Notes

Cross-sectional photo review involving kidney people with focus on MRI.
Isethionate sulfite-lyase (IseG) is a recently characterized glycyl radical enzyme (GRE) that catalyzes radical-mediated C-S bond cleavage of isethionate to produce acetaldehyde and sulfite. Herein, we use quantum mechanical/molecular mechanical (QM/MM) calculations to investigate the detailed catalytic reaction mechanism of IseG. Our calculations indicate that a previously proposed direct 1,2-elimination mechanism is disfavored. Instead, we suggest a new 1,2-migration mechanism for this enzymatic reaction a key stepwise 1,2-SO3- radical migration occurs after the catalytically active cysteinyl radical grabs a hydrogen atom from isethionate, followed by hydrogen atom transfer from cysteine to a 1-hydroxylethane-1-sulfonate radical intermediate. Finally, the elimination of sulfite from 1-hydroxylethane-1-sulfonate to result in the final product is likely to occur outside the enzyme. Glu468 in the active site is found to help orient the substrate rather than grabbing a proton from the hydroxyl group of the substrate. Our findings help reveal the mechanisms of radical-mediated C-S bond cleavage of organosulfonates catalyzed by GREs and expand the understanding of radical-based enzymatic catalysis.The natural products piperlongumine (1) and ligustrazine (2) have been reported to exert antiproliferative effects against various types of cancer cells by up-regulating the level of reactive oxidative species (ROS). However, the moderate activities of 1 and 2 limit their application. To improve their potential antitumor activity, novel piperlongumine/ligustrazine derivatives were designed and prepared, and their potential pharmacological effects were determined in vitro and in vivo. Among the derivatives obtained, 11 exerted more prominent inhibitory activities against proliferation of drug-sensitive/-resistant cancer cells with lower IC50 values than 1. Particularly, the IC50 value of 11 against drug-resistant Bel-7402/5-FU cells was 0.9 μM, which was about 9-fold better than that of 1 (IC50 value of 8.4 μM). TVB-3166 chemical structure Mechanistic studies showed that 11 demonstrated thioredoxin reductase (TrxR) inhibitory activity, increase of ROS levels, decrease of mitochondrial transmembrane potential levels, and occurrence of DNA damage and autophagy, in a dose-dependent manner, via regulation of DNA damage protein H2AX and autophagy-associated proteins LC3, beclin-1, and p62 in drug-resistant Bel-7402/5-FU cells. Finally, compound 11 at 5 mg/kg displayed potent antitumor activity in vivo with tumor suppression of 76% (w/w). Taken together, compound 11 may represent a promising candidate drug for the chemotherapy of drug-resistant hepatocellular carcinoma and warrant more intensive study.ConspectusLead halide perovskites are under the spotlight of current research due to their potential for efficient and cost-effective next-generation optoelectronic devices. The unique photonic and electronic properties of these solution-processable materials brought them to the forefront of materials science. However, the toxicity and instability of lead-based perovskites are the major hurdles for their commercialization. These issues initiated an effort towards the development of environmentally friendly, lead-free perovskites. In this context, bismuth halide perovskites (BHPs) were ideal rivals for lead-based congeners due to their excellent chemical stability, lower toxicity, and structural versatility. Understanding the crystal structure and optoelectronic properties of BHPs is crucial for designing them for specific, tailor-made applications. This Account aims to review our recent research progress on the role of functional organic spacer cations in modulating the electronic confinements, optical properties, and photoconductivity of BHPs. We have employed a comprehensive experimental and theoretical investigation to probe the intriguing optical and electronic properties of these materials. Our findings on the structure-optoelectronic property correlations will be valuable guidelines for the rational selection of organic spacer cations in designing BHPs featuring low exciton binding energy, narrow optical bandgap, enhanced visible light absorption, and high photoconductivity. One of our key findings is that by increasing the electron affinity of the organic spacer ligands, photoconductivity and visible light absorption of BHPs could be significantly enhanced. We hope that the fundamental level understanding of the photophysical properties discussed in this Account will lead to new design rules for developing high-performance BHP materials.The potential of copper(I)-zeolite catalysis was evaluated in the three-component KA2-coupling mediated synthesis of α-tertiary propargylamines. Our archetypal copper(I)-doped zeolite CuI-USY proved to be efficient under ligand- and solvent-free conditions at 80 °C. Usable up to four times, this catalytic material enables the coupling of diverse ketones, alkynes, and amines with a broad functional group tolerance. A decarboxylative and a desilylative version, respectively, involving an alkynoic acid and trimethylsilylacetylene as alkyne surrogates, was also set up to bypass selectivity issues and/or to access α-tertiary propargylamines that are unattainable under standard KA2 conditions. Interestingly, the KA2-type coupling reactions were successfully linked to other CuI-catalyzed reactions, thus resulting in sequential one-pot processes under full CuI-USY catalysis.A series of Cu(II) complexes, 1-4 and 6, were synthesized through a reaction of amine-functionalized pincer-like ligands, HL1,2, La,b, and a bidentate ligand L1 with CuCl2·2H2O. The chemical reduction of complex 1 using 1 equiv of sodium l-ascorbate resulted in a dimeric