Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screenin...Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.展开更多
Diamond based quantum sensing is a fast-emerging field with both scientific and technological significance.The nitrogen–vacancy(NV)center,a crystal defect in diamond,has become a unique object for microwave sensing a...Diamond based quantum sensing is a fast-emerging field with both scientific and technological significance.The nitrogen–vacancy(NV)center,a crystal defect in diamond,has become a unique object for microwave sensing applications due to its excellent stability,long spin coherence time,and optical properties at ambient condition.In this work,we use diamond NV center as atomic receiver to demodulate on–off keying(OOK)signal transmitted in broad frequency range(2 GHz–14 GHz in a portable benchtop setup).We proposed a unique algorithm of voltage discrimination and demonstrated audio signal transceiving with fidelity above 99%.This diamond receiver is attached to the end of a tapered fiber,having all optic nature,which will find important applications in data transmission tasks under extreme conditions such as strong electromagnetic interference,high temperatures,and high corrosion.展开更多
基金supported by Shandong Province Key R&D Program,China(Major Technological Innovation Project)(Grant No.:2021CXGC010501)Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine,China(Grant No.:CACM-2023-QNRC1-02)+8 种基金the National Natural Science Foundation of China(Grant Nos.:22107059,22007060,82302743)the Natural Science Foundation of Shandong Province,China(Grant Nos.:ZR2022QH304,ZR2021QH057,ZR2020QB166)the Program for Youth Innovation Technology in Colleges and Universities of Shandong Province of China(Grant No.:2021KJ035)Taishan Scholars Program,China(Grant Nos.:TSQN202211221,TSPD20181218)Shandong Science Fund for Excellent Young Scholars,China(Grant No.:ZR2022YQ66)Shandong Province Traditional Chinese Medicine Science and Technology Project,China(Grant No.:Q-2023059)Shenzhen Basic Research Project,China(Grant No.:JCYJ20190809160209449)the General Project of Shandong Natural Science Foundation,China(Grant No.:ZR2021MH341)Jinan Innovation Team Project of Colleges and Universities,China(Grant No.:2021GXRC072).
文摘Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)^(-/-)mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with medicinal effects.
基金the National Key Research and Development Program of China(Grant No.2021YFB2012600)。
文摘Diamond based quantum sensing is a fast-emerging field with both scientific and technological significance.The nitrogen–vacancy(NV)center,a crystal defect in diamond,has become a unique object for microwave sensing applications due to its excellent stability,long spin coherence time,and optical properties at ambient condition.In this work,we use diamond NV center as atomic receiver to demodulate on–off keying(OOK)signal transmitted in broad frequency range(2 GHz–14 GHz in a portable benchtop setup).We proposed a unique algorithm of voltage discrimination and demonstrated audio signal transceiving with fidelity above 99%.This diamond receiver is attached to the end of a tapered fiber,having all optic nature,which will find important applications in data transmission tasks under extreme conditions such as strong electromagnetic interference,high temperatures,and high corrosion.