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To study the importance of the adsorption mechanism of methane (CH4) and carbon dioxide (CO2) in coal for coalbed methane development, we aimed to reveal the influence mechanism of adsorption pressure, temperature, gas properties, water content, and other factors on gas molecular adsorption behavior from the molecular level. In this study, we selected the nonsticky coal in Chicheng Coal Mine as the research object. Based on the coal macromolecular model, we used the molecular dynamics (MD) and Monte Carlo (GCMC) methods to simulate and analyze the conditions of different pressure, temperature, and water content. The change rule and microscopic mechanism of the adsorption amount, equal adsorption heat, and interaction energy of CO2 and CH4 gas molecules in the coal macromolecular structure model establish a theoretical foundation for revealing the adsorption characteristics of coalbed methane in coal and provide technical support for further improving coalbed methane extraction.
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In order to study the importance of the diffusion mechanism of CH4 and CO2 in coal for the development of coalbed methane, the aim of this paper is to reveal the influence mechanism of pressure, temperature, water content and other factors on the molecular diffusion behavior of gas at the molecular level. In this paper, non-sticky coal in Chicheng Coal Mine is taken as the research object. Based on the molecular dynamics method (MD) and Monte Carlo (GCMC) method, the diffusion characteristics and microscopic mechanism of CH4 and CO2 in coal under different pressures (100 kPa-10 MPa), temperatures (293.15-313.15 K) and water contents (1-5%) were analyzed in order to lay a theoretical foundation for revealing the diffusion characteristics of CBM in coal, and provide technical support for further improving CBM extraction. The results show that high temperature is conducive to gas diffusion, while high pressure and water are not conducive to gas diffusion in the coal macromolecular model.
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The construction of an N-C chiral axis for N-aryl indole derivatives is meaningful as they widely exist in functionalized molecules. This work provides a novel method for this purpose via amination of amino acid derivatives at the C2 position of the indole and chiral center induced chiral axis formation. The protocol of this transformation is easily accessible, not requiring metal or an organic chiral catalyst, endowing this method with great potential in the construction of axis chiral N-aryl indoles.
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Indóis , Aminação , Indóis/química , CatáliseRESUMO
Based on the production conditions of the 10103 excavation working face of the Baozigou coal mine, this paper analyzes the potential sources of H2S and the expected emission concentrations of H2S in the working face. Considering the previous engineering practice for controlling H2S disasters in coal mine working faces, numerical simulations were conducted to investigate air flow and H2S migration and diffusion in the tunnel in the excavation working face. The migration and distribution of H2S in the coal seam mining face were studied, and the effects of outlet wind speed, duct location, and duct diameter on the H2S concentration distribution were explored. The higher the outlet wind speed, the more conducive to the emission of H2S gas, but too high a wind speed will be detrimental to the concentrated extraction and purification absorption of H2S; the closer the outlet position of the air duct is to the end of the working surface, the lower the H2S concentration in the vortex area at the corner; the air duct If the diameter is too small, the harmful gases released from hard-to-break coal cannot be entrained and taken away. When the diameter of the air duct is too large, the entrainment volume during the jet process will be expanded. To verify the field distribution of H2S concentration at the bottom, middle, and top of the boring machine, a CD4-type portable H2S instrument was used to analyze the distribution of H2S near the excavation working face.
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On the basis of the jet theory of airflow fields and the gas-solid two-phase flow theory, we studied the law of dust migration in a simulated dusting space. We used the control variable method and numerical simulation software to explore the airflow field and dust concentration distribution on the working surface of the dusting under different inlet wind speeds and different attached blades of the double-walled annular air curtain. We determined the speed of the inlet of the annular air curtain to be 30 m/s. When the angle of the attached blade was 30°, the dust concentration of the driver and other workers was controlled below 100 mg/m3, which produced the best dust control effect is the best. Using real data, we built a similar test platform to test the airflow field and dust concentration. Through data measurement and analysis, we proved that a dust control system with a double-wall attached-ring air curtain formed a circulating airflow field that could shield dust and effectively reduce dust concentration in the simulated space. The dust removal efficiency of total dust and exhaled dust reached 98.5% and 97.5%, respectively. We compared the test data and simulation results and concluded that the double-wall attached-ring air curtain could effectively ensure the safety of mine production and provide a better underground working environment for operators.
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Poeira , Vento , Humanos , Poeira/análise , Equipamentos de ProteçãoRESUMO
Wee1 is a kinase that regulates cell cycle arrest in response to DNA damage. Wee1 inhibition is a potential strategy to suppress the growth of tumors with defective p53 or DNA repair pathways. However, the development of Wee1 inhibitors faces some challenges. AZD1775, the first-in-class Wee1 inhibitor, has poor kinase selectivity and dose-limiting toxicity. Here, we report the discovery of 12h, a highly selective and potent Wee1 inhibitor with a favorable pharmacokinetic profile. 12h showed strong antiproliferative effects against Lovo cells, a colorectal cancer cell line, both in vitro and in vivo. Moreover, 12h showed a clean kinase profile and effectively induced cell apoptosis. Our results suggest that 12h is a promising drug candidate for further development as a novel anticancer agent.
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Antineoplásicos , Proteínas de Ciclo Celular , Proliferação de Células , Desenho de Fármacos , Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases , Humanos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/química , Animais , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/química , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Relação Estrutura-Atividade , Camundongos NusRESUMO
INTRODUCTION: DNA damage repair in most malignancies with mutation of p53 is more dependent on the G2/M checkpoint. Wee1 kinase is a key regulator of the G2/M checkpoint. If Wee1 is inhibited, it results in cells with unrepaired DNA damage entering mitosis prematurely, leading to mitotic catastrophe and subsequent cell death via the apoptotic program. Therefore, inhibition of Wee1 kinase which overexpressed in several cancer cell lines has emerged as a promising therapy for cancer treatment. AREAS COVERED: This review summarizes for the first time the structures of small-molecule inhibitors of Wee1 reported in patents published from 2003 to 2022 and the recent clinical developments. It also provides perspectives on the challenges and the future directions. We used different methods to search different databases (PubMed, Reaxys, clinicaltrials.gov)for the literature we needed. EXPERT OPINION: Although the small-molecule inhibitors of Wee1, Adavosertib, and ZN-C3 have entered the clinical phase II, the clinical toxicity exhibited by Adavosertib remains the subject of greater concern. The use of Wee1 inhibitors as monotherapy or in combination therapy remains the main trend in Wee1 inhibitors at present.
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Proteínas de Ciclo Celular , Neoplasias , Humanos , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Patentes como Assunto , Neoplasias/tratamento farmacológico , Neoplasias/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular TumoralRESUMO
ATM, a member of the PIKK-like protein family, plays a central role in responding to DNA double-strand breaks and other lesions to protect the genome against DNA damage. Loss of ATM's kinase function has been shown to increase the sensitivity of most cells to ionizing radiation. Therefore, ATM is thought to be a promising target for chemotherapy as a radiotherapy sensitizer. The mechanism of ATM in cancer treatment and the development of its inhibitors have become research hotspots. Here we present an overview of research concerning ATM protein domains, functions and inhibitors, as well as perspectives and insights for future development of ATM-targeting agents.