Search Results (7,968)

Background/Objectives: Osteosarcoma exhibits bimodal age distribution with distinct clinical behaviors between pediatric and adult patients. Despite genomic evidence supporting age-related molecular heterogeneity, systematic transcriptomic characterization remains lacking. This study aimed to delineate age-associated transcriptional differences and develop a pediatric-specific prognostic signature. Methods: Bulk RNA sequencing was performed on tumor specimens from 70 osteosarcoma patients stratified into pediatric (≤14 years, n = 37), adolescent (15–18 years, n = 22), and adult (≥19 years, n = 11) groups. Differential expression, functional enrichment, and immune infiltration analyses were conducted. A pediatric-specific signature was validated in the TARGET-OS cohort (n = 87). Results: Pediatric osteosarcoma exhibited a hyperproliferative phenotype, enriched in E2F targets, G2M checkpoint, and DNA replication pathways. Adolescent tumors showed heightened immune–inflammatory signatures, while adult tumors activated osteogenic differentiation programs. Regarding the immune microenvironment, only adolescent tumors demonstrated active immune infiltration; pediatric and adult groups exhibited immunologically “cold” features. We identified a 10-gene pediatric-specific transcriptomic signature that declined with increasing age. High signature scores were significantly associated with inferior overall survival (hazard ratio [HR] = 5.6, 95% confidence interval [CI]: 1.2–26.2, p = 0.01) and progression-free survival (HR = 2.1, 95% CI: 1.1–4.2, p = 0.03). These findings showed concordant trends in the independent TARGET-OS cohort. Conclusions: Pediatric, adolescent, and adult osteosarcoma harbor distinct transcriptional profiles representing biologically different disease entities. The pediatric-specific 10-gene signature may serve as a clinically actionable biomarker for risk stratification and guide age-adapted therapeutic strategies. Full article

Background/Objective: To identify the risks and outcomes of extensively drug-resistant Gram-negative bacilli (XDR-GNB) in neonates. Methods: This retrospective case–control study (1995–2024) included neonates with late-onset sepsis (n = 132) and XDR-GNB bacteremia (n = 26) compared with those without XDR-GNB (n = 106). Results: Median gestational age was 31 weeks and birth weight 1540 g. The prevalence of XDR-GNB was 19.7%. The most common XDR-GNB and non-XDR-GNB pathogens were Acinetobacter baumannii and Klebsiella pneumoniae. Sepsis onset occurred earlier in the XDR-GNB group than in the non-XDR-GNB group (7.0 vs. 12.5 days, p = 0.005). In multivariable analysis using Firth’s penalized likelihood method, the XDR-GNB group was more likely to have gastrointestinal anomalies (adjusted odds ratio 3.81, 95% confidence interval 1.24–12.01, p = 0.02) and history of umbilical arterial catheterization (adjusted odds ratio 3.04, 95% confidence interval 1.21–7.95, p = 0.02) compared to the non-XDR-GNB group. The XDR-GNB group had higher rates of septic shock (50.0% vs. 18.9%, p = 0.002) and inadequate empiric antimicrobial therapy (34.6% vs. 13.2%, p = 0.02). The non-susceptibility rates to third-generation cephalosporins, gentamicin, carbapenems, amikacin, and colistin were 83.3%, 58.3%, 48.1%, 30.4%, and 4.4%, respectively. Conclusions: Empirical colistin treatment is warranted for neonates in high-XDR environments who exhibit septic shock and have specific risk factors, such as gastrointestinal anomalies or the presence of an umbilical arterial catheter. Multimodal interventions, including antimicrobial stewardship programs, have been used to prevent or reduce the incidence of neonatal XDR-GNB sepsis. Full article

