Search Results (2,454)

Fat deposition plays an important role in yak metabolism, reproduction, and meat quality, and male yaks are often castrated to facilitate management and improve production performance. The effect of castration on the characteristics of fat deposition in male yaks and the molecular mechanisms of action was explored in this study. The subcutaneous fat thickness in castrated and common male yaks was measured, further the content of fatty acids in yak subcutaneous fat was detected using gas chromatography-mass spectrometer (GC-MS); the transcriptome, metabolome in the yak subcutaneous fat were detected using mRNA-Sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), respectively; the integrative analyses of differentially expressed genes (DEGs), different metabolites (DMs), fatty acids and fat thickness were carried out. The results showed that castration can strengthen the ability of fat deposition and improve the content of fatty acids, especially PUFAs, in male yaks, and both transcriptome and metabolome were significantly different between castrated male yaks and common male yaks. The effect of castration on the male yak fat deposition was closely related to the PPAR signaling pathway, citrate cycle, and insulin resistance. Data suggests that FASN, ACACA, AGPAT2, ACLY, ACSL5, SCD, GSK3B, and SLC2A4 may be the crucial control genes for the fat amount in yaks, and that FADS2, LPL, and ACSL4 may be the crucial control genes for the polyunsaturated fatty acids (PUFAs) content in yak adipose tissue. Further functional studies will be conducted to determine the specific role of each gene in regulating fat deposition and fatty acid composition in yaks. Full article

Lipid peroxidation (LPO) is a process where polyunsaturated fatty acids (PUFA) in cellular membranes are oxidized. This process is mediated by reactive oxygen species (ROS) and leads to the formation of reactive products, including 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and oxidized phospholipids. At low concentrations these products act as second messengers in adaptive redox signalling and metabolic homeostasis, whereas at higher concentrations they compromise membrane integrity and promote cell death. Lipid peroxidation plays a crucial role in anticancer therapies. Here we focus on three mechanistically complementary drugs—sorafenib, cisplatin, and olaparib—because each converges, directly or indirectly, on the redox/LPO axis (system xc−/GPX4 modulation, mitochondrial ROS, and SLC7A11 regulation, respectively), modulating tumor cell responses by inducing PUFA oxidation, mitochondrial dysfunction, and membrane damage. However, tumor cells have several protective pathways against oxidative stress, such as increased expression of glutathione peroxidase 4 (GPX4), the SLC7A11 system Xc, and detoxification of reactive aldehydes. Enrichment of membranes with PUFA increases susceptibility to lipid peroxidation and ferroptosis, thereby sensitizing tumor cells to therapy, whereas enrichment with monounsaturated fatty acids (MUFA), driven by the SREBP1–SCD1 axis, limits peroxidation and confers resistance. Among regulated cell death modalities, ferroptosis is strictly dependent on lipid peroxidation, whereas apoptosis, necrosis, necroptosis, pyroptosis, and immunogenic cell death can be modulated by lipid peroxidation but do not universally require it. Collectively, these mechanisms indicate that lipid peroxidation is an important—though not exclusive—determinant of anticancer drug sensitivity and resistance, and that its dual, context-dependent role (tumor-suppressive at high flux, tumor-promoting under chronic, sub-lethal exposure) must be considered when designing LPO-based therapeutic strategies. Full article

