Search Results (20,155)

Background: Osteocalcin is a bone-derived protein traditionally regarded as a marker of bone formation, but experimental and clinical studies have suggested potential endocrine effects on energy and glucose metabolism. In pediatric populations, particularly in the context of obesity, the relationships between circulating osteocalcin, adiposity, and metabolic health remain inconsistent and poorly defined. Objective: To investigate associations between serum total osteocalcin and anthropometric, metabolic, biochemical, and body composition parameters in children and adolescents with obesity, with particular emphasis on adiposity and mineral metabolism. Methods: This retrospective cross-sectional study included 155 children and adolescents aged 4–18 years with obesity. Anthropometric measurements, laboratory parameters, and body composition assessed by dual-energy X-ray absorptiometry were extracted from medical records. Associations between osteocalcin z-scores and clinical variables were evaluated using linear regression models. Multivariable and extended regression models were applied to assess independent associations. Results: Osteocalcin was positively associated with markers of mineral metabolism, including serum 25-hydroxyvitamin D₃ (β = 0.19, p = 0.012), serum calcium (β = 0.19, p = 0.015), and free triiodothyronine (β = 0.32, p < 0.001) in multivariable analyses. No independent associations were observed between osteocalcin and measures of adiposity, including body mass index, visceral adipose tissue index, leptin, or markers of glucose and lipid metabolism. Conclusions: In children and adolescents with obesity, circulating osteocalcin is primarily associated with mineral metabolism rather than adiposity or metabolic health. These findings support the interpretation of total osteocalcin as a clinically accessible marker of bone turnover and mineral homeostasis rather than a robust surrogate of metabolic dysfunction in pediatric obesity. Full article

Background/Objectives: CDKL5 deficiency disorder (CDD) is a rare X-linked developmental and epileptic encephalopathy characterized by early onset refractory epilepsy and severe neurodevelopmental impairment with autistic features. Despite advances in genetic diagnosis, objective biomarkers reflecting disease mechanisms remain limited. Extracellular vesicles (EVs) circulating in the blood may contain disease-related proteins derived from the central nervous system. This study aimed to characterize the plasma EV proteome in CDD in a hypothesis-generating exploratory framework and identify the candidate molecular pathways associated with this disorder. Methods: Plasma samples from seven patients with genetically confirmed CDD and seven neurotypical developmental controls were analyzed. Extracellular vesicle-containing preparations (EVs-cp) were isolated via immunoprecipitation using antibodies against CD9, CD63, and CD81. Proteomic profiling was performed using data-independent mass spectrometry. Differentially expressed proteins were identified using Welch’s t-test with a false discovery rate correction. Functional enrichment, protein interaction network, and correlation analyses were performed using CDKL5 Clinical Severity Assessment (CCSA) scores. Results: In total, 5617 proteins were identified, of which 3510 were used for quantitative analysis. Compared to the controls, 2108 proteins were upregulated and 158 were downregulated in the CDD samples. Enrichment analysis revealed alterations in vesicle-mediated transport, cytoskeletal organization, and immune-related pathways. Several proteins were also correlated with clinical severity scores. Conclusions: Plasma EV proteomics revealed molecular alterations associated with CDD and provided a potential approach for biomarker discovery and mechanistic investigation. Full article

