Abstract The study on the catalysis of ionic liquids for alkylation of benzene with 1-octadecene to synthesize LAB （linear alkylbenzenes） was performed. The results showed that the most important factor that governe...Abstract The study on the catalysis of ionic liquids for alkylation of benzene with 1-octadecene to synthesize LAB （linear alkylbenzenes） was performed. The results showed that the most important factor that governed the conversion of olefin and selectivity of LAB was reaction temperature. Moreover, the effects of different ionic liquids and molar ratio of benzene to 1-octadecene on the conversion and selectivity were obviously in different degrees. The reaction temperature, molar ratio of benzene to 1-octadecene and the amount of catalyst were lower, compared with the traditional reaction technologies. The experimental results demonstrated that the ionic liquid had higher activity at 30℃, with over 98% selectivity of monoalkylbenzene and 100% conversion of the olefin at the molar ratio 0.08 of FeCl3 in ionic liquid to 1-octadecene and 10 for benzene to 1-octadecene.展开更多
A systematic study of the nonselective and smooth etching of GaN/AIGaN het-erostructures was performed using C12/Ar/BCI3 inductively coupled plasmas (ICR).Nonselective etching can be realized by adjusting the BCI3 rat...A systematic study of the nonselective and smooth etching of GaN/AIGaN het-erostructures was performed using C12/Ar/BCI3 inductively coupled plasmas (ICR).Nonselective etching can be realized by adjusting the BCI3 ratio in the Cl2/Ar/BCI3 mixture (20%—60%), increasing the ICR power and dc bias, and decreasing the chamber pressure. Surface morphology of the etched heterostructures strongly depends on the gas chemistry and the chamber pressure. Specifically, with the addition of 20% BCI3 to Cl2/Ar (4:1) gas mixture, nonselective etching of GaN/Al0.28Ga0.72N heterostructures at high etch rate is maintained and the surface root-mean-square (rms) roughness is reduced from 10.622 to 0.495 nm, which is smoother than the as-grown sample. Auger electron spectroscopy (AES) analysis shows that the effective removal of residual oxygen from the surface of AIGaN during the etching process is crucial to the nonselective and smooth etching of GaN/AIGaN herterostructures at high etch rate.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration, with mortality rates approaching...Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration, with mortality rates approaching 100% among suckling piglets. The PEDV 3C-like protease (3CLpro) is essential for viral replication and regarded as a critical target for antiviral inhibitor development. In this study, we aimed to identify small-molecule inhibitors of PEDV by targeting 3CLpro. Virtual screening of 1.6 million compounds from the ChemDiv library identified four potential candidates. Molecular dynamics simulations, specifically analyzing RMSD, RMSF, and Rg, demonstrated increased structural stability of the compound-protease complexes compared to the monomeric enzyme. All compounds had low cytotoxicity in Vero cells (CC_(50) > 200 μM). Fluorescence resonance energy transfer-based assays demonstrated dose-dependent inhibitory activity of the compounds against 3CLpro. Among the candidates, compound F366-0161 exhibited the weakest inhibition, with an IC_(50) value of 151.5 μM. Two analogues, 3238-0395 (IC_(50) of 121.4 μM) and L878-0493 (IC_(50) of 123.6 μM), exhibited moderately enhanced activity. Y041-1672 was identified as the most effective inhibitor, with an IC_(50) of 86.48 μM. In viral replication inhibition assays, Y041-1672 reduced PEDV replication, with an EC_(50) of 17.97 μM and a selectivity index (SI) of 15.5 (CC_(50) /EC_(50) ). These results were validated by RT-qPCR, plaque assays, immunofluorescence, and Western blot analyses. In vitro validation confirmed Y041-1672 as the optimal antiviral candidate, and time-of-addition experiments indicated that inhibition primarily occurred during viral replication. This study identifies scaffold molecules for PEDV antiviral drug development, providing strategic insights for PED treatment.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of novel coronavirus disease 2019,can cause acute respiratory symptoms and even death globally.However,the immune escape mechanism and vi...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of novel coronavirus disease 2019,can cause acute respiratory symptoms and even death globally.However,the immune escape mechanism and viral pathogenesis remain poorly understood.Here,we report that the SARS-CoV-23C-like(3CL)protease specifically cleaves gasdermin D(GSDMD)at Q29 and Q193,producing two N-terminal fragments,GSDMD1-29 and GSDMD1-193.We also found that SARS-CoV-2 infection induced the cleavage of GSDMD.Then,we demonstrated that the ability to cleave GSDMD was dependent on the protease activity of the 3CL protease.Interestingly,unlike the GSDMD1-275 fragment cleaved by caspase-1,GSDMD1-29 and GSDMD1-193 did not trigger pyroptosis or inhibit SARS-CoV-2 replication.Additionally,various RNA viral proteases display different preferences for cleaving GSDMD at Q29 and Q193.Our findings reveal a mechanism by which SARS-CoV-2 and other RNA viruses inhibit pyroptosis,highlighting the critical role of the 3CL protease in immune evasion and viral replication.展开更多
基金Supported by the National Natural Science Foundation of China （No.20276038） and Beijing Natural Science Foundation （No.2052010）.
