Construction of 3,4-Dihydroquinolone Derivatives through Pd-Catalyzed [4+2] Cycloaddition of Vinyl Benzoxazinanones with α-Alkylidene Succinimides.

The construction of 3,4-dihydroquinolone derivatives has attracted a considerable amount of attention due to their extensive applications in medicinal chemistry. In this study, we present the Pd-catalyzed [4+2] cycloaddition of vinyl benzoxazinanones with α-alkylidene succinimides for the efficient synthesis of 3,4-dihydroquinolones. This approach presents numerous advantages, including the ready availability of starting materials, mild reaction conditions without the use of additional bases, and a wide range of substrates. In particular, all of the desired products can be easily afforded in high yields (≤99%) and excellent diastereoselectivities (>20:1). The practicality and reliability of this strategy were demonstrated by the successful scale-up synthesis and subsequent straightforward synthetic transformations.

Tyrosine phosphorylation of band 3 impairs the storage quality of suspended red blood cells in the Tibetan high-altitude polycythemia population.

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations.

Turn-on colorimetric detection of hydroquinone based on Au/CuO nanocomposite nanozyme.

CuO nanorods bearing Au nanoparticles (Au/CuO nanocomposites) were prepared by a solution-phase synthesis and exhibited efficient hydroquinone (HQ)-oxidase activity with good specificity. The Au/CuO nanocomposites effectively catalyzed the oxidation of colorless HQ to brown benzoquinone with an absorbance maximum at 376 nm but did not catalyze the conversions of catechol or resorcinol. Kinetic studies indicated that the Au/CuO nanocomposites exhibited a strong affinity for HQ, with a Michaelis-Menten constant of Km = 0.33 mM. Owing to the high catalytic activity and specificity, a strong color was observed at low concentrations of HQ. Quantitative measurement of HQ was performed via colorimetric analysis, which yielded a detection limit of 3 µM with a linear range of 5-200 µM. This colorimetric sensor was successfully applied to an HQ assay of real water samples with satisfactory results.

Mesoporous Core-Shell Pd@Pt Nanospheres as Oxidase Mimics with Superhigh Catalytic Efficiency at Room Temperature.

Mesoporous Pt-Pd bimetallic core-shell nanospheres (mPd@Pt NSs) with palladium-rich cores and platinum-rich shells were synthesized via a simple, two-step, wet chemical strategy mediated by nitrogen-doped carbon dots. The BET surface area of mPd@Pt NSs was found to be 210.4 m2·g-1, which is significantly higher than the currently reported unsupported Pt-based nanomaterials. Because of the large active surface area, the as-prepared mPd@Pt NSs show superhigh oxidase activity and exhibit excellent oxidase-like catalytic efficiency with a catalytic constant (Kcat) as high as 2.1 × 103 s-1 at room temperature, which is of the same order of magnitude as the natural horseradish peroxidase (HRP) (Kcat = 4.3 × 103 s-1) at 37 °C and five-fold greater than the reported Kcat values of oxidase-like nanozyme obtained at 30 °C.

Active control of terahertz waves based on p-Si hybrid PIT metasurface device under avalanche breakdown.

Active control of terahertz waves is a critical application for terahertz devices. Silicon is widely used in large-scale integrated circuit and optoelectronic devices, and also shows great potential in the terahertz field. In this paper, a p-Si hybrid metasurface device is proposed and its terahertz characteristics under avalanche breakdown effect is investigated. In the study, a plasmon-induced transparency (PIT) effect caused by the near-field coupling of the bright mode and the dark mode is observed in the transmission spectrum. Due to avalanche breakdown effect, the resonance of the PIT metamaterial disappears as the current increased. Carriers existed in the interface between the metasurface and substrate result to a dipole resonance suppression. When the current continues increasing, the maximal modulation depth can reach up to 99.9%, caused by the avalanche effect of p-Si. Experimental results demonstrate that the avalanche breakdown p-Si can achieve a performance modulation depth, bringing much more possibilities for terahertz devices.

Highly Chemoselective [2+1] Annulation of α-Alkylidene Pyrazolones with α-Bromonitroalkenes: Synthesis of Pyrazolone-Based Vinylcyclopropanes and Computational Studies.

A highly chemoselective [2+1] annulation of α-alkylidene pyrazolones with α-bromonitroalkenes has been achieved under mild conditions. α-Alkylidene pyrazolones were unprecedentedly used as a C1 synthon to participate in annulation reactions, providing access to diverse vinylcyclopropane-based pyrazolone products. In addition, a spectrum of pharmaceutically interesting pyrazole-fused pyranone oximes could be rapidly obtained through a [2+1] annulation/rearrangement sequential process. Computational studies disclosed the origin of the observed chemoselectivity of the [2+1] cycloaddition.

Ultrasensitive specific sensor based on all-dielectric metasurfaces in the terahertz range.

An ultrasensitive specific sensor based on all-dielectric metasurfaces in the terahertz range was proposed. The designed metasurfaces consist of multi pairs of tilted silicon bars on a SiO2 substrate with a high-Q Fano resonance feature. The peak of this high Q Fano resonance can form a wide reflection spectrum band by scanning the angle of the incident THz waves. Utilizing this angle-scanning strategy, we designed a metasurface sensor and its reflection spectrum band can cover the absorption peak of tyrosine and santonin. By depositing different thicknesses of tyrosine and santonin on the sensor, we have successfully identified them with a detection limit of 6.7 µg cm-2 and 59.35 µg cm-2, respectively. The performance of the sensor with high sensitivity has been analyzed in detail, showing an exciting prospect for identification of 'fingerprint' spectra in the terahertz region.

Increased cardio-ankle vascular index is independently associated with chronic kidney disease: A cross-sectional study in Chinese patients with type 2 diabetes mellitus.

AIMS: This cross-sectional study aimed to investigate the association between arterial stiffness and chronic kidney disease (CKD) in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This study included 1025 patients with T2DM (796 men, 229 women). The cardio-ankle vascular index (CAVI) served as an index to evaluate arterial stiffness. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or urinary albumin-creatine ratio ≥ 30 mg/g. Increased CAVI was defined as a value ≥9. RESULTS: The mean CAVI was 8.4 ±â€¯1.2. Among the patients, 314 (40%) had increased CAVI and 229 (22.3%) had CKD. Blood pressure, HbA1c levels, total cholesterol, low-density lipoprotein cholesterol, uric acid and CAVI were higher among patients with CKD than among those without CKD. Patients with increased CAVI were at a 1.82-fold (95% CI, 1.20-2.75; P < 0.001) higher prevalence of CKD after adjusting for other variables. The odds ratio for CKD was 2.69 (95% CI, 1.12-6.47; P = 0.027) in women and 1.62 (95% CI, 1.01-2.61; P = 0.045) in men. CONCLUSION: Increased CAVI was independently associated with CKD in patients with T2DM. Further longitudinal studies with large sample sizes are warranted to investigate the effect of CAVI on CKD in patients with T2DM.

Asymmetric synthesis of tetrahydroisoquinoline-fused spirooxindoles as Ras-GTP inhibitors that inhibit colon adenocarcinoma cell proliferation and invasion.

Here we report the synthesis of a library of chiral THIQ-fused spirooxindoles, which combine two privileged scaffolds in antitumor medicinal chemistry. Some of the library members inhibit the proliferation and invasion ability of Ras-mutated colon adenocarcinoma cells. Mechanistic studies suggest that the most potent compound, 3m, inhibits Ras-GTP and thereby suppresses downstream signaling mediated by MAPK, PI3K-Akt and Wnt. Ultimately this leads to mitochondrial apoptosis.