Search Results (4,090)

Background: Caffeine is one of the most widely consumed bioactive compounds worldwide. The available data regarding its effects on bone metabolism and skeletal health remain inconsistent. The aim of this study was to review experimental studies on the effects of caffeine on the skeletal system. Methods: A literature search was conducted using PubMed to identify original experimental studies investigating the effects of caffeine on the skeletal system published up to December 2025. The reviewed studies included in vivo studies on different animal models and in vitro studies on bone-related cells. Due to data heterogeneity, a narrative analysis was performed. Results: Fifty-three studies on caffeine effects were included in the review. The findings indicate that the effects of caffeine are dose-dependent and bidirectional. Low-to-moderate doses in vivo generally exerted neutral or sometimes beneficial effects on the skeletal system, whereas higher doses were associated with impaired bone development, reduced mineralization, and increased bone loss. In estrogen-deficient animals, moderate doses showed potential protective effects, while high doses exacerbated bone loss. In vitro studies demonstrated concentration-dependent effects, with high concentrations often reducing cell viability and osteogenic activity. Conclusions: The effects of caffeine on the skeletal system are complex and context-dependent. While high exposure may adversely affect bone, low-to-moderate intake appears to be safe and may exert beneficial effects under specific conditions. Full article

Background: Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders affecting biochemical pathways. Despite advances in diagnostic technologies, comprehensive understanding of their historical evolution, classification systems, and diagnostic approaches remains fragmented. Objectives: This systematic review and meta-analysis aimed to synthesize evidence on the historical development, classification frameworks, and diagnostic modalities for IEMs, diagnostic accuracy, and prevalence estimates, providing a comprehensive resource for clinicians and researchers. Methods: Following PRISMA 2020 guidelines, we conducted a systematic search of seven electronic databases (PubMed/MEDLINE, Embase, Scopus, Web of Science, Google Scholar, SciSpace and ArXiv) from January 2000 to March 2026. Studies addressing historical perspectives, classification systems, or diagnostic approaches for IEMs were included. Two independent reviewers performed screening, data extraction, and quality assessment. Meta-analyses were conducted using random-effects models for diagnostic accuracy and prevalence estimates. Results: From 1342 identified records, 54 studies met the inclusion criteria, encompassing 8,234,567 individuals across 35 countries. Historical analysis revealed 16 major milestones from Garrod’s 1902 “chemical individuality” concept to the current AI-powered diagnostics. Four major classification systems were identified: pathophysiological (intoxication, energy deficiency, complex molecule disorders), biochemical pathway (amino acid, organic acid, urea cycle, carbohydrate, fatty acid oxidation, mitochondrial, peroxisomal, lysosomal disorders), organelle-based, and the integrated Society for the Study of Inborn Errors of Metabolism (SSIEM) nosology. Meta-analysis demonstrated high diagnostic performance of tandem mass spectrometry (MS/MS) with a pooled sensitivity of 99.1% (95% CI: 98.6–99.5) and specificity of 99.8% (95% CI: 99.7–99.9%). The pooled global prevalence of IEMs was 50.9 per 100,000 live births (95% CI 45.2–56.8). Next-generation sequencing achieved a diagnostic yield of 42.8% (95% CI: 38.2–47.5%) in suspected cases. Emerging AI-powered diagnostic tools demonstrated high discrimination performance with area under the curve (AUC) values exceeding 0.95 for specific IEM, though external validation remains limited. Newborn screening expanded from single-disease to comprehensive panels detecting over 50 disorders. Conclusions: This comprehensive review demonstrates that IEMs have evolved from rare curiosities to systematically diagnosable conditions through technological advances. Integration of metabolomics, genomics, proteomics and artificial intelligence promises further diagnostic improvements. Standardized classification systems and evidence-based diagnostic algorithms are essential for optimal patient care. Future directions include artificial intelligence-enhanced diagnostics, expanded screening, and personalized medicine approaches. Full article

