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关键词： Metabolic adaptation   MCTs   Lactate   HMBA   Mammary gland carcinoma  

摘要： Monocarboxylate transporters (MCTs) play critical role in the progression of mammary gland carcinoma. The unregulated cell growth increased glycolytic phenotype via glycolysis pathway which leads to concomitant synthesis of lactate. Lactate facilitates acidification of tumour microenvironment (TME), metastasis, and immune evasion. Thus, MCTs inhibition has emerged as a novel approach to treat mammary gland carcinoma. Herein, the current study aim to identify and validate small molecule as dual MCT-1 and MCT-4 inhibitor for mammary gland chemoprevention. We performed structure based virtual screening of natural based library (HY-L057L) and outcomes underscore 2-Hydroxy-4-methoxybenzoic acid (HMBA) as potential compound. HMBA demonstrated higher molecular docking score, favourable ADMET profiling and ***, HMBA was examined for its cytotoxicity and apoptotic activity via in-vitro studies on MCF-7 cells. The results showed that HMBA possessed a substantial IC50 value of 4.8 μM and having apoptotic potential. Additionally, we tested its anticancer effects against a 7,12- dimethylbenz[a]anthracene) (DMBA)-induced tumour model in-vivo. Our findings demonstrated that the HMBA effectively corrected the altered histology and morphology. The altered levels of lactate and antioxidant were also restored by HMBA. In addition, HMBA regulate the mitochondrial apoptotic pathway and inhibit the hypoxia and angiogenesis and the lactate exchange transporters proteins, according to t

关键词： Alzheimer’s disease   amyloid-beta   autophagy   bridging integrator 1   cellular clearance   endolysosomal network   genetic risk factors   membrane dynamics   neurodegeneration   neuroinflammation   synaptic transmission   tau  

摘要： Alzheimer’s disease is a devastating neurodegenerative disorder affecting millions worldwide,with current treatments offering only limited *** to emerging research is the role of autophagy and endolysosomal pathways,which are essential for clearing misfolded proteins and damaged *** integrator 1(BIN1),traditionally recognized for its role in membrane remodeling and endocytosis,has recently emerged as a top genetic risk factor for Alzheimer’s disease,linking cellular clearance mechanisms to the development of toxic amyloid-beta plaques and tau *** this review,we provide an accessible overview of how disruptions in autophagy and endolysosomal trafficking contribute to the neurodegeneration process in Alzheimer’s disease,positioning BIN1 as a central mediator within this complex *** advances have shown that alterations in BIN1 expression and isoform distribution are associated with increased tau pathology and changes in amyloid-beta ***,BIN1 appears to also influence synaptic transmission,neuroinflammation,and overall cellular *** integration of recent findings not only deepens our understanding of Alzheimer’s disease pathology but also opens new avenues for the development of targeted *** timely perspective underscores the potential of modulating BIN1 activity to enhance cellular clearance mechanisms and offers hope for more effective interventions for Alzheimer’s disease.

关键词： Impaired hypoglycemia awareness   severe hypoglycemia   type 1 diabetes mellitus   diagnostic validity  