Zearalenone (ZEA) is a potent estrogenic mycotoxin known to disrupt reproductive functions, but its precise central neuroendocrine mechanisms remain unclear. This study investigated the effects of ZEA on the hypothalamic-pituitary Kiss1/GPR54 signaling pathway in weaned gilts. A total of 32 gilts were randomly assigned to four dietary treatments contained with 0, 0.15, 1.5, or 3.0 mg/kg ZEA for a 32-day feeding trial. Histopathology, immunohistochemistry, and mRNA/protein expression analyses of GPR30, Kiss1, GPR54, GnRH, and GnRHR in the hypothalamus and pituitary gland were conducted. ZEA exposure induced significant histological damage in both tissues. In the hypothalamus, Kiss1, GPR54, GnRH, and GnRHR exhibited a non-linear response, increasing at moderate doses and decreasing at 3.0 mg/kg ZEA, whereas GPR30 expression was continuously upregulated. In the pituitary gland, GnRHR showed a similar non-linear pattern. Furthermore, high-dose ZEA down-regulated pituitary Kiss1 and GPR54 while up-regulating GnRH and GPR30 expressions. In conclusion, ZEA induces reproductive neuroendocrine toxicity through a complex, dose-dependent modulation of the Kiss1/GPR54 signaling axis. The persistent upregulation of GPR30 suggests it acts as a crucial mediator in disrupting this endocrine feedback loop within the hypothalamus and pituitary gland. Full article

Background: This study investigated the mechanisms underlying diarrhea induced by a high-fat diet (HFD) under a state of fatigue, focusing on gut microbiota dysbiosis, bile acid metabolic disturbance, and gut–liver injury. Methods: Mice were assigned to a normal control diet (NCD) group, a HFD-induced diarrhea under fatigue (HFDM) group, and a HFD-induced diarrhea with aggravated dysbiosis (HFDMA) group. Histopathology, inflammatory factors, intestinal barrier-related proteins, small-intestinal microbiota, and colonic bile acid profiles were assessed, and correlation analyses were performed among gut microbiota, bile acids, and inflammatory factors. Results: Compared with the NCD group, both the HFDM and HFDMA groups showed diarrhea-like and fatigue-like phenotypes, histopathological injury in the small intestine and liver, increased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, and impaired intestinal barrier function. No significant differences in inflammatory factors were observed between the HFDM and HFDMA groups. Zonula occludens-1 (ZO-1) expression decreased in both model groups but reached statistical significance only in the HFDMA group, whereas Claudin-1 expression was significantly reduced in both groups. Gut microbiota analysis showed altered community structure, with downward trends in alpha diversity that did not reach statistical significance but clear separation trends in beta diversity. Proteobacteria and Streptococcus increased, whereas Ligilactobacillus decreased. Total bile acid levels did not differ significantly among groups; however, the ratio of secondary to primary bile acids was significantly reduced in both model groups, particularly in the HFDMA group, with decreases in representative secondary bile acids, including hyodeoxycholic acid (HDCA) and isolithocholic acid (isoLCA). Correlation analysis further supported close associations among gut microbial alteration, bile acid disturbance, and intestinal and hepatic inflammation. Conclusions: Gut microbiota dysbiosis may disrupt bile acid metabolism, impair intestinal barrier integrity, and promote intestinal and hepatic inflammatory responses, thereby contributing to diarrhea progression under fatigue and HFD conditions through the gut–liver axis. Full article

A 10-week feeding experiment was conducted to evaluate the effects of replacing fishmeal with cricket meal on the productive performance and transcriptional responses of genes related to nutrient metabolism and growth of blue tilapia (Oreochromis aureus). Five conventional tilapia feeds were formulated to replace fishmeal with cricket meal. Control diet (CD) was formulated with 20% fishmeal, and four diets gradually replaced fishmeal with cricket meal at 20, 40, 60, and 80% (D1–D4). A total of 200 fingerling tilapia (2.00 ± 0.09 g) were randomly distributed into 20 tanks (10 fish/tank), with four replicates per dietary treatment. The results showed that fish fed CD and D1 had higher growth performance values than those fed D2–D4. The feed conversion ratio (FCR) was significantly better in fish fed CD and D1 compared with fish fed D2–D4. The survival rate was similar for all treatments. The transcriptional response of genes related to nutrient digestion, absorption, and transport; lipid metabolism; and the somatotropic axis was marked downregulated in fish fed D2 and D4, whereas in fish fed D3, it exhibited a unique compensatory regulation across most pathways, likely sustained by its higher dietary lipid content. Although cricket meal did not prevent the metabolic effects associated with high soybean meal inclusion, survival remained high across all treatments. Cricket meal can replace up to 20% of the fishmeal in the feed for blue tilapia fingerlings, with soybean meal as the main protein source. Full article