This study evaluated the effects of dietary supplementation with N-Carbamylglutamate (NCG) on growth performance, immune function, intestinal metabolites, and microbiota in Danzhou chickens. In a 35-day feeding trial, a total of 480 one-day-old female chicks were randomly assigned to a control group (basal diet) and three experimental groups supplemented with 400, 800, or 1200 mg/kg NCG, with 120 chicks in each group (n = 120). The results demonstrated that NCG, particularly at 400 mg/kg, significantly improved growth parameters, including average daily gain and feed conversion ratio, while enhancing immune function by increasing serum levels of immunoglobulins (IgA, IgY) and malate dehydrogenase (p < 0.05). Metabolomic analysis revealed that NCG modulated key pathways such as sphingolipid metabolism and mTOR signaling pathway, leading to significant changes in metabolites including L-arginine, ceramide, and docosahexaenoic acid (p < 0.05). 16S rDNA sequencing indicated that NCG induced structural shifts in the gut microbiota, primarily affecting Bacteroidota and Firmicutes, with several bacterial genera showing strong correlations with the observed metabolic changes (p < 0.05). Mechanistically, NCG promotes growth by facilitating arginine synthesis via the urea cycle and activating the mTOR signaling pathway, while its regulation of sphingolipid metabolism enhances immunomodulatory capacity. In conclusion, NCG enhances feed efficiency and immune competence by orchestrating the gut microbiota-metabolite network, demonstrating its potential for poultry production. Full article

Background: Prepectoral breast reconstruction with an acellular dermal matrix (ADM) typically requires intraoperative manual tailoring, introducing structural variability and workflow delays. We developed the Polyhedral Matrix Configuration (PMC) technique—a geometric method for standardizing ADM shell creation—and compared it to our traditional “tear-drop” wrap to determine whether standardization improves structural integrity and operative efficiency. Methods: We reviewed all consecutive 227 patients undergoing immediate prepectoral reconstruction from January 2021 to December 2024 (tear-drop group: n = 155; PMC group: n = 72). PMC transforms planar ADM into a 3D dome using pre-designed wedge resections and butt-joint sutures, eliminating material overlap. Standardization permits back-table fabrication during mastectomy (“parallel two-team workflow”). We excluded bilateral cases for consistent operative time assessment and performed subgroup analysis to control for higher robotic mastectomy rates in the PMC cohort. Results: PMC reduced the plastic surgery time by a mean of 44.6 min (95% CI: 35.2–54.0) (p < 0.001), with subgroup analysis confirming efficiency gains across both conventional (32.8 min, 95% CI: 20.1–45.5, p < 0.001) and robotic mastectomies (60.8 min, 95% CI: 47.3–74.3, p < 0.001). Despite zero-overlap design, PMC showed no increase in major complications (p > 0.99) and lower rates of visible rippling (odds ratio 0.28, 95% CI: 0.08–0.97, p = 0.032). BREAST-Q “Satisfaction with Breasts” scores were higher in the PMC group (mean difference +7.3 points, 95% CI: 3.1–11.5, p = 0.001). Conclusions: Geometric standardization enables both design precision and operative efficiency. By separating reconstruction preparation from mastectomy through a reproducible protocol, PMC reduces the operative time while improving aesthetics through stable, single-layer construction. Full article

Polyethylene Glycol (PEG) precipitation and Nanotrap^® Microbiome Particles (NMP) are widely used methods for concentrating viruses in wastewater due to their simplicity, cost-effectiveness, efficiency, and rapid turnaround time. This study compared the performance of these methods in detecting noroviruses (GI and GII) and SARS-CoV-2 collected from two wastewater treatment facilities using quantitative PCR. Norovirus was detected in all samples (23/23) using both protocols, but PEG yielded higher mean concentrations for GI and GII than NMP, indicating improved quantitative recovery for non-enveloped viruses. For SARS-CoV-2, NMP showed significantly higher positive ratios for the N2 gene (Fisher’s Exact Test, p < 0.01), but no significant difference was observed for the N1 gene (p > 0.05), indicating comparable performance between the methods for this target. These findings highlight PEG’s effectiveness for non-enveloped viruses and NMP’s suitability for enveloped viruses, emphasizing the importance of selecting virus concentration methods based on viral structure. This study provides a framework for optimizing wastewater-based epidemiology (WBE) protocols and enhancing public health surveillance for diverse viral targets. Future research should focus on refining these methodologies and exploring their applicability to other viral pathogens to enhance public health surveillance frameworks. Full article

