The role of Testis-Specific Protein Y-encoded-Like 2 in kidney injury.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Recent findings suggest that Testis-Specific Protein Y-encoded-Like 2 (TSPYL2) plays a fibrogenic role in diabetes-associated renal injury. However, the role of TSPYL2 in IRI-induced kidney damage is not entirely clear. In this study, we found that the expression of TSPYL2 was upregulated in a mouse model of AKI and in the hypoxia/reoxygenation (H/R) cell model. Knockdown of TSPYL2 attenuated kidney injury after IRI. More specifically, the knockdown of TSPYL2 or aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) alleviated renal IRI-induced mitochondrial dysfunction and oxidative stress in vitro and in vivo. Further investigation showed that TSPYL2 regulated SREBP-2 acetylation by inhibiting SIRT1 and promoting p300 activity, thereby promoting the transcriptional activity of ACMSD. In conclusion, TSPYL2 was identified as a pivotal regulator of IRI-induced kidney damage by activating ACMSD, which may lead to NAD+ content and the damaging response in the kidney.

Novel non-invasive method for urine mapping: Deep-learning-enabled SERS spectroscopy for the rapid differential detection of kidney allograft injury.

The kidney allograft has been under continuous attack from diverse injuries since the very beginning of organ procurement, leading to a gradual decline in function, chronic fibrosis, and allograft loss. It is vital to routinely and precisely monitor the risk of injuries after renal transplantation, which is difficult to achieve because the traditional laboratory tests lack sensitivity and specificity, and graft biopsies are invasive with the risk of many complications and time-consuming. Herein, a novel method for the diagnosis of graft injury is demonstrated, using deep learning-assisted surface-enhanced Raman spectroscopy (SERS) of the urine analysis. Specifically, we developed a hybrid SERS substrate composed of gold and silver with high sensitivity to the urine composition under test, eliminating the need for labels, which makes measurements easy to perform and meanwhile results in extremely abundant and complex Raman vibrational bands. Deep learning algorithms were then developed to improve the interpretation of the SERS spectral fingerprints. The deep learning model was trained with SERS signals of urine samples of recipients with different injury types including delayed graft function (DGF), calcineurin-inhibitor toxicity (CNIT), T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), and BK virus nephropathy (BKVN), which explored the features of these types and achieved the injury differentiation with an overall accuracy of 93.03%. The results highlight the potential of combining label-free SERS spectroscopy with deep learning as a method for liquid biopsy of kidney allograft injuries, which can provide great potential to diagnose and evaluate allograft injuries, and thus extend the life of kidney allografts.

Research on the Model for the Friction Coefficient of Resin-Based Friction Material and Its Experimental Verification.

Resin-based friction materials have been widely used in the friction braking of automobiles and power machinery. Based on experiments for the variation law of friction and wear morphology, a new model for the friction coefficient of resin-based friction materials was proposed, which includes the effects of both the micro convex body on the surface of the friction material and the frictional film generated during the friction process. This quantitative model of friction coefficient materials was established for the modelling of shear strength, compressive strength, shear strength of the frictional film, contact load and wear morphology. The shear strength, compressive strength and wear morphology of the friction material were adjusted by changing the content of basalt fibers and flaky potassium magnesium titanate. Finally, the accuracy of this quantitative model of friction coefficient was verified through experiments on friction samples with different formulations and by changing the frictional contact load. The results show that the predicted friction coefficient of the model is in good agreement with the experimental friction coefficient, the difference between the upper and lower limits of the forecast is only 5.03% and 2.30%, respectively. Meanwhile, the influence of the ratio of shear strength to compressive strength on the friction coefficient is greater than the proportion of wear morphology. The proposed friction model provides a reference value for the study of new resin-based friction materials.

Sanghuangporus vaninii fruit body polysaccharide alleviates hyperglycemia and hyperlipidemia via modulating intestinal microflora in type 2 diabetic mice.

The disease of type 2 diabetes mellitus (T2DM) is principally induced by insufficient insulin secretion and insulin resistance. In the current study, Sanghuangporus vaninii fruit body polysaccharide (SVP) was prepared and structurally characterized. It was shown that the yield of SVP was 1.91%, and SVP mainly contains small molecular weight polysaccharides. Afterward, the hypoglycemic and hypolipidemic effects and the potential mechanism of SVP in T2DM mice were investigated. The results exhibited oral SVP could reverse the body weight loss, high levels of blood glucose, insulin resistance, hyperlipidemia, and inflammation in T2DM mice. Oral SVP increased fecal short-chain fatty acids (SCFAs) concentrations of T2DM mice. Additionally, 16S rRNA sequencing analysis illustrated that SVP can modulate the structure and function of intestinal microflora in T2DM mice, indicating as decreasing the levels of Firmicutes/Bacteroidetes, Flavonifractor, Odoribacter, and increasing the levels of Weissella, Alloprevotella, and Dubosiella. Additionally, the levels of predicted metabolic functions of Citrate cycle, GABAergic synapse, Insulin signaling pathway were increased, and those of Purine metabolism, Taurine and hypotaurine metabolism, and Starch and sucrose metabolism were decreased in intestinal microflora after SVP treatment. These findings demonstrate that SVP could potentially play hypoglycemic and hypolipidemic effects by regulating gut microflora and be a promising nutraceutical for ameliorating T2DM.

