Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

FAM3D inhibits gluconeogenesis in high glucose environment via DUSP1/ZFP36/SIK1 axis.

Hyperglycemia is the most important factor leading to the complications of type 2 diabetes mellitus (T2DM). The primary condition for the treatment of T2DM is to change the glucose and lipid metabolism disorders in the liver and other insulin-sensitive tissues. The current study aims to unearth the potential molecular mechanism of inhibiting liver gluconeogenesis to provide a new theoretical basis for the treatment of T2DM. High glucose (HG) induction of HepG2 cells followed by treatment with sequence-similar family 3 member D (FAM3D). Dual specificity phosphatases 1 (DUSP1), zinc finger protein 36 (ZFP36), salt-induced kinase 1 (SIK1), p-SIK1, posphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene and protein expression level were detected by quantitative real-time polymerase chain reaction and western blot. The PEPCK and G6Pase activities were detected by enzyme linked immunosorbent assay. Glucose production assay to determine glucose content. The RNA binding protein immunoprecipitation assay was used to detect the binding of ZFP36 to SIK1. FAM3D facilitated the expression of DUSP1 but suppressed the expression of gluconeogenesis-related factors in an HG environment. The expression of ZFP36 was up-regulated in an HG environment. ZFP36 could reverse the inhibition of gluconeogenesis caused by FAM3D. HG-induced upregulation of ZFP36 was downregulated by overexpression of DUSP1. ZFP36 bound to SIK1, and downregulation of ZFP36 promoted SIK1 expression and inhibits gluconeogenesis. Our study demonstrated FAM3D inhibited gluconeogenesis through the DUSP1/ZFP36/SIK1 axis in an HG environment, which provided a new theoretical basis for exploring the pathogenesis and treatment strategy of T2DM.

Clinical manifestations, prognosis, and treat-to-target assessment of pediatric lupus nephritis.

BACKGROUND: Pediatric lupus nephritis (pLN) is one of the most refractory secondary kidney diseases in childhood. The treat-to-target (T2T) strategy has become the standard treatment for systemic lupus erythematosus (SLE). This study reviewed clinical features, overall remission status, and factors affecting prognosis, to guide pLN management according to T2T strategy. METHODS: This single-center retrospective study studied 220 children diagnosed with LN from January 2012 to December 2018, with > 6-month follow-up data on 173 and complete data on 137 patients. Primary outcome was treatment failure (deterioration or no response) at the latest follow-up. RESULTS: The most common pLN manifestation was proteinuria (81.36%). Females presented more often with rash (P<0.001) and alopecia (P=0.026) than males. Class IV LN (33.33%) was the most common grade on kidney biopsy. Median follow-up was 27.20 months (IQR, 15.78-44.45 months). One-, 3-, and 5-year cumulative overall survival rates were 93.5%, 87.8%, and 86.5%, respectively. The 5-year cumulative kidney survival rate was 97.1%. Regarding initial therapy, efficacy of corticosteroids combined with immunosuppressive agents was significantly better than corticosteroids alone (P=0.010). Factors with P<0.05 in univariate analysis, including hypoalbuminemia, higher SCr at diagnosis, lower eGFR at diagnosis, anti-dsDNA positivity, heavy proteinuria, hypertension, nervous-system involvement, treatment non-compliance, and SLEDAI-2K score, were used for logistic regression analysis. Logistic regression analysis showed hypertension (OR=0.845, P=0.011), nervous-system involvement (OR=4.240, P=0.005), treatment non-compliance (OR=6.433, P=0.001), and lower estimated glomerular filtration rate at diagnosis (OR=1.020, P=0.021) affected prognosis. At end of follow-up, 34.31% achieved varying levels of remission, and 8.76% were in low disease activity state (LDAS). CONCLUSIONS: pLN usually presented with proteinuria, and class IV LN was the dominant pathology. Hypertension, nervous-system involvement, treatment non-compliance, and lower eGFR at diagnosis were independent risk factors for poor prognosis of kidney outcomes. Compared with renal remission rate and cumulative overall survival rate, the proportion of targets achieved was not ideal, suggesting T2T strategy should be used to guide pLN management. A higher resolution version of the Graphical abstract is available as Supplementary information.

Risk Factors for Poor Prognosis of Severe Infection in Children With Idiopathic Nephrotic Syndrome: A Double-Center, Retrospective Study.

