Clinical profiling of TPOAb and TGAb in patients with thyrotrophin receptor antibody-negative thyroid eye disease: A single-center observational study in China

BackgroundThyrotrophin receptor antibody (TRAb)-negative thyroid eye disease (TED) constitutes a clinically significant subset of TED, yet its features remain inadequately characterized. This study characterizes the clinical features of TRAb-negative TED patients.MethodsIn this cross-sectional study, conducted at a Chinese tertiary hospital, 86 TRAb-negative TED patients underwent comprehensive ocular examinations and thyroid function tests. Clinical characteristics were systematically analyzed.ResultsOf the 86 patients (mean age 45.24 ± 10.78 years; 53.5% female), 86.0% (n=74) exhibited bilateral ocular involvement. The primary manifestations included proptosis, eyelid edema, and eyelid retraction. The TPOAb (-)/TGAb (+) subgroup demonstrated significantly higher frequencies of eyelid erythema and lagophthalmos, along with severe NOSPECS grading, reduced visual acuity, elevated orbital pressure, and marked soft tissue involvement (all p<0.05). TPOAb-positive patients had significantly greater proptosis (p<0.05), while TGAb-positive patients showed an increased incidence of eyelid erythema (p<0.05). TGAb was identified as an independent risk factor for eyelid erythema (p<0.01).ROC analysis for TGAb predicting eyelid erythema yielded an AUC of 0.851 (sensitivity 0.778, specificity 0.831) at 3.980 IU/mL.ConclusionTRAb-negative TED displays distinct clinical features. TPOAb and TGAb levels are associated with specific manifestations, highlighting their potential value in the assessment and management of TRAb-negative TED

Identification and validation of glycolysis-related diagnostic signatures in diabetic nephropathy: a study based on integrative machine learning and single-cell sequence

BackgroundDiabetic nephropathy (DN) is a complication of systemic microvascular disease in diabetes mellitus. Abnormal glycolysis has emerged as a potential factor for chronic renal dysfunction in DN. The current lack of reliable predictive biomarkers hinders early diagnosis and personalized therapy.MethodsTranscriptomic profiles of DN samples and controls were extracted from GEO databases. Differentially expressed genes (DEGs) and their functional enrichments were identified. Glycolysis-related genes (GRGs) were selected by combining DEGs, weighted gene co-expression network, and glycolysis candidate genes. We established a diagnostic signature termed GScore via integrative machine learning framework. The diagnostic efficacy was evaluated by decision curve and calibration curve. Single-cell RNA sequence data was used to identify cell subtypes and interactive signals. The cMAP database was used to find potential therapeutic agents targeting GScore for DN. The expression levels of diagnostic signatures were verified in vitro.ResultsThrough the 108 combinations of machine learning algorithms, we selected 12 diagnostic signatures, including CD163, CYBB, ELF3, FCN1, PROM1, GPR65, LCN2, LTF, S100A4, SOX4, TGFB1 and TNFAIP8. Based on them, an integrative model named GScore was established for predicting DN onset and stratifying clinical risk. We observed distinct biological characteristics and immunological microenvironment states between the high-risk and low-risk groups. GScore was significantly associated with neutrophils and non-classical monocytes. Potential agents including esmolol, estradiol, ganciclovir, and felbamate, targeting the 12 diagnostic signatures were identified. In vitro, ELF3, LCN2 and CD163 were induced in high glucose-induced HK-2 cell lines.ConclusionAn integrative machine learning frame established a novel diagnostic signature using glycolysis-related genes. This study provides a new direction for the early diagnosis and treatment of DN

Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) α1 in mice fed high-fat diet

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Scope: Enhancing the formation and function of brown adipose tissue (BAT) increases thermogenesis and hence reduces obesity. Thus, we investigate the effects of resveratrol (Resv) on brown adipocyte formation and function in mouse interscapular BAT (iBAT). Methods and results: CD1 mice and stromal vascular cells (SVCs) isolated from iBAT were treated with Resv. Expression of brown adipogenic and thermogenic markers, and involvement of AMP-activated protein kinase (AMPK)α1 were assessed. In vivo, Resv-enhanced expression of brown adipogenic markers, PR domain-containing 16 (PRDM16) and thermogenic genes, uncoupling protein 1 (UCP1) and cytochrome C in iBAT, along with smaller lipid droplets, elevated AMPKα activity and increased oxygen consumption. Meanwhile, Resv promoted expression of PRDM16, UCP1, PGC1α, cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iBAT SVCs, suggesting that Resv enhanced brown adipocyte formation and function in vitro. In addition, Resv stimulated AMPKα and oxygen consumption in differentiated iBAT SVCs. However, the promotional effects of Resv were diminished by AMPK inhibition or AMPKα1 knockout, implying the involvement of AMPKα1 in this process. Conclusion: Resv enhanced brown adipocyte formation and thermogenic function in mouse iBAT by promoting the expression of brown adipogenic markers via activating AMPKα1, which contributed to the anti-obesity effects of Resv

Polymorphisms of Glutathione S-transferases Omega-1 among ethnic populations in China

