Insulin resistance (IR) is a central pathological feature of childhood obesity. Spexin (SPX), an emerging endogenous metabolic regulatory peptide, plays a key role in regulating energy metabolism. This study aimed to evaluate the association between IR and serum levels of SPX and adiponectin (ADP) and assess their biomarker potential for predicting IR in children with obesity. In total, the study enrolled 104 children (40 normal weight and 64 obese) aged 7–18 years. Further, children with obesity were categorized as having IR (n = 37) or not (n = 27) using a homeostatic model assessment of IR (HOMA-IR) cutoff of ≥ 3.0. Anthropometric measurements; biochemical profiles (including glucose, lipid, and liver enzyme levels); and serum concentrations of SPX, Gremlin-1, ADP, leptin (LEP), and tumor necrosis factor-alpha (TNF-α) were evaluated. The statistical analyses included correlation tests, multiple linear regression to identify independent determinants of HOMA-IR, and receiver operating characteristic (ROC) curve analysis to assess diagnostic performance. Children with obesity and IR exhibited significantly lower serum SPX levels compared with those without IR, indicating a biphasic pattern characterized by a “compensatory increase” followed by a “decompensated decrease.” Multiple linear regressions identified triglycerides (β = 0.211, p = 0.021), SPX (β = −0.398, p = 0.049), and ADP (β = −0.577, p = 0.005) as independent factors associated with HOMA-IR. ROC curve analysis revealed that ADP (area under the curve [AUC] = 0.634) and SPX (AUC = 0.602) had significant, albeit modest, diagnostic value for predicting IR, outperforming Gremlin-1, LEP, and TNF-α. Serum SPX and ADP levels are significantly associated with IR in children with obesity and show potential as complementary early biomarkers. The biphasic change in SPX, characterized by an initial compensatory rise followed by a decompensatory decline, suggests a complex role in metabolic adaptation and failure, underscoring its pathophysiological relevance in the progression from obesity to IR. Thus, a screening approach that combines SPX and ADP may improve early identification of children at risk of obesity.

This study aimed to compare serum levels of pentraxin-3 (PTX-3) in neonates with sepsis against those without sepsis and to assess the diagnostic value of PTX-3 in relation to conventional inflammatory markers. Between June and December 2020, a total of 109 neonates aged 1 to 21 days, with birth weights ranging from 1795 g to 4200 g, and who met the diagnostic criteria outlined in the “Expert Consensus on the Diagnosis and Treatment of Neonatal Sepsis” (2019) were examined in this prospective study, including 35 with sepsis, 36 with localized infections, and 38 without any infections. Neonates with congenital malformations, intrauterine viral infections, prior antibiotic treatment or without parental consent were excluded from the study. Blood samples were collected and analyzed for routine blood parameters, liver and kidney function metrics, levels of C-reactive protein (CRP), procalcitonin (PCT), lactic acid, and PTX-3. The incidence of premature rupture of membranes was significantly lower in the sepsis and localized infection groups compared to the non-infected group (22.86 What this paper adds