Regulated cell death is essential for tissue homeostasis, immune defense, and disease progression, yet the lipid-based regulatory mechanisms that coordinate cell death signaling remain incompletely understood. Protein palmitoylation is a dynamic and reversible lipid post-translational modification that controls protein membrane association, trafficking, stability, and signaling complex assembly. This review summarizes the regulatory roles of palmitoylation and depalmitoylation in major forms of regulated cell death, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-related cell death. Particular attention is given to representative palmitoylated substrates, including Fas cell surface death receptor (Fas), receptor-interacting protein kinase 1 (RIPK1), NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), autophagy-related 16 like 1 (ATG16L1), and Beclin1. These substrates illustrate how palmitoylation links membrane organization, metabolic status, inflammatory signaling, and cell fate decisions. Disease-oriented evidence further indicates that dysregulated palmitoylation contributes to cancer, neurodegenerative diseases, and inflammatory or immune-related disorders by modulating cell death resistance, inflammatory amplification, immune evasion, or impaired proteostasis. Current challenges include limited quantitative information on palmitoylation dynamics, incomplete evidence for some enzyme–substrate relationships, and insufficient distinction between disease-driving and secondary palmitoylation events. Targeting zinc finger Asp-His-His-Cys (zDHHC) palmitoyl acyltransferases, depalmitoylating enzymes, or specific palmitoylated substrates may provide new therapeutic opportunities. Overall, this review positions protein palmitoylation as a dynamic molecular switch linking lipid metabolism, membrane signaling, regulated cell death, and disease remodeling. Full article

Horse meat is a high-quality protein source. A total of 50 two-year-old male horses with similar body weights (300 ± 50 kg) were used: 30 for regional comparison (10 each from Bulgan province region of Mongolia (BPM), Tuv province region of Mongolia (TPM), and Inner Mongolia region of China (IMC)) and an additional 20 from the IMC region for muscle-site analysis. To elucidate the molecular mechanisms underlying regional and muscle-site differences in the meat quality of Mongolian horses, with particular emphasis on tenderness, this study analyzed chemical composition, minerals, fatty acids, and transcriptomes. Results showed that Mongolian horses from the Inner Mongolia region of China (IMC) had the highest contents of Se, C17:1, C18:2n6c, C18:3n3, ∑PUFA, PUFA/SFA, ∑n-3PUFA, ∑n-6PUFA (p < 0.05), and Fe (p < 0.01), and the lowest levels of C15:0 (p < 0.01) and C16:0 (p < 0.05). The Mongolian horses from the Tuv province region of Mongolia (TPM) had the highest Ca content (p < 0.05). The Mongolian horses from the Bulgan province region of Mongolia (BPM) had the highest ∑SFA (p < 0.01). The forelimb (FL) had the highest a*_45min, b*_45min (p < 0.01), Fe, Zn, and C17:1 (p < 0.05), and the lowest shear force and drip loss (p < 0.01). The HD had the highest pH_45min and cooking loss (p < 0.01). The hindlimb (HD) increased the L*_45min compared with the FL (p < 0.01). Transcriptomic analysis identified 513 differentially expressed genes (DEGs) between FL and HD, including SLC16A7, GPAM, FABP3, and TNNC1. KEGG enrichment analysis revealed that these DEGs were significantly enriched in the cGMP-PKG signaling pathway, glycerophospholipid metabolism, and PPAR signaling pathway. In summary, this study demonstrated that among Mongolian horses from three different regions, IMC horses exhibited superior meat quality and flavor characteristics, and the FL of IMC horses showed significantly better meat quality than other anatomical sites. Transcriptomic analysis identified a set of candidate genes related to meat quality and lipid metabolism, including SLC16A7, GPAM, FABP3, and TNNC1, providing a scientific basis for further understanding of muscle-specific molecular mechanisms in Mongolian horses. Furthermore, the observed differences in physicochemical and nutritional properties across regions and muscle sites established a systematic foundation for quality grading, targeted nutritional utilization, and processing optimization of Mongolian horse meat. Full article

Deoxynivalenol (DON) is a mycotoxin commonly found in food crops and animal feed worldwide. Its pronounced toxicity in pigs poses a serious risk to the swine industry and to human health. This study focused on two central features of ferroptosis—iron metabolism and lipid peroxidation—and examined how chlorogenic acid (CGA) affects DON-induced ferroptosis in porcine alveolar macrophages (PAMs) via cell-based assays and oxidative lipid metabolomics. These findings show that DON disrupts intracellular iron homeostasis by altering iron-handling proteins (upregulating TFR1 and DMT1 and downregulating FPN1), which may lead to iron overload. Concurrently, DON impairs the GPX4 antioxidant axis (downregulating GPX4, SLC3A2, SLC7A11, and GCLC) and increases ROS, and exposure led to a significant increase in numerous oxidized lipid metabolites, consistent with elevated lipid peroxidation, culminating in ferroptosis in PAMs. CGA mitigates these effects by restoring iron homeostasis and reestablishing GPX4 axis function, thereby reducing oxidative stress. Moreover, CGA suppresses lipid peroxidation pathways, notably linoleic acid oxidation metabolism. In conclusion, CGA protects PAMs and mitigates the proferroptotic effects of DON. Full article

