Renal and Vascular Mechanisms of Thiazolidinedione-Induced Fluid Retention

Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor subtype γ (PPARγ) activators that are clinically used as an insulin sensitizer for glycemic control in patients with type 2 diabetes. Additionally, TZDs exhibit novel anti-inflammatory, antioxidant, and antiproliferative properties, indicating therapeutic potential for a wide variety of diseases associated with diabetes and other conditions. The clinical applications of TZDs are limited by the common major side effect of fluid retention. A better understanding of the molecular mechanism of TZD-induced fluid retention is essential for the development of novel therapies with improved safety profiles. An important breakthrough in the field is the finding that the renal collecting duct is a major site for increased fluid reabsorption in response to rosiglitazone or pioglitazone. New evidence also indicates that increased vascular permeability in adipose tissues may contribute to edema formation and body weight gain. Future research should therefore be directed at achieving a better understanding of the detailed mechanisms of TZD-induced increases in renal sodium transport and in vascular permeability

External modulation method for generating accurate linear optical FMCW

Frequency modulation continuous wave (FMCW) lasers are key components in modern optical imaging. However, current intracavity modulation lasers do not exhibit low-frequency jitter rate and high linearity due to the inherent relaxation oscillations. Although this may be compensated in a direct modulation laser diode using an optoelectronic feedback loop, the available sweep speed is moderately small. In this letter, a special external modulation method is developed to improve the performance of FMCW. Since only the first sideband optical field is used during the entire generation process, phase noise is kept to a minimum and is also independent of the sweep speed. We demonstrate that the linearity and jitter rates do not deteriorate appreciably when the sweep speed is changed over three orders of magnitude, even up to the highest sweep speed of 2.5 GHz/ μs

SSC-RS: Elevate LiDAR Semantic Scene Completion with Representation Separation and BEV Fusion

Semantic scene completion (SSC) jointly predicts the semantics and geometry of the entire 3D scene, which plays an essential role in 3D scene understanding for autonomous driving systems. SSC has achieved rapid progress with the help of semantic context in segmentation. However, how to effectively exploit the relationships between the semantic context in semantic segmentation and geometric structure in scene completion remains under exploration. In this paper, we propose to solve outdoor SSC from the perspective of representation separation and BEV fusion. Specifically, we present the network, named SSC-RS, which uses separate branches with deep supervision to explicitly disentangle the learning procedure of the semantic and geometric representations. And a BEV fusion network equipped with the proposed Adaptive Representation Fusion (ARF) module is presented to aggregate the multi-scale features effectively and efficiently. Due to the low computational burden and powerful representation ability, our model has good generality while running in real-time. Extensive experiments on SemanticKITTI demonstrate our SSC-RS achieves state-of-the-art performance.Comment: 8 pages, 5 figures, IROS202

PPAR γ

Evidence had shown the detrimental effect of prostaglandin (PG) E2 in diabetic nephropathy (DN) of STZ-induced type-1 diabetes but its role in the development of DN of type-2 diabetes remains uncertain. The present study was undertaken to investigate the regulation of PGE2 synthetic pathway and the interaction between peroxisome proliferator-activated receptor (PPAR)γ and PGE2 synthesis in the kidneys of db/db mice. Strikingly, urinary PGE2 was remarkably elevated in db/db mice paralleled with the increased protein expressions of COX-2 and mPGES-1. In contrast, the protein expressions of COX-1, mPGES-2, cPGES, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were not altered. Following 1-week rosiglitazone (Rosi) therapy, urinary PGE2, but not other prostanoids, was reduced by 57% in parallel with significant reduction of mPGES-1 protein and EP4 mRNA expressions. By immunohistochemistry, mPGES-1 was significantly induced in the glomeruli of db/db mice, which was almost entirely abolished by Rosi. In line with the reduction of glomerular mPGES-1, the glomerular injury score showed a tendency of improvement after 1 week of Rosi therapy. Collectively, the present study demonstrated an inhibitory effect of PPARγ activation on renal mPGES-1/PGE2/EP4 pathway in type-2 diabetes and suggested that mPGES-1 may potentially serve as a therapeutic target for treating type-2 diabetes-associated DN