Background:The global surge in pediatric obesity is closely linked to insulin resistance (IR) and type 2 diabetes, where adipose tissue free fatty acid (FFA) overload and mitochondrial dysfunction play pivotal roles. Long non-coding RNAs (lncRNAs) are emerging regulators of metabolic diseases, but their mechanistic contributions to childhood obesity-associated IR remain underexplored. Objective:This study investigates whether lncRNA RP11-34D15.2 modulates FFA-induced IR through the miR-223/PGC-1α/irisin signaling axis in obese children. Methods:We analyzed serum FFA, insulin, irisin, and white adipose tissue (WAT) transcriptomes in 40 obese and 40 normal-weight children. Functional validation included dual-luciferase reporter assays, primary adipocyte models, and high-fat diet (HFD) mice treated with lncRNA-specific shRNA (n = 10 per group). Molecular interactions were verified via RNA immunoprecipitation and western blotting. Results:Obese children exhibited 2.1-fold higher FFA levels and HOMA-IR (P < 0.01), but 38% lower serum irisin compared to controls, with irisin inversely correlating with body fat percentage (r = -0.67, P = 0.003). lncRNA RP11-34D15.2 was downregulated by 4.3-fold in obese WAT and positively correlated with irisin expression (r = 0.603, P = 0.018). Mechanistic studies revealed that lncRNA directly binds miR-223 (RIP-seq fold enrichment = 5.2, P = 0.004), relieving miR-223-mediated suppression of PGC-1α. Overexpressing lncRNA in adipocytes increased PGC-1α (2.8-fold) and irisin (1.9-fold), upregulated mitochondrial genes (CPT-1: 3.1-fold; UCP-1: 2.4-fold, P < 0.01), and reduced extracellular FFA by 44%. In HFD mice, lncRNA knockdown exacerbated glucose intolerance (AUC increased 29%, P = 0.007), whereas irisin supplementation restored insulin sensitivity (P = 0.013). Conclusion:lncRNA RP11-34D15.2 functions as a ceRNA sponging miR-223 to activate PGC-1α/irisin-mediated mitochondrial β-oxidation and FFA clearance, identifying therapeutic targets for childhood obesity.

Purpose The relationship between moderate physical activity (MPA) and vigorous physical activity (VPA) concerning the risk of sarcopenia in adolescents remains unclear. We aimed to investigate the association between MPA, VPA, and the risk of sarcopenia in adolescents. Method This study utilized NHANES data from 2014 to 2018 from 6,415 adolescent participants. Weighted logistic regression, weighted multivariate restricted cubic spline (RCS), threshold effect model, and likelihood ratio tests were used to identify the relationship between physical activity (PA) and the risk of adolescent sarcopenia. PA patterns were classified according to inflection points. Results VPA decreased the risk of sarcopenia by 56%, whereas MPA reduced it by 24%. Nonlinear relationships were observed between MPA and VPA and the risk of sarcopenia, with inflection points at 40 min and 600 min per week, respectively. Nine distinct PA patterns were classified, ranging from patterns A to I. Compared to not engaging in any duration of VPA or MPA (pattern A), performing MPA < 40 min per week (pattern B) or engaging in VPA > 600 min and MPA > 40 min weekly (pattern I) did not reduce the risk of adolescent sarcopenia. The remaining six PA patterns (C-H) reduced the risk of adolescent sarcopenia compared to pattern A. Conclusions VPA and MPV showed nonlinear relationships with the risk of sarcopenia in adolescents. Both insufficient and excessive exercise did not reduce adolescent sarcopenia risk.

Objectives: Short stature is a multifactorial condition with significant genetic heterogeneity. This study aims to explore novel pathogenic genes associated with short stature. Subjects and methods Whole exome sequencing was performed on 138 patients with idiopathic short stature, familial short stature, small for gestational age (SGA) short stature, and short stature associated with other symptoms to explore their genetic basis. Sanger sequencing was used to validate the candidate genes. Conservation analysis and homology modeling were also conducted. Results We identified 22 heterozygous variants in genes related to the IHH signaling pathway in 22 patients. These include one variant in IHH (p.H382Y), two variants in SMO (p.V600M and p.T548I), three variants in PTCH1 (p.K202R, p.V965L, and p.P1131L), and three variants in PTCH2 (p.V430A, p.Q488L, and p.H376Y). Additionally, two variants in GLI1 (p.R510W and p.Q655H), two variants in GLI2 (p.E735K and p.L782P), and two variants in GLI4 (p.D327G and p.P155H) were found. SUFU had one variant (p.R343C), BOC had two variants (p.S480L and p.E620D), GAS1 had two variants (p.G289S and p.P85S), and CDON had two variants (p.C1120Y and p.I84V). These variants were confirmed to be rare through multiple genomic databases. Sequence alignment indicated that the affected amino acids are evolutionarily conserved among vertebrates. Structural modeling using SWISS-MODEL suggested that these variants may disrupt protein structure and function. Conclusion Our findings suggest that variants in genes associated with the IHH signaling pathway may represent new candidate genes for short stature, thereby expanding the spectrum of pathogenic genes related to short stature.

