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关键词： Corrosion inhibitors  

摘要： The present study explores the sustainable synthesis method for the preparation of a notable heterocyclic compound of N-(benzo[d]thiazol-2-yl) nicotinamide through environmentally benign propylphosphonic anhydride (T3P) as a coupling agent. The structure of the synthesised molecule has been characterized by using specific spectroscopic techniques, including UV–Visible, Fourier Transform Infrared (FT-IR), and NMR spectroscopy. The thermal behaviour of the molecule has been assessed through the thermogravimetric analysis (TGA) plot. Additionally, the cyclic voltametric technique has been used to understand the electrochemical profile. Using potentiodynamic polarisation and AC impedance spectroscopy techniques, the corrosion inhibition property of N-(benzo[d]thiazol-2-yl) nicotinamide on mild steel in 1 M HCl solution was investigated. Density Functional Theory (DFT) and Monte Carlo (MC) simulation techniques have been employed to compute the electronic distributions of the molecule, which is crucial in elucidating the structure–property relationship of the molecule. The inhibitor was discovered to influence both anodic and cathodic corrosion processes by forming a protective layer on the Fe (110) surface. The Temkin adsorption isotherm is compatible with the spontaneous formation of this protective layer. N-(Benzo[d]thiazol-2-yl) nicotinamide inhibitor spontaneously adsorbed onto the mild steel surface by both physical and chemical adsorption modes, as indicated by the computed Gibbs free energy (ΔGads), which was − 34.816 kJ/mol. The experimental results were further supported by computational investigations using density functional theory (DFT) and Monte Carlo (MC) simulations, which verified that bonds were formed between the Fe (110) surface and N-(benzo[d]thiazol-2-yl) nicotinamide in the 1 M HCl solution. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2025.

关键词： CKD   chronic nephropathy   clinical trial   kidney stones   renal function decline   genetic diseases and development  

摘要： Key PointsPrimary hyperoxaluria type 1 is a genetic disorder associated with hepatic oxalate overproduction, kidney failure, and systemic *** treatment for up to 60 months was associated with sustained reductions in urinary and plasma oxalate and encouraging clinical ***'s safety profile was acceptable with mild injection site reactions being the most common adverse *** hyperoxaluria type 1 (PH1) is characterized by hepatic oxalate overproduction, kidney stones, and progressive kidney disease. Lumasiran is the first approved treatment for ***-A (NCT03681184) was a 60-month pivotal, phase 3, multinational clinical trial of lumasiran which consisted of a 6-month double-blind, placebo-controlled period (6M DB), followed by a treatment extension period of up to 54 months in which all patients received lumasiran. Eligible patients were aged >= 6 years with genetically confirmed PH1, eGFR >= 30 ml/min per 1.73 m2, and mean 24-hour urinary oxalate (UOx) excretion >= 0.70 mmol/24 h per 1.73 *** 39 patients enrolled, 24 of 26 randomized to lumasiran in the 6M DB (lumasiran/lumasiran group) and 13 of 13 randomized to placebo in the 6M DB (placebo/lumasiran group) completed the study. Sustained reductions in 24-hour UOx were observed in both treatment groups. At month 60 relative to study baseline, the mean (SEM) 24-hour UOx percentage reductions were 54 (6) and 54% (8%) in the lumasiran/lumasiran and placebo/lumasiran groups, respectively, and the mean (SEM) plasma oxalate concentrations had decreased by 35 (5) and 38% (7%). eGFR remained stable through the end of the study in both treatment groups. Kidney stone event rates during the study were 0.47 (95% confidence interval, 0.36 to 0.62) and 0.54 (0.37 to 0.78) per patient-year in the lumasiran/lumasiran group and placebo/lumasiran group, respectively. Medullary nephrocalcinosis grade improved at the end of the study in 21 of 28 (75%) patients wit

关键词： Alkynes   Annulation   Ruthenium catalysis   Heterocycles   Homogeneous catalysis  

摘要： A one-pot synthesis of 1-alkoxyisoquinolines via ruthenium(II)-catalyzed aryl C-H activation and annulation with internal alkynes has been demonstrated. The reaction involves in situ generation of a benzimidate ester by the addition of nucleophilic alcohols and it acts as an "automatic directing group" (DG(auto)) for the aryl C-H activation and subsequent alkyne annulation. In contrast to conventional nitrogen-containing DG-assisted annulation approaches, this DG(auto)-assisted annulation of alkynes via C-H activation is advantageous as it reduces the number of reaction steps, simplifies the experimental procedure, and allows for easier handling of the corresponding precursors. Based on preliminary experimental observations, a plausible mechanism is disclosed for this transformation. Interestingly, most of the compounds show intense fluorescence emission, and their absorption and emission spectra are also presented in this work.

