in therapeutic efficacy, particularly in the response to neoadjuvant chemotherapy (NACT). Different immune cell subsets’ frequency, location, and functional orientation vary substantially between tumor types and individuals with apparently identical cancers. Currently, next-generation sequencing (NGS) has provided key insights into the composition of the tumor microenvironment. Simultaneously, immunohistochemistry (IHC) of paraffin-embedded biopsies allows the visualization of marker proteins within the immune infiltrate, thereby enhancing our understanding of the role of immune cells in cancer therapy. Methods: This exploratory study evaluated immune cell tumor infiltration using NGS with immune cell deconvolution, as well as automated IHC on Tru-Cut biopsies from 57 patients with locally advanced breast cancer. Image analysis was performed using Qupath v0.6.0 software. The percentage of infiltrating CD4+ or CD8+ T cells was determined, along with the expression of the markers FoxP3, LAG3, CTLA4, PD1, and TIM-3. We aimed to gain insights into the tumor microenvironment and its influence on the response to NACT in patients with breast cancer. Results: Transcriptomic immune deconvolution approaches suggested that a biased cytotoxic tumor environment is linked to chemosensitivity. IHC assays of individual markers reveal that baseline immune cell abundance and individual checkpoint expression did not differ significantly across the response groups. However, the functional organization and coordination of the tumor immune microenvironment showed distinct associations with chemosensitivity. Conclusions: Features representing immune balance, such as CD8/CD4 ratio and T cell-contextualized metrics, emerged as candidate predictors of pathological response to NACT, outperforming molecular phenotype alone in this exploratory cohort. Full article

Background/Objectives: This study aimed to determine the potential roles of miR-4295, miR-4720-5p, miR-4773, miR-6831-5p, and miR-7161-5p in colorectal cancer by evaluating their expression levels in matched tumor and adjacent non-tumor tissues from 86 patients. Methods: A total of 172 samples were analyzed, and the associations between miRNA expression levels and clinicopathological characteristics were assessed, along with correlations among the miRNAs. Functional enrichment analyses, including GO and KEGG pathway evaluations, were performed using DIANA-mirPath v.3 to characterize biological processes and signaling pathways associated with the predicted target genes. Results: The results showed that miR-4295 and miR-4720-5p were significantly upregulated in tumor tissues, while miR-4773 and miR-6831-5p were significantly downregulated (p < 0.001). No significant difference in miR-7161-5p expression was observed between tumor and non-tumor tissues (p = 0.877). KEGG analysis indicated that miR-4295, miR-4720-5p, miR-4773, and miR-6831-5p regulate genes involved in the TGF-β, mTOR, ErbB, FoxO, and endocytosis signaling pathways. Conclusions: These findings suggest that miR-4295 and miR-4720-5p may have oncogenic functions, while miR-4773 and miR-6831-5p may have tumor-suppressing functions, and that this relationship may contribute to the development of colorectal cancer. Full article

Background/Objectives: Cancer cachexia involves progressive skeletal muscle and adipose tissue loss, which is further aggravated by cisplatin chemotherapy via increased systemic inflammation, tissue catabolism, and renal toxicity. The present study aimed to evaluate whether a combination of amaranth protein hydrolysate and Agastache rugosa extract (AKE) could attenuate cisplatin-associated cachexia and nephrotoxicity in CT26 tumor-bearing mice. Methods: Cancer cachexia was induced by subcutaneous CT26 cell inoculation in 6-week-old male BALB/c mice, followed by a 7-day tumor establishment period. Cisplatin was then administered intraperitoneally, and AKE (125 or 250 mg/kg/day) was given daily by oral gavage for 14 days. Results: AKE administration significantly alleviated cisplatin-induced body weight loss and systemic inflammation, accompanied by preservation of skeletal muscle and adipose tissue mass, as well as increased myofiber cross-sectional area and adipocyte size. AKE markedly reduced serum inflammatory cytokines, blood urea nitrogen, and creatinine levels, indicating protection against cisplatin-induced renal injury. Mechanistically, AKE suppressed renal apoptosis through inhibition of mitogen-activated protein kinase signaling. In skeletal muscle, AKE attenuated muscle atrophy by modulating protein turnover pathways, including downregulation of muscle-specific ubiquitin ligases and restoration of Akt/mTOR and FoxO3a signaling. Furthermore, AKE mitigated adipose tissue wasting by suppressing AMP-activated protein kinase-dependent browning and restoring adipogenic signaling involved in lipid storage and differentiation. Conclusions: These findings demonstrate that AKE confers comprehensive protection against cisplatin-induced cachexia and nephrotoxicity by coordinately preserving muscle and adipose tissue and attenuating renal injury, suggesting its potential as a functional nutritional strategy to alleviate chemotherapy-associated tissue wasting. Full article

