Switchable Synthesis of 3‑Substituted 1<i>H</i>‑Indazoles and 3,3-Disubstituted 3<i>H</i>‑Indazole-3-phosphonates Tuned by Phosphoryl Groups

3-Alkyl/aryl-1<i>H</i>-indazoles and 3-alkyl/aryl-3<i>H</i>-indazole-3-phosphonates were synthesized efficiently through a 1,3-dipolar cycloaddition reaction between α-substituted α-diazomethylphosphonates and arynes under simple reaction conditions. The product distribution was controlled by the phosphoryl group, which acted both as a tuning group and a traceless group in the reaction

Synthesis of Chiral 1,1,1-Trifluoro-<i>α,α</i>-disubstituted 2,4-Diketones via Palladium-Catalyzed Asymmetric Allylation

Trifluoromethyl ketones are important enzyme inhibitors and versatile synthons for the preparation of trifluoromethylated heterocycles and complex molecules. An efficient methodology for the synthesis of chiral 1,1,1-trifluoro-α,α-disubstituted 2,4-diketones via palladium-catalyzed allylation with allyl methyl carbonates under mild conditions has been developed. This method surmounts the major obstacle of detrifluoroacetylation, and a chiral trifluoromethyl ketone library could be rapidly built up from simple substrates in good yields and enantioselectivities, thereby offering a new choice for scientists in pharmaceutical and material industries

Synthesis of Chiral 1,1,1-Trifluoro-<i>α,α</i>-disubstituted 2,4-Diketones via Palladium-Catalyzed Asymmetric Allylation

Trifluoromethyl ketones are important enzyme inhibitors and versatile synthons for the preparation of trifluoromethylated heterocycles and complex molecules. An efficient methodology for the synthesis of chiral 1,1,1-trifluoro-α,α-disubstituted 2,4-diketones via palladium-catalyzed allylation with allyl methyl carbonates under mild conditions has been developed. This method surmounts the major obstacle of detrifluoroacetylation, and a chiral trifluoromethyl ketone library could be rapidly built up from simple substrates in good yields and enantioselectivities, thereby offering a new choice for scientists in pharmaceutical and material industries

Additional file 1 of Prone versus lateral position in acute hypoxemic respiratory failure patients with HFNO therapy: study protocol for a multicentre randomised controlled open-label trial

Additional file 1. The standards for admitting patients to the ICU

βKlotho overexpression induced G1 to S phase arrest of hepatoma cells.

<p>(A, B) A representative data of flow cytometric analysis of Hep3B cells transfected with vector or βKlotho. (C, D) A representative data of flow cytometric analysis of SMMC-7721 cells transfected with vector or βKlotho. (E) The cell percentages in G0/G1, S and G2/M phase were measured in three independent experiments. * indicates <i>p</i> < 0.05.</p

Relationship between βKlotho expression and clinicopathologic features of patients with hepatocellular carcinoma.

<p>Relationship between βKlotho expression and clinicopathologic features of patients with hepatocellular carcinoma.</p

Regulation of Akt/GSK-3β/cyclin D1 signaling pathway by βKlotho.

<p>Western blotting analysis of βKlotho, cyclin D1, phosphorylated Akt (p-Akt), Akt, phosphorylated GSK-3β (p-GSK-3β), GSK-3β and tubulin levels in the indicated hepatoma cell lines transfected with vector or βKlotho. The experiments were performed independently three times at least.</p

βKlotho overexpression inhibited hepatoma cell proliferation.

<p>(A) Colony formation assay. Representative micrographs (left panel) and quantification (right panel) of crystal violet-stained Hep3B or SMMC-7721 cells transfected with either vector or βKlotho. (B) Viability of βKlotho-transfected or vector-transfected Hep3B cells were determined by MTT assay on days 1 to 5 after transfection. (C) Viability of βKlotho-transfected or vector-transfected SMMC-7721 cells were determined by MTT assay on days 1 to 5 after transfection. Each bar represents the average ± SD of three independent experiments. * indicates <i>p</i> < 0.05.</p

Decreased expression of βKlotho in HCC tissue and hepatoma cell lines.

<p>(A) Immunohistochemical analysis of βKlotho protein expression in non-tumor liver samples and HCC samples. Representative photographs were taken at ×200 or ×1000 magnifications. (B) Statistical quantification of relative MOD of βKlotho staining in non-tumor liver samples and HCC samples (47 cases). (C) Western blot analysis and (D) statistical quantification of βKlotho expression in hepatoma cell lines (HepG2, Hep3B, SMMC-7721 and Huh 7) and normal hepatocyte cell line (L02). Tubulin expression levels were used as internal controls. * indicates <i>p</i> < 0.05. The experiments were performed independently three times at least.</p

Liposomal Resveratrol Alleviates Platelet Storage Lesion via Antioxidation and the Physical Buffering Effect

Platelet transfusion is essential in the treatment of platelet-related diseases and the prevention of bleeding in patients with surgical procedures. Platelet transfusion efficacy and shelf life are limited mainly by the development of platelet storage lesion (PSL). Mitigating PSL is the key to prolonging the platelet shelf life and reducing wastage. Excess intracellular reactive oxygen species (ROS) are one of the main factors causing PSL. In this study, we explored a nanomedicine strategy to improve the quality and functions of platelets in storage. Resveratrol (Res), a natural plant product, is known for its antioxidative effect. However, medical applications of Res are limited due to its low water solubility and stability. Therefore, we used a resveratrol-loaded liposomal system (Res-Lipo) to better utilize the antioxidant effect of the drug. This study aimed to evaluate the effect of Res-Lipo on platelet oxidative stress and alleviation of PSL during the storage time. Res-Lipo scavenged intracellular ROS and inhibited platelet apoptosis and activation during storage. Res-Lipo not only maintained mitochondrial function but also improved platelet aggregation in response to adenosine 5′-diphosphate. These results revealed that Res-Lipo ameliorated PSL and prolonged the platelet survival time in vivo. The strategy provides a potential method for extending the platelet storage time and might be considered a potential and safe additive to alleviate PSL