Background: Renin is a hypoperfusion marker and a good index of renin–angiotensin–aldosterone system (RAAS) activity. The purpose of this study was to evaluate whether the plasma renin concentration (PRC) can represent a tissue perfusion marker for predicting mortality in patients with circulatory shock in intensive care. Methods: This prospective study included patients aged 18 years or older who were hospitalized in the intensive care unit (ICU). A total of 69 patients were enrolled, of whom 37 had circulatory shock and were all diagnosed with septic shock according to Sepsis-3 criteria, while 32 patients did not have shock. Patient groups were compared, and survival analysis was carried out. Mortality predictions of PRC, lactate and combined tests (including PRC, mottling scores, central venous saturation of oxygen, C-reactive protein, procalcitonin, and lactate) were investigated with ROC analysis. Results: ICU 28-day mortality was 36.2% (n = 25) and was significantly higher in patients with circulatory shock than those without (CS:21, 56.8% vs. NS:4, 12.5%, respectively, p < 0.001). The survival was significantly higher in patients without circulatory shock than those with shock (17 vs. 16 days; p = 0.038). The increase in mottling score (HR: 1.64 [95%CI: 1.15–2.33]; p < 0.01) and PRC (HR = 1.01 [95%CI: 1.00–1.02]; p < 0.05) levels and the decrease in glomerular filtration rate (GFR) (HR = 0.98 [95%CI: 0.96–0.99]; p < 0.05) were associated with decreased survival times in the ICU patients (p < 0.001). Combined tests yielded better prediction of mortality than PRC level alone. Conclusions: PRC may reflect circulatory shock and predict survival in critically ill patients; however, larger prospective studies incorporating serial PRC measurements are needed before it can be recommended as an independent biomarker of mortality. Full article

Background/Objectives: The pre-diagnosis dietary intake in newly diagnosed multi-ethnic paediatric inflammatory bowel disease (PIBD) is not well understood. This study aimed to describe the pre-diagnosis diet and environmental factors in children with newly diagnosed PIBD attending a single Australian tertiary children’s hospital. Methods: A pilot cross-sectional study was conducted from February 2022 to February 2023 involving children with newly diagnosed PIBD. Results: Of 56 children confirmed with PIBD, 54% had Crohn’s disease (CD)—mean ± SD age, 11.55 years ± 2.84—and 46% had Ulcerative Colitis (UC)—11.50 years ± 2.94 (45%, non-Caucasian). More Caucasians had an IBD family history (48.3% vs. 20%; p = 0.02 *). Non-Caucasian children demonstrated significantly lower mean serum vitamin D levels than Caucasian children (42.5 vs. 69 nmol/L; p ≤ 0.001 ***). Most children across ethnicities for both IBD subtypes had ‘regular’ intakes of red meat, whereas more Caucasian children had ‘regular’ intakes of processed/deli meat (72% vs. 39%; p = 0.02 *). A total of 64% of non-Caucasian children with CD reported a usual pre-diagnosis diet that differed from the traditional diet, compared to 42% with UC (p = 0.29). When eating out, fast foods were chosen regularly by most children with PIBD. Pre-diagnosis dietary intake data indicated that most with PIBD ‘rarely/never’ had whole-food sources of plant protein and had ‘infrequent’ intake of rice. Plant food diversity was low (mean 11 types/week). Conclusions: The significantly lower likelihood of IBD family history, along with relatively lower vitamin D levels, and the predominance of a Western-style dietary pattern among non-Caucasian children are compatible with the hypothesis that non-genetic factors may be important in PIBD, warranting further investigation into diet and environmental factors in this group. Further investigation of the pre-disease modifiable non-genetic factors contributing to the development of PIBD in the migrant population group is recommended. The finding across ethnicities of low pre-diagnosis plant food diversity was novel; however, due to the lack of healthy controls and the use of a novel but non-validated exposome tool, causality associations should be interpreted cautiously. Full article