This study presents a damage-based comparative assessment of reinforced concrete buildings affected by the 1992 Erzincan earthquake (Mw 6.8) and the 2023 Kahramanmaraş earthquake sequence (Pazarcık, Mw 7.7; Elbistan, Mw 7.6), two destructive earthquake events in Türkiye separated by nearly three decades. A distinctive contribution of the study is the presentation of original color photographs from the 1992 Erzincan earthquake, systematically documented and comparatively evaluated for the first time and directly compared with post-earthquake field observations from Malatya following the 2023 earthquake sequence. To complement the field-based evidence, representative strong ground motion records from both earthquake events were processed and compared using standard seismic intensity and spectral response parameters. The spectral evaluation indicates that the 1992 Erzincan ground motion and the 2023 Elbistan-related motion recorded in Malatya imposed comparable seismic demands relevant to typical reinforced concrete buildings, thereby providing a rational basis for cross-event damage interpretation. Despite substantial advances in Turkish seismic design codes, recurrent damage mechanisms were observed in both building stocks, particularly soft-story formation, short-column effects, inadequate transverse reinforcement, poor beam–column joint performance, and deficiencies in material quality and detailing. The findings demonstrate that seismic safety cannot be improved through code development alone unless design provisions are consistently translated into construction quality, detailing practice, inspection, and field implementation. Full article

Prenatal alcohol exposure (PAE) is recognized as a major public health concern due to its profound and lasting effects on the central nervous system (CNS) and its ability to induce fetal alcohol spectrum disorders (FASD), which encompass a wide range of cognitive, behavioural, and neuropsychiatric disorders that persist throughout life. Experimental and clinical studies have identified several mechanisms underlying ethanol impairing brain development, including apoptosis, oxidative stress, disruption of morphogen and growth factor signalling pathways, impaired neuronal proliferation and migration, neurotransmitter systems’ dysfunction, glial cells damage associated with deficient myelination, vascular and blood–brain barrier (BBB) alterations, and lasting epigenetic reprogramming. However, to date no widely accepted integrative framework explaining how these impairments underline the heterogeneous phenotype observed in FASD is available. The present brings together developmental neurobiology and computational neuroscience to conceptualize PAE as a disorder of emerging neural and functional architecture. Here, we summarize the pharmacokinetics of ethanol in pregnancy, critical windows of vulnerability, and the classical pathways of alcohol teratogenesis affecting neuronal survival, migration, synaptogenesis, myelination, and gene regulation. We have also reviewed MRI, diffusion imaging, and EEG/MEG evidence showing altered brain volumes, white matter microstructure, functional connectivity, and network organization in individuals with PAE. Finally, we propose a systems-level model that conceptualizes PAE as a disorder of emerging neuro-computational architecture, in which ethanol-induced cellular and molecular perturbations collectively alter the building blocks and self-organization rules of brain network assembly. Full article

Background: Avoidant/restrictive food intake disorder (ARFID) and selective eating are increasingly recognized in pediatric nutrition, but food selectivity has been predominantly studied in dedicated eating disorder settings and in underweight children, potentially underestimating its prevalence across broader clinical populations. This study aimed to characterize food selectivity as a transdiagnostic feature in children referred to a tertiary pediatric nutrition center, regardless of referral diagnosis or BMI status. Methods: This retrospective observational study included 417 consecutive children and adolescents (median age 9.3 years, IQR 4.1–12.9; 47.5% male) assessed at the General Pediatric Eating Disorders Outpatient Unit of Bambino Gesù Children’s Hospital IRCCS, Rome, Italy, between May 2024 and April 2026. Food selectivity was defined as clinician-documented avoidance of at least one of four food groups (vegetables, fruit, fish, and legumes). Patients were classified as having primary selective eating/ARFID (Group A, n = 141), unrecognized selective eating (Group B, n = 163), or no selectivity (Group C, n = 113). Results: Food selectivity was identified in 293 patients (70.3%), including 70.8% of those referred for obesity or overweight and 50.0% of those referred for eating disorders. Prevalence did not differ across BMI categories (p = 0.554), confirming that selective eating is independent of anthropometric status. Ferritin deficiency showed a significant gradient across groups (Group A 32.2%, Group B 17.9%, Group C 10.8%; p = 0.002). Screen use during meals and ultra-processed food consumption were similarly elevated in Groups A and B and significantly higher than in Group C (p = 0.002 and p < 0.001, respectively), with no difference between the two selective groups. Conclusions: Food selectivity is a transdiagnostic and BMI-independent feature affecting the majority of children referred for pediatric nutritional evaluation. Children with unrecognized selective eating share the same nutritional risks and behavioral correlates as those formally diagnosed with ARFID, supporting the integration of a brief food group avoidance screen into routine nutritional assessment regardless of the primary referral diagnosis. Full article