Sanghuangporus vaninii mixture ameliorated type 2 diabetes mellitus and altered intestinal microbiota in mice.

Type 2 diabetes mellitus (T2DM) is a chronic disease mainly caused by insufficient insulin secretion and insulin resistance. In addition, T2DM is often accompanied by dysregulation of lipid metabolism and inflammatory response. The effect of oral administration of a Sanghuangporus vaninii mixture (SVM) on T2DM mice was evaluated. The results showed that SVM intervention could change body weight and glucose/lipid metabolism-related indicators. In addition, it can also improve the level of inflammatory factors to play a protective role in the pancreas and the jejunum. 16S rRNA gene sequencing analysis indicated that SVM intervention significantly altered the intestinal microbiota in mice, elevating the relative abundances of Bacteroidetes, Verrucomicrobia, Akkermansia, Alloprevotella, and Blautia, and decreasing the relative abundances of Firmicutes, Lactobacillus, Flavonifractor, and Odoribacter in the feces of diabetic mice, compared with the model group. Moreover, the functional modules of fatty acid degradation, glycerolipid metabolism, purine metabolism, histidine metabolism, folate biosynthesis, GABAergic synapse, etc. were regulated by SVM intervention in T2DM mice. Additionally, integrative correlation analysis revealed that the representative intestinal microbes in response to SVM intervention in diabetic mice were markedly related to glucose/lipid metabolism-related indicators (e.g. blood glucose, insulin resistance, lipid indexes, and inflammatory factors). Hence, these findings suggest that the SVM could modulate the structure, abundance, and function of intestinal microbiota to potentially ameliorate T2DM and its complications (e.g. hyperglycemia, hyperlipidemia, and inflammation) in mice.

Ameliorating Effect on Glycolipid Metabolism of Spirulina Functional Formulation Combination from Traditional Chinese Medicine.

Insulin resistance is the major factor involved in the pathogenesis of type 2 diabetes. Although the oral drug metformin (MH) is widely used to reduce hyperglycemia, it is associated with adverse effects. Therefore, there is an urgent need to search for safe and natural foods that do not cause adverse effects as alternatives to commercial drugs. In this study, the active substances from Spirulina platensis, Grifola frondosa, Panax ginseng, and chromium-rich yeast were used to obtain Spirulina functional formulations (SFFs), and its therapeutic effects on mice with glycolipid metabolism disorder (GLD) were investigated. Results showed that SFFs not only improved glycolipid metabolism and reduced inflammation in mice with GLD but also showed good regenerative effects on the liver, jejunum, and cecum tissues. Moreover, SFFs could inhibit the growth of harmful microbes in the intestine and promote the proliferation of beneficial bacteria, thereby promoting the production of short-chain fatty acids and further regulating GLD. Additionally, SFFs significantly increased the expression of INS, INSR, IRS-1, PI3K, AKT-1, and GLUT-4 genes and significantly decreased that of GSK-3ß in the INS/PI3K/GLUT-4 signaling pathway. Therefore, the findings of this study suggest that SFFs can be further developed as a new class of therapeutic agents against GLD.

Use of contrast-enhanced ultrasound to monitor rabbit renal ischemia-reperfusion injury and correlations between time-intensity curve parameters and renal ICAM-1 expression.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is common in renal transplantation, shock, and nephrolithotomy. OBJECTIVE: To quantitatively assess rabbit renal IRI with contrast-enhanced ultrasound (CEUS) and investigate associations between renal cortical time-intensity curve (TIC) parameters and intracellular adhesion molecule-1 (ICAM-1) expression. METHODS: Eighteen white rabbits were randomly assigned into control and IRI groups (n = 9 each), and CEUS examination was performed 24 h after modeling. TIC parameters including arrival time (AT), time to peak intensity (TTP), changes in peak intensity, area under the curve (AUC), and slope of the ascending TIC, and correlations between these parameters and ICAM-1 expression were evaluated with linear correlation analyses. RESULTS: AT, TTP, and AUC were significantly increased in the IRI group (P < 0.05), and the slope of the ascending TIC was significantly lower than that in the control group (P < 0.05). ICAM-1 content in the renal cortex was significantly increased in the IRI group (P < 0.05). In addition, the slope of the ascending TIC negatively correlated with renal ICAM-1 expression (r = -0.923, P < 0.01), whereas AT and TTP positively correlated with ICAM-1 expression (r = 0.697 and 0.892, both P < 0.01). CONCLUSIONS: TIC parameters including the slope of the ascending TIC, AT, and TTP closely correlated with ICAM-1 in the renal cortex, and it is considered that the TIC can be used to quantitatively monitoring renal cortex blood perfusion and CEUS can be used to indirectly evaluate the degree of inflammatory reaction associated with renal IRI. CEUS may be a useful non-invasive method to identify inflammation caused by renal IRI-associated diseases.