Growing evidence implicates neuroinflammation, gut-derived endotoxemia, and dysregulated lipid metabolism in the pathogenesis of Parkinson’s disease (PD). However, the relationships among circulating lipopolysaccharide (LPS), LPS-handling proteins, systemic inflammatory activation, and lipid fractions remain insufficiently characterized. The aim of this study was to compare LPS levels, LPS-related inflammatory mediators, and plasma lipid parameters between PD patients and matched controls, and to explore correlations among these biomarkers. Twenty PD patients and twenty matched controls underwent fasting venous sampling. Circulating LPS, lipopolysaccharide binding protein (LBP), soluble cluster of differentiation 14 (sCD14), high-sensitivity C-reactive protein (hsCRP), and phospholipid transfer protein (PLTP) were quantified via LAL assay and ELISAs. Serum cholesterol, HDL cholesterol (HDL-C), phospholipids (PLs), HDL-PLs and triacylglycerols (TAGs) were assessed using validated biochemical techniques. LPS concentrations did not differ between groups. However, PD patients showed elevated sCD14 and hsCRP levels, reduced LBP, and increased PLTP. Lipid profiling revealed lower total cholesterol and reduced HDL-associated cholesterol and phospholipids in PD, while TAG levels remained unchanged. Correlation analyses indicated coordinated associations between inflammatory markers and lipid fractions, with distinct interaction patterns in PD compared with controls. These findings support a mechanistic interplay among endotoxemia, innate immune activation, and lipid dysregulation in the pathophysiology of PD. Full article

14-3-3 proteins are highly conserved regulatory proteins that integrate signaling pathways governing plant growth, development, and stress responses. However, the 14-3-3 gene family in oat (Avena sativa) has not been systematically investigated. Here, we performed a comprehensive analysis of oat 14-3-3 genes, including their physicochemical properties, gene structures, phylogeny, conserved motifs, promoter cis-elements, and selective pressures. A total of 19 AsGF14 genes were identified and classified into the ε and non-ε groups. The AsGF14 gene family expanded primarily through segmental duplications and has been under strong purifying selection during evolution. qRT-PCR analysis revealed that six AsGF14 genes were significantly upregulated at one or more time points under drought stress. Notably, AsGF14k exhibited sustained and significant upregulation. Subcellular localization analysis showed that AsGF14k localized to both the nucleus and the cytoplasm. Furthermore, Y2H assays indicated that AsGF14k does not form homodimers. Our results provide a systematic characterization of the AsGF14 gene family and their drought-responsive expression patterns, establishing a preliminary basis for the functional validation of AsGF14 genes under drought stress. Full article

This study aimed to evaluate the effects of lowering crude protein (CP) levels in the diet of dairy cows alone or in combination with a yeast probiotic on nitrogen utilization, digestion, and rumen microbial protein synthesis. In total, six cows were included in a 3 × 3 Latin square design. Each study period consisted of 23 days of diet adaptation and 5 days for sampling and data collection. Cows were randomly assigned to one of the three diets according to protein level and supplementation: control diet with 16.5 CP%DM (CTR), a diet with 14.5 CP%DM without Actisaf Sc 47 supplementation (LCP), and a diet with 14.5 CP%DM with Actisaf Sc 47 supplementation at 5 g/cow/day (LCPActisaf). Reducing protein content from 16.5 to 14.5 CP%DM alone or in combination with Actisaf Sc 47 significantly reduced nitrogen intake. Regarding fecal nitrogen (FN), no difference was observed between the CTR and LCP groups. However, FN was significantly lower in the LCPActisaf group compared with that of the CTR group. There was a tendency for lower FN in the LCPActisaf group compared with the LCP group. Compared with CTR, urinary nitrogen (UN) was not impacted by LCP but tended to decrease with LCPActisaf (p = 0.1). Compared with CTR and LCP, supplementation with Actisaf Sc 47 increased nitrogen use efficiency (NUE) (p < 0.05). A tendency for higher NUE was observed in the LCP group compared with the CTR group (p = 0.07). Crude protein digestibility was similar between the CTR and LCP groups and tended to increase with Actisaf Sc 47 supplementation. Compared with CTR, neutral detergent fiber (NDF) digestibility was not impacted by LCP but increased by LCPActisaf (p = 0.05); LCPActisaf did not impact NDF digestibility compared with LCP. Organic matter (OM) digestibility was similar among treatments. Although there was no difference between the three groups on rumen microbial protein synthesis (RMP), supplementation with Actisaf Sc 47 increased RMP. Reducing protein content in combination with Actisaf Sc 47 appears to be a good strategy, enabling both the environmental footprint linked to nitrogen losses to be reduced, and fiber digestibility and rumen microbial protein synthesis to increase. Full article