Augmentations in Hypergraph Contrastive Learning: Fabricated and Generative

This paper targets at improving the generalizability of hypergraph neural networks in the low-label regime, through applying the contrastive learning approach from images/graphs (we refer to it as HyperGCL). We focus on the following question: How to construct contrastive views for hypergraphs via augmentations? We provide the solutions in two folds. First, guided by domain knowledge, we fabricate two schemes to augment hyperedges with higher-order relations encoded, and adopt three vertex augmentation strategies from graph-structured data. Second, in search of more effective views in a data-driven manner, we for the first time propose a hypergraph generative model to generate augmented views, and then an end-to-end differentiable pipeline to jointly learn hypergraph augmentations and model parameters. Our technical innovations are reflected in designing both fabricated and generative augmentations of hypergraphs. The experimental findings include: (i) Among fabricated augmentations in HyperGCL, augmenting hyperedges provides the most numerical gains, implying that higher-order information in structures is usually more downstream-relevant; (ii) Generative augmentations do better in preserving higher-order information to further benefit generalizability; (iii) HyperGCL also boosts robustness and fairness in hypergraph representation learning. Codes are released at https://github.com/weitianxin/HyperGCL.Comment: NeurIPS 2022. Supplementary materials are available at https://weitianxin.github.io/files/neurips22_hypergcl_appendix.pd

Localization of cyclophilin A and cyclophilin C mRNA in murine kidney using RT-PCR

Localization of cyclophilin A and cyclophilin C mRNA in murine kidney using RT-PCR. Cyclosporin A (CsA), which is widely used as an immunosuppressant, has a nephrotoxic side effect. The mechanism of this nephrotoxicity is not well understood; however, recent studies suggest that cyclophilin (cyp) is responsible for mediating the immunosuppressive action of CsA through the interaction with the Ca2+ - and calmodulin-dependent phosphatase, calcineurin. While cyp A mRNA is expressed ubiquitously, cyp C mRNA has been shown to be topically expressed, including in the kidney. We examined: (1) distribution of cyp A and cyp C mRNA in microdissected murine nephron segments, using a combination of reverse transcription and polymerase chain reaction (RT-PCR) techniques, and (2) the effect of CsA administration on cyp C mRNA expression in proximal convoluted tubule. Among the nephron segments examined, large signals for cyp C PCR product were detected in proximal convoluted tubule and proximal straight tubule. Our data showed that the distribution of cyp C mRNA was uneven, and it mainly existed in segments that are relatively sensitive to CsA toxicity. In contrast, cyp A mRNA was found to be distributed almost equally along the nephron segments examined. By CsA administration, the signal for cyp C mRNA PCR product was increased. These results suggest that cyp C may play some role in the renal tubular disorder observed in CsA nephrotoxicity

SuperLine3D: Self-supervised Line Segmentation and Description for LiDAR Point Cloud

Poles and building edges are frequently observable objects on urban roads, conveying reliable hints for various computer vision tasks. To repetitively extract them as features and perform association between discrete LiDAR frames for registration, we propose the first learning-based feature segmentation and description model for 3D lines in LiDAR point cloud. To train our model without the time consuming and tedious data labeling process, we first generate synthetic primitives for the basic appearance of target lines, and build an iterative line auto-labeling process to gradually refine line labels on real LiDAR scans. Our segmentation model can extract lines under arbitrary scale perturbations, and we use shared EdgeConv encoder layers to train the two segmentation and descriptor heads jointly. Base on the model, we can build a highly-available global registration module for point cloud registration, in conditions without initial transformation hints. Experiments have demonstrated that our line-based registration method is highly competitive to state-of-the-art point-based approaches. Our code is available at https://github.com/zxrzju/SuperLine3D.git.Comment: 17 pages, ECCV 2022 Accepte

Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice

Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2 on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2 or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2 (control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2 had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2 significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2 showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2 had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities

Total ginsenosides suppress monocrotaline-induced pulmonary hypertension in rats: involvement of nitric oxide and mitogen-activated protein kinase pathways

AbstractBackgroundGinsenosides have been shown to exert beneficial pharmacological effects on the central nervous, cardiovascular, and endocrine systems. We sought to determine whether total ginsenosides (TG) inhibit monocrotaline (MCT)-induced pulmonary hypertension and to elucidate the underlying mechanism.MethodsMCT-intoxicated rats were treated with gradient doses of TG, with or without NG-nitro-l-arginine methyl ester. The levels of molecules involving the regulation of nitric oxide and mitogen-activated protein kinase pathways were determined.ResultsTG ameliorated MCT-induced pulmonary hypertension in a dose-dependent manner, as assessed by the right ventricular systolic pressure, the right ventricular hypertrophy index, and pulmonary arterial remodeling. Furthermore, TG increased the levels of pulmonary nitric oxide, endothelial nitric oxide synthase, and cyclic guanosine monophosphate. Lastly, TG increased mitogen-activated protein kinase phosphatase-1 expression and promoted the dephosphorylation of extracellular signal-regulated protein kinases 1/2, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase 1/2.ConclusionTG attenuates MCT-induced pulmonary hypertension, which may involve in part the regulation of nitric oxide and mitogen-activated protein kinase pathways