Background: Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraine (CM), yet the accompanying neurochemical changes remain incompletely characterized. Objective: To evaluate the effects of BoNT-A on plasma substance P (SP), γ-aminobutyric acid (GABA), glutamate, glutamine, and 5-hydroxytryptamine (5-HT), and on urinary 5-HT, and to explore relationships with clinical outcomes. Methods: In this prospective study, plasma neurotransmitters were analyzed in CM patients (n = 31) at baseline and one month after BoNT-A (155 U; PREEMPT protocol) and in healthy controls (n = 30). Plasma SP was measured using enzyme-linked immunosorbent assay (ELISA); plasma GABA, glutamate, and glutamine were quantified via liquid chromatography–tandem mass spectrometry (LC–MS/MS) with isotopically labeled internal standards; plasma and urinary 5-HT were determined by high-performance liquid chromatography (HPLC). Clinical outcomes included monthly headache frequency, Visual Analog Scale (VAS), and Migraine Disability Assessment (MIDAS). Statistical analyses applied appropriate parametric or non-parametric tests with p < 0.05 considered significant. Results: One month post-BoNT-A, headache frequency, MIDAS, and VAS were significantly reduced (all p < 0.001). SP levels were significantly higher after BoNT-A than at baseline and versus controls. Plasma 5-HT increased post-BoNT-A, while urinary 5-HT decreased. Plasma GABA was elevated in patients versus controls without statistical significance. Glutamine was significantly higher before treatment, whereas the Glu/Gln ratio increased after BoNT-A. Correlations revealed that higher GABA was associated with lower VAS and attack frequency post-treatment. Conclusions: BoNT-A provided short-term clinical improvement with distinct neurochemical changes, including increased plasma SP and 5-HT, decreased urinary 5-HT, reduced glutamine, and a higher Glu/Gln ratio. These biomarkers, particularly Glu/Gln, may serve as indicators of cortical excitability and therapeutic response in CM. Full article

The sustainable management and valorisation of agricultural and agro-industrial residues are essential to reduce environmental impacts, enhance resource efficiency, and support circular economy strategies. In Mediterranean regions, large quantities of residual biomass are annually produced from olive and citrus supply chains, representing promising feedstocks for biochar production. In this study, biochar was obtained at 600 °C in a fixed-bed reactor under a N₂ atmosphere from four representative feedstocks: olive pruning (OPr), citrus pruning (CPr), olive pomace (OPo), and citrus peel (CPe). The resulting biochar was characterized in terms of physico-chemical, energetic, and structural properties, including proximate and ultimate analyses, fuel properties, cation exchange capacity (CEC), pH, elemental ratios (O/C, H/C, N/C), thermal stability, bulk density, metal content, and surface morphology (SEM), in order to assess parameters relevant to environmental potential applications. The results highlighted clear feedstock-dependent differences. OPoB and CPeB exhibited the highest thermal stability (0.56–0.66), indicating a strong potential for long-term carbon sequestration. CPeB showed the highest CEC (47.2 cmol kg⁻¹). From an application-oriented perspective, this high CEC suggests that, when applied to soil at typical amendment rates (2–5 wt%), CPeB could potentially increase soil CEC by approximately 10–30%, thereby improving nutrient retention and cation availability. Energy yields were highest for citrus-derived biochar (42.0–47.5%), while OPoB exhibited the lowest solid yield due to its higher volatile content. SEM analysis revealed marked structural differences, with OPrB retaining an ordered lignocellulosic porous structure, whereas OPoB and CPeB displayed highly irregular morphologies, favorable for surface reactivity. Overall, this study demonstrates that olive and citrus residues are suitable feedstocks for producing biochar with differentiated properties, and that a rapid screening methodology can support feedstock selection and biochar design for targeted energy, soil amendment, and carbon management applications. Full article

