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Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P  <  0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P  =  0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A. Show less

In the present work, the 3T3-L preadipocytes were utilized to explore the impact of Obtained results showed the ability of RCE to reduce lipid overloads in hypertrophic adipocytes associated with the down-regulation of mRNA expressions of adipogenic transcription factors such as Show less

Interleukin (IL)-41, a type of cytokine also known as Metrnl, is involved in the pathogenesis of various inflammatory and immune-related diseases. However, its role in Ankylosing Spondylitis (AS), a field yet to be explored, remains a mystery. This study therefore assesses the diagnostic utility of IL-41 in patients with AS and examines the correlations among IL-41 levels, disease activity, and patients' demographic and clinical data. Such novel insights could have significant implications for the diagnosis and management of AS. Eighty-eight patients diagnosed with AS were enrolled from the Rheumatology Unit at Baghdad Teaching Hospital. Participants were categorized into two groups based on disease status: inactive (n = 44) and active (n = 44). Additionally, 44 matched healthy individuals were included as controls. Comprehensive medical histories were obtained, including disease duration, body mass index, sex, and age. Laboratory parameters related to the disease-such as C-reactive protein, human leukocyte antigen (HLA-B27), and rheumatoid factor-were also measured. Serum IL-41 levels were quantified using an enzyme-linked immunosorbent assay. The study revealed a significant difference in levels of IL-41 in patients with AS (17.721±0.705 ng/L) compared to controls (8.495±0.984 ng/L; P = 0.009). The mean serum IL-41 concentration was highest in the active group (23.037±5.268 ng/L), followed by the inactive group (12.411±1.672 ng/L; p = 0.001) and controls (8.495±0.984 ng/L). Serum IL-41 levels demonstrated strong validity for diagnosing AS, with a cutoff value of ≥ 9.35 ng/mL and an area under the curve of 0.991. The sensitivity, specificity, and accuracy were 97.7%, 79.5%, and 92.38%, respectively (p = 0.002). IL-41 is a potential new diagnostic biomarker for AS and associated with patient's disease activity. These insights could potentially transform the way we diagnose and manage AS, offering new avenues for improved patient care and outcomes. Show less

The clinical significance of numerous cardiovascular gene variants remains to be determined. CRISPR/Cas9 allows for the introduction and/or correction of a certain variant in induced pluripotent stem cells (iPSCs). The resulting isogenic iPSC lines can be differentiated into cardiomyocytes and used as a platform to assess the pathogenicity of the variant. In this study, isogenic iPSC lines were generated for a variant of unknown significance found previously in a patient with hypertrophic cardiomyopathy (HCM), p.N515del (c.1543₁₅₄₅delAAC) in Show less

This study aimed to investigate the effects of short-term exposure of Bisphenol A (BPA) on the growth and lactation performance, blood parameters, and milk composition of lactating rabbits and explore its potential molecular mechanisms. Eight lactating rabbits with similar body weight were selected and randomly divided into the experimental group (BPA) and the control group (Ctrl). The group BPA was orally administered 80 mg/kg/day BPA on the 15th day postpartum, while the group Ctrl received a corresponding volume of vehicle. Blood and milk samples were collected after 7 days treatment. The results showed that short-term ingestion of BPA did not obviously alter the body weight, feed intake, or milk yield of the lactating rabbits. ELISA assays indicated that BPA did not significantly affect the plasma levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), creatinine (CRE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), and urea. Utilizing untargeted metabolomics, we first depicted the metabolomic profile of rabbit milk, and identified 277 differential metabolites (DMs), with 141 DMs upregulated (e.g., BPA, and its metabolites including Cetirizine N-oxide) and 136 DMs downregulated (e.g., Oleamide, Tiglic acid, PC O-38:4) in the group BPA. KEGG analysis revealed that the DMs were mainly enriched in pathways comprising fatty acid metabolism, fatty acid degradation, and phosphatidylinositol signaling system, emphasizing the effect of BPA on milk fat metabolism. Hence, we established the BPA-induced MAC-T model, and the results showed that BPA significantly reduced cell viability and impacted lipid synthesis, as evidenced by reduced lipid droplets (BODIPY and Oil Red O staining) and decreased expression of genes related to lipid synthesis (e.g., Show less