We evaluated the interplay between systemic total antioxidant capacity (TAC), oxidative stress (OS) (lipid hydroperoxides), inflammation, iron status, and oral contraception (OC) use in 182 healthy 23-year-old women (76 OC-users, and 106 non-OC-users). In all women, blood TAC (FORD units) values were significantly inversely associated with OS (FORT units), high-sensitivity C-reactive protein (hsCRP), and transferrin; and positively associated with transferrin saturation (TfS%). No significant associations were observed for hemoglobin, hematocrit, red blood cells, serum iron, soluble transferrin receptor (sTfR), sTfR/log(ferritin) ratio (sTfR-F index), ferritin, folate, uric acid, or creatinine. OS hydroperoxides were positively associated with hsCRP and transferrin, and inversely associated with TfS%. sTfR was positively correlated with hydroperoxides in non-OC-users and with folate in all women and non-OC-users, but was not associated with hsCRP in any group. The combined abnormal condition of low TAC and elevated OS (n = 71) was significantly more frequent among OC-users (OR = 39.0), women with hsCRP ≥ 3 mg L⁻¹ (OR = 10.1), transferrin ≥ 330 mg dL⁻¹ (OR = 6.58), and smokers (OR = 3.76). OC use modulated the TAC/OS balance and inflammation. Low TAC and elevated OS may impact health status. Enhanced TAC/OS knowledge may increase awareness of effects of OC use among fertile-age women. Ferritin was independent of TAC/OS status and OC use, supporting its reliability as an iron biomarker. Full article

This study conducted a genome-wide identification and functional analysis of the glutathione S-transferase (GST) gene family in the xerophytic desert shrub Reaumuria soongorica. A total of 67 GST genes were identified, classified into seven subfamilies, including Phi and Tau, with family expansion primarily attributed to small-scale duplication events. The findings revealed that ResoGST52, a member of the Tau subfamily, serves as a core gene in drought response, exhibiting significant upregulation of 2.40-fold in leaves and 9.01-fold in roots under drought stress. Mechanistic investigations indicated that the expression of ResoGST52 is likely directly regulated by the transcription factor ResoDof17, with specific hydrogen bonding interactions identified between the two. Co-expression network analysis further demonstrated that ResoGST52 cooperates with key pathways such as plant hormone signaling, MAPK cascades, and glutathione metabolism to collectively respond to drought stress. Notably, evolutionary analysis revealed that ResoGST52 has undergone positive selection, with three positively selected sites identified. Among these, the p.Ala115Ser mutation increases the volume of the protein’s active site pocket, while the remaining mutations enhance surface hydrophobicity, thereby improving protein stability and catalytic efficiency under extreme drought conditions. In summary, this study not only systematically identifies the GST gene family in R. soongorica but also elucidates the central role of ResoGST52 in drought adaptation through multiple layers—from transcriptional regulation and co-expression networks to protein structural adaptive evolution—providing valuable candidate genes and theoretical insights for genetic improvement of drought tolerance in crops. Full article