Meteorin-like protein (METRNL) has emerged as a novel adipokine involved in metabolic regulation. However, its role in pediatric obesity and its relationship with insulin resistance remain largely unexplored. In this cross-sectional study, we enrolled 55 children with obesity (34 boys, 21 girls) and 49 normal-weight controls (31 boys, 18 girls). Serum levels of METRNL, inflammatory markers (IL-6, TNF-α), and adipokines (leptin, adiponectin) were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance. Correlations between METRNL and metabolic parameters were analyzed, and multiple regression analysis was performed to identify factors independently associated with insulin resistance. Serum METRNL levels were significantly higher in children with obesity compared to controls (4.62 ± 1.24 vs 2.84 ± 0.76 ng/mL, p < 0.05). METRNL levels showed positive correlations with BMI (r = 0.624, p < 0.05), HOMA-IR (r = 0.594, p < 0.05), inflammatory markers (IL-6: r = 0.528, p < 0.05; TNF-α: r = 0.486, p < 0.05), and leptin (r = 0.546, p < 0.05), while negatively correlating with adiponectin (r = − 0.482, p < 0.05). Multiple regression analysis revealed that METRNL was independently associated with HOMA-IR (standardized β = 0.384, p < 0.05) after adjusting for potential confounders. Conclusion: Serum METRNL levels are elevated in children with obesity and independently associated with insulin resistance. These findings suggest that METRNL might play a significant role in the pathophysiology of pediatric obesity and its metabolic complications.

The aim of this study was to investigate the changes in the gut microbiota and proteins related to metabolism and immunity caused by childhood obesity and insulin resistance (IR) and to assess the underlying relationship between the gut microbiota and IR in children. Nineteen children with obesity and sixteen healthy children were recruited. Children with obesity were divided into two groups: obese with IR and obese without IR. All of the obese children participated in a 1-month lifestyle-based weight loss program. Faecal metagenomics and serum Olink proteomics combined with clinical parameters were used to identify the metabolic alterations associated with childhood obesity and IR. The gut microbiota and serum protein were significantly altered in obese children with IR. The relative abundances of Akkermansia muciniphila, IGFBP1 and GP6 were decreased in obese children with IR. Butyricicoccus sp. AM29-23AC, DLK1, CD163, CCL16 and CTSD levels were recovered after IR improved. TNFR1 had a significant indirect effect on the interaction between s-Citrobacter.freundii and fasting insulin. In conclusion, obese children with IR have abnormal gut microbiota and serum proteins related to metabolism and immunity, which can be improved after weight loss. The gut microbiome of children with obesity may contribute to the development of IR by triggering metabolic inflammation.Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2300072179).

The association between moderate physical activity (MPA) and vigorous physical activity (VPA) with the risk of sarcopenia in adolescents remains unclear. This study aims to examine their relationships systematically. This study utilized NHANES data from 2011 to 2018 from 6,415 adolescent participants. Weighted logistic regressions were conducted to investigate the effect of MPV and VPA on the risk of sarcopenia. Using weighted logistic regression with restricted cubic splines (RCS) to model potential nonlinear associations, threshold effect analysis to identify critical inflection points, and likelihood ratio tests for model comparison. Based on these thresholds, participants were stratified into six MVPA exposure groups: no-moderate (MPA = 0), low-moderate (0 < MPA < threshold), high-moderate (MPA ≥ threshold), no-vigorous (VPA = 0), low-vigorous (0 < VPA < threshold), and high-vigorous (VPA ≥ threshold). Distinct exercise patterns were derived from systematic combinations of these exposure categories. Weighted logistic regression was used to analyze the effect of exercise pattern. After adjusting for multiple covariates, VPA decreased the risk of sarcopenia by 56