This study evaluated the effects of supplementing methionine to a low-protein diet on nutrient digestibility, nitrogen (N) metabolism, growth performance, serum biochemical parameters, fur quality, and intestinal microbiota composition in blue foxes (Vulpes lagopus) during the fur-growing period. Fifty 17-week-old blue foxes were randomly allocated to five experimental groups (n = 10 per group). The control group received a diet containing 28% crude protein (CP), while the experimental groups were fed a 22% CP diet supplemented with 0%, 0.35%, 0.55%, or 0.75% methionine on a dry matter (DM) basis, designated as M0, M1, M2, and M3, respectively. Results demonstrated that the final body weight (FW), total weight gain (TW), and average daily gain (ADG) of the M3 group were comparable to the control group (p > 0.05). Methionine supplementation significantly enhanced fur quality and stimulated hair follicle development (p < 0.05). Although the reduction in dietary protein level led to decreased N intake and fecal N excretion, the M2 and M3 groups exhibited significantly higher N retention compared to the control, M0, and M1 groups (p < 0.05). Regarding nutrient digestibility, the M2 and M3 groups showed higher DM digestibility (p < 0.05), while the M3 group maintained organic matter (OM) digestibility comparable to the control group (p > 0.05). The highest CP digestibility was observed in the M3 group (p < 0.05). Additionally, ether extract (EE) digestibility was significantly improved in the methionine-supplemented groups (M1–M3) relative to the control (p < 0.05). Serum analysis revealed dose-dependent increases in total protein (TP), albumin (ALB), and high-density lipoprotein (HDL) concentrations in the M2 and M3 groups. Conversely, low-density lipoprotein (LDL) levels were elevated in these groups compared to the control and M0 groups (p < 0.05). Liver function parameters were also significantly improved in the M2 and M3 groups (p < 0.05). Furthermore, methionine supplementation enhanced the diversity and richness of the intestinal microbiota and altered its composition at the phylum and genus levels. In conclusion, supplementing low-protein diets with methionine can maintain growth performance, improve fur quality, enhance nutrient utilization efficiency, and support intestinal microbiota homeostasis in blue foxes. The optimal supplementation level is 0.75%, resulting in a total dietary methionine concentration of 1.1% on a DM basis. Full article

In the context of polarized media discourse, this study examines how outlets with distinct political leanings constructed multimodal representations of the 2025 Los Angeles protests. Adopting a corpus-assisted Multimodal Critical Discourse Analysis (MCDA) framework, this study integrates Entman’s framing theory with Kress and van Leeuwen’s visual grammar to analyze news coverage of the protests. The results reveal a divergence in multimodal strategies. Fox News employs a delegitimization frame through a dominant strategy of reinforcement, where images serve as direct evidence for textual claims. Conversely, CNN constructs a conditional legitimacy frame via a more nuanced strategy, through which the outlet strategically utilizes multimodal contradiction to negotiate with the “protest paradigm” and mitigate the visual reality of disorder. The findings demonstrate how partisan media leverage distinct multimodal strategies to reconstruct opposing social realities. The study contributes to political discourse research by going beyond textual bias to reveal how multimodal strategies function in media polarization environments. Full article

