Smoking and Mortality in Tianjin, China: A Death Registry-Based Case-Control Study, 2010-2014.

Introduction: We conducted a mortality case-control study to assess the risks of all-cause and major causes of death attributable to smoking in Tianjin from 2010 through 2014. The death registry-based study used data from The Tianjin All Causes of Death Surveillance System, which collects information routinely on smoking of the deceased in the death certificate of Tianjin Centers for Disease Control and Prevention.

Methods: Cases (n = 154,086) and controls (n = 25,476) were deaths at 35 to 79 years from smoking-related and nonsmoking-related causes, respectively.

Discovery of novel 3-hydroxypicolinamides as selective inhibitors of HIV-1 integrase-LEDGF/p75 interaction.

Currently, three HIV-1 integrase (IN) active site-directed inhibitors are in clinical use for the treatment of HIV infection. However, emergence of drug resistance mutations have limited the promise of a long-term cure. As an alternative, allosteric inhibition of IN activity has drawn great attention and several of such inhibitors are under early stage clinical development.

Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization.

Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two imidazonaphthyridinone frameworks with 1,8- and 3,5-disubstitution pattern as class I and class II c-Met kinase inhibitors, respectively. Further structural optimization on type II inhibitors by truncation of the imidazonaphthyridinone core and incorporation of an N-phenyl cyclopropane-1,1-dicarboxamide pharmacophore led to the discovery of novel imidazopyridine-based c-Met kinase inhibitors, displaying nanomolar enzyme inhibitory activity and improved Met kinase selectivity.

Discovery of a novel 5-carbonyl-1H-imidazole-4-carboxamide class of inhibitors of the HIV-1 integrase-LEDGF/p75 interaction.

Though much progress has been made in the inhibition of HIV-1 integrase catalysis, clinical resistance mutations have limited the promise of long-term drug prescription. Consequently, allosteric inhibition of integrase activity has emerged as a promising approach to antiretroviral discovery and development. Specifically, inhibitors of the interaction between HIV-1 integrase and cellular cofactor LEDGF/p75 have been validated to diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity.

Design of cell-permeable stapled peptides as HIV-1 integrase inhibitors.

HIV-1 integrase (IN) catalyzes the integration of viral DNA into the host genome, involving several interactions with the viral and cellular proteins. We have previously identified peptide IN inhibitors derived from the α-helical regions along the dimeric interface of HIV-1 IN. Herein, we show that appropriate hydrocarbon stapling of these peptides to stabilize their helical structure remarkably improves the cell permeability, thus allowing inhibition of the HIV-1 replication in cell culture.

Repositioning HIV-1 integrase inhibitors for cancer therapeutics: 1,6-naphthyridine-7-carboxamide as a promising scaffold with drug-like properties.

Among a large number of HIV-1 integrase (IN) inhibitors, the 8-hydroxy-[1,6]naphthyridines (i.e., L-870,810) were one of the promising class of antiretroviral drugs developed by Merck Laboratories.

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways.

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508).

Two new metabolites from the mangrove endophytic fungus no. 2106.

Two new metabolites, named no. 2106 A (1) and cyclo-(N-MeVal-N-MeAla) (2), have been produced by the endophytic fungus no. 2106 isolated from the seeds of the mangrove Avicennia marina in Hong Kong.

Four new aromatic allenic ethers from the fungus Xylaria sp. No. 2508.

Four new aromatic allenic ethers, (7E)-3-(4-buta-2,3-dienyloxy-3-methoxy-phenyl)-acrylic acid methyl ester (1), (7E)-3-[4-(4-buta-2,3-dienyloxy-benzyloxy)-phenyl]-acrylic acid methyl ester (2), 4-(4-buta-2,3-dienyloxy-benzyloxy)-benzoic acid methyl ester (3), (7E)-3-[4-(4-buta-2,3- dienyloxy-benzyloxy)-3-methoxy-phenyl]-acrylic acid methyl ester (4) were isolated from the fungus Xylaria sp. No. 2508.