Explore the vast range of titles available.

The protective role of sodium glucose cotransporter 2 (SGLT2) inhibitors in renal outcomes has been revealed by large cardiovascular outcome trials among patients with type 2 diabetes. However, the effect of SGLT2 inhibitors on lupus nephritis (LN) and its underlying mechanisms remain unknown. We applied empagliflozin treatment to lupus-prone MRL/ mice to explore the renal protective potential of SGLT2 inhibitors. An SGLT2 knockout monoclonal podocyte cell line was generated using the CRISPR/Cas9 system to examine the cellular and molecular mechanisms. In MRL/ mice treated with empagliflozin, the levels of mouse anti-dsDNA IgG-specific antibodies, serum creatinine and proteinuria were markedly decreased. For renal pathology assessment, both the glomerular and tubulointerstitial damages were lessened by administration of empagliflozin. The levels of SGLT2 expression were increased and colocalised with decreased synaptopodin in the renal biopsy samples from patients with LN and MRL/ mice with nephritis. The SGLT2 inhibitor empagliflozin could alleviated podocyte injury by attenuating inflammation and enhanced autophagy by reducing mTORC1 activity. Nine patients with LN treated with SGLT2 inhibitors with more than 2 months of follow-up showed that the use of SGLT2 inhibitors was associated with a significant decrease in proteinuria from 29.6% to 96.3%. Moreover, the estimated glomerular filtration rate (eGFR) was relatively stable during the treatment with SGLT2 inhibitors. This study confirmed the renoprotective effect of SGLT2 inhibitors in lupus mice, providing more evidence for non-immunosuppressive therapies to improve renal function in classic autoimmune kidney diseases such as LN.

The ability for a quadrotor with a slung load to perform agile and accurate maneuvers expands the variety of scenarios where load transportation can be applied and enhances its efficiency. Due to the complexity of the system dynamics, slung-load transportation remains a challenging problem, which also causes trajectory generation a time-consuming task. We propose a framework to efficiently generate aggressive load-swing trajectories. Trajectory generation for the load aims to minimize the fifth order time derivative of the load position which, indirectly, minimizes the quadrotor angular velocity actuation. Aggressive load-swing trajectories are obtained by having the constraints for load cable direction embedded into the trajectory generation via constraints on the load acceleration. The trajectory generation, together with an accurate trajectory tracking controller, allows the aggressive maneuvers to be easily performed on the quadrotor with a slung-load. Simulation and experimental results of three dimensional aggressive maneuvers are presented to validate the proposed trajectory generation methodology, including the quadrotor slung-load traversing a window by tilting the cable, and also going through an environment with obstacles that must avoided.

In order to solve the problem of low accuracy of pedestrian detection of real traffic cameras and high missed detection rate of small target pedestrians, this paper combines autoencoding neural network and AdaBoost to construct a fast pedestrian detection algorithm. Aiming at the problem that a single high-level output feature map has insufficient ability to express pedestrian features and existing methods cannot effectively select appropriate multilevel features, this paper improves the traditional AdaBoost algorithm structure, that is, the sample weight update formula and the strong classifier output formula are reset, and the two-input AdaBoost-DBN classification algorithm is proposed. Moreover, in view of the problem that the fusion video is not smoothly played, this paper considers the motion information of the video object, performs pixel interpolation by motion compensation, and restores the frame rate of the original video by reconstructing the dropped interframe image. Through experimental research, we can see that the algorithm constructed in this paper has a certain effect.

Taurine-upregulated gene 1 (TUG1) has been involved in tumorigenesis of several human cancers, but its precise biological role in bladder cancer remains largely elusive. In this study, we found that TUG1 was upregulated in bladder cancer and the expression of TUG1 was positively and negatively correlated with CCND2 and miR-194-5p, respectively. MiR-194-5p expression was frequently decreased through promoter hypermethylation, while it was epigenetically increased following cisplatin and 5-aza-2′-deoxycytidine (5-Aza-DC) treatment. Furthermore, knockdown of TUG1 attenuated the expression of epigenetic regulator Enhancer of zeste homolog 2 (EZH2), and it alleviated the promoter hypermethylation of miR-194-5p and induced its expression. Increased miR-194-5p expression or decreased TUG1 expression significantly sensitized bladder cancer cells to cisplatin, inhibited the proliferation, and induced apoptosis. Besides, CCND2 was a direct target of miR-194-5p, while miR-194-5p was regulated by TUG1. CCND2 could partially restore the tumor-suppressive effects on cell proliferation and cisplatin resistance following TUG1 silencing. Additionally, TUG1 expression was correlated with clinical stage, lymphatic metastasis, and patient prognosis. In conclusion, TUG1 promotes bladder cancer cell growth and chemoresistance by regulating CCND2 via EZH2-associated silencing of miR-194-5p. Our study may be conducive to elucidating the molecular mechanism of and providing novel therapeutic target and biomarker for bladder cancer.

