This study evaluated the effects of a mixture of rumen undegradable protein (RUP) sources including soybean meal (SBM), corn gluten meal (CGM) and fish meal (FM) on performance, meat quality, and relative expression of μ-calpain-1 (CAPN1), calpastatin (CAST), and heart- fatty acid binding protein (H-FABP) genes in fattening lambs. Twenty-one male Lori-Bakhtiari lambs (140 ± 15 days of age, 33 ± 2.5 kg) were randomly fed one of the three experimental diets each formulated to contain similar RUP%, containing 13% SBM (RUP1), 5% SBM + 3.5% CGM (RUP2), and 5% SBM + 2% CGM + 2% FM (RUP3) for a period of 60 days. Findings showed that the mixture of three sources of RUP (RUP3) enhanced growth performance (9%), altered meat composition, and modulate the expression of genes related to meat quality. Feeding lambs with RUP3 increased blood total protein and shifted toward more fat deposition in meat (P < 0.05). Meat of lambs in RUP3 showed an increase fat content but a decrease in crude protein percentage (P < 0.05). Fatty acid profile of meat remained unchanged except for an improvement in docosahexaenoic acid (C22:6 n-3) and n-3: n-6 ratio in RUP3 group (P < 0.05). The relative gene expression of H-FABP was upregulated in RUP3 while CAPN1 and CAST remained unchanged. In conclusion, the results suggested that using a blend of RUP sources improved growth performance, altered chemical composition and upregulated H-FABP genes without negative effects on physicochemical properties of meat in fattening lambs.

Astrocytes have traditionally been cast as supportive glia, but they are increasingly recognized as metabolic hubs that regulate cholesterol synthesis, fatty acid detoxification, lipid droplet dynamics and redox homeostasis in the CNS. Neurons have a limited intrinsic capacity for lipid storage and detoxification and rely heavily on astrocytes to maintain a safe lipid environment. Emerging evidence indicates that dysregulation of astrocytic lipid homeostasis precedes overt neuronal degeneration in a range of neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, frontotemporal dementia and Huntington disease. Perturbations in astrocytic lipid handling can drive maladaptive reactive states, promote oxidative stress, impair lysosomal and mitochondrial function and disrupt neuron-glia lipid exchange, collectively creating an environment that leads to neurodegeneration. Therefore, lipid dysregulation within astrocytes could trigger or amplify neuronal vulnerability. In this Review, we assess evidence that astrocytic lipid metabolism is not solely protective or pathological but has instructive physiological roles and that astrocytic lipid dysregulation is an early driver of neurodegeneration. We critically evaluate disease-specific evidence, distinguishing correlative observations from causal mechanisms. We propose that targeting of astrocytic lipid homeostasis represents a promising strategy for preventing or minimizing neurodegeneration and opens new avenues for early detection and biomarker development.

Metabolic crosstalk between cancer cells and immune cells is now recognized as a major determinant of immune escape and resistance to anticancer treatments. Cancer cells profoundly reshape the metabolic landscape of the tumor microenvironment, driving nutrient competition, hypoxia, and the accumulation of immunosuppressive oncometabolites that collectively blunt antitumor immunity. Effector T cells, NK cells, and dendritic cells are exposed to nutrient deprivation and suppressive metabolites, including lactate, adenosine, and kynurenine, resulting in impaired T cell proliferation and cytotoxic function and expansion of metabolically adapted regulatory T cells and myeloid-derived suppressor cells. Cancer-associated fibroblasts further reinforce this metabolic reprogramming through extracellular matrix remodeling, secretion of immunosuppressive metabolites, and nutrient recycling that supports tumor growth. Abnormal tumor vasculature sustains metabolic stress by causing uneven perfusion, hypoxia, and acidosis, thereby limiting immune cell infiltration, and promoting immune exhaustion. In addition, diet- and microbiome-driven metabolic cues dynamically shape cancer-immunity interactions and therapeutic responses. Targeting key metabolic checkpoints, including glycolysis, adenosine signaling, tryptophan metabolism, fatty acid oxidation, and lactate production, has emerged as a promising strategy to restore antitumor immunity. Nevertheless, metabolic heterogeneity, context-dependent immune responses, and safety concerns pose persistent challenges to its successful implementation. Recent advances in biomarker development, patient stratification, and rational combination strategies underpin the clinical translation of metabolic-immune vulnerabilities in cancer therapy. Integrating metabolic interventions with immune checkpoint blockade or adoptive cell therapies has demonstrated synergistic effects in preclinical and early clinical studies, enhancing T cell persistence and cytotoxic function within metabolically hostile tumor microenvironments. This review addresses these issues and delineates the mechanistic basis of the dynamic interplay between cancer metabolism and immune regulation. It discusses how anti-cancer therapies affect metabolic and immune pathways and highlights next-generation, metabolically targeted therapies that leverage newly uncovered, tumor-specific rewiring of glycolysis, mitochondrial function, and nutrient uptake. Special emphasis is given to the development of first-in-class inhibitors targeting glutaminase, lipid biosynthesis, one-carbon pathways, and redox homeostasis, which, when paired with immunotherapy or conventional treatments, offer unprecedented opportunities to overcome metabolic barriers, abrogate resistance, and achieve durable immune control of cancer.