Over the last years, incretin receptor agonists—including glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) and the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist tirzepatide—have dramatically improved the management of type 2 diabetes, overweight and obesity. However, as the use of incretin receptor agonists continues to increase worldwide, micronutrient deficiencies—including iron deficiency—have emerged as newly recognized adverse effects of these drugs. The present article aims to discuss recent preliminary observational evidence on the potential relationship between incretin receptor agonist-based therapies and the development of iron deficiency and iron deficiency anemia (IDA), as well as the potential mechanisms by which incretin receptor agonists may affect iron homeostasis. Potential mechanisms and factors underlying the development of iron deficiency and IDA in patients treated with incretin receptor agonist-based therapies include inadequate dietary iron intake (due to incretin receptor agonist-mediated reduction in food intake and/or gastrointestinal adverse effects of incretin receptor agonists), low dietary variety, monotonous diets, and changes in food preferences, as well as impairment of intestinal iron absorption (due to delayed gastric emptying, reduced small intestinal motility and/or decreased gastric acid secretion caused by incretin receptor agonists). Moreover, vitamin B2 (riboflavin) deficiency and changes in gut microbiota composition are hypothetical mechanisms that may partly explain iron deficiency in patients treated with incretin receptor agonists, although these hypotheses require confirmation through mechanistic studies. Even though iron deficiency and IDA currently appear to be uncommon adverse effects of incretin receptor agonist-based therapies, clinicians should be aware of the possibility of their occurrence to ensure appropriate prevention and management of these nutritional complications. Nevertheless, future prospective studies are certainly needed to better establish the causal relationship between the initiation of incretin receptor agonist-based therapies and the development of iron deficiency/IDA, as well as the exact mechanisms underlying the potential development of these nutritional complications in patients treated with incretin receptor agonists. Meanwhile, the prescription of incretin receptor agonists should not be unjustifiably restricted by the possible and modest risk of iron deficiency and IDA in patients with one or more approved indications for therapeutic use of these agents. Since no established guidelines currently exist for the prevention and management of iron deficiency and IDA in patients treated with incretin receptor agonists, we herein propose practical strategies to address these possible nutritional complications of incretin receptor agonist-based therapies. These proposed strategies should only be regarded as practical clinical approaches deriving from the existing recommendations for the prevention and management of iron deficiency and IDA, although their cost-effectiveness for the prevention and management of incretin receptor agonist-associated iron deficiency/IDA should be appropriately assessed in future clinical trials. Full article

Background: Cirrhosis is a progressive liver disease often associated with sarcopenia. Vitamin D and IGF-1 alterations may contribute to muscle loss and disease progression. This study evaluated their relationship in cirrhotic patients. Methods: A total of 90 patients with liver cirrhosis were included in this retrospective observational study. Clinical and laboratory data were collected, and disease severity was assessed using Child–Pugh and MELD-Na scores. Sarcopenia was evaluated using CT-based skeletal muscle index at the L3 level with sex-specific cut-offs. Patients with malignancy, acute liver failure, recent surgery, or muscle-affecting conditions were excluded. Vitamin D and IGF-1 levels were classified using standard and age-adjusted reference ranges. Results: A total of 90 patients were included, of whom 42 were alive, and 48 died during follow-up. Gender distribution was similar between groups (p = 0.388). Skeletal muscle area was significantly lower in non-survivors (110 vs. 140 cm², p = 0.002), while body mass index did not differ (p = 0.570). Vitamin D levels were significantly lower (10.0 vs. 17.9 ng/mL, p < 0.001), and hemoglobin levels were reduced in the non-survivor group (10.76 ± 2.13 vs. 12.87 ± 2.57 g/dL, p = 0.001). In multivariate analysis, age (OR 1.046, p = 0.032), MELD-Na score (OR 1.200, p = 0.001), and vitamin D level (OR 0.920, p = 0.024) were independently associated with mortality. Conclusions: CT-based sarcopenia assessment is a useful adjunct in cirrhosis when interpreted with disease severity. Radiological muscle depletion is common and associated with worse outcomes, while vitamin D deficiency independently associated with mortality, highlighting its potential as a biomarker and therapeutic target. Full article

