Do matrix metalloproteinase and cathepsin K inhibitors work synergistically to reduce dentin erosion?

Objectives: To evaluate the effects of matrix metalloproteinase (MMP) and cathepsin K (catK) inhibitors on resistance to dentin erosion. Methodology: A total of 96 dentin specimens (3×3×2 mm) were prepared and randomly assigned into four groups (n=24): deionized water (DW); 1 µM odanacatib (ODN, catK inhibitor); 1 mM 1,10-phenanthroline (PHEN, MMP inhibitor); and 1 µM odanacatib + 1 mM 1,10-phenanthroline (COM). Each group was further divided into two subgroups for the application of treatment solutions before (PRE) and after erosive challenges (POST). All specimens were subjected to four daily erosive challenges for 5 d. For each erosive challenge, the specimens in subgroup PRE were immersed in the respective solutions before cola drinks, while the specimens in subgroup POST were immersed in the respective solutions after cola drinks (the immersion duration was 5 min in both cases). All specimens were stored in artificial saliva at 37°C between erosive challenges. The erosive dentin loss (EDL) was measured by profilometry. The residual demineralized organic matrix (DOM) of specimens was removed using type VII collagenase and evaluated by profilometry. Both the EDL and thickness of the residual DOM were statistically analyzed by two-way analysis of variance (ANOVA) and Bonferroni’s test (α=0.05). The surface topography and transverse sections of the specimens were observed using SEM. MMPs and catK were immunolabeled in the eroded dentin and in situ zymography was performed to evaluate the enzyme activity. Results: Significantly lower EDL was found in the groups ODN, PHEN, and COM than in the control group (all p<0.05), while no significant difference in EDL was found among the groups ODN, PHEN, and COM (all p>0.05). The application sequence showed no significant effect on the EDL of the tested groups (p=0.310). A significantly thicker DOM was observed in the group ODN than in the control group regardless of the application sequence (both p<0.05). The treatment with ODN, PHEN, and COM inhibited the gelatinolytic activity by approximately 46.32%, 58.6%, and 74.56%, respectively. Conclusions: The inhibition of endogenous dentinal MMPs and catK increases the acid resistance of human dentin but without an apparent synergistic effect. The inhibition of MMPs and catK is equally effective either before or after the acid challenge

Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice

Alzheimer’s disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research

VQ-NeRF: Vector Quantization Enhances Implicit Neural Representations

Recent advancements in implicit neural representations have contributed to high-fidelity surface reconstruction and photorealistic novel view synthesis. However, the computational complexity inherent in these methodologies presents a substantial impediment, constraining the attainable frame rates and resolutions in practical applications. In response to this predicament, we propose VQ-NeRF, an effective and efficient pipeline for enhancing implicit neural representations via vector quantization. The essence of our method involves reducing the sampling space of NeRF to a lower resolution and subsequently reinstating it to the original size utilizing a pre-trained VAE decoder, thereby effectively mitigating the sampling time bottleneck encountered during rendering. Although the codebook furnishes representative features, reconstructing fine texture details of the scene remains challenging due to high compression rates. To overcome this constraint, we design an innovative multi-scale NeRF sampling scheme that concurrently optimizes the NeRF model at both compressed and original scales to enhance the network's ability to preserve fine details. Furthermore, we incorporate a semantic loss function to improve the geometric fidelity and semantic coherence of our 3D reconstructions. Extensive experiments demonstrate the effectiveness of our model in achieving the optimal trade-off between rendering quality and efficiency. Evaluation on the DTU, BlendMVS, and H3DS datasets confirms the superior performance of our approach.Comment: Submitted to the 38th Annual AAAI Conference on Artificial Intelligenc

Metformin and Lactic Acidosis in Diabetic Patients

Metformin is the basic drug in the clinical treatment of Diabetes, often used in the treatment of Type 2 Diabetes Mellitus (T2DM).Its effect has been fully verified in the clinical treatment of T2DM. However, in the treatment of T2DM with metformin, there is still a certain probability of related lactic acidosis, and the fatality rate is high. Therefore, is the use of metformin drug treatment a direct risk factor for lactic acidosis in diabetic patients? This paper will review the hypoglycemic mechanism of metformin and related studies on lactic acidosis, so as to further explore the relationship between metformin and lactic acidosis in diabetic patients, and provide help and reference for metformin drugs in the clinical treatment of T2DM

Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis

Chronic leucine supplementation improves glycemic control in etiologically distinct mouse models of obesity and diabetes mellitus

Leucine may function as a signaling molecule to regulate metabolism. We have previously shown that dietary leucine supplementation significantly improves glucose and energy metabolism in diet-induced obese mice, suggesting that leucine supplementation could potentially be a useful adjuvant therapy for obesity and type 2 diabetes. Since the underlying cause for obesity and type 2 diabetes is multifold, we further investigated metabolic effects of leucine supplementation in obese/diabetes mouse models with different etiologies, and explored the underlying molecular mechanisms. Leucine supplementation was carried out in NONcNZO10/LtJ (RCS10) - a polygenic model predisposed to beta cell failure and type 2 diabetes, and in B6.Cg-Ay/J (Aʸ) - a monogenic model for impaired central melanocortin receptor signaling, obesity, and severe insulin resistance. Mice in the treatment group received the drinking water containing 1.5% leucine for up to 8 months; control mice received the tap water. Body weight, body composition, blood HbA1c levels, and plasma glucose and insulin levels were monitored throughout and/or at the end of the study period. Indirect calorimetry, skeletal muscle gene expression, and adipose tissue inflammation were also assessed in Aʸ mice. Leucine supplementation significantly reduced HbA1c levels throughout the study period in both RCS10 and Aʸ mice. However, the treatment had no long term effect on body weight or adiposity. The improvement in glycemic control was associated with an increased insulin response to food challenge in RCS10 mice and decreased plasma insulin levels in Aʸ mice. In leucine-treated Aʸ mice, energy expenditure was increased by ~10% (p < 0.05) in both dark and light cycles while the physical activity level was unchanged. The expression levels of UCP3, CrAT, PPAR-alpha, and NRF-1, which are known to regulate mitochondrial oxidative function, were significantly increased in the soleus muscle of leucine-treated Ay mice whereas the expression levels of MCP-1 and TNF-alpha and macrophage infiltration in adipose tissue were significantly reduced. Chronic leucine supplementation significantly improves glycemic control in multiple mouse models of obesity and diabetes with distinct etiologies. The metabolic benefits of leucine supplementation are likely mediated via multiple mechanisms in different tissues, but are not necessarily dependent of weight reduction

Evaluating Shanghai new towns' maturity of urban form : an exploration index based on new urban data

The natural evolution of urban forms over time is a key issue in urban morphology. With the rapid development of 7quantitative analytical tools and new urban data, new research potential has emerged. This study attempts to develop an analytical framework for evaluating the urban maturation process. Using street blocks as the analytical unit, this study integrates the spatial design network analysis (sDNA), Spacematrix, Points-of-Interests (POIs), and Open Street Map (OSM) in the geographical information system (GIS) to calculate the urban maturation index in the context of big data. Shanghai, a metropolitan city with a long urbanisation history and a series of new towns, was selected as the case study. The validation of this new index was first achieved by comparing this maturation index between several districts located in the city centre and suburban new towns. Insights in this direction would help generate new urban design guidance for creating vibrant urban places. This study also aimed to introduce new quantitative thinking into the previously qualitative and intuition-based fields of urban morphology and urban design

Protocol for a Single-Center Randomized Controlled Trial of Percutaneous Coronary Intervention Via Distal Transradial Access Versus Transradial Access

Background: Although transradial access (TRA) has become the main vascular access for coronary intervention, its high radial artery occlusion rate limits its application in some patients. Studies have shown that compared with TRA, distal transradial access (dTRA) with the snuffbox area or the Hegu acupoint area as the puncture point significantly decreases the incidence of radial artery occlusion. However, no randomized controlled study has confirmed the safety and efficacy of coronary artery intervention via dTRA in China. Methods and analyses: This single-center, prospective, randomized controlled, superiority open-label study will enroll 428 consecutive patients with coronary heart disease undergoing percutaneous coronary intervention as the study population. After preoperative evaluation, the participants will be randomly divided into a study group (dTRA) and control group (TRA) in a 1:1 ratio. The primary endpoint (radial artery occlusion at 24 hours after operation) and secondary endpoint events will be evaluated and recorded. Study registration: This study has been registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2300073902)