Rapid urban expansion across southwestern Florida has led to extensive habitat fragmentation and degradation, presenting significant ecological challenges for the persistence of multiple species, including the Big Cypress fox squirrel (Sciurus niger avicennia; BCFS), a state threatened and imperiled subspecies endemic to the Big Cypress Basin. This study uses high-resolution ecological modeling, Omniscape, to assess the functional connectivity of BCFS habitat within the urbanizing landscape of Fort Myers, Florida, and a green infrastructure (GI) transect-based approach to identify strategies for improving habitat and connectivity within the urban landscape. Results demonstrate that BCFS movement is disproportionately represented in high-density urban zones, with priority bottleneck patterns emerging in surrounding lower-density, transitional land use areas such as suburban neighborhoods and golf courses. By combining spatial modeling and applied GI design, this study offers a replicable framework for embedding species conservation into local and regional planning processes. Given the model-based and species-specific scope of this study, future research should focus on empirical validation and extending this framework across multiple species and scales. Overall, the findings emphasize the importance of multiscalar, landscape-sensitive planning strategies to mitigate anthropogenic fragmentation, enhance ecological resilience, and support the long-term persistence of native species in rapidly developing regions. Full article

A comb model with periodic potential in side branches is introduced. A comb model is a model of geometrically constrained diffusion, such that the diffusion process along the comb’s main axis (backbone) is coupled to the diffusion process in fingers, the side branches of the comb. Here, we consider a generalized version of this complex process by enabling a periodic potential function in the fingers. We aim to understand how the potential function added affects the asymptotic transport scalings in the backbone. A set of exact results pertaining to the generalized model is obtained. It is shown that the relaxation process in fingers leads directly to the occurrence of a non-equilibrium stationary state (NESS) in comb geometry, provided that the total energy is zero. Also, it is shown that the spatial distribution of the probability density in proximity to NESS is given by the Mathieu distribution with zero energy. The latter distribution is found to be the direct result of relaxation towards stationarity of the Mathieu eigenspectrum. It is suggested that the generalized model can characterize anisotropic particle dispersion in beta-plane atmospheric (alternatively, electrostatic drift-wave plasma) turbulence and the subsequent formation of layered structures, zonal flows, and staircases. In this regard, the inherent interconnection between combs and staircases is discussed in some detail. Full article

Background: The Qingyuan partridge chicken is a high-quality local chicken breed in China. Its weight gain directly affects breeding efficiency. This study used RNA sequencing to analyze gene expression dynamics in the breast muscle tissue of Qingyuan partridge chickens at 1, 35, 70, and 105 days of age. Methods: This study employed RNA-sequencing, integrated with differential expression analysis, weighted gene co-expression network analysis (WGCNA), and short time-series expression miner (STEM) analysis, to systematically investigate the transcriptomic dynamics in breast muscle tissue across four developmental stages. Results: Phenotypic analysis revealed a significant increase in both body weight (BW) and breast muscle weight with age (p < 0.05). Transcriptomic analysis identified 3521 genes specifically expressed at the age of one day compared with the other 3 ages. These were significantly enriched in pathways related to ribosomal biosynthesis, cytoskeletal regulation, and cell proliferation (p < 0.05). Turquoise and black modules were identified by WGCNA, containing 1563 hub genes, which significantly correlated with BW. Integration of differentially expressed genes and STEM analysis selected 26 BW-related key genes closely associated with muscle growth, including calmodulin 2 (CALM2), heat shock protein 90 alpha family class A member 1 (HSP90AA1), and cholinergic receptor nicotinic delta subunit (CHRND). Protein–protein interaction analysis revealed two functional networks centered around these genes. Enrichment analysis of the STEM profiles indicated that upregulated genes were significantly enriched in autophagy and the ErbB, FoxO, mTOR, and insulin signaling pathways, while genes related to the ribosome, cell cycle, and PPAR signaling pathways were downregulated. Conclusions: This study identified BW-related key genes and pathways, enriching our knowledge of the functional maintenance of chicken BW. Full article