Mucopolysaccharidosis (MPS) are a group of inherited lysosomal storage genetic disorders that affect the body’s ability to break down glycosaminoglycans (GAGs) due to the deficiency of required enzymes. This leads to depositions of these GAGs in various tissues and organs resulting in multi-systemic manifestations including pulmonary and sleep related issues. In recent years, there have been significant advancements in therapeutic options and supportive management which have led to the overall improvement in respiratory care, culminating in improved quality of life for MPS patients. Management of pulmonary and sleep disorders in mucopolysaccharidosis requires a multidisciplinary approach due to the multi-systemic affectation of the genetic disorders. Therapeutic options such as enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT) have yielded varying success in mitigating respiratory complications. Emerging treatments such as gene therapies have shown exciting and promising results thus far. Supportive therapies such as airway clearance, regular vaccination and use of positive airway pressure devices are also essential. Pre-operative airway and anesthesia planning is critical to mitigate peri-operative and post-operative complications. Early diagnosis, close monitoring and a patient focused individualized approach are essential for respiratory optimization and overall improvement in clinical outcomes. This review article aims to discuss these advancements in a comprehensive format, making it accessible to medical providers who care for this subset of patients. Full article

Background/Objectives: White–Sutton syndrome (WHSUS; OMIM 616364) is a rare neurodevelopmental disorder caused by pathogenic variants in the POGZ gene and characterized by developmental delay, intellectual disability, speech impairment, autism spectrum features, and dysmorphic traits. Although most reported cases are sporadic, inherited forms are exceptionally rare. We describe a familial case of WHSUS involving an affected mother and two children carrying a heterozygous POGZ nonsense variant, highlighting marked intra-familial phenotypic variability and expanding the clinical spectrum of the disorder. Methods: Clinical evaluation included multidisciplinary assessments. Genetic testing was performed using clinical exome sequencing (CES) with a virtual neurodevelopmental disorder (NDD) gene panel, followed by Sanger confirmation and segregation analysis in family members. The POGZ transcript reference NM_015100.3 was used for variant nomenclature and verified with the Mutalyzer tool. CNV detection from NGS data was performed using the Alissa CNV caller (Agilent) and visualized via IGV; the Xp11.22 microduplication was confirmed by chromosomal microarray (aCGH) and parental segregation analyses. Results: CES identified the heterozygous pathogenic POGZ variant c.1522C>T (p.Arg508*) in the female proband (III₆), an infant presenting with global developmental delay, hypotonia, speech impairment, gait abnormalities, and characteristic dysmorphic features. Segregation analysis demonstrated maternal inheritance and confirmed the presence of the variant in her affected brother (III₄), who also carries a de novo 1.79 kb microduplication at Xp11.22, while the maternal grandparents tested negative, indicating a de novo origin in the mother. The mother exhibited an attenuated phenotype, including mild neuropsychiatric and gastrointestinal manifestations. The variant is predicted to undergo nonsense-mediated decay (NMD), consistent with a moderate clinical presentation; however, experimental validation was not performed. Conclusions: This report documents a rare familial occurrence of WHSUS with highly variable expressivity. Our findings broaden the phenotypic and molecular characterization of POGZ-related disorders and emphasize the importance of comprehensive segregation studies and early genomic diagnosis. While experimental data link POGZ deficiency to DNA repair defects, no longitudinal clinical studies have demonstrated increased cancer risk in WHSUS; therefore, formal malignancy screening guidelines cannot be established at present, and this issue deserves future study in larger cohorts or registries. Full article

Online parameter identification is important for sensorless permanent magnet synchronous motor (PMSM) drives because motor parameter variation can reduce the accuracy of the controller and observer. However, in the background of sensorless control, the accuracy of online parameter identification is significantly affected by rotor position estimation errors and inverter nonlinearity. To address these problems, this paper proposes a high-frequency d-axis voltage injection-based online parameter identification method with inverter nonlinearity compensation. The proposed online identification method can identify the stator resistance and d-axis inductance independently. It not only overcomes the rank-deficiency problem in conventional voltage-equation-based identification, but also shows through theoretical analysis that the identification results are insensitive to rotor position estimation errors. To improve the identification accuracy, the influence and importance of inverter nonlinearity on parameter identification are analyzed, and a compensation method based on zero-sequence voltage characteristics and a feedforward neural network is developed. The identified voltage error is compensated through equivalent dead-time correction. Simulation and experimental results verify the advantages of the proposed method under different operating conditions. Full article