Background: Infection is the most common complication of Idiopathic Nephrotic Syndrome (INS) and the main cause of INS recurrence, severe infection and even leading to mortality. The purpose of this study was to investigate the risk factors of severe infection in INS children and the clinical parameters influencing prognosis. Methods: Totally 147 children with INS and concomitant infections were enrolled and classified into the severe infection group (SIG) and Non-severe infection group (Non-SIG). The clinical characteristics and auxiliary examination results were compared between the two groups, and the early-warning parameters for severe infection and risk factors for poor prognosis were evaluated. Results: There were 49 patients in the SIG, 98 patients in the Non-SIG. In the SIG, the most common severe infections disease included severe pneumonia (63.6%), severe sepsis (30.6%), septic shock (4.1%). In SIG, Gram-positive bacteria (GPB) were more common, as was respiratory syncytial virus (RSV), and the three most common strains were Pseudomonas aeruginosa, Staphylococcus aureus (SA) and Staphylococcus epidermidis. There were more steroid-resistant nephrotic syndrome and combination of steroids and immunosuppressants in SIG, compared with the Non-SIG (P = 0.000). Patients in the SIG has lower complement 3 (C3, ≤ 0.55 g/L,) and absolute lymphocyte count (ALC, ≤ 1.5 × 109/L) (P = 0.004). Logistic regression analysis revealed that the independent risk factors for severe infections were the combined use of immunosuppressants [95% confidence interval (CI):1.569-463.541, P = 0.023], steroid resistance (95% CI: 4.845-2,071.880, P = 0.003), C-reactive protein (CRP) ≥8 mg/L (95% CI: 43.581-959, 935.668, P = 0.001), and infections caused by GPB (95% CI: 27.126-2,118, 452.938, P = 0.002), influenza (95% CI: 2.494-1, 932.221, P = 0.012) and RSV (95% CI: 5.011-24 963.819, P = 0.007). The patients in the SIG were classified into the survival group (N = 39) and the mortality group (N = 5). Logistic regression analysis showed that white blood cell count (WBC) >15 × 109/L (95% CI: 1.046-2.844, P = 0.033) was an independent risk factor of poor prognosis for these patients. Conclusions: Resistance to steroids, combined with steroids and IS agents, and GPB infections (especially SA) are high-risk factors for severe infection in children with INS. We should monitor CRP ≥ 8 mg/L, C3 ≤ 0.55 g/L and ALC ≤ 1.5 × 109/L to avoid developing severe infection. Accompanied by an increase in ANC, WBC significantly increased, suggesting a fatal infection.

Mycophenolate Mofetil in the Treatment of Steroid-Dependent or Frequently Relapsing Nephrotic Syndrome in Children: A Meta-Analysis.

Objectives: This meta-analysis aims to evaluate the efficacy and safety of the mycophenolate mofetil (MMF) in the treatment of steroid-dependent nephrotic syndrome (SDNS) or frequently relapsing nephrotic syndrome (FRNS) in children. Methods: We searched for the studies especially the randomized controlled trials in PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wan Fang database. The data were analyzed by Review Manager 5.3 software. We used the GRADE pro-Guideline Development Tool online software to evaluate the quality of evidence. Results: Finally, we identified 620 studies, of which we included five randomized controlled trials and one prospective cohort study with 447 children. The results showed the following: (1) the relapse-free survival rate within 1 year-the MMF group was superior to the levamisole group [ratio difference (RD) = 0.13, 95% CI (0.02, 0.24), P = 0.02] but not to the calcineurin inhibitors (CNIs) group [RD = -0.27, 95%CI (-0.40, -0.14), P < 0.0001]; (2) the number of relapses within 1 year-the MMF group was less than that in the CNIs and levamisole group [mean difference (MD) = -0.26, 95%CI (-0.45, -0.08), P = 0.005]; (3) the cumulative prednisone dosage-the MMF group was lower than that in the control group [standardized mean difference (SMD) = -0.32, 95%CI (-0.53, -0.11), P = 0.003]; (4) incidence of adverse reactions-there was no significant difference between the MMF group and the control group [RD = 0.02, 95%CI (-0.04, 0.09), P = 0.46]. Conclusion: The therapy of mycophenolate mofetil in the treatment of SDNS or FRNS in children has a certain advantage in reducing the number of relapses and cumulative prednisone dosage within 1 year when compared with the CNIs and levamisole. However, due to the limited quantity and quality of the included studies, the conclusions above need to be confirmed by more high-quality randomized controlled trials.