Residual network improves the prediction accuracy of genomic selection.

Genetic improvement of complex traits in animal and plant breeding depends on the efficient and accurate estimation of breeding values. Deep learning methods have been shown to be not superior over traditional genomic selection (GS) methods, partially due to the degradation problem (i.e. with the increase of the model depth, the performance of the deeper model deteriorates). Since the deep learning method residual network (ResNet) is designed to solve gradient degradation, we examined its performance and factors related to its prediction accuracy in GS. Here we compared the prediction accuracy of conventional genomic best linear unbiased prediction, Bayesian methods (BayesA, BayesB, BayesC, and Bayesian Lasso), and two deep learning methods, convolutional neural network and ResNet, on three datasets (wheat, simulated and real pig data). ResNet outperformed other methods in both Pearson's correlation coefficient (PCC) and mean squared error (MSE) on the wheat and simulated data. For the pig backfat depth trait, ResNet still had the lowest MSE, whereas Bayesian Lasso had the highest PCC. We further clustered the pig data into four groups and, on one separated group, ResNet had the highest prediction accuracy (both PCC and MSE). Transfer learning was adopted and capable of enhancing the performance of both convolutional neural network and ResNet. Taken together, our findings indicate that ResNet could improve GS prediction accuracy, affected potentially by factors such as the genetic architecture of complex traits, data volume, and heterogeneity.

The potential association between metabolic disorders and pulmonary tuberculosis: a Mendelian randomization study.

BACKGROUND: Metabolic disorders (MetDs) have been demonstrated to be closely linked to numerous diseases. However, the precise association between MetDs and pulmonary tuberculosis (PTB) remains poorly understood. METHOD: Summary statistics for exposure and outcomes from genome-wide association studies (GWASs) for exposures and outcomes were obtained from the BioBank Japan Project (BBJ) Gene-exposure dataset. The 14 clinical factors were categorized into three groups: metabolic laboratory markers, blood pressure, and the MetS diagnostic factors. The causal relationship between metabolic factors and PTB were analyzed using two-sample Mendelian Randomization (MR). Additionally, the direct effects on the risk of PTB were investigated through multivariable MR. The primary method employed was the inverse variance-weighted (IVW) model. The sensitivity of this MR analysis was evaluated using MR-Egger regression and the MR-PRESSO global test. RESULTS: According to the two-sample MR, HDL-C, HbA1c, TP, and DM were positively correlated with the incidence of active TB. According to the multivariable MR, HDL-C (IVW: OR 2.798, 95% CI 1.484-5.274, P = 0.001), LDL (IVW: OR 4.027, 95% CI 1.140-14.219, P = 0.03) and TG (IVW: OR 2.548, 95% CI 1.269-5.115, P = 0.009) were positively correlated with the occurrence of PTB. TC (OR 0.131, 95% CI 0.028-0.607, P = 0.009) was negatively correlated with the occurrence of PTB. We selected BMI, DM, HDL-C, SBP, and TG as the diagnostic factors for metabolic syndrome. DM (IVW, OR 1.219, 95% CI 1.040-1.429 P = 0.014) and HDL-C (IVW, OR 1.380, 95% CI 1.035-1.841, P = 0.028) were directly correlated with the occurrence of PTB. CONCLUSIONS: This MR study demonstrated that metabolic disorders, mainly hyperglycemia, and dyslipidemia, are associated with the incidence of active pulmonary tuberculosis.

IAIH-PG consensus for histological criteria of AIH: Multicentre validation with focus on chronic liver diseases in China.

BACKGROUND AND AIMS: The International AIH Pathology Group (IAIH-PG) put forward the new histological criteria of autoimmune hepatitis (AIH) in 2022, which have not undergone adequate verification. In this study, we verified the applicability of the new histological criteria in the population of Chinese patients with chronic liver disease, comparing it with the simplified criteria. METHODS: The gold standard for diagnosis in all patients was based on histological findings, combined with clinical manifestations and laboratory tests and determined after a follow-up period of at least 3 years. A total of 640 patients with various chronic liver diseases from multiple centres underwent scoring using the new histological criteria and the simplified criteria, comparing their diagnostic performance. RESULTS: In this study, the new histological criteria showed a sensitivity of 73.6% and 100% for likely and possible AIH, with specificities of 100% and 69.0% respectively. The coincidence rates of possible AIH for the new histological criteria, simplified histological criteria and simplified score were 81.7%, 72.8% and 69.7% respectively. For likely AIH, the rates were 89.2%, 75.9% and 65.6% respectively. Based on the new histological criteria, all patients with AIH were correctly diagnosed. Specifically, 73.6% were diagnosed with likely AIH and 26.4% were possible AIH. Additionally, the simplified histological criteria achieved a diagnosis rate of 98.6% for AIH, while the simplified score could only diagnose 53.8% of AIH. CONCLUSIONS: Compared with the simplified score and simplified histological criteria, the sensitivity and specificity of the new histological criteria for AIH were significantly improved. The results indicate that the new histological criteria exhibit high sensitivity and specificity for diagnosing AIH in China.