There are 266 nature parks in Türkiye, including Aşıkpaşa Nature Park, covering a total area of approximately 109,023 ha; however, information regarding soil organic carbon stocks (SOCS), soil nitrogen stocks (NS), and nutrient stoichiometry in these protected forests remains limited. This study evaluates the influence of tree species, altitude, aspect, and soil depth on nutrient stocks and stoichiometry using a 3 × 2 × 3 × 3 factorial experimental design. The findings indicate that mixed stands (Black Pine + Cedar) significantly optimize nutrient storage, reaching peak N (3.531 ± 0.115 t ha⁻¹) and P (0.948 ± 0.016 t ha⁻¹) stocks. SOC and N stocks reached 66.34 ± 1.86 t ha⁻¹ and 4.032 ± 0.123 t ha⁻¹, respectively, along the altitudinal gradient. Soil pH exhibited a steady rise with altitude (from 7.86 to 8.15), contrary to typical leaching patterns, while bulk density varied depending on Altitude × Aspect × Depth interactions. Stoichiometric analyses revealed that Cedar stands maintain higher C:K ratios (3.457 ± 0.258), reflecting superior nutrient use efficiency. Furthermore, sunny aspects prioritized nitrogen mineralization (N:P ratio: 4.540), whereas shaded aspects facilitated phosphorus retention. These results prove that soil fertility and carbon sequestration are modulated by complex topographic–biotic interactions, suggesting that preserving mixed forest structures is of vital importance for ecological sustainability and forest resilience. Full article

Background: Ischemic stroke remains the most feared complication of atrial fibrillation (AF), and thromboembolic risk is commonly estimated using clinical scores that may not fully capture the cardiometabolic dimension of cerebrovascular vulnerability. The aim of this research was to assess whether additional parameters can be used, to predict ischemic stroke risk in patients with AF, in order to explore whether TG/HDL-C may complement conventional clinical risk scores for ischemic stroke risk stratification in PAF, and to better characterize a metabolically high-risk phenotype beyond the recommendations provided by the CHA₂DS₂-VA score, which is useful but still far from perfect in predicting AF-associated ischemic stroke risk. Methods: In this retrospective, single-center observational study, we evaluated whether the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDLc), a simple surrogate of atherogenic dyslipidemia and insulin resistance, is associated with ischemic stroke risk in patients with paroxysmal atrial fibrillation (PAF). We screened 1111 consecutive AF admissions between 1 January 2015 and 31 December 2016 and, from these 1111 AF cases, we extracted only the patients with PAF for analysis. Patients were stratified based on TG/HDLc values into two groups, Group 1 (TG/HDLc > 2.5; n = 155) and Group 2 (TG/HDLc < 2.5; n = 194). Statistical analysis was performed with MedCalc v23.4.0 using Chi-square and unpaired/Welch’s t-tests as appropriate, Pearson correlations, Kaplan–Meier analysis with log-rank testing, Cox regression for first ischemic stroke, and multivariable logistic regression to identify independent correlates of TG/HDLc > 2.5. Results: Patients with TG/HDLc > 2.5 had a significantly higher prevalence of ischemic stroke after AF onset compared with those with TG/HDLc < 2.5 (37.4% vs. 21.1%, p = 0.0008), despite similar CHA₂DS₂-VA and HAS-BLED scores, and also exhibited a higher burden of cerebrovascular and neurodegenerative findings, including cortical atrophy and cerebral lacunarism. Ischemic stroke-free survival curves diverged significantly over time (log-rank p = 0.0186), and an elevated TG/HDLc ratio was associated with a 68% higher hazard of first ischemic stroke (HR 1.68; 95% CI 1.09–2.60). In multivariable analysis, type 2 diabetes mellitus (OR 4.53), hyperuricemia (OR 3.83), dyslipidemia (OR 1.94), stroke (OR 1.77), and cortical atrophy (OR 4.48) were independently associated with TG/HDLc > 2.5. Conclusions: These findings suggest that TG/HDLc identifies a metabolically high-risk PAF phenotype associated with greater cerebrovascular burden and reduced ischemic stroke-free survival, providing an inexpensive and broadly available marker that may complement conventional clinical risk scores. Full article