摘要： Objective Impaired awareness of hypoglycemia (IAH) contributes to severe hypoglycemia (SH) in adults with type 1 diabetes mellitus (T1DM). This study compared the validity of the Gold, Clarke, and Pedersen-Bjergaard methods for predicting SH in Japanese adults with T1DM. Methods IAH was assessed at baseline using three methods, and a prospective cohort study was conducted in adults with T1DM. Multivariate Cox proportional hazards regression models adjusted for covariates were used to compare the three methods for predicting SH, and diagnostic validity was calculated. Patients We enrolled 286 participants (mean age: 50.5 +/- 14.6 years, men: 36.7%, diabetes duration: 17.6 +/- 11.1 years, mean HbA1c level: 7.7%+/- 0.9%). Results The prevalence of IAH identified using the Gold, Clarke, and Pedersen-Bjergaard methods was 12.2%, 19.2%, and 30.1%, respectively. The Clarke method showed the strongest association with SH [adjusted hazard ratio (aHR), 8.27;95% confidence interval (CI), 3.43-20.0, P<0.001], whereas the Gold and Pedersen-Bjergaard methods had associations of aHR 1.90 (95% CI: 0.67-5.36, P=0.227) and aHR 2.65 (95% CI: 1.16-6.03;P=0.020), respectively. The Clarke method demonstrated 65.2% sensitivity, 84.8% specificity, a 27.3% positive predictive value, a 96.5% negative predictive value, a positive likelihood ratio of 4.29, a negative likelihood ratio of 0.41, and an overall diagnostic validity of 83.2%. Conclusion Among the three methods, the Clarke method demonstrated the highest validity for predicting SH development. This information may assist physicians in assessing IAH in clinical practice. Clinical trial registry no. UMIN000039475.

关键词： Imidazo[1,2-a]pyridine   green approaches   one-pot synthesis   microwave-assisted synthesis   synthesis via cyclization   nitrogen  

摘要： A well-known heterocyclic scaffold, imidazopyridine, is recognized for its important role in the development of therapeutic drugs. This is because imidazopyridine possesses a wide range of biological characteristics. The aim of this study is to provide a comprehensive outline of various synthetic techniques (2018-2024) employed in the synthesis of Imidazo[1,2-a] pyridine derivatives, highlighting both traditional and modern methodologies. The review article includes approaches like one-pot and microwave-assisted synthesis in addition to traditional multistep synthesis. The review also looks at green chemistry strategies, emphasizing environmentally friendly techniques that reduce the usage of dangerous solvents and reagents. It includes forty different synthetic strategies, with respect to "green" methods, "one-pot" reactions, "microwave-assisted" methods, and "cyclization-based" strategies. This review aims to assist researchers in selecting the most effective strategies for the efficient synthesis of imidazopyridine derivatives, thereby promoting their broader application in medicinal chemistry and related fields.

关键词： Badercharge   Dehydrogenation   NH3adsorption   O-precovered Al(1 1 1)   Surfaceheterogeneity   Transition-state theory  

摘要： NH₄H₂PO₄ effectively suppresses aluminum dust explosions, but the microscopic interaction between its decomposition product NH₃ and aluminum surfaces remains unclear. Here, density functional theory is used to study NH₃ adsorption, stepwise dehydrogenation and temperature-dependent kinetics on clean and O‑precovered Al(1 1 1). Pre‑adsorbed O raises the work function and induces local charge redistribution, creating a heterogeneous landscape of neighboring oxidized sites, screening regions and remote metallic sites, and giving a cooperative global-suppression/local-activation mechanism for site-selective NH₃ adsorption. Bader charge analysis along reaction pathways establishes polynomial scaling relations between the charge of the dissociating H atom and its bond distances. Kinetic calculations show that O coverage promotes the initial dehydrogenation of NH₃ only within a limited temperature window, whereas above ∼430 K it strongly suppresses deep dehydrogenation to surface N. Overall, NH₃ prefers to form a stable, partially dehydrogenated NH_x (x = 1–3) adlayer on oxidized aluminum, passivating highly reactive Al sites and reducing further oxidation and heat release. These results provide an atomistic basis for quantitative design of NH₄H₂PO₄ and other nitrogen-containing suppressants and for optimizing aluminum-based flame-retardant and passivation strategies.