关键词： CGM   Diabetic retinopathy   HbA(1c)   Type 1 diabetes   Updated GMI  

摘要： Aims/hypothesis This study aimed to compare the predictive performance of HbA(1c )and a continuous glucose monitoring (CGM)-based updated glucose management indicator (uGMI) in assessing incident diabetic retinopathy risk. Methods We used the data from a previously published longitudinal case-control study that collected CGM data for up to 7 years prior to diagnosis of incident diabetic retinopathy or no retinopathy (control participants) among adults with type 1 diabetes. Mutual information scores (MIS), receiver operating characteristics (ROC) curves and machine learning models were used to assess the associations of diabetic retinopathy with HbA(1c), uGMI and CGM-derived metrics. Results The uGMI demonstrated a stronger association with incident diabetic retinopathy (MIS 0.148) compared with HbA(1c )(MIS 0.078). ROC analysis showed that uGMI had a modestly higher AUC (AUC 0.733) than HbA(1c )(AUC 0.704). Decision tree models incorporating both HbA(1c )and uGMI did not improve clinically significant diabetic retinopathy risk prediction. Machine learning models confirmed the better predictive value of uGMI, especially for HbA(1c )values between 54 mmol/mol (7.1% NGSP) and 58 mmol/mol (7.5% NGSP), where diabetic retinopathy risk escalated significantly. Conclusions/interpretation The uGMI is a slightly stronger predictor of diabetic retinopathy risk compared with HbA(1c). HbA(1c )and uGMI do not appear to be complementary for diabetic retinopathy risk prediction.

关键词： azobenzene   beta-cells   calcium imaging   cannabinoids   photopharmacology  

摘要： Intracellular Ca2+ regulates insulin secretion from pancreatic beta-cells and is influenced by cannabinoid signaling. However, the hydrophobicity and complex pharmacology of cannabinoid ligands prevent precision receptor targeting, limiting our understanding of their roles in modulating insulin release. Here, we use fluorescent Ca2+ imaging to examine how the light-activatable CB2 receptor agonist azo-HU308 modulates Ca2+ dynamics in INS-1 beta-cells. UV-A photoactivation of azo-HU308 triggered robust, repeatable Ca2+ transients, and pharmacological profiling revealed this effect was independent of CB2 receptor activation but was instead mediated by extracellular Ca2+ influx through TRPC channels. These findings position azo-HU308 as a novel optical tool for controlling beta-cell Ca2+ levels and highlight a non-GPCR pathway by which synthetic cannabinoids can modulate Ca2+ dynamics in excitable cells.

关键词： Cadmium   Chitosan nanoparticles   Pro-inflammatory cytokines Antioxidant activities   Oxidative stress  

摘要： The current aim was to evaluate the protective effects of chitosan nanoparticles against cadmium chloride (CdCl2)-induced hepatic and renal toxicity and to elucidate the underlying mechanisms with a focus on the modulation of oxidative stress, inflammation, and apoptosis via the Nrf2/HO-1 and NF-kappa B/iNOS signaling pathways. Four groups were used: group I (control), group II (CS-NPs), group III (CdCl2), and group IV (CdCl2 + CS-NPs). Biochemical, histopathological, and immunohistochemical studies of hepatorenal parameters were performed. Cadmium showed renal dysfunction (increased creatinine and urea), hepatic dysfunction (elevated ALT, AST, and ALP), and disturbed oxidative homeostasis (elevated MDA and decreased antioxidant enzyme activities;SOD, CAT, and GPx in the liver and kidney). The pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were significantly increased in tissues. In addition, cadmium displayed histopathological alterations in the architecture of the kidney and liver, elevated the expression levels of caspase-3, NF-kappa B, and iNOS, and decreased Nrf2 and HO-1. Interestingly, CS-NPs significantly restored kidney function, liver function, and oxidative homeostasis. CS-NPs also reduced pro-inflammatory mediators (IL-6, TNF-alpha, and IL-1 beta), restored renal and hepatic architecture, decreased the expression levels of caspase-3, NF-kappa B, and iNOS, and increased Nrf2 and HO-1 levels. Therefore, cadmium caused hepatorenal toxicity by causing oxidative stress and affecting NF-kappa B/iNOS and Nrf2/HO-1 pathways. These findings demonstrate that chitosan nanoparticles effectively alleviate cadmium-induced renal and hepatic injury through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms by modulating Nrf2/HO-1 and NF-kappa B/iNOS pathways. Chitosan nanoparticles may represent a promising nanotherapeutic approach against heavy metal-induced organ toxicity.