文摘Abstract The study on the catalysis of ionic liquids for alkylation of benzene with 1-octadecene to synthesize LAB （linear alkylbenzenes） was performed. The results showed that the most important factor that governed the conversion of olefin and selectivity of LAB was reaction temperature. Moreover, the effects of different ionic liquids and molar ratio of benzene to 1-octadecene on the conversion and selectivity were obviously in different degrees. The reaction temperature, molar ratio of benzene to 1-octadecene and the amount of catalyst were lower, compared with the traditional reaction technologies. The experimental results demonstrated that the ionic liquid had higher activity at 30℃, with over 98% selectivity of monoalkylbenzene and 100% conversion of the olefin at the molar ratio 0.08 of FeCl3 in ionic liquid to 1-octadecene and 10 for benzene to 1-octadecene.
基金the Foundation for Key Projects of Basic Research (TG2000036601)the '863' High Tech Foundation (2002AA31119Z, 2001AA312190) the National Natural Science Foundation of China (Grant No. 60244001).
文摘A systematic study of the nonselective and smooth etching of GaN/AIGaN het-erostructures was performed using C12/Ar/BCI3 inductively coupled plasmas (ICR).Nonselective etching can be realized by adjusting the BCI3 ratio in the Cl2/Ar/BCI3 mixture (20%—60%), increasing the ICR power and dc bias, and decreasing the chamber pressure. Surface morphology of the etched heterostructures strongly depends on the gas chemistry and the chamber pressure. Specifically, with the addition of 20% BCI3 to Cl2/Ar (4:1) gas mixture, nonselective etching of GaN/Al0.28Ga0.72N heterostructures at high etch rate is maintained and the surface root-mean-square (rms) roughness is reduced from 10.622 to 0.495 nm, which is smoother than the as-grown sample. Auger electron spectroscopy (AES) analysis shows that the effective removal of residual oxygen from the surface of AIGaN during the etching process is crucial to the nonselective and smooth etching of GaN/AIGaN herterostructures at high etch rate.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
基金supported by the National Key Research and Development Program of China(2021YFD1800303)the National Natural Science Foundation of China(32473044).
文摘Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV), is a highly contagious gastrointestinal disease characterized by vomiting, diarrhea, and dehydration, with mortality rates approaching 100% among suckling piglets. The PEDV 3C-like protease (3CLpro) is essential for viral replication and regarded as a critical target for antiviral inhibitor development. In this study, we aimed to identify small-molecule inhibitors of PEDV by targeting 3CLpro. Virtual screening of 1.6 million compounds from the ChemDiv library identified four potential candidates. Molecular dynamics simulations, specifically analyzing RMSD, RMSF, and Rg, demonstrated increased structural stability of the compound-protease complexes compared to the monomeric enzyme. All compounds had low cytotoxicity in Vero cells (CC_(50) > 200 μM). Fluorescence resonance energy transfer-based assays demonstrated dose-dependent inhibitory activity of the compounds against 3CLpro. Among the candidates, compound F366-0161 exhibited the weakest inhibition, with an IC_(50) value of 151.5 μM. Two analogues, 3238-0395 (IC_(50) of 121.4 μM) and L878-0493 (IC_(50) of 123.6 μM), exhibited moderately enhanced activity. Y041-1672 was identified as the most effective inhibitor, with an IC_(50) of 86.48 μM. In viral replication inhibition assays, Y041-1672 reduced PEDV replication, with an EC_(50) of 17.97 μM and a selectivity index (SI) of 15.5 (CC_(50) /EC_(50) ). These results were validated by RT-qPCR, plaque assays, immunofluorescence, and Western blot analyses. In vitro validation confirmed Y041-1672 as the optimal antiviral candidate, and time-of-addition experiments indicated that inhibition primarily occurred during viral replication. This study identifies scaffold molecules for PEDV antiviral drug development, providing strategic insights for PED treatment.
基金supported by the National Natural Science Foundation of China(82370015).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the causative agent of novel coronavirus disease 2019,can cause acute respiratory symptoms and even death globally.However,the immune escape mechanism and viral pathogenesis remain poorly understood.Here,we report that the SARS-CoV-23C-like(3CL)protease specifically cleaves gasdermin D(GSDMD)at Q29 and Q193,producing two N-terminal fragments,GSDMD1-29 and GSDMD1-193.We also found that SARS-CoV-2 infection induced the cleavage of GSDMD.Then,we demonstrated that the ability to cleave GSDMD was dependent on the protease activity of the 3CL protease.Interestingly,unlike the GSDMD1-275 fragment cleaved by caspase-1,GSDMD1-29 and GSDMD1-193 did not trigger pyroptosis or inhibit SARS-CoV-2 replication.Additionally,various RNA viral proteases display different preferences for cleaving GSDMD at Q29 and Q193.Our findings reveal a mechanism by which SARS-CoV-2 and other RNA viruses inhibit pyroptosis,highlighting the critical role of the 3CL protease in immune evasion and viral replication.