Expression of Fascin-1 and its diagnostic value in liver cancer.

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.

CircNSD1 promotes cardiac fibrosis through targeting the miR-429-3p/SULF1/Wnt/ß-catenin signaling pathway.

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

Effects of fructooligosaccharides and Saccharomyces boulardii on the compositional structure and metabolism of gut microbiota in students.

Fructooligosaccharides (FOS) are a common prebiotic widely used in functional foods. Meanwhile, Saccharomyces boulardii is a fungal probiotic frequenly used in the clinical treatment of diarrhea. Compared with single use, the combination of prebiotics and probiotics as symbiotics may be more effective in regulating gut microbiota as recently reported in the literature. The present study aimed to investigate the effects of FOS, S. boulardii and their combination on the structure and metabolism of the gut microbiota in healthy primary and secondary school students using an in vitro fermentation model. The results indicated that S. boulardii alone could not effectively regulate the community structure and metabolism of the microbiota. However, both FOS and the combination of FOS and S. boulardii could effectively regulate the microbiota, significantly inhibiting the growth of Escherichia-Shigella and Bacteroides, and controlling the production of the gases including H2S and NH3. In addition, both FOS and the combination could significantly promote the growth of Bifidobacteria and Lactobacillus, lower environmental pH, and enhance several physiological functions related to synthesis and metabolism. Nevertheless, the combination had more unique benefits as it promoted the growth of Lactobacillus, significantly increased CO2 production and enhanced the functional pathways of carbon metabolism and pyruvic acid metabolism. These findings provide guidance for clinical application and a theoretical basis for the development of synbiotic preparations.

Precirrhotic Primary Biliary Cholangitis with Portal Hypertension: Bile Duct Injury Correlate.

Background/Aims: : The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: : This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: : Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: : Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Leonurus japonicus Houtt. modulates neuronal apoptosis in intracerebral hemorrhage: Insights from network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People's Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear. AIMS OF THE STUDY: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH. MATERIALS AND METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms. RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo's potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression. CONCLUSION: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.

Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a prevalent cause of low back pain and a leading contributor to disability. IVDD progression involves pathological shifts marked by low-grade inflammation, extracellular matrix remodeling, and metabolic disruptions characterized by heightened glycolytic pathways, mitochondrial dysfunction, and cellular senescence. Extensive posttranslational modifications of proteins within nucleus pulposus cells and chondrocytes play crucial roles in reshaping the intervertebral disc phenotype and orchestrating metabolism and inflammation in diverse contexts. This review focuses on the pivotal roles of phosphorylation, ubiquitination, acetylation, glycosylation, methylation, and lactylation in IVDD pathogenesis. It integrates the latest insights into various posttranslational modification-mediated metabolic and inflammatory signaling networks, laying the groundwork for targeted proteomics and metabolomics for IVDD treatment. The discussion also highlights unexplored territories, emphasizing the need for future research, particularly in understanding the role of lactylation in intervertebral disc health, an area currently shrouded in mystery.

Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal tract. Glucocorticoids remain the most common treatment method. However, disease relapse and glucocorticoid dependence remain notable problems. To date, few studies have illuminated the prognosis of EGE and risk factors for disease relapse. AIM: To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term follow-up. METHODS: This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and 2022. Clinical records were collected and analyzed. Kaplan-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival (RFS). RESULTS: EGE showed a median onset age of 38 years and a slight female predominance (56.4%). The main clinical symptoms were abdominal pain (89.1%), diarrhea (61.8%), nausea (52.7%), distension (49.1%) and vomiting (47.3%). Forty-three (78.2%) patients received glucocorticoid treatment, and compared with patients without glucocorticoid treatments, they were more likely to have elevated serum immunoglobin E (IgE) (86.8% vs 50.0%, P = 0.022) and descending duodenal involvement (62.8% vs 27.3%, P = 0.046) at diagnosis. With a median follow-up of 67 mo, all patients survived, and 56.4% had at least one relapse. Six variables at baseline might have been associated with the overall RFS rate, including age at diagnosis < 40 years [hazard ratio (HR) 2.0408, 95% confidence interval (CI): 1.0082-4.1312, P = 0.044], body mass index (BMI) > 24 kg/m2 (HR 0.3922, 95%CI: 0.1916-0.8027, P = 0.014), disease duration from symptom onset to diagnosis > 3.5 mo (HR 2.4725, 95%CI: 1.220-5.0110, P = 0.011), vomiting (HR 3.1259, 95%CI: 1.5246-6.4093, P = 0.001), total serum IgE > 300 KU/L at diagnosis (HR 0.2773, 95%CI: 0.1204-0.6384, P = 0.022) and glucocorticoid treatment (HR 6.1434, 95%CI: 2.8446-13.2676, P = 0.003). CONCLUSION: In patients with EGE, younger onset age, longer disease course, vomiting and glucocorticoid treatment were risk factors for disease relapse, whereas higher BMI and total IgE level at baseline were protective.