Neurodegenerative diseases are increasingly recognized as disorders of due to disrupted cellular homeostasis, with mitochondrial dysfunction playing a central and early role in disease progression. This review explores the intricate relationship between mitochondrial function and neuronal health, emphasizing the pivotal role of the solute carrier family 25 (SLC25) transporters in maintaining mitochondrial homeostasis. We provide a comprehensive overview of mitochondrial biology in the central nervous system, including energy metabolism, calcium signaling, redox regulation, organelle interactions and mitochondrial dynamics. We delve into the SLC25 transporter family, highlighting their transport mechanisms, substrates and roles in brain metabolism and neuroprotection. SLC25 on one hand and proteins involved in the regulation of mitochondrial morphology and calcium signaling on the other hand are two sides of the same coin influencing each other. A critical analysis follows, examining how mitochondrial dysfunction contributes to mitochondrial abnormalities in a spectrum of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, ALS and rare mitochondrial encephalopathies. Finally, we assess emerging therapeutic strategies targeting mitochondrial pathways and SLC25 function, including metabolic modulation, gene therapies, antioxidants and pharmacological agents. This review underscores mitochondria and the SLC25 transporters as promising targets for disease-modifying interventions in neurodegeneration and raises key questions about the causality between mitochondrial failure and neuronal death. Full article

The yak lung functions as a vital adaptive organ in cold, low-oxygen environments. Hypoxia can induce pathological remodeling in yak lung tissue, so we need to understand the molecular mechanisms of this remodeling. For this study, we used cross-omics comparative approaches, including transcriptomics, label-free proteomics, and untargeted metabolomics, to examine both normal and diseased yak lung tissues. From histological observations, the disease phenotype was identified as pulmonary emphysema. Our results showed a significant up-regulation of differentially expressed genes such as MTTP, CXCL8, RETN, and NNAT, while genes like SLC45A1, IL10, SDSL, and COL12A1 were clearly down-regulated. In the differential protein analysis, proteins such as RASSF4, EDC4, CTSC, and FECH were notably up-regulated, whereas CYP27A1, FKBP9, RAD23A, and PLSCR2 were significantly down-regulated. Metabolomic profiling revealed that palmitoyl-L-carnitine, decanoyl-L-carnitine, and o-acetylcarnitine were significantly higher in emphysematous lung tissue, whereas racemethionine and L-methionine S-oxide were significantly much lower. Also, when we compared of bulk RNA-seq, label-free proteomics, and untargeted metabolomics data revealed enrichment in three common pathways: the asthma pathway, the linoleic acid metabolism pathway, and the gastric acid secretion pathway. Of note, histamine levels were higher in both the asthma and gastric acid secretion pathways. While the mRNA expression level of BoLA-DQB was increased in the asthma pathway, its protein expression level was decreased. This study offers some initial cross-omics evidence about what happens. These findings give us a scientific basis for developing effective prevention and control strategies, which in turn can help the protection of yak health and the sustainable development of plateau animal husbandry. Full article