This study provides a comprehensive characterization of volatile and nonvolatile compounds in scallion-braised sea cucumber by integrating solid-phase microextraction gas chromatography-mass spectrometry (SPME-GC-MS) and widely targeted metabolomics. A total of 43 volatile compounds and 1792 nonvolatile metabolites were identified, with amino acids and their derivatives being the most abundant. Multivariate statistical analysis identified 11 key aroma-active volatiles and 619 significantly differential metabolites. Correlation network analysis demonstrated that characteristic flavors were primarily formed through coordinated pathways involving protein degradation, lipid oxidation, and carbohydrate metabolism during high-temperature braising. Terpenoids from seasonings, lipid-derived aldehydes and furans, and Maillard reaction products jointly shaped the distinctive aroma profile. This work clarifies the molecular mechanisms of flavor formation in scallion-braised sea cucumber and provides theoretical support for improving flavor regulation, processing standardization, and product quality evaluation in commercial sea cucumber production. Full article

De-S-acylation enzymes mediate the reversible S-acylation cycle and play critical roles in plant development and stress responses. However, the precise origin and evolutionary dynamics of this gene family in plants remain poorly understood. In this study, a total of 718 ABAPT genes were identified across 73 plant genomes, including 622 ABHD17 and 96 ABHD13 homologs, which share only a 20–30% conserved sequence identity between them. We further performed comprehensive analyses of gene duplication and structure, protein properties, synteny networks, and expression profiles to establish a systematic framework by classifying ABAPT genes in land plants. Our results revealed that ABHD13 genes have been retained as a single copy in most angiosperm genomes, whereas ABHD17 genes have undergone extensive expansion. ABAPT genes formed three major evolutionary clades: Clade 1 contained ABHD13 homologs, while Clades 2 and 3 harbored ABHD17 homologs. The three clades showed distinct disparities in intron–exon structural patterns and IDR properties. Phylogenomic synteny network analyses revealed the deeply conserved genomic syntenies within each of the six ABAPT subclades among the three clades, while Cluster4-Monocot was more dynamic and showed distinct lineage-specific duplication patterns restricted to Poaceae. ABHD13s exhibited constitutive expression patterns, while the tissue-specific expression genes were predominantly found within the ABHD17s subfamily. Notably, the ABAPT8/9 subgroups were specifically expressed in reproductive organs, and the weighted gene co-expression network identified specific groups to find ABAPT-specific regulatory features, implying the presence of potential modules for the protein S-acylation cycle during pollen development. Additionally, our results suggested that C-terminal Cys-rich region was required for ABAPT10 localization. Altogether, this study sheds light on the evolutionary divergence of the ABAPT subclades across major green plant lineages and emphasizes the need for future functional characterizations. Full article

This study developed a dual-antigen enzyme-linked immunosorbent assay (ELISA) based on σB protein and genotype 5-specific σC protein of avian reovirus (ARV). First, σB and σC proteins were expressed and purified using recombinant technology. Through optimization of coating conditions, the optimal antigen combination was determined to be a mixture of the two proteins at a 1:3 molecular ratio (total concentration: 0.8 μg/mL). Key parameters of the indirect ELISA were optimized via checkerboard titration. Validation confirmed that the dual-antigen ELISA exhibited a sensitivity of 1:3200 against genotype 5 ARV-positive sera, with no cross-reactivity and a coefficient of variation of 2.9–8.6%, demonstrating excellent reproducibility. In application testing, the method specifically detected serum antibodies against genotype 5 ARV variant strains, achieving a 100% positive detection rate in experimental chickens within the first week post-challenge and effectively monitoring dynamic antibody changes in infected flocks. Furthermore, the detection rate for genotype 5-positive serum samples (100%) was significantly higher than that of a commercial kit (75%). This dual-antigen indirect ELISA overcomes the sensitivity limitations associated with conventional genotype 5 ARV detection methods and provides a reliable tool for epidemiological surveillance and infection monitoring. Full article