The valorization of agro-industrial byproducts is attracting attention due to its potential to support circular bioeconomy development in food systems. Dragon fruit (Selenicereus spp.) peel, representing approximately one-third of total fruit mass, is an underutilized biomass that is high in pectin content. Unlike standardized commercial citrus and apple pectins, pectin from dragon fruit peel exhibit variability in their galacturonic acid content, degree of esterification, molecular weight, and rhamnogalacturonan-I branching structure, which are dependent on how the pectin is extracted. These structural attributes influence the solubility, rheological properties, gelation mechanisms, emulsifying capacity, and water-holding properties. There is emerging evidence that rhamnogalacturonan-I-enriched fractions promote the growth of beneficial microorganisms and may also increase the in vitro production of short-chain fatty acid, thereby exhibiting potential prebiotic activity. In addition, low methoxyl pectin has been shown to provide excellent properties for the calcium-mediated encapsulation of probiotics, as well as for pH-sensitive release in the gastrointestinal tract, thus supporting the synbiotic concept. The purpose of the current paper is to provide an overview of recent findings related to extraction technologies, structural characterization, structure-function relationship, fermentation behavior, potential delivery of probiotics, and the regulatory requirements for using dragon fruit peel pectin in the development of functional foods.

Background/Objectives: Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the dose-dependent impact of butyrate on inflammatory signaling and epithelial architecture in ex vivo intestinal biopsies from patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Methods: Intestinal biopsies from six IBD patients (four UC, two CD) were cultured ex vivo for 24 h with calcium butyrate (5, 10, 100 mM). Cytokine secretion was analyzed by multiplex immunoassay, total protein release was quantified, and glandular morphology was assessed by stereological analysis. Results: Butyrate was associated with a dose-dependent reduction in pro-inflammatory cytokines-including TNF-α, IFN-γ, IL-6, and IL-17-in both inflamed and non-inflamed tissue. Non-linear responses were observed for specific mediators, such as IP-10, which displayed a biphasic pattern in inflamed UC biopsies. Notably, UC and CD biopsies exhibited distinct response profiles: UC samples showed marked cytokine modulation, including reduction in IL-15, whereas CD samples, evaluated at 5 and 10 mM, showed limited modulation across conditions. A trend toward reduced total protein secretion was observed in diseased UC biopsies following butyrate exposure. Stereological analysis revealed preservation of glandular area at 5 mM, reduction at 10 mM, and extensive tissue disruption at 100 mM precluding structural evaluation. Conclusions: In this pilot study, butyrate exerts dose-dependent and disease-specific effects in human IBD mucosa within a narrow therapeutic window. These exploratory findings suggest that dose-optimized strategies for butyrate-based interventions may be particularly relevant in UC, although larger confirmatory studies are needed.

Age-related pulmonary fibrosis (PF) imposes a growing global burden with limited therapies. This study explored the role of Lactobacillus paracasei L9 (L9) in alleviating PF in C57BL/6J mice and its mechanisms. Nine-month oral administration of L9 (4 × 109 CFU/mL) suppressed collagen (Col-) I deposition in aged mice, with no significant effect on Col-III. Mechanistically, L9 inhibited the JNK-HSF1 signaling pathway, thereby resulting in a 61% decrease in HSP47 expression, which is crucial for Col-I synthesis. L9 reshaped the gut microbiota by increasing short-chain fatty acid (SCFA)-producing bacteria (e.g., Blautia), leading to a 97% increase in serum propionic acid and 193% increase in butyric acid; notably, the levels of SCFAs in the lungs were below the limit of detection. In L9-treated mice, pulmonary IL-17A levels and Th17 cell populations were reduced. In vitro, SCFAs directly inhibited Th17 cell differentiation and IL-17A secretion, and IL-17A was confirmed to promote Col-I synthesis via the JNK-HSF1 pathway in pulmonary fibroblasts. Consequently, L9 modulates the gut microbiota to produce SCFAs, which regulate naïve CD4+ T cell differentiation and migration via the gut-lung axis. This reduces pulmonary Th17 cells and IL-17A, thereby suppressing Col-I synthesis in pulmonary fibroblasts and ultimately alleviating age-related PF. In conclusion, this study highlights L9 as a microbiome-targeted precision nutrition strategy for the adjuvant therapy of age-related PF via the novel gut-lung axis mechanism.

