Iridium-Catalyzed Asymmetric Hydrogenation of 2<i>H</i>‑Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives

A highly efficient (a<i>S</i>)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2<i>H</i>-chromenes and substituted benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides is described. A series of 2<i>H</i>-chromenes and benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92–99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds

Iridium-Catalyzed Asymmetric Hydrogenation of 2<i>H</i>‑Chromenes: A Highly Enantioselective Approach to Isoflavan Derivatives

A highly efficient (a<i>S</i>)-Ir/In-BiphPHOX-catalyzed asymmetric hydrogenation of substituted 2<i>H</i>-chromenes and substituted benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides is described. A series of 2<i>H</i>-chromenes and benzo­[<i>e</i>]­[1,2]­oxathiine 2,2-dioxides were hydrogenated to give the target products in high yields (92–99%) with excellent enantioselectivities (up to 99.7% ee) using our catalytic system. This reaction provides a direct and efficient method for the construction of chiral benzo six-membered oxygen-containing compounds

The <i>myotrophin</i> rs17168525 C/T variant occurs in the let-7/miR-98 binding site.

<p>The variant rs17168525 is a C to T change (mRNA sequence as reference) located in the predicted binding site for let-7/miR-98 in the 3′-UTR of the <i>myotrophin</i> gene. C-allele at rs17168525 base-paired with G in Watson—Crick mode (shown with a solid line). However, when the T-allele is present, base-pairing complementarity is interrupted (shown with a dashed line).</p

Let-7c suppresses the protein expression level of myotrophin <i>in vitro</i> cellular model.

<p>Cardiomyocytes were infected with PremiR miRNA precursor or Anti-miR miRNA inhibitor of let-7c (<i>A</i> and <i>B</i>). Myotrophin expression was analyzed by immunoblot 48 h after infection. *p < 0.05.</p

Testing the interaction between let-7c and <i>myotrophin</i> using a lucisferase reporter assay.

<p>Hela cells were co-transfected with <i>myotrophin</i>-pMIR-C or <i>myotrophin</i>-pMIR-T, and either negative control miRNA (PremiR-NC) or let-7c. 48 h after transfection, luciferase activities were measured. Firefly luciferase activity was normalized to <i>Renilla</i> luciferase expression, and mean activities ± S.E. from four independent experiments are shown. For <i>myotrophin</i>-pMIR-C transfection, PremiR-NC versus let-7c, P = 0.002; for <i>myotrophin</i>-pMIR-T transfection, PremiR-NC versus let-7c, P = 0.626.</p

Possible associations between <i>myotrophin</i> variant and hypertension or left ventricular hypertrophy in the case-control study.

<p>^a:Compared to controls. Adjusted ORs (95% CIs) were stratified by age, gender, BMI, SBP, DBP, smoking status, alcohol consumption and glucose.</p><p>Possible associations between <i>myotrophin</i> variant and hypertension or left ventricular hypertrophy in the case-control study.</p

Baseline characteristics in controls and hypertensive patients.

<p>Values are means ±SD or percentage.</p><p>*P <0.05 and</p><p>**P <0.01 compared with controls.</p><p>BMI, body mass index; BP, blood pressure; SBP, systolic BP; DBP, diastolic BP; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triacylglycerol.</p><p>Baseline characteristics in controls and hypertensive patients.</p

The <i>myotrophin</i> rs17168525 C/T variant occurs in the let-7/miR-98 binding site.

<p>The variant rs17168525 is a C to T change (mRNA sequence as reference) located in the predicted binding site for let-7/miR-98 in the 3′-UTR of the <i>myotrophin</i> gene. C-allele at rs17168525 base-paired with G in Watson—Crick mode (shown with a solid line). However, when the T-allele is present, base-pairing complementarity is interrupted (shown with a dashed line).</p

Specially-Made Lipid-Based Assemblies for Improving Transmembrane Gene Delivery: Comparison of Basic Amino Acid Residue Rich Periphery

Cationic lipid based assemblies provide a promising platform for effective gene condensation into nanosized particles, and the peripheral properties of the assemblies are vital for complexation and interaction with physical barriers. Here, we report three cationic twin head lipids, and each of them contains a dioleoyl-glutamate hydrophobic tail and a twin polar head of lysine, arginine, or histidine. Such lipids were proven to self-assemble in aqueous solution with well-defined nanostructures and residual amino-, guanidine-, or imidazole-rich periphery, showing strong buffering capacity and good liquidity. The assemblies with arginine (RL) or lysine (KL) periphery exhibited positive charges (∼+35 mV) and complete condensation of pDNA into nanosized complexes (∼120 nm). In contrast, assemblies composed of histidine-rich lipids (HL) showed relatively low cationic electric potential (∼+10 mV) and poor DNA binding ability. As expected, the designed RL assemblies with guanidine-rich periphery enhanced the <i>in vitro</i> gene transfection up to 190-fold as compared with the golden standard PEI_25k and Lipofectamine 2000, especially in the presence of serum. Meanwhile, interaction with cell and endo/lysosome membrane also revealed the superiority of RL complexes, that the guanidine-rich surface efficiently promoted transmembrane process in cellular internalization and endosomal disruption. More importantly, RL complexes also succeeded beyond others <i>in vivo</i> with significantly (∼7-fold) enhanced expression in HepG2 tumor xenografts in mice, as well as stronger green fluorescence protein imaging in isolated tumors and tumor frozen sections

Bifunctional Cascading Nanozymes Based on Carbon Dots Promotes Photodynamic Therapy by Regulating Hypoxia and Glycolysis

Photodynamic therapy (PDT) still faces great challenges with suitable photosensitizers, oxygen supply, and reactive oxygen species (ROS) accumulation, especially in the tumor microenvironment, feathering hypoxia, and high glucose metabolism. Herein, a carbon dots (CDs)-based bifunctional nanosystem (MnZ@Au), acting as photosensitizer and nanozyme with cascading glucose oxidase (GOx)- and catalase (CAT)-like reactivity, was developed for improving hypoxia and regulating glucose metabolism to enhance PDT. The MnZ@Au was constructed using Mn-doped CDs (Mn-CDs) as a core and zeolitic imidazolate framework-8 (ZIF-8) as a shell to form a hybrid (MnZ), followed by anchoring ultrasmall Au nanoparticles (AuNPs) onto the surface of MnZ through the ion exchange and in situ reduction methods. MnZ@Au catalyzed glucose consumption and oxygen generation by cascading GOx- and CAT-like nanozyme reactions, which was further enhanced by its own photothermal properties. In vitro and in vivo studies also confirmed that MnZ@Au greatly improved CDs penetration, promoted ROS accumulation, and enhanced PDT efficacy, leading to efficient tumor growth inhibition in the breast tumor model. Besides, MnZ@Au enabled photoacoustic (PA) imaging to provide a mapping of Mn-CDs distribution and oxygen saturation, showing the real-time catalytic process of MnZ@Au in vivo. 18F-Fluorodeoxy­glucose positron emission tomography (18F-FDG PET) imaging also validated the decreased glucose uptake in tumors treated by MnZ@Au. Therefore, the integrated design provided a promising strategy to utilize and regulate the tumor microenvironment, promote penetration, enhance PDT, and finally prevent tumor deterioration