The relationships between the properties of PVC-MBS polyblend and of the MBS multiphase structure and between the MBS structure and polymerization parameters are studied theoretically and experimentally. MBS resin syn...The relationships between the properties of PVC-MBS polyblend and of the MBS multiphase structure and between the MBS structure and polymerization parameters are studied theoretically and experimentally. MBS resin synthesized from the molecule design principle is suitable to prepare PVC-MBS polyblend with good transparency and high impact strength.展开更多
Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of ac...Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.展开更多
With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless,...With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons （MBs）, a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.展开更多
A new distributed node localization algorithm named mobile beacons-improved particle filter （MB-IPF） was proposed. In the algorithm, the mobile nodes equipped with globe position system （GPS） move around in the wi...A new distributed node localization algorithm named mobile beacons-improved particle filter （MB-IPF） was proposed. In the algorithm, the mobile nodes equipped with globe position system （GPS） move around in the wireless sensor network （WSN） field based on the Gauss-Markov mobility model, and periodically broadcast the beacon messages Each unknown node estimates its location in a fully distributed mode based on the received mobile beacons. The localization algorithm is based on the IPF and several refinements, including the proposed weighted centroid algorithm, the residual resampling algorithm, and the markov chain monte carlo （MCMC） method etc., which were also introduced for performance improvement. The simulation results show that our proposed algorithm is efficient for most applications.展开更多
基金Project supported by the National Natural Science Foundation of China
文摘The relationships between the properties of PVC-MBS polyblend and of the MBS multiphase structure and between the MBS structure and polymerization parameters are studied theoretically and experimentally. MBS resin synthesized from the molecule design principle is suitable to prepare PVC-MBS polyblend with good transparency and high impact strength.
基金This work was financially supported by the Shandong Province Key R&D Program(Major Technological Innovation Project)(2021CXGC010501,China)National Natural Science Foundation of China(Nos.22107059,22007060)+5 种基金Natural Science Foundation of Shandong Province(ZR2021QH057,ZR2022QH304,ZR2020QB166,China)Innovation Team of Shandong Higher School Youth Innovation Technology Program(2021KJ035,China)Taishan Scholars Program(TSQN202211221,China)Shandong Science Fund for Excellent Young Scholars(ZR2022YQ66,China)Young Elite Scientists Sponsorship Program of China Association for Science and Technology(CACM-2023-QNRC1-02)Academic Promotion Programme of Shandong First Medical University(No.2019LJ003,China)。
文摘Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.
基金supported by grants from the National Key R&D Program of China (Grant Nos. 2016YFA0501603 and 2016YFA0100702)the National Natural Science Foundation of China (Grant Nos. 31771583 and 81371613)+1 种基金the Beijing Natural Science Foundation (Grant No. 7162114)the 1000 Young Talent Program of China
文摘With numerous advancements in novel biochemical techniques, our knowledge of the role of RNAs in the regulation of cellular physiology and pathology has grown significantly over the past several decades. Nevertheless, detailed information regarding RNA processing, trafficking, and localization in living cells has been lacking due to technical limitations in imaging single RNA transcripts in living cells with high spatial and temporal resolution. In this review, we discuss tech- niques that have shown great promise for single RNA imaging, followed by highlights in our recent work in the development of molecular beacons （MBs）, a class of nanoscale oligonucleotide-probes, for detecting individual RNA transcripts in living cells. With further refinement of MB design and development of more sophisticated fluorescence microscopy techniques, we envision that MB-based approaches could promote new discoveries of RNA functions and activities.
文摘A new distributed node localization algorithm named mobile beacons-improved particle filter （MB-IPF） was proposed. In the algorithm, the mobile nodes equipped with globe position system （GPS） move around in the wireless sensor network （WSN） field based on the Gauss-Markov mobility model, and periodically broadcast the beacon messages Each unknown node estimates its location in a fully distributed mode based on the received mobile beacons. The localization algorithm is based on the IPF and several refinements, including the proposed weighted centroid algorithm, the residual resampling algorithm, and the markov chain monte carlo （MCMC） method etc., which were also introduced for performance improvement. The simulation results show that our proposed algorithm is efficient for most applications.