Phoenixin (PNX), a newly discovered neuropeptide associated with reproduction, has been speculated to be involved in precocious puberty. Therefore, we assessed serum PNX levels in girls with precocious puberty. Serum phoenixin-14 (PNX-14) and phoenixin-20 (PNX-20) levels were determined in girls with central precocious puberty (CPP) and premature thelarche (PT) and in healthy controls (n = 58 per group). Spearman’s correlation was used to analyze the correlations between variables. Receiver operating characteristic curves were used to evaluate the performance of PNX for the diagnosis of CPP. Significant predictors of serum PNX levels were determined using least absolute shrinkage and selection operator regression and multiple linear regression analyses. Serum PNX-14 and PNX-20 levels were significantly higher in girls with CPP than in the controls; however, no significant differences in serum PNX-14 and PNX-20 levels were observed between girls with PT and the controls. PNX-20 levels were positively correlated with basal luteinizing hormone (LH) levels, peak LH levels, the peak LH to follicle-stimulating hormone (FSH) ratio, and estradiol levels. No significant correlation was observed between PNX-14 levels and any of these parameters. Multivariate linear regression analysis revealed that PNX-20 levels exhibited the strongest correlation with peak LH/FSH values. The areas under the curve (AUCs) of PNX-14 and PNX-20 for predicting CPP were 0.628 (cut-off value, 100.12 pg/mL; sensitivity, 44.6

Introduction: Childhood obesity is a global health problem that is associated with various metabolic complications, such as insulin resistance, type 2 diabetes, dyslipidemia, and cardiovascular diseases. The mechanisms underlying the development of insulin resistance in childhood obesity are not fully understood. Nephroblastoma overexpressed gene (NOV), also known as CCN3, is a member of the CCN family of matricellular proteins that modulate cell proliferation, differentiation, adhesion, migration, and survival. Previous studies have shown that NOV/CCN3 is involved in glucose metabolism and insulin signaling in various tissues and cell types. However, the role of NOV/CCN3 in childhood obesity and insulin resistance remains unclear. Methods: In this study, we aimed to investigate the association between plasma NOV/CCN3 levels and insulin resistance in 58 obese and 43 non-obese children aged 6–12 years. We measured plasma NOV/CCN3 levels by enzyme-linked immunosorbent assay and assessed insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR). We also collected clinical and biochemical data, such as body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting glucose (FG), fasting insulin (FI), lipid profile, and inflammatory markers. Results: We found that plasma NOV/CCN3 levels were significantly higher in obese children than in non-obese children (p < 0.001) and positively correlated with BMI (r = 0.42, p < 0.001), WC (r = 0.38, p < 0.001), BP (r = 0.35, p < 0.001), FG (r = 0.31, p < 0.001), FI (r = 0.45, p < 0.001), HOMA-IR (r = 0.48, p < 0.001), triglycerides (r = 0.28, p < 0.001), low-density lipoprotein cholesterol (r = 0.26, p < 0.001), and C-reactive protein (CRP) (r = 0.32, p < 0.001). Multiple linear regression analysis revealed that plasma NOV/CCN3 levels were independently associated with HOMA-IR after adjusting for age, sex, BMI, WC, BP, FG, FI, lipid profile, and CRP (β = 0.36, p < 0.001). Conclusion: These results suggest that plasma NOV/CCN3 levels are elevated in childhood obesity and are associated with insulin resistance, indicating that NOV/CCN3 may play a role in the pathogenesis of metabolic disorders in obese children.

