Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-est...Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-established clinical history in effectively managing fever. However, the specific mechanisms underlying their efficacy remain unclear. Following the screening for lead compounds that inhibit PGE2from antipyretic herbs, alkynylated active molecule probes were designed and synthesized to track and identify potential targets. The target investigation revealed that three antipyretic compounds, namely cinnamaldehyde, 2,4-decadienal, and perillaldehyde, containing α,β-unsaturated aldehyde groups irreversibly targeted the microsomal PGES1-TM4 helix(m PGES1-TM4) at Ser139. This specific interaction effectually inhibited PGE2 production in the cerebral vasculature, leading to exert potent antipyretic effects.α,β-Unsaturated aldehydes targeting m PGES1-TM4 offer a new approach for antipyretic effects with significant potential for various applications.展开更多
The Jinchuan magmatic Ni-Cu-PGE deposit is the largest single Ni sulfide deposit in the world.It consists primarily of orebody-24 in segment I,and orebody-1 and orebody-2 in segment II.The contents of platinum-group e...The Jinchuan magmatic Ni-Cu-PGE deposit is the largest single Ni sulfide deposit in the world.It consists primarily of orebody-24 in segment I,and orebody-1 and orebody-2 in segment II.The contents of platinum-group elements(PGE)in these orebodies decrease significantly from west to east across the deposit.However,the PGE characteristics of platinum-group minerals(PGM)and alloys,as well as their roles during mineralization in different orebodies,remain unclear.In this study,PGM and alloy occurrences in orebody-24 and orebody-2 had been observed by scanning electron microscopy(SEM)and spherical-aberration corrected scanning transmission electron microscope(Cs-STEM).The PGE contents were analyzed by SEM‒EDS for submicron-scale PGM and alloys.The results show that olivine in lherzolite mainly hosts PGM of PtTe and PdBi2,whereas pyroxene contains small amounts of PdBiTe.Pyrrhotite predominantly hosts(Ir-Rh-Pt)AsS,Pd(BiTe),and other PGM,as well as PtSn and PtOs alloys.Pentlandite mainly encloses Pd(BiTe),PdBi/PdBi2 and other PGM,as well as PtSn and PtFe alloys.Chalcopyrite primarily encloses PdBi/PdBi2,and other PGM,along with PtSn and IrOs.Distinct distribution patterns of PGE in PGM and alloys had been observed between different orebodies.Orebody-24 contains more(Ir-Rh-Pt)AsS minerals and PtFe/PtSn alloy grains,whereas orebody-2 has a higher proportion of Pt-and Pd-bearing PGM.The presence of euhedral alloys in silicate minerals from orebody-24 suggests that its parent magma had a higher PGE content before sulfide saturation than that of orebody-2.More than 90%of PGM and alloys in both orebody-24 and orebody-2 contain Pt and Pd,emphasizing their contributions to the elevated Pt and Pd concentrations.The different PGE distributions of PGM and alloys in the two orebodies suggest that thermodynamic conditions(fO2 and fS2)and semimetals,especially As,play critical roles in controlling PGE behavior and occurrence.展开更多
基金supported by the National Key R&D Program of China (Nos. 2022YFC3500800 and 2022YFC3500805)。
文摘Prostaglandin E2(PGE2) serves as the ultimate mediator of fever induced by infiammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-established clinical history in effectively managing fever. However, the specific mechanisms underlying their efficacy remain unclear. Following the screening for lead compounds that inhibit PGE2from antipyretic herbs, alkynylated active molecule probes were designed and synthesized to track and identify potential targets. The target investigation revealed that three antipyretic compounds, namely cinnamaldehyde, 2,4-decadienal, and perillaldehyde, containing α,β-unsaturated aldehyde groups irreversibly targeted the microsomal PGES1-TM4 helix(m PGES1-TM4) at Ser139. This specific interaction effectually inhibited PGE2 production in the cerebral vasculature, leading to exert potent antipyretic effects.α,β-Unsaturated aldehydes targeting m PGES1-TM4 offer a new approach for antipyretic effects with significant potential for various applications.
基金financially supported by NKPRP of China(2022YFC2903504)the National Natural Science Foundation of China(Grant Nos.42272069,42303023,91962212 and 41872075)+2 种基金Postdoctoral Fellowship Program of CPSF(GZC20231005)Qinghai Jinchuan Mining Co.,Ltd.R&D Project(0511-HHKY-FY-[2023])Key Laboratory of Strategic Mineral Resources of the Upper Yellow River,Ministry of Natural Resources(YSMRKF202202).
文摘The Jinchuan magmatic Ni-Cu-PGE deposit is the largest single Ni sulfide deposit in the world.It consists primarily of orebody-24 in segment I,and orebody-1 and orebody-2 in segment II.The contents of platinum-group elements(PGE)in these orebodies decrease significantly from west to east across the deposit.However,the PGE characteristics of platinum-group minerals(PGM)and alloys,as well as their roles during mineralization in different orebodies,remain unclear.In this study,PGM and alloy occurrences in orebody-24 and orebody-2 had been observed by scanning electron microscopy(SEM)and spherical-aberration corrected scanning transmission electron microscope(Cs-STEM).The PGE contents were analyzed by SEM‒EDS for submicron-scale PGM and alloys.The results show that olivine in lherzolite mainly hosts PGM of PtTe and PdBi2,whereas pyroxene contains small amounts of PdBiTe.Pyrrhotite predominantly hosts(Ir-Rh-Pt)AsS,Pd(BiTe),and other PGM,as well as PtSn and PtOs alloys.Pentlandite mainly encloses Pd(BiTe),PdBi/PdBi2 and other PGM,as well as PtSn and PtFe alloys.Chalcopyrite primarily encloses PdBi/PdBi2,and other PGM,along with PtSn and IrOs.Distinct distribution patterns of PGE in PGM and alloys had been observed between different orebodies.Orebody-24 contains more(Ir-Rh-Pt)AsS minerals and PtFe/PtSn alloy grains,whereas orebody-2 has a higher proportion of Pt-and Pd-bearing PGM.The presence of euhedral alloys in silicate minerals from orebody-24 suggests that its parent magma had a higher PGE content before sulfide saturation than that of orebody-2.More than 90%of PGM and alloys in both orebody-24 and orebody-2 contain Pt and Pd,emphasizing their contributions to the elevated Pt and Pd concentrations.The different PGE distributions of PGM and alloys in the two orebodies suggest that thermodynamic conditions(fO2 and fS2)and semimetals,especially As,play critical roles in controlling PGE behavior and occurrence.