Background/Objectives: The gene solute carrier family 52 member 3 (SLC52A3) encodes riboflavin transporter-3, a transmembrane protein essential for riboflavin absorption. Emerging evidence suggests that metabolic transporters may play a role in tumor biology. This study aimed to investigate the expression patterns, prognostic significance, genetic alterations, and functional associations of SLC52A3 in gynecological cancers. Methods: A comprehensive bioinformatic analysis was conducted using multi-omics datasets from The Cancer Genome Atlas (TCGA). Gene expression and survival analyses were performed via GEPIA3. Genetic alterations, including mutations and copy number variations, were assessed using cBioPortal. Immune infiltration correlations were analyzed through TIMER3. Protein–protein interactions and gene enrichment analyses were performed using STRING and GEPIA2, followed by Gene Ontology (GO) and KEGG pathway analyses. Results: SLC52A3 expression was significantly upregulated in ovarian, cervical, and endometrial cancers. Reduced expression of SLC52A3 was associated with poorer overall survival and shorter progression-free interval specifically in endometrial cancer. Genetic alterations in SLC52A3 were not significantly associated with survival outcomes (OS, DFS, and PFS). Functional enrichment analysis indicated that SLC52A3 is involved in biological processes such as cell junction organization and protein localization to the plasma membrane. Additionally, SLC52A3 expression showed positive correlations with genes implicated in tumor progression and metastasis, including NECTIN4, PROM2, TACSTD2, PKP3, SEMA4B, and CD46. Conclusions: These findings suggest that SLC52A3 may serve as a potential prognostic biomarker in endometrial cancer and could play a role in tumor progression pathways. Its functional associations highlight its potential relevance as a therapeutic target, warranting further experimental validation. Full article

The Na⁺/I⁻ symporter (NIS) is the plasma membrane (PM) protein that actively mediates iodide (I⁻) transport into the thyroid gland. Pathogenic variants in the SLC5A5 gene cause iodide transport defects (ITDs). A heterozygous G288S NIS variant was identified in a Spanish family in which female carriers developed thyroid dysfunction during pregnancy. Here, we characterized the functional significance of the G288S variant and other substitutions at residue 288 of human NIS. Human NIS (hNIS) expression and maturation were analyzed by immunoblotting, its subcellular localization was analyzed by immunofluorescence and flow cytometry, and its activity was analyzed by radioiodide uptake assays. The G288S variant does not affect hNIS maturation, membrane trafficking, or I⁻ uptake capacity, but significantly reduces I⁻ affinity while preserving substantial transport activity. In contrast, substitutions introducing charged residues (arginine, aspartic acid, or glutamic acid) or proline severely disrupted NIS maturation, plasma membrane targeting, and iodide transport. Because the variant was identified in heterozygosity, we evaluated residue 288 substitutions under heterozygous-like conditions. Co-expression of the patient-derived G288S variant with WT NIS produced an intermediate apparent K_m without reducing V_max compared with WT, consistent with a modest co-expression-dependent kinetic effect rather than a strong dominant-negative mechanism. In contrast, the severely disruptive G288E substitution reduced cell-surface NIS expression under co-expression conditions, providing proof-of-principle evidence that severe alteration of residue 288 can impair NIS plasma membrane delivery. These findings highlight residue 288 as a key determinant of hNIS functionality and underscore the need to carefully evaluate heterozygous SLC5A5/NIS variants, as they may become clinically relevant under conditions of increased physiological iodine demand and contribute to partial iodide transport impairment. Full article

Recent studies indicate that ferroptosis shows unique advantages in oncotherapy, particularly in reversing multidrug resistance (MDR). Despite current therapeutic advancements, the treatment of high-incidence malignancies with dismal prognoses continues to face challenges, including limited clinical efficacy, significant side effects, and drug resistance. In recent years, Chinese herbal medicine (CHM) has gained increasing attention in anti-tumor therapy. CHM bioactive components are highly effective in inducing tumor cell ferroptosis, inhibiting tumor proliferation and migration, and reversing drug resistance. Additionally, some components can protect normal cells and improve the tumor microenvironment. This review systematically summarizes the regulatory roles of various CHM bioactive components in ferroptosis across common human cancers. We further analyze the underlying molecular mechanisms, focusing on the modulation of key regulatory targets (e.g., GPX4, SLC7A11, and Nrf2) and critical signaling cascades (e.g., PI3K/AKT/mTOR and p53). Furthermore, the differential effects of bioactive compounds from CHM on common tumors were evaluated, alongside their potential in combination therapy. This review provides a theoretical foundation for the development of novel anticancer drugs targeting ferroptosis regulation and offers new perspectives for the clinical application of CHM in oncology. Full article