Given the high morbidity, mortality, and hereditary risk of cardiovascular diseases (CVDs), their prevention and control have garnered widespread attention and remain central to clinical research. This study aims to assess the feasibility and necessity of haplotyping-based preimplantation genetic testing for the prevention of inherited CVD. A total of 15 preimplantation genetic testing for monogenic defect (PGT-M) cycles were performed in 12 CVD families from January 2016 to July 2022. All couples were affected by CVDs and carried specific causative genes (including MYH7, MYBPC3, TTN, TPM1, LMNA, KCNQ1, FBN1 and LDLR). Among the 10 couples with adequate genetic pedigree information, we utilized the karyomapping assay to obtain single-nucleotide polymorphisms (SNPs) allele data. For the 2 couples who had no reference in their family, we used single sperm next-generation sequencing (NGS) to realize haplotype construction. Linkage analysis was performed to deduce embryonic genotype, and aneuploidy was screened simultaneously. Prenatal diagnostic testing via amniocentesis at 18-22 weeks of gestation was performed to verify the genetic conditions of transferred embryos. In total, 120 embryos were examined in this study, and the results showed that only 26.7% (32/120) were mutation-free and euploid-confirmed embryos. Additionally, for female CVD patients, we convened a multidisciplinary team (MDT) to advise the couple on their fertility concerns and management measures during pregnancy and delivery. With our cooperation, 10 couples successfully obtained healthy babies not carrying the pathogenic mutations. The results of prenatal diagnostics were consistent with the results of PGT-M. Our study demonstrates that PGT-M based on haplotype analysis is reliable and necessary for the prevention of inherited CVDs. It also highlights the important value of multidisciplinary collaboration for CVD prevention and treatment. Inherited cardiovascular diseases (CVDs) present as a huge challenge for modern medical and health systems. Hundreds of genetic variants have been reported to cause CVD and the number of people with the disease is enormous and still on the rise globally. Here we recruited twelve couples suffering from inherited CVD and provided them with effective pre-implantation genetic testing for monogenic defect (PGT-M) strategy to avoid the occurrence of genetic defects in the offspring. Specifically, after embryo biopsy, we utilized karyomapping assay (for 10 couples with a family history) or next-generation sequencing (NGS) (for 2 couples having no reference in their pedigree) to obtain single-nucleotide polymorphisms (SNPs) allele data and then performed linkage analysis to deduce embryonic genotype. A total of 120 embryos from 15 PGT-M cycles were examined and 12 variants in 8 genes linked to inherited CVD were identified. Thirty-two mutation-free and euploid confirmed embryos were considered suitable for embryo transfer. Besides, for female CVD patients, we called up a multidisciplinary team (MDT) advising the couple on their fertility concerns and management measures of pregnancy and delivery. With our cooperation, 10 couples successfully obtain healthy babies not carrying the pathogenic mutations. Our study further validated the reliability of PGT-M utilizing linkage analysis as a means to prevent the transmission of genetic disorders to future generations, and offered valuable insights for multidisciplinary clinical practices on CVD. Show less

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer related deaths globally. Despite advancements in treatment, drug resistance and adverse side effects have spurred the search for novel therapeutic strategies. This study aimed to investigate how the Show less

CETP inhibitors are a class of lipid-lowering drugs in development for treatment of coronary heart disease (CHD). Genetic studies in East Asian ancestry have interpreted the lack of CETP signal with low-density lipoprotein cholesterol (LDL-C) and lack of drug target Mendelian randomization (MR) effect on CHD as evidence that CETP inhibitors might not be effective in East Asian participants. Capitalizing on recent increases in sample size of East Asian genetic studies, we conducted a drug target MR analysis, scaled to a standard deviation increase in high-density lipoprotein cholesterol. Despite finding evidence for possible neutral effects of lower CETP levels on LDL-C, systolic blood pressure and pulse pressure in East Asians (interaction p-values < 1.6 × 10 Show less

Digitalization, as a crucial engine for promoting sustainable development, has created new prospects for enterprise green transformation. Utilizing panel data from enterprises registered in China's resource-based cities from 2010 to 2021, this study innovatively examines the role of digitalization in promoting green transformation across two key performance dimensions. The findings indicate that enterprise digitalization significantly enhances the green innovation performance, while its impact on environmental performance, although positive, is not statistically significant. Overall, enterprise digitalization greatly facilitates green transformation. Moreover, mechanism analysis reveals that enterprise digitalization promotes green transformation through the alleviation of financial mismatch and the increase of external market attention. In addition, heterogeneity analysis shows that the effectiveness of enterprise digitalization in promoting green transformation is significantly different in different opportunist risk scenarios, proving more effective in areas with low-marketization, high-competition industries, and high environmental regulation intensity. In terms of the policy level, the National Big Data Comprehensive Pilot Zone (NBDCPZ) and the Carbon Emission Trading Policy (CETP) played a positive stimulating role in the process of enterprise digitalization affecting green transformation. This paper broadens the scope of research on green transformation, offers new development philosophy for enterprises in resource-based cities, and provides new directions for the synergistic development of digitalization and greenization. Show less

In this study, the pathogenic genes of depression were calculated and analyzed by bioinformatics method, and then the key genes of Shaoyao Gancao Decoction in the treatment of depression were deduced and predicted through the correlation study with the target of Shaoyao Gancao Decoction. Through the production of LPS depression model mice, drug treatment, behavioral test and hippocampal tissue sample detection, it was found that Shaoyao Gancao Decoction can regulate the levels of IL-10, TNF- α, BDNF, SMAD3, FGFR1 and FGFR2 to improve depression, which can provide a theoretical basis for exploring the efficacy of Shaoyao Gancao Decoction in the treatment of depression. Show less

The development of multitargeted therapeutics has evolved as a promising strategy to identify efficient therapeutics for neurological disorders. We report herein new quinolinone hybrids as dual inhibitors of acetylcholinesterase (AChE) and Aβ aggregation that function as multitargeted ligands for Alzheimer's disease. The quinoline hybrids ( Show less

Acquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1R Show less