关键词： Magnetron sputtering   Oxidation resistance   Oxygen adsorption   Oxygen diffusion   Thin films   Transition metal diboride  

摘要： Transition metal diboride (TMB₂) films are attractive for high-temperature applications, yet their oxidation resistance is constrained by porous, unstable oxide scales. Aluminum doping improves this by forming dense, adherent Al₂O₃, which enhances oxide layer integrity and restrict oxygen ingress. However, the influence of Al concentration remains insufficiently understood. Here, we investigate the oxidation behavior of Hf_1−xAl_xB_2±δ films (x = 0–0.69) combined with first-principles calculations to clarify how Al content regulates phase evolution and oxygen transport. Oxidation resistance shows a non-monotonic dependence on Al content, peaking at x  = 0.60, where annealing at 800 °C for 8 h produces an ultrathin oxide scale of 79.1 ± 14 nm. To reveal the atomic-scale origin, structural models of Hf_1−yAl_yB₂ (y = 0–0.750) were constructed. The calculations show that for y ≥ 0.500, oxygen adsorbs at Al-containing hollow sites, which promotes the nucleation of a dense alumina layer. At y = 0.625, the oxygen diffusion barrier reaches a maximum of 12.21 eV, effectively suppressing inward oxygen transport. Appropriate Al incorporation stabilizes the oxide scale and increases the oxygen diffusion barrier, significantly improving oxidation resistance. This experimental–computational evidence provides a mechanistic basis for composition-driven optimization of next-generation oxidation-resistant TMB₂ films.

关键词： CO2 absorption   DBN-ethylene glycol   Kinetics   Non-aqueous solution   Stability   Thermal degradation  

摘要： 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)-ethylene glycol solution is a promising absorbent for CO₂ capture due to its low regeneration energy. The thermal stability of DBN-ethylene glycol solution was systematically investigated, including the degradation products, the effects of moisture and CO₂ loading, and the degradation kinetics with/without CO₂ loading. Furthermore, the densities, viscosities, surface tensions, conductivities, and CO₂ absorption capacities of the solutions before and after thermal degradation were also measured. The results show that DBN-ethylene glycol solution without CO₂ and water exhibits excellent thermal stability. However, in DBN-ethylene glycol-CO₂ solution, the degradation ratios of DBN are 25.7% without additional water and 69.9% with 5 wt% H₂O after 25 days at 80 °C when the CO₂ loadings are kept at 0.5 mol·mol⁻¹ DBN. Meanwhile, ethylene glycol exhibits higher stability (degraded <13%) than DBN. Water promotes the hydrolysis of DBN and DBNH⁺ to 1-(3-aminopropyl)-2-pyrrolidone, while inhibiting the thermal degradation of ethylene glycol. The hydrolysis rates of DBN and DBNH⁺ are proportional to their respective concentrations and to the content of water. CO₂ accelerates the hydrolysis rate. The apparent activation energies for the hydrolysis of DBN and DBNH⁺ are 66.32 kJ·mol⁻¹ and 48.79 kJ·mol⁻¹, respectively. The CO₂ capacity decreases 17.6% with 12.9% DBN degraded. Regardless of the presence of water or CO₂ in DBN-ethylene glycol solution, its density, viscosity, and conductivity decrease after degradation. Meanwhile, the surface tension decreases in the absence of water but increases when water is present. It is recommended to prevent the entrance of moisture in the system for CO₂ capture.

关键词： 1,2-Dichloroethane   Catalytic oxidation   CePO4-based catalysts   Chlorinated byproducts   Environmental catalysis   Multiphase interfaces  

