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ABSTRACT Objective: To investigate the efficacy and safety of febuxostat on renal function in CKD stage 3 diabetic nephropathy patients. Methods: Patients in our hospital with chronic kidney disease (CKD) stage 3 diabetic nephropathy (DN) complicated by high serum uric acid (360 µmol/L) were recruited. Patients were then divided into treatment group and control group according to the random number table method. All the patients received low purine diet, renin-angiotensin-aldosterone system (RAAS) inhibitors, and adequate routine hypoglycemic treatment. Febuxostat was employed only in the treatment group. The levels of blood uric acid (sUA), serum creatinine (Scr), cystatin C (cys-c), eGFR, 24-hour urine protein quantification, albuminuria, and creatinine ratio (ACR) were evaluated in all patients before and after treatment at 4, 8, 12, and 24 week. Results: No difference was found before treatment between the two groups. After treatment at 4, 8, 12, and 24 week, the levels of sUA, SCr, cys-c, and eGFR between the two groups were significant different (P

High-risk neuroblastoma often develops resistance to high-dose chemotherapy. The mTOR signaling cascade is frequently deregulated in human cancers and targeting mTOR signaling sensitizes many cancer types to chemotherapy. Here, using a panel of neuroblastoma cell lines, we found that the mTOR inhibitor INK128 showed inhibitory effects on both anchorage-dependent and independent growth of neuroblastoma cells and significantly enhanced the cytotoxic effects of doxorubicin (Dox) on these cell lines. Treatment of neuroblastoma cells with INK128 blocked the activation of downstream mTOR signaling and enhanced Dox-induced apoptosis. Moreover, INK128 was able to overcome the established chemoresistance in the LA-N-6 cell line. Using an orthotopic neuroblastoma mouse model, we found that INK128 significantly inhibited tumor growth in vivo. In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma.

Transition state (TS) on the potential energy surface (PES) plays a key role in determining the kinetics and thermodynamics of chemical reactions. Inspired by the fact that the dynamics of complex systems are always driven by rare but significant transition events, we herein propose a TS search method in accordance with the Q‐learning algorithm. Appropriate reward functions are set for a given PES to optimize the reaction pathway through continuous trial and error, and then the TS can be obtained from the optimized reaction pathway. The validity of this Q‐learning method with reasonable settings of Q‐value table including actions, states, learning rate, greedy rate, discount rate, and so on, is exemplified in 2 two‐dimensional potential functions. In the applications of the Q‐learning method to two chemical reactions, it is demonstrated that the Q‐learning method can predict consistent TS and reaction pathway with those by ab initio calculations. Notably, the PES must be well prepared before using the Q‐learning method, and a coarse‐to‐fine PES scanning scheme is thus introduced to save the computational time while maintaining the accuracy of the Q‐learning prediction. This work offers a simple and reliable Q‐learning method to search for all possible TS and reaction pathway of a chemical reaction, which may be a new option for effectively exploring the PES in an extensive search manner. [ABSTRACT FROM AUTHOR]

Nitrogen oxide (NOX) gas pollutants pose severe threats to human health, the ozone layer, and the global climate, and thus finding suitable materials and methods to efficiently remove NOX has been of great interest for years. By studying the related photocatalysis and surface reactions, we herein propose to use the graphitic carbon nitride (g-CN) film with N-vacancies (g-CNNV) to decompose NOX. Based on density functional theory (DFT) and time-dependent DFT calculations, we revealed the decomposition mechanism of NO/NO2 gas on g-CNNV. We found that the N–O bond cleavage of NOX is usually accompanied by the N occupying the N-vacancy and oxygen formation, and subsequent light excitation promotes the oxygen desorption from the g-CN surface through photochemical processes of intersystem crossing and conical intersection. We demonstrated that the g-CNNV film under illumination can effectively decompose NOX into harmless oxygen. Therefore, coating the g-CNNV film on the outer walls of buildings or chimneys may be a promising green and economical strategy for NOX removal, given that the sunlight and surface defects can synergistically affect the electronic states of adsorbates and facilitate their favorable transformation by gas–solid interaction. This work offers a deep understanding of the fundamental process of surface photocatalytic reactions. [ABSTRACT FROM AUTHOR]

This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti‐inflammatory and antioxidant effects, primarily targeting the TGF‐β, NF‐κB/TLR4, PI3K/AKT, and Nrf2/HO‐1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti‐HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial‐mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols. [ABSTRACT FROM AUTHOR]