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Background The relationship between handgrip strength (HGS) and depression in patients undergoing hemodialysis (HD) was unknown. Therefore, we aimed to clarify this association in a cohort of patients. Methods HGS was used as a representative indicator of muscle strength and was measured with a handheld dynamometer. Depressive symptoms were assessed with the self-reported Patient Health Questionnaire-9. A multivariable logistic regression model and restricted cubic spline analysis were used to assess the relationship between HGS and depression. Results The prevalence of depression in our study was 34% in 568 Chinese patients undergoing HD. Compared with patients in the lowest tertiles of absolute and weighted HGS, patients in the highest tertiles of HGS had an approximately 59% lower [odds ratio (OR)=0.41, 95% confidence interval (CI)=0.24–0.68; OR=0.41, 95%CI=(0.24– 0.69)] prevalence of depressive symptoms after multivariate adjustments. Besides, the risk of depression in hemodialysis patients decreased by 33% (OR=0.67, 95%CI=0.53–0.85) and 32% (OR=0.68, 95%CI=0.54–0.85) for each standard deviation increase in absolute HGS and weighted HGS, respectively. The prevalence of depressive symptoms decreased with both increasing absolute HGS and weighted HGS after multivariate adjustments (p for trend<0.05). Furthermore, a linear dose-response relationship was observed between absolute HGS and weighted HGS and the prevalence of depressive symptoms (pnonlinearity>0.05). Conclusions This study suggests that lower handgrip strength, a simple and modifiable parameter, is associated with a higher prevalence of depression in Chinese patients undergoing HD. Considering that depression is often unrecognized or underdiagnosed in HD patients, lowered muscle strength should be an important indicator and incentive for medical staff to screen for depression. [ABSTRACT FROM AUTHOR]

The intelligent maintenance of railway equipment plays a pivotal role in advancing the sustainability of transportation and manufacturing. Railway turnouts, being an essential component of railway infrastructure, often encounter various faults, which present operational challenges. Existing fault diagnosis methods for railway turnouts primarily utilize vectorized monitoring data, interpreted either through vector-based models or distance-based measurements. However, these methods exhibit limited interpretability or are heavily reliant on standard curves, which impairs their performance or restricts their generalizability. To address these limitations, a railway turnouts fault diagnosis method with monitoring signal images and support matrix machine is proposed herein. In addition, a pinball loss-based multiclass support matrix machine (PL-MSMM) is designed to address the noise sensitivity limitations of the multiclass support matrix machine (MSMM). First, the time-series monitoring signals in one dimension are transformed into images in two dimensions. Subsequently, the image-based feature matrix is constructed. Then, the PL-MSMM model is trained using the feature matrix to facilitate the fault diagnosis. The proposed method is evaluated using a real-world operational current dataset, achieving a fault identification accuracy rate of 98.67%. This method outperforms the existing method in terms of accuracy, precision, and F1-score, demonstrating its superiority. [ABSTRACT FROM AUTHOR]

Introduction. The pathophysiology of diabetic nephropathy (DN) is fundamentally dependent on glomerular endothelial cells (GECs), which are a crucial portion of the glomerular filtration barrier. This study aimed to identify biomarker candidates associated with GECs dysfunction in DN by combining microarray and single-cell sequencing dataset analysis. Methods. Microarray dataset GSE30528 was downloaded from the Gene expression omnibus (GEO) database. Key gene sets for diabetic kidney disease (DKD) were selected by using weighted gene co-expression network analysis (WGCNA). Biomarker candidates were then identified using least absolute shrinkage and selection operator (LASSO) logistic regression. The single-cell sequencing data (GSE131882) was used to explore the biological functional differences in glomerular endothelium between the control and DKD groups. The diagnostic efficiency of the selected biomarker was tested in the Receiver operating characteristic (ROC) curve. Moreover, we used the single-sample gene set enrichment analysis (ssGSEA) to compare immune cell infiltration between DKD and control groups. RT-PCR was used to validate the selected gene expression in cultured glomerular endothelial cells under high glucose stimulation. Results. Phosphatase and actin regulator 4 (PHACTR4) was ultimately selected as the key GEC-related biomarker in DKD. Significantly downregulated PHACTR4 mRNA expression was further validated in human glomerular endothelial cells (HGECs) under high glucose stimulation by using RT-PCR. The decreased PHACTR4 was found to be associated with abnormal endothelial proliferation and neo-angiogenesis. Additionally, immune infiltration analysis revealed that PHACTR4 was negatively associated with inflammatory infiltration, especially pro-inflammatory cells including activated CD4 and CD8 T cells, B cells, and Mast cells, indicating PHACTR4 downregulation may exacerbate inflammatory reaction. Conclusion. PHACTR4 is a potential diagnostic marker for DKD and plays an essential role in aberrant glomerular endothelial proliferation and inflammation in DKD. [ABSTRACT FROM AUTHOR]

