From July to December 2000, ambient methane concentrations were continuously monitored at one sampling site 92 m above ground in Beijing city. Together with meteorological data measured at 22 municipal stations, a backward trajectory inversion model was developed to calculate methane emissions in the city. Model results were compared with a methane emission inventory established with updated emission factors and intensive survey of sources.From the source inventory, the total methane emissions were estimated to be 296.4Gg/yr, while municipal solid waste and fossil fuel account for 54.5% and 32.4% of total emissions. This showed that methane emissions in Beijing were dominated by anthropogenic sources. The inversion model described real-time methane emitted into the mixing layer along a backward trajectory path and also the exchange between reservoir layer and mixing layer. The Singular Value Decomposition (SVD) matrix inversion technique was used to calculate the methane emissions in each grid in the simulated region. The source distribution and quantitative results from model agreed well with the emission inventory, and the largest uncertainty in it was the distribution of methane emission from coal mines due to lack of trajectories covering coal mine areas.

Emission inventory

Mixing ratio

10.3184/095422902782775308

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Citations (4)

Design, Synthesis, and Biological Evaluation of the First c-Met/HDAC Inhibitors Based on Pyridazinone Derivatives

ACS Medicinal Chemistry Letters (2017)

Dong Lu Juan Yan Lang Wang Hong‐Chun Liu Limin Zeng

Simultaneous blockade of more than one pathway is considered to be a promising approach to overcome the low efficacy and acquired resistance of cancer therapies. Thus, a novel series of c-Met/HDAC bifunctional inhibitors was designed and synthesized by merging pharmacophores of c-Met and HDAC inhibitors. The most potent compound, 2m, inhibited c-Met kinase and HDAC1, with IC50 values of 0.71 and 38 nM, respectively, and showed efficient antiproliferative activities against both EBC-1 and HCT-116 cells with greater potency than the reference drug Chidamide. Western blot analysis revealed that compound 2m inhibited phosphorylation of c-Met and c-Met downstream signaling proteins and increased expression of Ac-H3 and p21 in EBC-1 cells in a dose-dependent manner. Our study presents novel compounds for the further exploration of dual c-Met/HDAC pathway inhibition achieved with a single molecule.

HDAC1

IC50

10.1021/acsmedchemlett.7b00172

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Citations (43)

Development of multi-channel whole-air sampling equipment onboard an unmanned aerial vehicle for investigating volatile organic compounds' vertical distribution in the planetary boundary layer

Atmospheric measurement techniques (2023)

Suding Yang Xin Li Limin Zeng Xuena Yu Ying Liu

Abstract. To achieve near-continuous vertical observations of volatile organic compounds (VOCs) in the planetary boundary layer (PBL), multi-channel whole-air sampling equipment onboard an unmanned aerial vehicle (UAV) platform was developed in this study. The equipment consists of a multi-position solenoid valve and specially designed lightweight quartz sampling canisters. The canisters have little adsorption loss of VOCs and good inter-canister reproducibility. The 7 d recovery test shows that most VOC species (97 %) had a 1-week decay within 20 %. Online instruments for measuring O3, NO2, CO, SO2, and meteorological parameters are also integrated into the UAV platform. During one take-off and landing, the UAV platform can reach 800 m above the ground within 40 min and take whole-air samples at six heights. Vertical profiles of VOCs and trace gases during the evolution of the PBL in south-western China are successfully obtained by deploying the newly developed UAV system.

Trace gas

10.5194/amt-16-501-2023

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Optimization and Synthesis of Pyridazinone Derivatives as Novel Inhibitors of Hepatitis B Virus by Inducing Genome-free Capsid Formation

ACS Infectious Diseases (2016)

Dong Lu Feifei Liu Weiqiang Xing Xiankun Tong Lang Wang

The capsid of hepatitis B virus (HBV) plays a vital role in virus DNA replication. Targeting nucleocapsid function has been demonstrated as an effective approach for anti-HBV drug development. A high-throughput screening and mechanism study revealed the hit compound 4a as an HBV assembly effector (AEf), which could inhibit HBV replication by inducing the formation of HBV DNA-free capsids. The subsequent SAR study and drug-like optimization resulted in the discovery of the lead candidate 4r, with potent antiviral activity (IC50 = 0.087 ± 0.002 μM), low cytotoxicity (CC50 = 90.6 ± 2.06 μM), sensitivity to nucleoside analogue-resistant HBV mutants, and synergistic effect with nucleoside analogues in HepG2.2.15 cells.

Antiviral drug

Nucleoside analogue

10.1021/acsinfecdis.6b00159

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Citations (15)

DGAT1 inhibitors protect pancreatic β-cells from palmitic acid-induced apoptosis

Acta Pharmacologica Sinica (2020)

Jun‐Shang Huang Binbin Guo Gaihong Wang Limin Zeng Youhong Hu

Pancreatic Islets

Lipotoxicity

Proinflammatory cytokine

10.1038/s41401-020-0482-7

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Citations (22)

Discovery of Phthalazinone Derivatives as Novel Hepatitis B Virus Capsid Inhibitors

Journal of Medicinal Chemistry (2020)

Wuhong Chen Feifei Liu Qiliang Zhao Xinna Ma Dong Lu

HBV capsid assembly has been viewed as an attractive target for new antiviral therapies against HBV. On the basis of a lead compound 4r, we further investigated this target to identify novel active compounds with appropriate anti-HBV potencies and improved pharmacokinetic (PK) properties. Structure–activity relationship studies based on metabolic pathways of 4r led to the identification of a phthalazinone derivative 19f with appropriate anti-HBV potencies (IC50 = 0.014 ± 0.004 μM in vitro), which demonstrated high oral bioavailability and liver exposure. In the AAV-HBV/mouse model, administration of 19f resulted in a 2.67 log reduction of the HBV DNA viral load during a 4-week treatment with 150 mg/kg dosing twice daily.

IC50

10.1021/acs.jmedchem.0c00346

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Citations (21)