The China Hypertrophic Cardiomyopathy Project (CHCMP): The Rationale and Design of a Multicenter, Prospective, Registry Cohort Study.

Hypertrophic cardiomyopathy (HCM) is associated with adverse outcomes, such as heart failure, arrhythmia, and mortality. Sudden cardiac death (SCD) is a common cause of death in HCM patients, and identification of patients at a high risk of SCD is crucial in clinical practice. The China Hypertrophic Cardiomyopathy Project is a hospital-based, multicenter, prospective, registry cohort study of HCM patients, covering a total of 3000 participants and with a 5-year follow-up plan. A large number of demographic characteristics and clinical data will be fully collected to identify prognostic factors in Chinese HCM patients. Furthermore, the main purpose of this study is to integrate demographic and clinical characteristics to establish new 5-year SCD risk predictive equations for Chinese HCM patients by the use of machine learning technologies. The project has crucial clinical significance for risk stratification and determination of HCM patients with high risk of adverse outcomes. CLINICAL TRIALS REGISTRATION: ChiCTR2300070909.

Triangular pulley traction facilitates endoscopic full-thickness resection of exogenous gastric tumor in the fornix of the stomach.

A 65-year-old woman was diagnosed with an exogenous submucosal tumor located in the fornix of the stomach, on the basis of the endoscopic ultrasound and enhanced CT findings. She refused surgery and referred for EFTR. It is difficult to perform EFTR at the gastric fornix and suture the large surgical defect. Therefore, we created technique of triangular pulley traction combined with pre-closure.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis.

BACKGROUND: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure. METHOD: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods. RESULTS: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors. CONCLUSION: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Breaking the Hoff/Le Bel rule by an electron-compensation strategy: the global energy minimum of NGa4S4.

In tetracoordinate chemistry, there is an attractive scientific problem of how to make the planar configuration more stable than the tetrahedral configuration. For tetracoordinate nitrogen, the abundant studies indicate that the planar tetracoordinate nitrogen (ptN) is far less stable than the tetrahedral tetracoordinate nitrogen (ttN). Herein, we introduced four S atoms to the unstable ptN-NGa4+ and stable ttN-NGa4+ by following an electron-compensation strategy. Surprisingly, ptN-NGa4S4+ is more stable than ttN-NGa4S4+. Thermodynamically, ptN-NGa4S4+ is the global energy minimum, which is 46.7 kcal mol-1 lower in energy than ttN-NGa4S4+. Dynamically, the BOMD simulations indicated that ptN-NGa4S4+ has excellent dynamic stability at 4, 298, 500 and 1000 K, but the ttN-NGa4S4+ is isomerized at 1000 K. Electronically, the HOMO-LUMO gap of ptN-NGa4S4+ (6.91 eV) is much wider than that of ttN-NGa4S4+ (5.25 eV). Moreover, AdNDP analyses showed that the eight 2c-2e Ga-S σ-bonds eliminated the 4s2 lone pair/4s2 lone pair repulsion between the four Ga atoms and provided a strong spatial protection for ptN-NGa4S4+; and that the four 3c-2e Ga-S-Ga π back-bonds could compensate electrons for Ga, weakening the electron-deficiency of Ga. Simultaneously, the double 6σ/2π aromaticity further enhanced the stability of ptN-NGa4S4+. Thus, as the dynamically stable global energy minimum displaying double aromaticity, ptN-NGa4S4+ will be more promising than ttN-NGa4S4+ in gas phase generation.

The impact of visit-to-visit heart rate variability on all-cause mortality in atrial fibrillation.

