Fracture of modified urethane - methacrylate resins

Fracture and toughening mechanisms in rubber modified and hybridized urethane-methacrylate resins have been investigated. Fracture mechanisms are defect-dominated in the unmodified resin. The relationships between defect size and fracture strength are characterized through the critical stress intensity factor KIC. Low fracture toughness and high crack sensitivity of the unmodified resin is due to lack of plastic deformation at the crack tip. A 10-fold increase in fracture resistance in the resin has been achieved through rubber modification. The main reason for the improvement is due to occurring of intensive plastic deformation in the presence of rubber, which effectively eases stress concentrations and spreads them away from the crack tip. Deformation mechanisms in rubber-modified resins are shear-dominated. Cavitation of rubber plays a key role in inducing shear deformation in the matrix. Fracture processes in rubber-modified resins start from coalescence and linkage of voids initiated inside rubber particles within rubber domains, which leads to final fracture in the resin matrix. Further increase in KIC was also obtained by incorporation of filler in a matrix toughened with rubber. This increase is not due to the effect of crack front pinning but due to increase in Young’s modulus in the presence of rigid filler. The same deformation and fracture mechanisms operate in the hybrid resins as in the rubber-modified ones.Ph

Improved Regret Bounds for Linear Adversarial MDPs via Linear Optimization

Learning Markov decision processes (MDP) in an adversarial environment has been a challenging problem. The problem becomes even more challenging with function approximation, since the underlying structure of the loss function and transition kernel are especially hard to estimate in a varying environment. In fact, the state-of-the-art results for linear adversarial MDP achieve a regret of $\tilde{O}(K^{6/7})$ ($K$ denotes the number of episodes), which admits a large room for improvement. In this paper, we investigate the problem with a new view, which reduces linear MDP into linear optimization by subtly setting the feature maps of the bandit arms of linear optimization. This new technique, under an exploratory assumption, yields an improved bound of $\tilde{O}(K^{4/5})$ for linear adversarial MDP without access to a transition simulator. The new view could be of independent interest for solving other MDP problems that possess a linear structure

Advances in metabolic reprogramming of renal tubular epithelial cells in sepsis-associated acute kidney injury

Sepsis-associated acute kidney injury presents as a critical condition characterized by prolonged hospital stays, elevated mortality rates, and an increased likelihood of transition to chronic kidney disease. Sepsis-associated acute kidney injury suppresses fatty acid oxidation and oxidative phosphorylation in the mitochondria of renal tubular epithelial cells, thus favoring a metabolic shift towards glycolysis for energy production. This shift acts as a protective mechanism for the kidneys. However, an extended reliance on glycolysis may contribute to tubular atrophy, fibrosis, and subsequent chronic kidney disease progression. Metabolic reprogramming interventions have emerged as prospective strategies to counteract sepsis-associated acute kidney injury by restoring normal metabolic function, offering potential therapeutic and preventive modalities. This review delves into the metabolic alterations of tubular epithelial cells associated with sepsis-associated acute kidney injury, stressing the importance of metabolic reprogramming for the immune response and the urgency of metabolic normalization. We present various intervention targets that could facilitate the recovery of oxidative phosphorylation-centric metabolism. These novel insights and strategies aim to transform the clinical prevention and treatment landscape of sepsis-associated acute kidney injury, with a focus on metabolic mechanisms. This investigation could provide valuable insights for clinicians aiming to enhance patient outcomes in the context of sepsis-associated acute kidney injury

Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT

Background/Aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time. Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan–Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model. Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues. Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA

Neutrophil-to-lymphocyte ratio and incident end-stage renal disease in Chinese patients with chronic kidney disease: results from the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE)

Abstract Background Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1–4 CKD. Methods Patients with stages 1–4 CKD (18–74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. Results Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52–5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. Conclusion Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 )https://deepblue.lib.umich.edu/bitstream/2027.42/148285/1/12967_2019_Article_1808.pd