Monitoring the soil–plant system in forest ecosystems is crucial for preserving their ecological functions and services. This study assessed carbon and nitrogen stable isotopes and ecoenzymatic stoichiometry as suitable indicators for characterizing the soil–plant system as a functional unit of ecological processes. To this end, in June 2021 six plots (1 m² each) were selected in two typical Mediterranean forest ecotypes: a coastal stone pine forest (Pinus pinea L., PF) and a meso-hygrophilous broadleaf forest (RV). Soil samples (0–15 and 15–30 cm depth) and litter samples (40 × 40 cm) were collected and characterized in terms of physical, chemical and biochemical properties. t-tests revealed significant differences between RV and PF, indicating distinct microbial nutrient acquisition strategies. The higher C:N ratio in PF suggested lower litter quality and greater recalcitrance to microbial decomposition. Consistently, RV showed a more pronounced ¹³C and ¹⁵N enrichment from litter to SOM down to a 30 cm depth, confirming faster organic matter decomposition and mineralization. Enzyme activity patterns supported these findings. The higher β-glucosidase and butyrate esterase activities in RV reflected its greater microbial potential to activate biogeochemical cycles. Both forests exhibited a higher microbial demand for C and P than for N to maintain ecological stoichiometric balance, with stronger C limitation at the surface and P limitation in the subsoil, particularly in RV soil. This integrated monitoring approach provides insights into nutrient cycling and ecosystem resilience and offers tools to evaluate ecosystem functionality under changing environmental conditions, supporting sustainable forest management. Full article

MASH is a progressive liver disease closely associated with cellular senescence, which is present in more than 80% of hepatocytes in patients who develop hepatocellular carcinoma (HCC). Although MASH affects both sexes, the incidence of MASH-related HCC is two to four times higher in males. Our group has previously described two apoptotic switches during MASH progression and HCC development, implicating the ATP1A1 signalosome in the late switch. Here, we investigated the role of ATP1A1 and sex-specific differences in the early apoptotic switch during preclinical MASH progression. Male and female C57BL/6J mice (7 weeks old) were fed normal mouse chow (NMC) or a high-fat diet (HFD) for 12, 24, or 48 weeks (n = 5/sex/group). Total body weight (TBW) and body composition were assessed by serial measurement and echo-MRI. Plasma was analyzed by non-targeted metabolomics and glutathione profiling using LC-MS/MS. NAFLD activity scores (NAS), hepatic senescence, and apoptosis were quantified in liver tissue. Statistical analyses were performed using GraphPad Prism and R. Males gained greater TBW and lean and fat mass than females (p < 0.05). At 24 W, males demonstrated higher GSH:GSSG ratios and lower ophthalmate levels than females (p < 0.05), consistent with altered redox balance. HFD-fed females showed increased succinic and deoxycholic acid levels, whereas males exhibited higher butyric acid levels across all time points (p < 0.05). Males had a higher mTOR 1 expression at 24 W and pT53 at 12 W compared to females on HFD, but a lower Grb2 expression at 24 W (p < 0.05). By 24 W, males had lower fibrosis scores and reduced apoptotic activity compared with females (p < 0.05), despite similar levels of cellular senescence. The expression of ATP1A1, survivin, and SMAC did not differ by sex or diet, although an upregulation trend in both ATP1A1 and survivin was noted in the male-HFD group. There is sexual dimorphism in the response to HFD during the transition from senescence to the apoptosis-first apoptotic switch in MASH progression. Full article