Cu(I) complex 5 in excellent yield. All of the complexes, 1-6, were thoroughly characterized using various physicochemical characterization techniques, single-crystal X-ray structure determination, and density functional theory calculations. Ligands HL1,2 and La,b behaved as tridentated donors by the coordination of the amine side arm in their respective Cu(II) complexes, and the amine side arm remained as a pendant in Cu(I) complexes. All of these complexes (1-6) were explored for copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) reaction at room temperature in water under air. Complex 5 directly served as an active catalyst; however, complexes 1-4 and 6 required 1 equiv of sodium l-ascorbate to generate their corresponding iazoles having medicinal, catalytic, and targeting properties.The analytical ultracentrifuge (AUC) and the modern field of analytical ultracentrifugation found its inception approximately a century ago. We highlight the scope of its major experimental opportunities as a transport-based method, contemporary and up-and-coming investigation potential for polymers, polymer-drug conjugates, polymer assemblies, as well as medical nanoparticles. Special focus lies on molar mass estimates of unimeric polymeric species, self-assemblies in solution, and (co)localization of multicomponent systems in solution alongside the material-biofluid interactions. We close with present challenges and incentives for future research.Bioactive substances, displaying excellent biocompatibility, chemical stability, and processability, could be extensively applied in biomedicine and tissue engineering. In recent years, plant-based bioactive substances such as flavonoids, vitamins, terpenes, and lignin have received considerable attention due to their human health benefits and pharmaceutical/medical applications. Among them is lignin, an amorphous biomacromolecule mainly derived from the combinatorial radical coupling of three phenylpropane units (p-hydroxypenyl, guaiacyl, and syringyl) during lignification. Lignin possesses intrinsic bioactivities (antioxidative, antibacterial, anti-UV activities, etc.) against phytopathogens. Lignin also enhances the plant resistance (adaptability) against environmental stresses. The abundant structural features of lignin offer other significant bioactivities including antitumor and antivirus bioactivities, regulation of plant growth, and enzymatic hydrolysis of cellulose. This Review reports the latest research results on the bioactive potential of lignin and lignin-based substances in biomedicine, agriculture, and biomass conversion. Moreover, the interfacial reactions and bonding mechanisms of lignin with biotissue/cells and other constituents were also discussed, aiming at promoting the conversion or evolution of lignin from industrial wastes to value-added bioactive materials.We develop a new family of electronic structure methods for capturing at the same time the dynamic and nondynamic correlation effects. We combine the natural orbital functional theory (NOFT) and many-body perturbation theory (MBPT) through a canonicalization procedure applied to the natural orbitals to gain access to any MBPT approximation. We study three different scenarios corrections based on second-order Møller-Plesset (MP2), random-phase approximation (RPA), and coupled-cluster singles doubles (CCSD). Several chemical problems involving different types of electron correlation in singlet and multiplet spin states have been considered. Our numerical tests reveal that RPA-based and CCSD-based corrections provide similar relative errors in molecular dissociation energies (De) to the results obtained using a MP2 correction. With respect to the MP2 case, the CCSD-based correction improves the prediction, while the RPA-based correction reduces the computational cost.Despite the formation of mechanically inferior fibrocartilage, microfracture (MF) still remains the gold standard to repair the articular cartilage defects in clinical settings. To date, although many tissue-engineering scaffolds have been developed to enhance the MF outcome, the clinical outcomes remain inconsistent. Decellularized extracellular matrix (dECM) is among the most promising scaffold for cartilage repair due to its inheritance of the natural cartilage components. However, the impact of dECM from different developmental stages on cellular chondrogenesis and therapeutic effect remains elusive, as the development of native cartilage involves the distinct temporal dependency of the ECM components and various growth factors. Herein, we hypothesized that the immature cartilage dECM at various developmental stages was inherently different, and would consequently impact the chondrogenic potential BMSCs. In this study, we fabricated three different unidirectional collagen-dECM scaffolds sourced from neonatal, childhood, and adolescent rabbit cartilage tissues, and identified the age-dependent biological variations, including DNA, cartilage-specific proteins, and growth factors; along with the mechanical and degradation differences. Consequently, the different local cellular microenvironments provided by these scaffolds led to the distinctive cell morphology, circularity, proliferation, chondrogenic genes expression, and chondrogenesis of BMSCs in vitro, and the different gross morphology, cartilage-specific protein production, and subchondral bone repair when in combination with microfracture in vivo. Together, this work highlights the immature cartilage dECM at different developmental stages that would result in the diversified effects to BMSCs, and childhood cartilage would be considered the optimal dECM source for the further development of dECM-based tissue engineering scaffolds in articular cartilage repair.
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