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ABSTRACTRadiation-induced liver disease (RILD), also known as radiation hepatitis, is a serious side effect of radiotherapy (RT) for hepatocellular carcinoma. The therapeutic dose of RT can damage normal liver tissue, and the toxicity that accumulates around the irradiated liver tissue is related to numerous physiological and pathological processes. RILD may restrict treatment use or eventually deteriorate into liver fibrosis. However, the research on the mechanism of radiation-induced liver injury has seen little progress compared with that on radiation injury in other tissues, and no targeted clinical pharmacological treatment for RILD exists. The DNA damage response caused by ionizing radiation plays an important role in the pathogenesis and development of RILD. Therefore, in this review, we systematically summarize the molecular and cellular mechanisms involved in RILD. Such an analysis is essential for preventing the occurrence and development of RILD and further exploring the potential treatment of this disease.

ABSTRACTThe cGAS/STING signaling pathway is an important part of the cytoplasmic DNA sensor, which can trigger a type I interferon response to microbial infection when pathogenic DNA is detected. However, continuous inhibition of cGAS/STING signaling by viral infection may be an important cause of tumorigenesis. At the same time, recent studies have shown that although the cGAS/STING signaling pathway also plays a core role in anti-tumor immunity and cell senescence, the inflammatory response induced by cGAS/STING signaling will also promote tumorigenesis in different backgrounds. Here, we discuss the role of cGAS/STING in the context of infection, senescence, and tumors, especially with respect to progression, to facilitate a better understanding of the mechanism of the cGAS/STING pathway.

ABSTRACTThe maintenance of cellular cholesterol homeostasis is essential for normal cell function and viability. Excessive cholesterol accumulation is detrimental to cells and serves as the molecular basis of many diseases, such as atherosclerosis, Alzheimer’s disease, and diabetes mellitus. The peripheral cells do not have the ability to degrade cholesterol. Cholesterol efflux is therefore the only pathway to eliminate excessive cholesterol from these cells. This process is predominantly mediated by ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein. ABCA1 is known to transfer intracellular free cholesterol and phospholipids to apolipoprotein A-I (apoA-I) for generating nascent high-density lipoprotein (nHDL) particles. nHDL can accept more free cholesterol from peripheral cells. Free cholesterol is then converted to cholesteryl ester by lecithin:cholesterol acyltransferase to form mature HDL. HDL-bound cholesterol enters the liver for biliary secretion and fecal excretion. Although how cholesterol is transported by ABCA1 to apoA-I remains incompletely understood, nine models have been proposed to explain this effect. In this review, we focus on the current view of the mechanisms underlying ABCA1-mediated cholesterol efflux to provide an important framework for future investigation and lipid-lowering therapy.

The mitochondrial enzyme arginase‐2 (Arg‐2) is implicated in the pathophysiology of contrast‐induced acute kidney injury (CI‐AKI). Therefore, Arg‐2 represents a candid target for CI‐AKI prevention. Here, layer‐by‐layer (LbL) assembled renal‐targeting polymeric nanoparticles are developed to efficiently deliver small interfering RNA (siRNA), knockdown Arg‐2 expression in renal tubules, and prevention of CI‐AKI is evaluated. First, near‐infrared dye‐loaded poly(lactic‐co‐glycolic acid) (PLGA) anionic cores are electrostatically coated with cationic chitosan (CS) to facilitate the adsorption and stabilization of Arg‐2 siRNA. Next, nanoparticles are coated with anionic hyaluronan (HA) to provide protection against siRNA leakage and shielding against early clearance. Sequential electrostatic layering of CS and HA improves loading capacity of Arg‐2 siRNA and yields LbL‐assembled nanoparticles. Renal targeting and accumulation is enhanced by modifying the outermost layer of HA with a kidney targeting peptide (HA‐KTP). The resultant kidney‐targeting and siRNA loaded nanoparticles (PLGA/CS/HA‐KTP siRNA) exhibit proprietary accumulation in kidneys and proximal tubular cells at 24 h post‐tail vein injection. In iohexol‐induced in vitro and in vivo CI‐AKI models, PLGA/CS/HA‐KTP siRNA delivery alleviates oxidative and nitrification stress, and rescues mitochondrial dysfunction while reducing apoptosis, thereby demonstrating a robust and satisfactory therapeutic effect. Thus, PLGA/CS/HA‐KTP siRNA nanoparticles offer a promising candidate therapy to protect against CI‐AKI. Utilizing electrostatic layer‐by‐layer adsorption between polymers and arginase‐2 (Arg‐2) small interfering RNA (siRNA), the delivery system of poly(lactic‐co‐glycolic acid)/chitosan/siRNA/hyaluronan and surface decoration with kidney targeting peptide (KTP) achieves high renal selectivity through KTP‐megalin and hyaluronan‐CD44 interactions. Specific silencing of renal tubule Arg‐2 mitigates oxidative/nitrifying stress and apoptosis, restores mitochondrial homeostasis, and achieves prevention of contrast‐induced acute kidney injury.