Objective: Accumulating evidence demonstrates that melatonin is involved in modulating granulosa cell function and follicular development. lncRNAs (long non-coding RNAs) and circRNAs (circular RNAs) have been reported to participate in multiple biological processes. This study aimed to explore the candidate circRNAs and lncRNAs related to molecular mechanisms when exploring the role of melatonin in regulating ovarian function. Methods: Bovine ovary granulosa cells were collected 48 h after treatment with melatonin at 10⁻⁷ M. The lncRNA and circRNA profiles of bovine granulosa cells were further explored using high-throughput sequencing in the absence/presence of melatonin. The differentially expressed lncRNAs and circRNAs were analyzed through the annotation information of source transcripts for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: We identified 99 differentially expressed lncRNAs and 28 differentially expressed circRNAs. Enrichment analysis of differentially expressed lncRNAs and circRNAs showed they were enriched in multiple pathways involved in development, apoptosis, and reproductive function, such as the mTOR (mammalian Target of Rapamycin) signaling pathway, FoxO (Forkhead box O) signaling pathway, MAPK (Mitogen-Activated Protein Kinase) signaling pathway, Hippo signaling pathway, TGF-beta (Transforming Growth Factor-β) signaling pathway, PI3K-Akt (Phosphatidylinositol 3-Kinase-Akt) signaling pathway, apoptosis, and Rap1 (Ras-related protein 1), most of which were mainly related to granulosa cell function and the crosstalk between granulosa cells and oocytes. The present analysis indicated the potential role of melatonin in granulosa cell function by regulating lncRNA and circRNA expression and, thus, mediating follicular development. An lncRNA/circRNA and miRNA regulatory network was also constructed to take their interactions into account. Conclusions: Our study offers details of lncRNA and circRNA expression in bovine granulosa cells and further provides insight into the potential role of melatonin in regulating reproduction by modulating lncRNA and circRNA expression. Full article

Bt Cry toxins remain the cornerstone of transgenic crop protection against Lepidopteran pests, yet field-evolved resistance, particularly in invasive species such as Spodoptera frugiperda and Helicoverpa armigera, can threaten their long-term efficacy. This review presents a comprehensive and unified mechanistic framework that synthesizes current understanding of Bt Cry toxin modes of action and the complex, multilayered regulatory mechanisms of field-evolved resistance. Beyond the classical pore-formation model, emerging evidence highlights signal transduction cascades, immune evasion via suppression of Toll/IMD pathways, and tripartite toxin–host–microbiota interactions that can dynamically modulate protoxin activation and receptor accessibility. Resistance arises from target-site alterations (e.g., ABCC2/ABCC3, Cadherin mutations), altered midgut protease profiles, enhanced immune regeneration, and microbiota-mediated detoxification, orchestrated by transcription factor networks (GATA, FoxA, FTZ-F1), constitutive MAPK hyperactivation (especially MAP4K4-driven cascades), along with preliminary emerging findings on non-coding RNA involvement. Countermeasures now integrate synergistic Cry/Vip pyramiding, CRISPR/Cas9-validated receptor knockouts revealing functional redundancy, Domain III chimerization (e.g., Cry1A.105), phage-assisted continuous evolution (PACE), and the emerging application of AlphaFold3 for structure-guided rational redesign of resistance-breaking variants. Future sustainability hinges on system-level integration of single-cell transcriptomics, midgut-specific CRISPR screens, microbiome engineering, and AI-accelerated protein design to preempt resistance trajectories and secure Bt biotechnology within integrated resistance and pest management frameworks. Full article

The red fox (Vulpes vulpes) is a widely distributed and highly adaptive small carnivore known by its generalist diet, which includes small mammals, invertebrates, and fruits. Despite its ecological relevance, how habitat heterogeneity affects its diet across the Mediterranean, a biodiversity hotspot shaped by long-term human disturbance, remains insufficiently synthesized. In this review, we synthesized and analyzed published studies that reported habitat-specific data on the red fox diet in the Mediterranean. Only 12 studies met the selection criteria, and no study directly compared two different habitats. The studied areas covered three dominant habitats: forests, scrublands (garrigue), and agroecosystems, and diet items were grouped in 7 categories: birds, carcasses, fruits, invertebrates, lagomorphs, small mammals, and reptiles. Overall diet composition varied significantly, with invertebrates and fruits being the most frequent diet items. In turn, lagomorphs and reptiles were the least frequent. In turn, diet composition varied little across habitats, indicating that diet variation follows specific local resource abundance regardless of habitat type. Despite the analytical limitations associated with the limited availability of habitat-explicit studies. The results highlight the pronounced dietary plasticity of the red fox and its capacity to integrate resource availability across heterogeneous Mediterranean landscape mosaics. This trophic adaptability and top predator role support various ecosystem functions such as controlling invertebrate and small mammal populations, dispersing seeds, and cycling nutrients, reinforcing the potential of the red fox as functional bioindicator in the Mediterranean. Therefore, sustainable land management, especially in agricultural areas, and restoration efforts for degraded areas should consider the beneficial roles of generalist carnivores like the red fox. Full article