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment. [ABSTRACT FROM AUTHOR]

Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular disorders. Astragaloside IV (AslV) possesses potent antioxidant properties against oxidative stress through undefined mechanism(s). We sought to investigate whether AsIV protects human umbilical vein endothelial cells (HUVECs) from hydrogen peroxide ([H.sub.2][O.sub.2]) induced oxidative stress focusing on eNOS uncoupling and the NADPH oxidase--ROS--NF-κB pathway. Compared with HUVECs incubated with [H.sub.2][O.sub.2] alone, pretreatment with AsIV significantly increased the viability of HUVECs, which was accompanied with apparent increase in nitric oxide (NO) production and decrease in intracellular superoxide anion production. Furthermore, pretreatment with AsIV increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (B[H.sub.4]) content, decreased Nox4 protein expression (the most abundant Nox isoform in HUVECs), inhibited translocation of NF-κB p65 subunit into nuclear fraction while enhanced the protein expression of IkB-o (the inhibitor of NF-κB p65), reduced the levels of IL-1β, IL-6, and TNF-a in HUVECs medium, and decreased iNOS protein expression. These results suggest that AsIV may protect HUVECs from [H.sub.2][O.sup.2]-induced oxidative stress via inhibiting NADPH oxidase--ROS NF-κB pathway and eNOS uncoupling. Key words: Astragaloside IV, human umbilical vein endothelial cells, hydrogen peroxide, eNOS uncoupling, NF-κB, NADPH oxidase, tetrahydrobiopterin, superoxide anion. Les dommages causes aux cellules endotheliales par les derives reactifs de l'oxygene (ROS) jouent un role essentiel dans la pathogenese des troubles cardiovasculaires. L'astragaloside IV(AsIV) dispose de puissantes proprietes anti-oxydantes contre le stress oxydatif qui sont portees par des mecanismes toujours indetermines. Nous nous sommes employes a etudier si l'AsIV permet de proteger les cellules endotheliales des veines ombilicales humaines (HUVEC) du stress oxydatif provoque par le peroxyde d'hydrogene ([H.sub.2][O.sub.2]) en centrant nos efforts sur le decouplage de l'oxyde nitrique synthase endotheliale (eNOS) et la voie de signalisation NADPH oxydase--ROS--NF-κB. Comparativement a l'incubation avec le [H.sub.2][O.sub.2] seul, le pretraitement des cellules HUVEC avec de l'AsIV a permis d'augmenter nettement leur viabilite, ce qui etait accompagne d'une augmentation apparente de la production d'oxyde nitrique (NO) et d'une diminution de la production d'anions superoxyde dans le milieu intracellulaire. En outre, le pretraitement avec de l'AsIV a permis d'augmenter le ratio dimeres/monomeres de l'eNOS et les taux de tetrahydrobiopterine (B[H.sub.4]) (son cofacteur essentiel), de diminuer l'expression de la proteine Nox4 (l'isoforme des proteines Nox la plus abondante dans les cellules HUVEC) et d'inhiber la translocation de la sous-unite p65 du facteur NF-κB dans la fraction nucleaire. Ces phenomenes etaient accompagnes d'une augmentation de l'expression de la proteine IκB-α (la proteine inhibitrice de la sous-unite p65 du NF-κB) ainsi que d'une diminution des taux d'IL-1β, d'IL-6 et de TNF-α dans le milieu des cellules HUVEC; l'expression de la proteine iNOS etait aussi diminuee. Ces resultats laissent entendre que l'AsIV pourrait proteger les cellules HUVEC du stress oxydatif cause par le [H.sub.2][O.sub.2] par l'intermediaire de l'inhibition de la voie de signalisation NADPH oxydase--ROS NFκB et du decouplage de l'eNOS. [Traduit par la Redaction] Mots-cles : astragaloside IV, cellules endotheliales des veines ombilicales humaines, peroxyde d'hydrogen, decouplage de l'eNOS, NF-κB, NADPH oxydase, tetrahydrobiopterine, anion superoxyde., Introduction It has been demonstrated that oxidative stress plays a pivotal role in the development of the endothelial dysfunction associated with many cardiovascular disease (Hermida and Balligand 2014; Makarenko et [...]