Cross-presentation of exogenous antigens by dendritic cells (DCs) relies on the cytosolic pathway, enabling proteasomal processing and subsequent loading of antigenic peptides onto major histocompatibility complex class I (MHC-I) molecules. Although this pathway is central to CD8⁺ T-cell activation, the molecular mechanisms that regulate intracellular antigen processing and redistribution during cross-presentation remain incompletely defined. In this study, we investigated the contribution of the large-pore channel Pannexin-1 (Panx1) to antigen handling during cross-presentation. Using confocal microscopy and quantitative image analysis in granulocyte–macrophage colony-stimulating factor/interleukin-4 (GM-CSF/IL-4)-derived inflammatory bone marrow-derived dendritic cell (BMDC)-like cellsexposed to ovalbumin (OVA)–Alexa Fluor 488, we observed time-dependent changes in intracellular antigen distribution that were altered upon pharmacological inhibition of Panx1 with the blocking peptide 10Panx1. In parallel, functional assays revealed that Panx1 inhibition significantly reduced SIINFEKL peptide-dependentactivation of B3Z CD8⁺ T-cell hybridomas following pulsing with full-length OVA. Similar effects were observed in the cross-presentation-competent MUTU1940 dendritic cell line. Importantly, Panx1 inhibition did not significantly affect dendritic-cell viability or LPS-induced activation under the experimental conditions tested. In contrast, pharmacological inhibition or genetic deficiency of P2X7 receptor (P2X7) did not produce comparable reductions in cross-presentation, and combined inhibition did not result in additive effects under the experimental conditions tested. Together, these findings provide functional evidence supporting a role for Panx1 in regulating intracellular antigen redistribution associated with cross-presentation. While not establishing direct genetic causality, our data identify Panx1 as a modulatory component influencing antigen-processing events that culminate in CD8⁺ T-cell activation, thereby expanding the current framework of intracellular antigen-processing mechanisms involved in dendritic-cell-mediated cross-presentation. Full article

Background: Retinoid signaling is implicated in regulating membrane-bound polyunsaturated fatty acids (PUFAs), which serve as substrates for oxylipin biosynthesis. Dysregulated vitamin A status and altered oxylipin profiles have both been associated with the development of metabolic diseases. However, whether early-life vitamin A deficiency (VAD) causally influences oxylipin metabolism and liver health remains unclear. Methods: C57BL/6J mouse pups were exposed to either a vitamin A-deficient (VD) or vitamin A-replete (VR) AIN-93G-based diet during the fetal and suckling periods, and they weremaintained on the same diet from weaning (3 weeks of age) to 9 weeks of age. Oxylipin composition in plasma, liver and cerebral tissues was analyzed by liquid chromatography–mass spectrometry. Hepatic and cerebral expressions of genes involved in inflammation, phospholipid and PUFA catabolism, and oxylipin synthesis were analyzed using RT-qPCR. Results: Dietary deprivation induced severe VAD, which significantly altered 21 oxylipins in the liver and 34 oxylipins in the cerebrum, but did not affect the plasma oxylipin profile. In the liver, all altered oxylipins were elevated by VAD, the majority being ω-6-derived species with pro-inflammatory properties. In contrast, 27 altered oxylipins were lower in the VD cerebrum, including more ω-3-derived species. Multivariate analysis identified 11,12-EpETrE, 8,9-EpETrE, and 20-HETE as key hepatic oxylipins distinguishing VAD. VAD also altered hepatic expression of genes involved in membrane phospholipid remodeling (PNPLA8, PLA2G6, LPCAT3), and oxylipin metabolism (ALOX5, EPHX2), and it upregulated inflammatory signaling in the liver only, while fibrosis markers (TGFB1, COL1A1) remained unchanged. Conclusions: These findings demonstrate that early-life VAD is associated with tissue-specific alterations in oxylipin metabolism and hepatic inflammatory responses. Full article