To tackle the issues of high energy consumption, substantial carbon emission intensity in the cement industry, as well as under-utilization of agricultural waste, this study took an 8000 t/d cement production line at a plant in Indonesia as the research object. Using a Computational Fluid Dynamics (CFD)-based numerical method, the co-firing of pulverized coal with rice husk was simulated in both In-Line Calciner (ILC) and Separate-Line Calciner (SLC) precalciners. Four rice husk replacement levels (10%, 20%, 30%, and 40%) were evaluated in terms of temperature distribution, species concentration, raw meal calcination, and pollutant formation. The results indicate that increasing the rice husk ratio reduces the high-temperature region, lowers the peak temperature, and decreases overall thermal levels. The decomposition rate of CaCO₃ at the outlet of the ILC-type precalciner decreased from 81.11% to 75.32%, while that of the SLC-type precalciner fell from 93.27% to 88.50%. CO₂ and NO_X emissions were remarkably reduced, with the emission reduction effect positively correlated with the rice husk substitution ratio. Taking into account both decomposition rate requirements and emission reduction targets, it is recommended that the blending ratio of rice husk in ILC precalciners should be controlled at 10%, while for SLC precalciners, it can be increased to 40%. This provides a technical reference for low-carbon transformation and biomass resource utilization in the cement industry. Full article

Mastitis is one of the most prevalent diseases in dairy cows, leading to significant economic losses and increased antibiotic usage. The development of safe and effective alternatives is therefore urgently needed. In this study, we investigated the protective effects of Forsythiaside A (FTA), a natural compound, against LPS-induced mastitis in bovine mammary epithelial (MAC-T) cells and a murine model. FTA significantly reduced intracellular reactive oxygen species (ROS), decreased lipid peroxidation, and restored antioxidant capacity. Furthermore, FTA increased the expression of GPX4 and SLC7A11, indicating inhibition of ferroptosis. The ferroptosis inducer RSL3 partially reversed these protective effects, supporting the involvement of GPX4-associated ferroptosis regulation in the protective effects of FTA. In vivo, FTA alleviated mammary tissue injury, reduced inflammatory cell infiltration, and improved redox balance. These findings suggest that FTA may serve as a potential natural therapeutic agent for mastitis, providing a promising alternative to antibiotic-based treatments in dairy production. Full article

Background: Creatine deficiency syndromes (CDS) are rare neurometabolic disorders caused by defects in creatine biosynthesis (AGAT and GAMT deficiencies) or creatine transport (SLC6A8 deficiency). Early biochemical recognition is crucial for timely treatment of AGAT and GAMT deficiencies and for improving neurodevelopmental outcomes. In Morocco, expanding the liquid chromatography-tandem mass spectrometry (LC-MS/MS) biomarker panel for inherited metabolic disorders is a priority to strengthen diagnostic capacity and reduce diagnostic delay. Methods: We developed and validated a rapid LC-MS/MS method for the simultaneous quantification of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn) in plasma and urine using isotopically labelled internal standards and a standardized sample preparation procedure. Analytical performance, including linearity, precision, accuracy, sensitivity, matrix effects, carryover, inter-sample contamination, stability, and measurement uncertainty, was assessed in accordance with ISO 15189:2022 requirements. Results: The assay showed excellent linearity across the analytical range (r² > 0.99), with robust intra- and inter-day precision (CV < 10%). Limits of detection (LOD) were 0.05 µmol/L for Cr and 0.03 µmol/L for GAA in urine, and 0.05 µmol/L for Cr and GAA in plasma. The total run time was 1.1 min per sample, supporting high-throughput implementation. Method performance was further supported by satisfactory results in ERNDIM external quality assessment schemes. Preliminary internal reference ranges and expanded measurement uncertainty were calculated from the available anonymized dataset. Conclusions: This rapid LC-MS/MS method enables the measurement of key CDS biomarkers and contributes to expanding the LC-MS/MS biomarker panel for inherited metabolic disorders in Morocco. Full article