Membranes are usually treated as passive containers in origin-of-life models, confining prebiotic chemistry, buffering diffusion, and sustaining gradients. Here, we argue that early membranes provided the physical substrate for candidate informational bodies: boundaries whose physical properties can stabilize, store, and select patterns of interaction with the environment. Within the Membrane Information Organization (MIO) framework, we place protocells in a low-dimensional organizational space defined by a triplet of body parameters: boundary strength, memory, and identity persistence. These parameters quantify sustained inside-outside asymmetry, history dependence beyond instantaneous forcing, and the reproducibility of organizational types across growth-division cycles. In this view, the origin of life is cast as a transition in which amphiphile-based vesicles cross jointly calibrated thresholds in boundary strength, memory, and identity, thereby becoming candidate selectable units prior to fully genetic inheritance. We outline how these quantities can be estimated in fatty-acid and hybrid protocells using microfluidic driving, Laurdan-based lipid-order imaging, curvature reconstruction, and fluorescent internal reporters, and how they can be incorporated into computational models of protocell ecologies. This boundary-centered perspective complements RNA-world, metabolism-first, and autonomy-based scenarios by specifying membrane-level conditions under which replicators, reaction networks, and proto-metabolisms can become evolutionarily stable. The result is not a new chemistry, but a concrete measurement language for identifying when a membrane ceases to be "just a vesicle" and enters a candidate minimal evolvable informational-body regime.

Massive rotator cuff tears (MRCT) remain a clinical challenge, characterized by poor tendon-bone interface (TBI) healing, severe muscle degeneration, and high postoperative retear rates. Tissue engineering scaffolds offer promising alternatives, yet traditional biomaterials often lack sufficient bioactivity to orchestrate comprehensive tissue regeneration. Herein, we developed a novel graphene oxide (GO)-engineered porcine type I collagen (GO/Col) scaffold and systematically investigated its therapeutic efficacy and underlying molecular mechanisms via multi-omics analyses. Comprehensive characterization showed that GO incorporation improved scaffold stability, wettability, and biocompatibility. In vitro, the GO/Col scaffold enhanced mesenchymal stem cell adhesion and proliferation, promoted osteogenic and chondrogenic differentiation, and suppressed adipogenesis. In a macrophage model system, GO/Col was associated with a shift toward a more reparative, anti-inflammatory phenotype. Using a clinically relevant chronic MRCT rat model, we observed that GO/Col scaffolds significantly improved motor function, biomechanical properties, and tendon-bone regeneration, while inhibiting muscle fibrosis and fatty infiltration. Mechanistically, integrated transcriptomics, proteomics, and mass cytometry analyses revealed GO-mediated modulation of critical signaling pathways involved in immune regulation, stem cell differentiation, and tissue regeneration. Notably, GO activated pro-osteogenic/chondrogenic pathways and anti-inflammatory signatures, while downregulating adipogenic and pro-inflammatory pathways. Collectively, these findings support the potential of GO/Col scaffolds as a bioactive tissue-engineering strategy for chronic MRCT repair.

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by progressive lower motor neuron loss, resulting in severe muscle atrophy, fatty degeneration, and impaired tissue perfusion. These changes increase susceptibility to pressure-related soft tissue injuries and delay wound healing. We report a rare case of free flap reconstruction in a pediatric patient with SMA type 2 who developed a cast-related pressure ulcer. A 9-year-old girl underwent bilateral hamstring release and distal femoral extension osteotomy followed by long leg circular casting. After cast removal, a progressive anterolateral crural pressure ulcer with exposed necrotic muscle developed despite conservative treatment. Reconstruction was performed using an anterolateral thigh (ALT) free flap. Due to extensive muscle atrophy, fibrosis, and loss of normal anatomical planes, a modified en bloc myocutaneous flap elevation based on antegrade pedicle dissection was used instead of standard perforator-based dissection. The flap was successfully anastomosed to the posterior tibial vessels without complications. At 6-month follow-up, complete and stable wound healing was achieved. This case emphasizes the reconstructive challenges in SMA patients and demonstrates that free flap reconstruction can be safely performed using adapted surgical techniques.