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.

Contrast-induced nephropathy (CIN) is a frequent cause of hospital-acquired acute kidney injury. Previous animal models developed to explore the pathogenesis of CIN were based primarily on surgery or indomethacin treatment. Thus, we sought to explore a novel CIN rat model comparable to the human CIN.

Previously published equations to estimate glomerular filtration rate (GFR) have limited accuracy in Asian populations. We aimed to develop and validate a more accurate equation for estimated GFR (eGFR) in the Chinese population, using data from 8571 adults who were referred for direct measurement of GFR by renal dynamic imaging (mGFR) at 3 representative hospitals in China. Patients from the Third Xiangya Hospital were included in our development (n=1730) and internal validation sets (n=1042) and patients from the other hospitals comprised the external validation set (n=5799). We excluded patients who were prescribed medications known to influence the tubular secretion of creatinine, patients on dialysis, kidney transplant recipients, and patients with missing creatinine values or with creatinine >700 μmol/l. We derived a novel eGFR equation by linear regression analysis and compared the performance to 12 creatinine-based eGFR equations, including previously published equations for use in Chinese or Asian populations. In the development and internal validation sets, the novel Xiangya equation had high accuracy (accuracy within 30% [P30], 79.21% and 84.33%, respectively), low bias (mean difference between mGFR and eGFR, -1.97 and -1.85 ml/min per 1.73 m2, respectively), and high precision (interquartile range of the differences, 21.13 and 18.88 ml/min per 1.73 m2, respectively). In external validation, the Xiangya equation had the highest P30 among all eGFR equations, with P30 ≤ 75% for the other 12 equations. This novel equation provides more accurate GFR estimates in Chinese adults and could replace existing eGFR equations for use in the Chinese population.

Diltiazem is a benzothiazepine calcium blocker and widely used in renal transplant patients since it improves the level of tacrolimus or cyclosporine A concentration. Several population pharmacokinetic (PopPK) models had been established for cyclosporine A and tacrolimus but no specific PopPK model was established for diltiazem. The aim of the study is to develop a PopPK model for diltiazem in renal transplant recipients and provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study. Patients received tacrolimus as primary immunosuppressant agent after renal transplant and started administration of diltiazem 90 mg twice daily on 5th day. The concentration of diltiazem at 0, 0.5, 1, 2, 8, and 12 h was measured by high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). Genotyping for CYP3A4*1G, CYP3A5*3, and MDR13435 was conducted by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). 25 covariates were considered in the stepwise covariate model (SCM) building procedure. One-compartment structural pharmacokinetic model with first-order absorption and elimination was used to describe the pharmacokinetic characteristics of diltiazem. Total bilirubin (TBIL) influenced apparent volume of distribution (V/F) of diltiazem in the forward selection. The absorption rate constant (Ka), V/F, and apparent oral clearance (CL/F) of the final population pharmacokinetic (PopPK) model of diltiazem were 1.96/h, 3550 L, and 92.4 L/h, respectively. A PopPK model of diltiazem is established in Chinese renal transplant recipients and it will provide relevant pharmacokinetic parameters of diltiazem for further pharmacokinetic interaction study.

Montmorillonite/SBS composite modifed asphalts were prepared by mixing montmorillonite with SBS-modified asphalt, further the corresponding asphalt mixtures were obtained. The paving technical indexes of the mixture such as physical properties, moisture suscepyibility, and high temperature stability were tested, and compared with that of the corresponding SBS-modifed asphalt mixture and base asphalt mixture. The results demonstrate that the montmorillonite/SBS composite modifed asphalt mixture exhibites enhanced stability, improved flow value and moisture susceptibility, and increased high temperature stability.

As the renewable energy (wind energy, solar energy) being utilized more and more, there is strong demand for improvement on the policies of energy storage management. Several papers have shown that hybrid storage system is more efficient and economic than single storage system. In this paper, a policy based on the accurate prediction of wind speed in the near future is introduced and compared with state-of-charge (SOC) management approach and single storage system. The current simulation results demonstrate that the new policy proposed has a minor improvement on the set-up cost and the system performance over the state-of-charge policy.

Advanced data assimilation method is used for the short-term wind power forecasting based on a meso-scale model. Considerable forecast error reduction is concluded from a case study in China, where a better resolved high-resolution initial condition is introduced via assimilating various in-situ observations.