Ovarian cancer (OC) comprises multiple histotypes with distinct mechanisms, molecular features, and clinical behavior. We used Mendelian randomization (MR) to map histotype-stratified metabolic pathways and connect them to drug targets, establishing a translatable target–metabolic node–histotype risk chain. We built a multi-stage MR framework using Integrative Epidemiology Unit (IEU) OpenGWAS summary statistics. After screening 1400 plasma metabolites against overall ovarian cancer in UK Biobank and Ovarian Cancer Association Consortium (OCAC) with KEGG enrichment, we traced a prespecified amino acid/energy–nitrogen axis using histotype-stratified univariable MR and pathway-restricted multivariable MR. We then performed cis drug-target MR for PPARG, DPP4, ABCC8/KCNJ11, and SLC5A2, integrated triangulation, colocalization, and mediation analyses, and experimentally interrogated the prioritized PPARG/ABCC8-KCNJ11–lactate–invasive mucinous ovarian cancer (IMOC) triangle. Screening nominated 55 and 72 metabolites in UK Biobank and OCAC, respectively (IVW p < 0.05), highlighting amino-acid nitrogen and central-carbon metabolism. Univariable Mendelian randomization (UVMR) showed marked heterogeneity: alanine increased low-grade serous ovarian cancer (LGSOC) risk, glutamate was protective for endometrioid OC, and lactate-related traits most consistently implicated the low-grade/borderline serous lineage. In multivariable Mendelian randomization (MVMR), tryptophan and lactate levels emerged as independent risk nodes for serous low-grade plus low malignant potential (LG + LMP). Drug-target MR prioritized PPARG as protective (OR = 0.18) and ABCC8/KCNJ11 as risk-increasing (OR = 7.50) for IMOC, with opposite target → lactate effects supporting a directionally symmetric target–lactate–IMOC triangle. Experimental perturbation in mucinous ovarian cancer models produced concordant reciprocal changes in lactate and malignant phenotypes, extending this triangle biologically. This integrative MR framework delineates histotype-specific metabolic drivers and links them to actionable targets, providing a roadmap from genetic prioritization to mechanistic and translational validation. Full article

Background/Objectives: Kangaroo Mother Care (KMC) has been proposed as a protective intervention that may modulate the epigenetic regulation of stress-related genes, such as SLC6A4, which encodes the serotonin transporter. Few studies have explored this association in humans. This study aimed to evaluate whether KMC affects the methylation status of SLC6A4 in preterm newborns. Methods: This longitudinal observational study included preterm infants with birth weight ≤ 1800 g and gestational age between 25 and 34 weeks. Blood samples were collected at birth, Neonatal Intensive Care Unit discharge, and hospital discharge. Methylation levels at 13 CpG sites within the SLC6A4 promoter region were quantified by bisulfite conversion and pyrosequencing. Methylation dynamics were analyzed using linear mixed-effects models adjusted for clinical covariates. Results: 75 preterm infants were analyzed (51 KMC; 24 non-KMC). Methylation levels ranged from 0.78% to 10.76% across all CpG sites and remained stable over time. At hospital discharge, the KMC group exhibited lower methylation at CpG6 than the non-KMC group (median = 0.96% vs. 1.21%, p = 0.021), but this difference was not statistically significant after correction for multiple testing. No significant differences were observed at other sites or in longitudinal methylation trajectories between groups. Conclusions: KMC was not associated with major longitudinal changes in SLC6A4 methylation during the neonatal period. The nominal difference at CpG6 should be interpreted as exploratory and warrants further investigation. Larger, multicenter studies with long-term follow-up are needed to clarify the epigenetic mechanisms linking early caregiving experiences with stress regulation and neurodevelopmental outcomes in preterm infants. Full article