Fecal microbiota transplantation (FMT) has become a powerful experimental tool for dissecting microbiota-driven mechanisms in murine models of gastrointestinal and systemic disease. This review provides a comprehensive methodological and translational overview of FMT in mice, focusing on lessons learned from inflammatory bowel disease (IBD) research and emerging perspectives in short bowel syndrome (SBS). We first outline the fundamental role of the gut microbiota in immune regulation, metabolic homeostasis, and maintenance of epithelial barrier integrity, establishing the rationale for modulating microbial communities through FMT. A detailed methodological analysis follows, highlighting how donor selection, recipient conditioning, sample handling, administration route, and environmental variables critically influence microbial engraftment and experimental reproducibility. The review then synthesizes current evidence from key murine IBD models, demonstrating that FMT can restore epithelial integrity, rebalance adaptive immunity, modulate cytokine networks, and enrich beneficial short-chain fatty-acid-producing taxa. Concepts such as functional engraftment, viability of transferred communities, and host-microbe metabolic interactions are discussed as central determinants of FMT efficacy. Finally, we address the emerging but challenging application of FMT in SBS. Profound alterations in intestinal anatomy, transit, oxygen tension, and substrate availability limit the integration of donor microbiota in SBS models, necessitating adapted strategies such as anaerobic handling, pre-conditioned consortia, synbiotics, and optimized delivery systems. Piglet models and computational approaches for donor-recipient matching are highlighted as promising translational tools. Overall, this review underscores the need for methodological standardization and physiologically tailored approaches to advance the reliability, mechanistic insight, and translational potential of FMT in both IBD and SBS.

Severe hypokalemia-induced rhabdomyolysis is rare but potentially fatal, particularly among chronic alcohol abusers who are predisposed to multiple electrolyte disturbances. This case report describes an early 40s male with chronic heavy alcohol consumption who presented with progressive neck stiffness and shoulder discomfort over several days, ultimately resulting in inability to stand. Laboratory findings revealed profound hypokalemia (1.4 mEq/L), hypophosphatemia, markedly elevated creatine kinase, and macrocytic hyperchromic anemia, suggesting alcohol-related organ dysfunction. Despite supportive care, the patient died suddenly 18 h after admission. Forensic autopsy revealed diffuse rhabdomyolysis involving skeletal muscle including the diaphragm, myoglobin cast nephropathy, advanced fatty liver with fibrosis, and structural cardiac abnormalities such as apical hypertrophic cardiomyopathy. The identified cause of death was a fatal arrhythmia triggered by severe hypokalemia, potentiated by underlying cardiac pathology. This case highlights the importance of early recognition and continuous cardiac monitoring in metabolic rhabdomyolysis, as well as the multifactorial pathogenesis of sudden unexpected death in chronic alcohol abusers.

The aim was to produce red cabbage microgreen foams and dry them by cast-tape drying (CTD), freeze-drying (FD), and oven drying (OD) to obtain powder and characterize them. The foam composition was water (74.7%), microgreens (14.2%), emulsifier (6.5%), pre-gelatinized starch (2.8%), and maltodextrin (1.8%). Drying conditions were CTD (98°C, 2-3 mm thick), FD (0.14 mbar, -58°C, for 48 h), and OD (70°C, 2-3 mm thick). Drying times were 32 min for CTD, 2880 min for FD, and 150 min for OD (moisture <0.1 g/g). The foam spreads easily in the CTD, enabling quick drying, whereas OD and FD processes take longer. The FD powder exhibited higher levels of phenolics, flavonoids, anthocyanins, and antioxidant activity despite high water activity and a greener coloration. The Fourier transform infrared spectroscopy (FTIR) spectrum of the powders, especially FD and CTD, indicated the presence of bioactive compounds (flavonoid compounds), carbohydrates (starch, maltodextrin, cellulose, and hemicellulose), and fatty acids (esterified carboxyl groups). CTD enabled rapid and scalable processing but led to greater bioactive degradation due to temperature and light exposure, whereas OD provided an intermediate balance between process efficiency and compound preservation. Foam formulation resulted in low moisture and water activity in CTD and OD powders. Overall, the findings highlight trade-offs between drying efficiency and nutritional quality, supporting the use of microgreen powders in value-added food formulations. PRACTICAL APPLICATIONS: Powdered microgreens are versatile and easy to incorporate into most meals and beverages as a neutral nutritional booster or even a flavor enhancer. The foam red cabbage microgreens dehydrated by freeze-drying, cast-tape drying, and hot-air drying produce purple cabbage powders with interesting physicochemical properties and significant amounts of bioactive compounds, such as phenolics and anthocyanins, particularly in those obtained by freeze-drying. These characteristics highlight the great potential for utilization and possible applications of these products in various fields of food, nutrition, and pharmaceuticals.