<p>Abstract</p> <p>Background</p> <p>Glutathione S-transferases (GSTs) is a genetic factor for many diseases and exhibits great diversities among various populations. We assessed association of the genotypes of Glutathione S-transferases Omega-1 (GSTO1) A140D with ethnicity in China.</p> <p>Results</p> <p>Peripheral blood samples were obtained from 1314 individuals from 14 ethnic groups. Polymorphisms of GSTO1 A140D were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was employed to adjustment for regional factor. The frequency of GSTO1 140A allele was 15.49% in the total 14 ethnic populations. Compared to Han ethnic group, two ethnic populations were more likely to have AA or CA genotype [odds ratio (OR): 1.77, 95% confidence interval (95% CI): 1.05–2.98 for Uygur and OR: 1.78, 95% CI: 1.18–2.69 for Hui]. However, there were no statistically significant differences across 14 ethnic groups when region factor was adjusted. In Han ethnicity, region was significantly associated with AA or CA genotype. Han individuals who resided in North-west of China were more likely to have these genotypes than those in South of China (OR: 1.63, 95% CI: 1.21–2.20).</p> <p>Conclusion</p> <p>The prevalence of the GSTO1 140A varied significantly among different regional populations in China, which showed that geography played a more important role in the population differentiation for this allele than the ethnicity/race.</p

Conflicts in top management teams and team/firm outcomes

PurposeThe purpose of this paper is to examine how different conflict‐handling approaches moderate the relationship between conflicts and TMT as well as firm performance by adopting the Thomas terminology.Design/methodology/approachCEOs, TMT members, and lower‐level employees of 200 firms in the telecommunication industry in Mainland China were surveyed. Survey data collected from 123 CEOs, 442 TMT members, and 894 employees and archival data of firm performance were matched for hierarchical regression modeling (HRM) analyses.FindingsResults show relationship conflict reduces team cohesiveness and both relationship and task conflicts are negatively related to firm performance. With relationship conflict, the results show using compromising approach could help reduce its negative effects on TMT cohesiveness and firm performance; but avoiding either type of conflict will undermine both team and firm outcomes. Accommodating approach does not have significant moderating effect on conflict‐outcome relationships.Research limitations/implicationsThe study reveals some interesting insights, but it does not include any contextual variables such as firm culture or team norms or climate which are shown to relate to both conflict types and conflict management approaches.Originality/valueBy examining the interplay between conflict types and conflict management approaches, the paper offers interesting insights into the connection between nature of conflicts, conflict management, employee‐rated TMT effectiveness, and objective firm performance.</jats:sec

Evaluation of bi-directional causal association between obstructive sleep apnoea syndrome and diabetic microangiopathy: a Mendelian randomization study

BackgroundThe relationship between obstructive sleep apnea syndrome (OSAS) and diabetic microangiopathy remains controversial.ObjectiveThis study aimed to use bidirectional two-sample Mendelian Randomization (MR) to assess the causal relationship between OSAS and diabetic microangiopathy.MethodsFirst, we used the Linkage Disequilibrium Score Regression(LDSC) analysis to assess the genetic correlation. Then, the bidirectional two-sample MR study was conducted in two stages: OSAS and lung function-related indicators (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)) were investigated as exposures, with diabetic microangiopathy as the outcome in the first stage, and genetic tools were used as proxy variables for OSAS and lung function-related measures in the second step. Genome-wide association study data came from the open GWAS database. We used Inverse-Variance Weighted (IVW), MR-Egger regression, Weighted median, Simple mode, and Weighted mode for effect estimation and pleiotropy testing. We also performed sensitivity analyses to test the robustness of the results. Furthermore, we performed multivariate and mediation MR analyses.ResultsIn the LDSC analysis, We found a genetic correlation between OSAS, FVC, FEV 1, and diabetic microangiopathy. In the MR analysis, based on IVW analysis, genetically predicted OSAS was positively correlated with the incidence of diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). In the subgroup analysis of DR, there was a significant causal relationship between OSAS and background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR). The reverse MR did not show a correlation between the incidence of diabetic microangiopathy and OSAS. Reduced FVC had a potential causal relationship with increased incidence of DR and PDR. Reduced FEV1 had a potential causal relationship with the increased incidence of BDR, PDR, and DKD. Multivariate MR analysis showed that the association between OSAS and diabetic microangiopathy remained significant after adjusting for confounding factors. However, we did not find the significant mediating factors.ConclusionOur results suggest that OSAS may be a cause of the development of diabetic microangiopathy, and OSAS may also be associated with a high risk of diabetic microangiopathy, providing a reference for a better understanding of the prevention of diabetic microangiopathy

Drag Reduction and Efficiency Enhancement in Wide-Range Electric Submersible Centrifugal Pumps via Bio-Inspired Non-Smooth Surfaces: A Combined Numerical and Experimental Study

Wide-range electric submersible centrifugal pumps (ESPs) are critical for offshore oilfields but suffer from narrow high-efficiency ranges and frictional losses under dynamic reservoir conditions. This study introduces bio-inspired dimple-type non-smooth surfaces on impeller blades to enhance hydraulic performance. A combined numerical-experimental approach was employed: a 3D CFD model with the k-&omega; turbulence model analyzed oil&ndash;water flow (1:9 ratio) to identify optimal dimple placement, while parametric studies tested diameters (0.6&ndash;1.2 mm). Experimental validation used 3D-printed prototypes. Results revealed that dimples on the pressure surface trailing edge reduced boundary layer separation, achieving a 12.98% head gain and 8.55% efficiency improvement at 150 m3/d in simulations, with experimental tests showing an 11.5% head increase and 4.6% efficiency gain at 130 m3/d. The optimal dimple diameter (0.9 mm, 2% of blade chord) balanced performance and manufacturability, demonstrating that bio-inspired surfaces improve ESP efficiency. This work provides practical guidelines for deploying drag reduction technologies in petroleum engineering, with a future focus on wear resistance in abrasive flows