The consumption of high-fat diets (HFD) and an imbalance in gut microbiome are linked to obesity. However, the intricate connection between them and the underlying mechanisms involved in lipid digestion and absorption remain largely unclear. This study shows that after 12 weeks of HFD feeding, C57BL/6J mice exhibit two distinct metabolic phenotypes with significant differences in gut microbiota composition. The LOW and LOW FMT group mice with increased Bacteroides are protected from obesity, insulin resistance, and lipid accumulation. Supplementation with B. vulgatus or cholic acid (CA) alleviates HFD-induced obesity and metabolic dysfunction. This is due to the accumulation of lipid droplets and the retention of chyle particles in jejunal epithelial cells, which reduces chyle intake in the jejunal mesentery after HFD. Decreased 5-HT synthesis in the jejunal enterochromaffin cells of these mice, along with reduced chyle intake in the jejunal mesentery after HFD in Tph1△IEC, suggests that intestinal 5-HT is required for host lipid absorption. TRPV1, a calcium-permeable ion channel, mediates the basolateral 5-HT-induced increase of Isc and ion channel open probability. This study uncovers a novel signaling axis of microbiota-metabolite-5-HT and intracellular calcium-dependent lipid absorption, which may serve as the potential therapeutic targets for treating HFD-induced obesity.

Introduction Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children. Methods Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound. Results Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis. Conclusion These results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders.

AbstractDietary habits are essential in the mean age at menarche (AAM). However, the causal relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between dietary habits and AAM. Genetic summary statistics for dietary habits were obtained from the UK Biobank. GWAS summary data for AAM was obtained from the ReproGen Consortium. Linkage disequilibrium score regression was used to test genetic correlations between dietary habits and AAM. The Mendelian randomization (MR) analyses used the inverse-variance weighted method. Genetic correlations with AAM were identified for 29 candi-date dietary habits, such as milk type (skimmed, semi-skimmed, full cream; coefficient = 0.2704, Pldsc = 1.13 × 10−14). MR evaluations revealed that 19 dietary habits were associated with AAM, including bread type (white vs. any other; OR 1.71, 95% CI 1.28–2.29, Pmr = 3.20 × 10−4), tablespoons of cooked vegetables (OR 0.437, 95% CI 0.29–0.67; Pmr = 1.30 × 10−4), and cups of coffee per day (OR 0.72, 95% CI 0.57–0.92, Pmr = 8.31 × 10−3). These results were observed to be stable under the sensitivity analysis. Our study provides potential insights into the genetic mechanisms underlying AAM and evidence that dietary habits are associated with AAM.

BackgroundDespite emerging evidence linking alterations in gut microbiota to childhood obesity, the metabolic mechanisms linking gut microbiota to the lipid profile during childhood obesity and weight loss remain poorly understood.MethodologyIn this study, children with obesity were treated with lifestyle weight loss therapy. Metagenomics association studies and serum untargeted lipidomics analyses were performed in children with obesity and healthy controls before and after weight loss.Main findingsWe identified alterations in gut microbiota associated with childhood obesity, as well as variations in circulating metabolite concentrations. Children with obesity showed significant decreases in the levels of s-Rothia_kristinae and s-Enterobacter_roggenkampii, alongsige elevated levels of s-Clostridiales_bacterium_Marseille-P5551. Following weight loss, the levels of s-Streptococcus_infantarius and s-Leuconostoc_citreum increased by factors of 3.354 and 1.505, respectively, in comparison to their pre-weight loss levels. Correlation analyses indicated a significant positive relationship between ChE(2:0) levels and both with s-Lachnospiraceae_bacterium_TF09-5 and fasting glucose levels. CoQ8 levels were significantly negatively correlated with s-Rothia_kristinae and HOMA-IR.ConclusionWe linked altered gut microbiota and serum lipid levels in children with obesity to clinical indicators, indicating a potential impact on glucose metabolism via lipids. This study contributes to understanding the mechanistic relationship between altered gut microbiota and childhood obesity and weight loss, suggesting gut microbiome as a promising target for intervention.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=178971, ChiCTR2300072179.