The objective of this research was to investigate how injectable trace minerals and vitamins influence the mineral and vitamin status, hematological parameters, antioxidant capacity, metabolic profile, and performance of Nellore calves during the pre-weaning phase. A total of 38 grazing Nellore male calves with access to creep feeding were randomly assigned to two treatments: injectable supplementation of saline solution (saline; n = 19) or injectable supplementation of trace minerals (copper, manganese, zinc, and selenium) and vitamins (A and E) (ITMV; n = 19), administered on days 75 and 150 of the calves’ age. The injectable supplementation did not affect (p > 0.05) body weight, average daily gain, body measurements, or carcass measurements throughout the experimental period from 75 to 218 days (7 days before weaning) of age. However, ITMV-treated calves showed higher (p ≤ 0.05) liver concentrations of Cu and Se on day 195 than saline calves. Higher plasma concentrations of Cu (days 195 and 218) and Se (days 135, 195, and 218) were observed for ITMV calves compared to the saline group. Furthermore, the ITMV group showed greater (p ≤ 0.05) glutathione peroxidase activity, higher red blood cell count, hemoglobin, and hematocrit levels, and a lower neutrophil/lymphocyte ratio (p = 0.04). In the metabolic profile, only a day effect was observed (p ≤ 0.05). In conclusion, the injectable supplementation of trace minerals and vitamins in suckling Nellore calves improved copper and selenium status and optimized antioxidant capacity and hematological parameters, in addition to modulating the immune response towards a less inflammatory state, although it did not affect performance or the metabolic profile. Full article

Background/Objectives: Dental caries remains one of the most prevalent chronic diseases worldwide, making enamel remineralization a key objective in minimally invasive dentistry. This in vitro study compared the remineralization efficacy of five therapeutic toothpastes containing fluoride, NovaMin, CPP-ACP, nano-hydroxyapatite, arginine, and xylitol. Methods: Sixty enamel specimens were prepared from extracted human posterior teeth and artificially demineralized. Samples were randomly allocated into six groups (n = 10): one negative control (C1) stored in artificial saliva and five treatment groups (P1–P5). A 28-day remineralization protocol with twice-daily applications was performed. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were used to assess surface morphology and elemental composition (Ca, P, F, Na, O, Ca/P ratio) at days 1, 14, and 28. Vickers microhardness testing was used to evaluate changes in mechanical properties. Statistical analysis included one-way ANOVA, repeated measures ANOVA, Tukey’s post hoc test, and Kruskal–Wallis where appropriate (α = 0.05). Results: All therapeutic toothpastes produced some increase in mineral content compared to the demineralized control. At day 28, significant intergroup differences were observed for calcium, phosphorus, and fluoride (p < 0.001). The arginine–fluoride formulation (P4) and the NovaMin-based formulation (P3) showed the most consistent increases in Ca and P, with SEM revealing the formation of a continuous, compact surface layer and marked reduction in prismatic porosities. Fluoride-containing toothpastes (P1, P3, P4) showed significant fluoride incorporation (p < 0.001 vs. control). The nano-hydroxyapatite/xylitol prototype (P5) produced a delayed but progressive increase in Ca and P, with partial filling of prismatic spaces. The CPP-ACP-based toothpaste (P2) led to limited changes, with only slight differences vs. control at day 28. Vickers microhardness values increased significantly in groups P1, P3, P4, and P5 (p < 0.05), in agreement with the higher mineral levels found in these samples. Conclusions: Under the present in vitro conditions, toothpastes containing fluoride in combination with NovaMin or arginine, as well as nano-hydroxyapatite/xylitol, demonstrated the highest remineralization potential under the present in vitro conditions, both chemically and mechanically. Xylitol-based formulations without a direct mineral supply showed limited effects. The pH and active composition of the toothpaste strongly influenced enamel remineralization outcomes. Full article

