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The metabolism of dairy cows with inactive ovaries differs from that of healthy dairy cows. However, the molecular mechanisms underpinning these physiological and metabolic changes remain unclear. The purpose of this study was to investigate follicular fluid metabolite changes in dairy cows with inactive ovaries. Untargeted metabolomics technology and multivariate statistical analysis were used to screen differential metabolites in follicular fluid samples between inactive ovaries and estrus cows at 45-60 d postpartum. Fourteen differential metabolites were identified, consisting of amino acids, lipids, sugars, and nucleotides. When compared with healthy animal samples, eight follicular fluid metabolites were significantly increased, and six metabolites were significantly decreased in dairy cows with inactive ovaries. Metabolic pathway analyses indicated that differential metabolites were primarily involved in glycerol phospholipid metabolism, arachidonic acid metabolism, valine, leucine and isoleucine biosynthesis, and phenylalanine metabolism. These metabolites and their enrichment pathways indicate that the enhancement of lipid metabolism and the weakening of carbohydrate production of amino acids in dairy cows with impaired follicular development. Overall, these data provide a better understanding of the changes that could affect follicular development during the postpartum period and lay the ground for further investigations.Brain metastasis (BM) is a typical type of metastasis in renal cell carcinoma (RCC) patients. The early detection of BM is likely a crucial step for RCC patients to receive appropriate treatment and prolong their overall survival. The aim of this study was to identify the independent predictors of BM and construct a nomogram to predict the risk of BM. Demographic and clinicopathological data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database for RCC patients between 2010 and 2015. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors, and then, a visual nomogram was constructed. Multiple parameters were used to evaluate the discrimination and clinical value. We finally included 42577 RCC patients. Multivariate logistic regression analysis showed that histological type, tumor size, bone metastatic status, and lung metastatic status were independent BM-associated risk factors for RCC. We developed a nomogram to predict the risk of BM in patients with RCC, which showed favorable calibration with a C-index of 0.924 (0.903-0.945) in the training cohort and 0.911 (0.871-0.952) in the validation cohort. The calibration curves and decision curve analysis (DCA) also demonstrated the reliability and accuracy of the clinical prediction model. The nomogram was shown to be a practical, precise, and personalized clinical tool for identifying the RCC patients with a high risk of BM, which not only will contribute to the more reasonable allocation of medical resources but will also enable a further improvements in the prognosis and quality of life of RCC patients.Copper nanoparticles (Cu-Nps) are one of the promising materials for the advancement of nanoscience and technology. In this work, we synthesized telmisartan copper nanoparticles and 2-pyrimidinamines via Biginelli reaction using telmisartan copper nanoparticles (Cu-Nps) as a reusable catalyst. The synthesis of 2-pyrimidinamine derivatives (1a-c) was achieved in water and under solvent-free condition (Green chemistry approach). Synthesis of 2-pyrimidinamine with telmisartan copper nanoparticle (Cu-Nps-Pyr) unexpected product was also isolated from synthesis of 2-pyrimidinamine preparation. Antioxidant and cytotoxic activities were carried out both in 2-pyrimidinamine (1a-1c) and 2-pyrimidinamine with telmisartan copper nanoparticles (Cu-Nps-Pyr). The synthesized 2-pyrimidinamine derivatives (1a-c) were characterized from FT-IR, 1H and 13C NMR spectroscopy, mass and elemental analyses. The synthesized telmisartan copper nanoparticles (Cu-Nps) were characterized from UV spectroscopy, XRD, SEM, EDX, AFM (atomic force microscopy), profile, waviness, and roughness analyses. Antioxidant activity was screened based on ABTS·+ radical scavenging and linoleic acid peroxidation performance. Cu-Nps-Pyr-1b showed substantial antioxidant (97.2%) activity against ABTS·+ assay and 91.2% activity against AAPH assays compared with Trolox. Cytotoxicity was evaluated using HepG2, HeLa, and MCF-7 cell lines, the Cu-Nps-Pyr-1a is high in toxicities (GI50 = 0.01 μm) against the HeLa cancel cell line compared with doxorubicin. The developed copper NPs with 2-pyrimidinamine (Cu-Nps-Pyr) could provide promising advances as antioxidant activities; this nanocomposition could be considered an anticancer treatment in future investigations.Gastric cancer (GC) is associated with high incidence and mortality rates worldwide. Differentially expressed gene (DEG) analysis and weighted gene coexpression network analysis (WGCNA) are important bioinformatic methods for screening core genes. In our study, DEG analysis and WGCNA were combined to screen the hub genes, and pathway enrichment analyses were performed on the DEGs. SBNO2 was identified as the hub gene based on the intersection between the DEGs and the purple module in WGCNA. The expression and prognostic value of SBNO2 were verified in UALCAN, GEPIA2, Human Cancer Metastasis Database, Kaplan-Meier plotter, and TIMER. We identified 1974 DEGs, and 28 modules were uncovered via WGCNA. The purple module was identified as the hub module in WGCNA. SBNO2 was identified as the hub gene, which was upregulated in tumour tissues. find more Moreover, patients with GC and higher SBNO2 expression had worse prognoses. In addition, SBNO2 was suggested to play an important role in immune cell infiltration. In summary, based on DEGs and key modules related to GC, we identified SBNO2 as a hub gene, thereby offering novel insights into the development and treatment of GC.Wilms' tumor (WT) is a common embryonal tumor, and nephrogenic rests play a critical role in WT development. The transforming growth factor β (TGF-β) signaling pathway is fundamental to embryo development and cell growth and proliferation. Moreover, TGF-β contributes to WT development, but the mechanisms of disease pathogenicity are unknown. This study investigated whether the TGF-β signaling pathway was involved in WT and whether blocking TβRI receptor inhibited WT growth, proliferation, and invasion. A total of 60 WT patients with clinical data and surgical specimens were evaluated. Immunohistochemistry (IHC) was used to detect the expression of TGF-β1 and P-smad2/3. In vitro, the proliferation, migration, apoptosis, and epithelial-mesenchymal transition (EMT) protein expression were analyzed using the CCK8 assay, wound healing assay, transwell assay, flow cytometry, and western blot, respectively. In vivo, tumor morphology, tumor size, toxicity, and EMT protein expression were analyzed in tumor-bearing mice treated with a TβRI kinase inhibitor or PBS.
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