BackgroundGut microbiota and obesity are deeply interconnected. However, the causality in the relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between gut microbiota and childhood obesity.MethodsGenetic summary statistics for the gut microbiota were obtained from the MiBioGen consortium. Genome-wide association studies (GWAS) summary data for childhood obesity were obtained from North American, Australian, and European collaborative genome-wide meta-analyses. Mendelian randomization (MR) analyses were performed using the inverse variance weighting method. 16 children with obesity and 16 without obesity were included for clinical observation, and their weight, body mass index, blood lipid levels, and gut microbiology were assessed. Paired t-test was the primary method of data analysis, and statistical significance was set at P < 0.05.ResultsMR identified 16 causal relationships between the gut microbiome and childhood obesity. In the case–control study, we found that five gut microorganisms differed between children with and without obesity, whereas three gut microorganisms changed after weight loss in children with obesity.ConclusionOur study provides new insights into the genetic mechanisms underlying gut microbiota and childhood obesity.Trial registration numberChiCTR2300072179Name of registryChange of intestinal flora and plasma metabolome in obese children and their weight loss intervention: a randomized controlled triaURL of registryhttps://www.chictr.org.cn/showproj.htmlDate of registration2023-06-06Date of enrolment of the first participant to the trial2023-06-07

The academic success of children contributes to their income, social status, and public health. This study was conducted with 217 elementary school students from western China. Scores on the Chinese Children Dietary Index (CCDI), Dietary Approaches to Stop Hypertension (DASH), adjusted DASH, and KIDMED index were calculated to evaluate diet quality. Eating behavior and sleep quality were assessed using the Children's Eating Behavior Questionnaire (CEBQ) and Children's Sleep Habits Questionnaire (CHSQ), respectively. Academic achievement was measured using school-provided average grades. Higher CCDI scores, longer sleep time, lower total CHSQ scores, and lower subscores on "satiety responsiveness," "slowness in eating," "emotional undereating," and "food fussiness" dimensions of the CEBQ were associated with high academic achievement. In conclusion, good diet quality, sleep quality, healthy eating behaviors, and adequate sleep duration were associated with better academic performance. Interventions are recommended to be developed in education system to improve healthy diets and lifestyles, enhancing academic achievement.

OBJECTIVE:Diet is an important factor influencing central precocious puberty (CPP). This study aimed to investigate the relationship among diet quality, pro-inflammatory diets, and CPP in Chinese girls. DESIGN, PATIENTS AND MEASUREMENTS:This case-control study enroled 112 Chinese girls with CPP and 131 healthy controls. Children's dietary intake was assessed using a validated food frequency questionnaire, anthropometric and sociodemographic data were collected and serum interleukin-6 levels were measured. We calculated the Children's Dietary Inflammatory Index (C-DII), Chinese Children's Dietary Index (CCDI), Dietary Approaches to Stop Hypertension (DASH) score, and the adjusted Dietary Approaches to Stop Hypertension (aDASH) score. The association between diet and the risk of CPP was analysed using logistic regression models. RESULTS:After adjustment, higher C-DII scores were associated with an increased risk of CPP (P for trend = 0.034), and aDASH scores were significantly negatively associated with the risk of CPP (P for trend = 0.048). Serum IL-6 levels were significantly higher in the case group than in the control group and were positively correlated with the risk of CPP (P for trend = 0.006). CONCLUSIONS:High-quality dietary patterns and an anti-inflammatory diet may contribute to the prevention of CPP in Chinese girls.