摘要： 1,2-Dichloroethane (DCE), a common chlorinated volatile organic compound (CVOC), poses serious environmental and health risks owing to its toxicity and persistence. Achieving its efficient and eco-friendly removal remains challenging, largely due to the inevitable formation of hazardous byproducts such as vinyl chloride (VC) and polychlorinated compounds during treatment. In this study, we demonstrate that the 1% Ru–15% Zr/CePO₄ catalyst exhibits outstanding performance in DCE oxidation, characterized by high activity, excellent stability, and remarkable water resistance, while effectively suppressing the generation of VC and polychlorinated byproducts. This superior behavior originates from synergistic interactions among multiple interfacial structures: CePO₄, ZrOₓ/CePO₄, Ru⁰/CePO₄, RuOₓ/CePO₄, and RuOₓ–ZrOₓ/CePO₄. DCE initially undergoes dehydrochlorination at acid–base sites on CePO₄ and ZrOₓ/CePO₄ interfaces; however, their limited redox capability restricts further oxidation of VC. Neighboring RuOₓ–ZrOₓ/CePO₄ interfaces facilitate rapid low-temperature oxidation and hydrolysis of VC, thereby preventing its accumulation and subsequent chlorination. Additionally, the RuOₓ–ZrOₓ/CePO₄ interfaces also promote direct hydrolytic dechlorination–oxidation of DCE. Electron transfer from CePO₄ to Ru species at Ru⁰/CePO₄ and RuOₓ/CePO₄ interfaces enhances CCl cleavage at Ce³⁺ sites and concurrently suppresses β‑hydrogen elimination at PO₄³⁻ groups. The resulting electron-rich Ru sites at Ru⁰/CePO₄ and RuOₓ/CePO₄ interfaces enhance oxygen activation, thereby accelerating the deep oxidation of dechlorinated intermediates (e.g., *CH₂CH₂Cl) via both Mars–van Krevelen (MvK) and Langmuir–Hinshelwood (L–H) pathways. This multi-interface synergy establishes an efficient and e

关键词： Cyclic voltammetry  

摘要： A new redox-active tetradentate ONNO-type ligand containing electron-withdrawing chlorine substituents in the phenylene ring, namely N,N'-bis(3,5-di‑tert‑butyl‑2-hydroxyphenyl)-4,5-dichloro-1,2-phenylenediamine (LH₄), has been synthesized. Its coordination behavior was studied with tin(IV), zinc(II), and cadmium(II) ions. The reaction with Sn(IV) precursor yields the complex LSnMe₂ (1), where the ligand is fully deprotonated and coordinated in its dianionic form. However, in solution, L undergoes intramolecular cyclization within the metal coordination sphere, resulting in the formation of a phenoxazine moiety and, consequently, a new ligand L' in the isolated complex L'SnMe₂ (2). For Zn(II) and Cd(II), the structures of the resulting compounds — (LH)₂Zn (3), (LH)₂Cd (4), L'₂Zn (5), and L'₂Cd (6) — are determined by the choice of oxidant (p-benzoquinone or atmospheric oxygen) used during the synthesis. The structures of the synthesized complexes were established using a combination of NMR, IR, and UV spectroscopy, along with elemental analysis. SC-XRD was carried out for the tin(IV) and zinc(II) compounds. It was shown that the obtained derivatives possess redox-amphoteric properties and exhibit intense absorption in the near-IR region.

关键词： Cyclization  

摘要： Substituted 1,2,4-triazole derivatives are scientifically important molecules due to their potent biological activities and broad pharmacological application potential. For this purpose, the substituted 1,2,4-triazole-based phenyl naphthalene-2-sulfonates were synthesized, and the structures of the compounds were characterized using IR, ¹H NMR, ¹³C NMR, and elemental analysis methods. The biological activities of the 1,2,4-triazole-based naphthalene-2-sulfonates were evaluated for both enzyme inhibition and anticancer effects. The enzyme-inhibitory effects of the 1,2,4-triazole-based naphthalene-2-sulfonates were evaluated against α-glucosidase (α-Gly), α-amylase (α-Amy), glutathione S-transferase (GST), and acetylcholinesterase (AChE). Their IC₅₀ values were found in the range of 1.093±0.450 µM - 3.310±0.689 µM for α-Gly, 1.741±1.223 µM - 2.595±0.901 µM for α-Amy, 1.246±0.370 µM - 2.585±0.320 µM for AChE, and 1.432±0.057 µM - 2.707±0.164 µM for GST. The cytotoxic effects on HepG2 and U87 cells were evaluated at 24 and 48 h of incubation in the concentration range of 1.583–200 µM. Molecular docking studies have determined the binding energies of 1,2,4-triazole-based naphthalene-2-sulfonates to related proteins and detailed the interaction mechanisms.