OBJECTIVE: We aimed to investigate the association between visit-to-visit heart rate variability (VVHRV) and all-cause mortality in patients diagnosed with atrial fibrillation (AF). Previous studies have shown a positive correlation between VVHRV and several adverse outcomes. However, the relationship between VVHRV and the prognosis of AF remains uncertain. METHODS: In our study, we aimed to examine the relationship between VVHRV and mortality rates among 3983 participants with AF, who were part of the AFFIRM study (Atrial Fibrillation Follow-Up Investigation of Rhythm Management). We used the standard deviation of heart rate (HRSD) to measure VVHRV and divided the patients into four groups based on quartiles of HRSD (1st, <5.69; 2nd, 5.69-8.00; 3rd, 8.01-11.01; and 4th, ≥11.02). Our primary endpoint was all-cause death, and we estimated the hazard ratios for mortality using the Cox proportional hazard regressions. RESULTS: Our analysis included 3983 participants from the AFFIRM study and followed for an average of 3.5 years. During this period, 621 participants died from all causes. In multiple-adjustment models, we found that the lowest and highest quartiles of HRSD independently predicted an increased risk of all-cause mortality compared to the other two quartiles, presenting a U-shaped relationship (1st vs 2nd, hazard ratio = 2.28, 95% CI = 1.63-3.20, p < .01; 1st vs. 3rd, hazard ratio = 2.23, 95% CI = 1.60-3.11, p < .01; 4th vs. 2nd, hazard ratio = 1.82, 95% CI = 1.26-2.61, p < .01; and 4th vs. 3rd, hazard ratio = 1.78, 95% CI = 1.25-2.52, p < .01). CONCLUSION: In patients with AF, we found that both lower VVHRV and higher VVHRV increased the risk of all-cause mortality, indicating a U-shaped curve relationship.

Development and validation of a noninvasive prediction model of autoimmune hepatitis in patients with liver diseases.

BACKGROUND AND AIMS: There is no golden standard for the diagnosis of autoimmune hepatitis which still dependent on liver biopsy currently. So, we developed a noninvasive prediction model to help optimize the diagnosis of autoimmune hepatitis. METHODS: From January 2017 to December 2019, 1739 patients who had undergone liver biopsy were seen in the second hospital of Nanjing, of which 128 were here for consultation. Clinical, laboratory, and histologic data were obtained retrospectively. Multivariable logistic regression analysis was employed to create a nomogram model that predicting the risk of autoimmune hepatitis. Internal and external validation was both performed to evaluate the model. RESULTS: A total of 1288 patients with liver biopsy were enrolled (1184 from the second hospital of Nanjing, the remaining 104 from other centers). After the univariate and multivariate logistic regression analysis, nine variables including ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender were selected to establish the noninvasive prediction model. The nomogram model exhibits good prediction in diagnosing autoimmune hepatitis with AUROC of 0.967 (95% CI: 0.776-0.891) in internal validation and 0.835 (95% CI: 0.752-0.919) in external validation. CONCLUSIONS: ALT, IgG, ALP/AST, ALB, ANA, AMA, HBsAg, age, and gender are predictive factors for the diagnosis of autoimmune hepatitis in patients with unexplained liver diseases. The predictive nomogram model built by the nine predictors achieved good prediction for diagnosing autoimmune hepatitis.

l-valine supplementation disturbs vital molecular pathways and induces apoptosis in mouse testes.

The branched-chain amino acids (BCAAs: leucine, isoleucine and valine) are essential for animal growth and metabolic health. However, the effect of valine on male reproduction and its underlying molecular mechanism remain largely unknown. Here, we showed that l-valine supplementation (0.30% or 0.45%, water drinking for 3 weeks) did not change body and testis weights, but significantly altered morphology of sertoli cells and germ cells within seminiferous tubule, and enlarged the space between seminiferous tubules within mouse testis. l-valine treatment (0.45%) increased significantly the Caspase3/9 mRNA levels and CASPASE9 protein levels, therefore induced apoptosis of mouse testis. Moreover, gene expression levels related to autophagy (Atg5 and Lamb3), DNA 5 mC methylation (Dnmt1, Dnmt3a, Tet2 and Tet3), RNA m6A methylation (Mettl14, Alkbh5 and Fto), and m6A methylation binding proteins (Ythdf1/2/3 and Igf2bp1/2) were significantly reduced. Protein abundances of ALKBH5, FTO and YTHDF3 were also significantly reduced, but not for ATG5 and TET2. Testis transcriptome sequencing detected 537 differentially expressed genes (DEGs, 26 up-regulated and 511 down-regulated), involved in multiple important signaling pathways. RT-qPCR validated 8 of 9 DEGs (Cd36, Scd1, Insl3, Anxa5, Lcn2, Hsd17b3, Cyp11a1, Cyp17a1 and Agt) to be decreased significantly, consistent with RNA-seq results. Taken together, l-valine treatment could disturb multiple signaling pathways (autophagy and RNA methylation etc.), and induce apoptosis to destroy the tissue structure of mouse testis.