This study aimed to investigate the association between the weight-adjusted waist index (WWI), a novel obesity metric, and the prevalence of chronic obstructive pulmonary disease (COPD) in a nationally representative sample of U.S. adults, and to compare its predictive utility for COPD against conventional obesity indices. This cross-sectional study utilized data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). COPD diagnosis was based on self-report. The association between WWI and COPD was investigated using multivariable logistic regression models, adjusting for key covariates including age, gender, race/ethnicity, smoking status, hypertension, and diabetes. Restricted cubic splines (RCS) were used to explore potential non-linear relationships. Receiver operating characteristic (ROC) curves were used to assess WWI's predictive performance. All statistical analyses were conducted using R software, accounting for the complex survey design and weighting. This study comprised 3,111 participants, among whom the prevalence of COPD was 8.5%. The findings indicated a significant positive association between WWI and the prevalence of COPD (OR = 1.30, 95% CI: 1.02-1.66). When analyzed by quartiles, a significant positive dose-response relationship was observed (P for trend = 0.031). Furthermore, receiver operating characteristic (ROC) analysis revealed that WWI had significantly better predictive performance for COPD (Area Under the Curve [AUC] = 0.662) than conventional obesity indices. Our findings suggest a significant positive association between WWI and the self-reported prevalence of COPD. WWI shows promise as a simple, non-invasive anthropometric tool that may aid in identifying individuals with higher odds of having COPD in clinical and public health settings.

Ubiquitination is vital for multiple cellular processes via dynamic modulation of proteins related to cell growth, proliferation, and survival. Of the ubiquitination system components, E3 ubiquitin ligases and deubiquitinases have the most prominent roles in modulating tumor metastasis. This review will briefly summarize the observations and underlying mechanisms of multiple E3 ubiquitin ligases and deubiquitinases to regulate tumor metastasis. Further, we will discuss the relationship and importance between ubiquitination components and tumor progression.

Alternative splicing represents a critical posttranscriptional regulation of gene expression, which contributes to the protein complexity and mRNA processing. Defects of alternative splicing including genetic alteration and/or altered expression of both pre-mRNA and trans-acting factors give rise to many cancers. By integrally analyzing clinical data and splicing data from TCGA and SpliceSeq databases, a number of splicing events were found clinically relevant in tumor samples. Alternative splicing of KLK2 (KLK2_51239) was found as a potential inducement of nonsense-mediated mRNA decay and associated with poor survival in prostate cancer. Consensus K-means clustering analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers. By random forest survival algorithm, prognostic prediction signatures with well performances were constructed for 31 cancers by using survival-associated alternative splicing events. Furthermore, an online tool for visualization of Kaplan–Meier plots of splicing events in 31 cancers was explored. Briefly, alternative splicing was found of significant clinical relevance with cancers.

As a DNA receptor, cyclic GMP-AMP synthase (cGAS) plays a crucial role in the immune system by recognizing abnormal DNA in the cytoplasm and activating the stimulator of interferon genes (STING) signaling pathway. This signaling cascade reaction leads to an immune response produced by type I interferon and other immune mediators. Recent advances in research have enhanced our current understanding of the potential role of the cGAS/STING pathway in anticancer therapy; however, in some cases, chronic STING activation may promote tumorigenesis. The present review article discusses the biological mechanisms of the cGAS/STING pathway, its dichotomous role in tumors, and the latest advances with respect to STING agonists and antagonists.

In this paper, we develop a combination of algorithms, including camera motion detector (CMD), deep learning models, class activation mapping (CAM), and periodical feature detector for the purpose of evaluating human gastric motility by detecting the presence of gastric peristalsis and measuring the period of gastric peristalsis. Moreover, we use visual interpretations provided by CAM to improve the sensitivity of the detection results. We evaluate the performance of detecting peristalsis and measuring period by calculating accuracy, F1, and area under curve (AUC) scores. Also, we evaluate the performance of the periodical feature detector using the error rate. We perform extensive experiments on the magnetically controlled capsule endoscope (MCCE) dataset with more than 100,000 frames (100,055 specifically). We have achieved high accuracy (0.8882), F1 (0.8192), and AUC scores (0.9400) for detecting human gastric peristalsis, and low error rate (8.36%) in measuring peristalsis periods from the clinical dataset. The proposed combination of algorithms has demonstrated the feasibility of assisting in the evaluation of human gastric motility.

Renal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.