Background: Micronutrient deficiencies and physical inactivity can adversely affect child growth and development. This study assessed the effects of school-based physical activity and multi-micronutrient supplementation on micronutrient status among schoolchildren in Kilombero district, Tanzania. Methods: In a cluster-randomized trial, children aged 6–12 years were allocated to physical activity, multi-micronutrient supplementation, combined physical activity plus supplementation, or placebo control. Anthropometric and biochemical assessments were conducted at baseline, 14 months, and 26 months. Dried blood spot samples were available for 923 children at baseline. Complete-case analyses used biomarker-specific subsamples with valid baseline and 26-month measurements. Results: The primary complete-case sample included 243 children with valid paired measurements for zinc and serum transferrin receptor; vitamin D analyses were restricted to 52 children because of missing or invalid samples. At baseline, iron and vitamin D deficiencies were common, affecting 42.8% and 39.9% of children, respectively, while zinc deficiency affected 11.9%. At 26 months, allocation to the physical activity intervention was associated with lower odds of zinc deficiency, both when delivered alone (OR = 0.16) and when combined with supplementation (OR = 0.57). Supplementation alone was not significantly associated with reduced zinc deficiency. Iron status did not differ between intervention groups. Vitamin D findings should be interpreted with caution because analyses were based on a very small biomarker-specific subsample. Conclusions: School-based physical activity, alone or combined with multi-micronutrient supplementation, was associated with lower odds of zinc deficiency among Tanzanian schoolchildren. Supplementation alone showed no clear benefit for zinc or iron status. Vitamin D findings remain inconclusive because of substantial biomarker-specific missingness. Future trials should strengthen adherence monitoring, biomarker follow-up, and repeated assessment of dietary and contextual factors. Full article

Brain-derived neurotrophic factor (BDNF) is a key regulator of neural development, plasticity, and behaviour. Recent work has enabled the generation of a viable adult bdnf^−/− zebrafish line, which provides a unique opportunity to investigate how complete loss of bdnf affects social behaviour. Here, we examined three-dimensional shoaling behaviour in adult male and female AB wild-type and bdnf^−/− knock-out zebrafish to determine whether the extensive molecular and behavioural alterations previously observed in individual-based assays extend to collective contexts. The bdnf^−/− shoals showed no differences in group structure, as inter-fish distance, shoal volume, shoal area, distance to the centroid, and homogeneity index were comparable to wild-type groups. Vertical spatial distribution was also largely preserved, although bdnf^−/− fish shifted toward the upper regions of the tank earlier during the trial. By contrast, horizontal distribution revealed a clear genotype effect: bdnf^−/− shoals spent more time in peripheral regions and displayed a pronounced early peak in peripheral occupancy. These findings indicate that bdnf loss does not impair shoal formation or cohesion but selectively modulates specific components of spatial exploration. The results also highlight a dissociation between the vertical and horizontal axes of behaviour, as well as between individual- and group-based phenotypes, underscoring the importance of social context in shaping the behavioural consequences of BDNF deficiency. Full article

This study evaluated the effects of dietary sulphur-containing amino acid (SAA) levels provided during the early (1–28 d) and late (29–63 d) growth stages on production traits and feather follicle gene expression in 63-day-old Jiangnan white goslings. A total of 288 one-day-old male goslings were assigned to a 2 × 2 factorial design with two early SAA levels (0.64% and 0.87%) and two late SAA levels (0.62% and 0.74%), which created four treatments: Dd (low–low), Dg (low–high), Gd (high–low), and Gg (high–high). All measurements were performed on 63-day-old birds. Final body weight was significantly affected only by early SAA levels (p = 0.03), with the high early groups (Gd and Gg) showing a 3% higher weight (3.99 vs. 3.88 kg) than the low early groups. Late SAA levels had no effect on growth but markedly reduced breast muscle cooking loss (p < 0.01) from 26.64% (low late) to 22.70% (high late), which represents a 15% relative improvement in water-holding capacity. A significant early × late interaction (p = 0.03) indicated that late high SAA levels partially compensated for early deficiency. High late SAA levels also slightly reduced dry matter digestibility (73.45% → 73.16%, p = 0.03), while high early SAA levels increased crude ash digestibility (33.59% → 35.66%, p = 0.04). The Dg treatment (low early + high late) caused significantly elevated serum low-density lipoprotein (2.06 vs. 1.42–1.58 mmol/L) and uric acid (348.15 vs. 243.60–294.97 μmol/L), which indicates metabolic stress (p < 0.01 and p = 0.02 for interaction). Transcriptomic analysis of feather follicles from the Gg and Gd groups (both receiving identical high early SAA supplementation) identified 121 differentially expressed genes, including the downregulation of MAT1 (cysteine/methionine metabolism) and upregulation of GHRHR (neuroactive ligand–receptor interaction) in Gg, providing a molecular basis for improved feather growth. q-PCR validated five selected genes. In conclusion, final body weight is determined by early SAA supply, while late SAA supplementation improves meat juiciness, but abrupt increases from low to high SAA levels cause metabolic disturbances. Under this test conditions, The optimal feeding strategy is 0.87% SAAs (1–28 d) followed by 0.74% SAAs (29–63 d). Full article