Abdominal fat deposition in chickens significantly impacts production efficiency and is influenced by complex genetic and molecular mechanisms. This review summarizes current genomic and transcriptomic research on the regulation of adipogenesis and fat accumulation in chickens, highlighting key genes and loci identified through genome-wide association studies as well as other candidates involved in lipogenesis, lipolysis, and transcriptional regulation. Major metabolic pathways, including MAPK, AMPK, PI3K/AKT/mTOR, TGFβ1/Smad3, FoxO, JAK–STAT, Wnt/β-catenin, and Sonic Hedgehog signaling, are examined for their roles in fat deposition. The regulatory functions of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are discussed, focusing on their interactions with target mRNAs and signaling networks that control lipid metabolism, adipocyte differentiation, and energy balance. Integrating insights from both avian and human studies, this review emphasizes the molecular mechanisms underlying adipogenesis and highlights potential strategies for genetic selection aimed at reducing excessive abdominal fat and improving poultry productivity. Full article

This paper aims to obtain the ${}_{\xi }\mathsf{\Psi }_{\eta }$-extended Whittaker function and its integral representations. This function is defined by using the ${}_{\xi }\mathsf{\Psi }_{\eta }$-confluent hypergeometric function, which was recently extended in terms of the Fox–Wright function. Furthermore, we discuss properties including a transformation formula, integral transforms (Laplace–Mellin and Hankel transforms), and a differential formula. Our results provide a unified framework for several known generalizations of the Whittaker function and highlight potential applications in applied mathematics and theoretical physics. Full article

Background: The anabolic window hypothesis suggests a limited post-exercise period for optimal nutrient uptake and utilization. Prior research indicates that miRNAs in extracellular vesicles (EVs) may regulate post-exercise adaptation by influencing protein synthesis. This study aimed to examine the effects of resistance exercise (RE) on physiological parameters and the expression and function of miRNAs transported in EVs. Methods: Twenty resistance-trained male participants (22 ± 2 years) completed a five-week RE program designed for hypertrophy. They consumed maltodextrin and whey protein based on assigned nutrient timing: immediately post-exercise (AE), three hours post-exercise (AE3), or no intake (CTRL). Body composition and knee extensor strength were assessed. Small EVs were isolated and then validated via three methods. Nanoparticle tracking analysis determined EV concentration and size, followed by pooled miRNA profiling and signaling pathway analysis. Results: Skeletal muscle mass significantly increased in AE (p = 0.001, g = 2) and AE3 (p = 0.028, g = 1), and it was higher in AE compared to CTRL (p = 0.013, η² = 0.41), while knee extensor strength improved only in AE (p = 0.032, g = 0.9). Body fat percentage significantly decreased in all groups, AE (p = 0.005, g = 1.5), AE3 (p = 0.024, g = 1), and CTRL (p = 0.005, g = 1.7). Vesicle concentration significantly increased in the AE group (p = 0.043, r = 0.7), while it decreased in the CTRL group (p = 0.046, r = 0.8). Distinct miRNA expression profiles emerged post-intervention: 20 miRNAs were upregulated in AE, while 13 in AE3 and 15 in CTRL were downregulated. Conclusions: Nutrient timing influences training adaptation but is not more critical than total macronutrient intake. Changes in EV-transported miRNAs may regulate anabolic processes via the PI3K-AKT-mTOR and FoxO pathways through PTEN regulation. Full article