Background/Objectives: Current data-driven dietary pattern methods have limitations in identifying disease-specific dietary structures. We developed network-derived dietary scores based on type 2 diabetes (T2D)-differential food co-consumption networks and examined their associations with incident T2D risk. Methods: Using the Korean Genome and Epidemiology Study-CArdioVascular disease Association Study (KoGES-CAVAS, n = 16,665), we constructed food co-consumption networks from cumulative average intakes stratified by incident T2D status. The network centrality scores from edges appearing exclusively in either T2D or non-T2D networks were used to generate a differential co-consumption network-derived (D_CCN) score, with higher scores indicating a greater alignment with diabetes-specific structures. CAVAS-derived scores were applied to the Health Examinee Study (KoGES-HEXA, n = 51,206) for cross-cohort validation. Incidence rate ratios (IRRs) were estimated using modified Poisson regression with robust error estimation. Results: During follow-up, 953 and 2190 new cases of T2D were identified in CAVAS and HEXA, respectively. Rice and vegetable dishes were primary hub foods in both networks, with rice showing exclusively negative correlations. Non-T2D networks were more complex, whereas T2D networks were simpler and centered on refined flour-based foods. The D_CCN score was associated with a higher T2D risk in CAVAS (IRR = 1.45, 95% CI: 1.21–1.74), and this association was validated in HEXA (IRR = 1.58, 95% CI: 1.40–1.78), with consistent dose–response relationships (both p-trend < 0.0001). Conclusions: Differential network analysis identified T2D-specific co-consumption structures, and the D_CCN score consistently predicted T2D risk across cohorts. This approach highlights the utility of network-based methods for capturing disease-relevant dietary structures beyond traditional approaches. Full article

The aim of this study was to investigate the effects of dietary supplementation with 0.11% N-carbamylglutamate (NCG) during early pregnancy (0–90 days) on reproductive performance and fetal development, and to elucidate the underlying placental regulatory mechanisms in primiparous Hu sheep. Twenty-two 10-month-old sexually mature primiparous Hu sheep meeting the mating criteria were randomly assigned to two groups. The control group was fed a basal diet, while the NCG group received the basal diet supplemented with 0.11% NCG, with both feeding regimens maintained for 90 days. By measuring uterine and fetal growth indices, maternal plasma biochemical parameters, and amino acid levels, as well as assessing cotyledon indices and observing cotyledon morphology and histological structure, basic data related to placental function and fetal growth in pregnant ewes was collected. Combined with transcriptomic sequencing of maternal placental tissue, the mechanism by which NCG influences placental function and fetal growth and development in pregnant ewes was further investigated. The supplementation of NCG could increase the number of fetuses, total weight of fetuses, the number of corpus luteum and the ratio of fetuses to corpus luteum, but the difference was not significant (p > 0.05). The levels of plasma NO, inducible Nitric Oxide Synthase (iNOS) and several amino acids were significantly increased (p < 0.05). In ewes’ uteri, the average uterine weight, number of uterine glands, total cotyledon weight, and average weight per cotyledon were significantly increased (p < 0.05), whereas uterine mucosal thickness was markedly decreased. The Quantitative Real-time PCR (q-PCR) results for differentially expressed genes were consistent with those of transcriptomic analysis, showing significant changes in the expression levels of certain differentially expressed genes in maternal placental tissues. These changes regulated pathways such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), phosphatidylinositol 3-kinase–protein kinase B (PI3K–AKT) signaling pathways and Mitogen-Activated Protein Kinase (MAPK) pathway, which are involved in angiogenesis, energy supply and metabolism, and somatic growth and development. Dietary supplementation with NCG during early pregnancy can significantly improve the reproductive performance of primiparous Hu sheep, optimize the intrauterine environment and nutrient supply, and thereby facilitate pregnancy maintenance and fetal development. The underlying mechanism may involve promoting endogenous arginine synthesis in ewes, increasing plasma levels of NO, arginine, and certain amino acids, which collectively validate the positive effects of NCG on the reproductive performance and growth of Hu sheep during early pregnancy at the molecular level. Full article