Epilepsy is a chronic neurological disorder characterized by recurrent seizures. Despite various treatment approaches, a significant number of patients continue to experience uncontrolled seizures, leading to refractory epilepsy. The emergence of novel anti-epileptic drugs, such as perampanel (PER), has provided promising options for effective epilepsy treatment. However, the specific mechanisms underlying the therapeutic effects of PER remain unclear. This study aimed to investigate the intrinsic molecular regulatory mechanisms involved in the downregulation of GluA2, a key subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, following epileptic seizures. Primary mouse hippocampal neurons were cultured and subjected to an epilepsy cell model. The expression levels of GluA2 and autophagy-related proteins were assessed using Western blotting and real-time fluorescent quantitative PCR. Immunofluorescence and immunohistochemistry techniques were employed to investigate the nuclear translocation of CREB-regulated transcriptional coactivator 1 (CRTC1). Additionally, status epilepticus animal models were established to further validate the findings. The epilepsy cell model exhibited a significant decrease in GluA2 expression, accompanied by elevated levels of autophagy-related proteins. Immunofluorescence analysis revealed the nuclear translocation of CRTC1, which correlated with the expression of autophagy-related genes. Treatment with an autophagy inhibitor reversed the decreased expression of GluA2 in the epilepsy cell model. Furthermore, the calcium/calmodulin-dependent protein phosphatase inhibitor FK506 and CaN overexpression affected the dephosphorylation and nuclear translocation of CRTC1, consequently influencing GluA2 expression. Animal model results further supported the involvement of these molecular mechanisms in epilepsy. Our findings suggest that the downregulation of GluA2 following epileptic seizures involves the activation of autophagy and the regulation of CRTC1 nuclear translocation. These intrinsic molecular regulatory mechanisms provide potential targets for developing novel therapeutic strategies to alleviate refractory epilepsy and preserve cognitive functions in patients.

Follistatin-like protein 1 (FSTL1) has been identified as a secreted glycoprotein that plays an important role in obesity. However, its role in children with metabolic-associated fatty liver disease (MAFLD) has not been investigated. This study aimed at characterizing the relationship between serum FSTL1 concentration and MAFLD in children with obesity. A total of 121 subjects were recruited from the Second Affiliated Hospital of Xi’an Jiaotong University, including 45 obese children with MAFLD, 31 obese children without MAFLD, and 45 healthy controls. Anthropometric parameters, biochemical data were measured and circulating FSTL1 levels were detected by ELISA. The levels of FSTL1 in obese children with MAFLD were higher than that in obese children without MAFLD: 1.31 (0.35–2.29) ng/mL vs. 0.55 (0.36–1.38) ng/mL. Correlation analysis illustrated that FSTL1 was associated with nonesterified free fatty acid and leptin (r = 0.278, P < 0.05 and r = 0.572, P < 0.05, respectively). Binary logistic regression suggested that increased FSTL1 was a risk factor for MAFLD in children (OR = 1.105, 95

ObjectiveTo investigate serum TL1A levels and their correlation with Th17 cells, IL-17, and IL-21 in children with Graves’ disease (GD).MethodsThirty-seven children (12 males and 25 females) aged 9-14 years with newly diagnosed and untreated GD were enrolled in this study. Serum TL1A, IL-17, and IL-21 levels were measured using enzyme-linked immunosorbent assay (ELISA). The percentage of Th17 cells in peripheral blood was determined by flow cytometry. The correlation between serum TL1A levels and Th17 cells, IL-17, and IL-21 was analyzed using Pearson’s correlation coefficient.ResultsSerum TL1A levels and the percentage of Th17 cells were significantly higher in children with GD compared to healthy controls (P<0.05). Serum IL-17 and IL-21 levels were also significantly elevated in GD patients (P<0.05). Serum TL1A levels positively correlated with the percentage of Th17 cells (r=0.625, P<0.05), IL-17 (r=0.573, P<0.05), and IL-21 (r=0.542, P<0.05) in children with GD.ConclusionSerum TL1A levels are increased in children with GD and positively correlate with Th17 cells, IL-17, and IL-21, suggesting that TL1A may play a role in the pathogenesis of GD by regulating Th17 cell differentiation and the production of IL-17 and IL-21.