High-power fiber-to-fiber coupling is extensively used in fiber laser applications,and its performance is determined by coupling efficiency.We demonstrate a novel method for alignment and monitoring efficiency by dete...High-power fiber-to-fiber coupling is extensively used in fiber laser applications,and its performance is determined by coupling efficiency.We demonstrate a novel method for alignment and monitoring efficiency by detecting backscattering power at the fiber end cap.The relationship between alignment error and backscattering power is determined by simulations and experiments.Through this method,a state-of-the-art kW-level fiberto-fiber optic switch is developed(transmission efficiency>97%).It performs well for longer than 60 min.To the best of our knowledge,it is the first time to establish the mathematical model based on this method.Our results can provide guidance in high-power fiber-to-fiber coupling.展开更多
The lipid nanoparticle(LNP)has been so far proven as a strongly effective delivery system for mRNA and siRNA.However,the mechanisms of LNP's distribution,metabolism,and elimination are complicated,while the transp...The lipid nanoparticle(LNP)has been so far proven as a strongly effective delivery system for mRNA and siRNA.However,the mechanisms of LNP's distribution,metabolism,and elimination are complicated,while the transportation and pharmacokinetics(PK)of LNP are just sparsely investigated and simply described.This study aimed to build a model for the transportation of RNA-LNP in Hela cells,rats,mice,and humans by physiologically based pharmacokinetic(PBPK)and quantum mechanics(QM)models with integrated multi-source data.LNPs with different ionizable lipids,particle sizes,and doses were modeled and compared by recognizing their critical parameters dominating PK.Some interesting results were found by the models.For example,the metabolism of ionizable lipids was first limited by the LNP disassembly rate instead of the hydrolyzation of ionizable lipids;the ability of RNA release from endosomes for three ionizable lipids was quantitively derived and can predict the probability of RNA release.Moreover,the biodegradability of three ionizable lipids was estimated by the QM method and the is generally consistent with the result of PBPK result.In summary,the transportation model of RNA LNP among various species for the first time was successfully constructed.Various in vitro and in vivo pieces of evidence were integrated through QM/PBPK multi-level modeling.The resulting new understandings are related to biodegradability,safety,and RNA release ability which are highly concerned issues of the formulation.This would benefit the design and research of RNA-LNP in the future.展开更多
基金supported by the National Key Research and Development Program of China(No.2017YFB1104402).
文摘High-power fiber-to-fiber coupling is extensively used in fiber laser applications,and its performance is determined by coupling efficiency.We demonstrate a novel method for alignment and monitoring efficiency by detecting backscattering power at the fiber end cap.The relationship between alignment error and backscattering power is determined by simulations and experiments.Through this method,a state-of-the-art kW-level fiberto-fiber optic switch is developed(transmission efficiency>97%).It performs well for longer than 60 min.To the best of our knowledge,it is the first time to establish the mathematical model based on this method.Our results can provide guidance in high-power fiber-to-fiber coupling.
基金supported by the UM Macao PhD Scholarship(China),UM Postdoctoral Fellow of UM Talent Programme(China),the University of Macao Multi-Year Research Grant e Collaborative Research Grant(MYRG-CRG2022-00008-ICMS,China)the Shenzhen-Hong Kong-Macao Science and Technology Program(Category C)of Shenzhen Science and Technology Innovation Commission(SGDX20210823103802016,China)Industry-university-research cooperation project and Zhuhai-Hong Kong-Macao cooperation project from Zhuhai Science and Technology Innovation Bureau(ZH22017002210010PWC,China).
文摘The lipid nanoparticle(LNP)has been so far proven as a strongly effective delivery system for mRNA and siRNA.However,the mechanisms of LNP's distribution,metabolism,and elimination are complicated,while the transportation and pharmacokinetics(PK)of LNP are just sparsely investigated and simply described.This study aimed to build a model for the transportation of RNA-LNP in Hela cells,rats,mice,and humans by physiologically based pharmacokinetic(PBPK)and quantum mechanics(QM)models with integrated multi-source data.LNPs with different ionizable lipids,particle sizes,and doses were modeled and compared by recognizing their critical parameters dominating PK.Some interesting results were found by the models.For example,the metabolism of ionizable lipids was first limited by the LNP disassembly rate instead of the hydrolyzation of ionizable lipids;the ability of RNA release from endosomes for three ionizable lipids was quantitively derived and can predict the probability of RNA release.Moreover,the biodegradability of three ionizable lipids was estimated by the QM method and the is generally consistent with the result of PBPK result.In summary,the transportation model of RNA LNP among various species for the first time was successfully constructed.Various in vitro and in vivo pieces of evidence were integrated through QM/PBPK multi-level modeling.The resulting new understandings are related to biodegradability,safety,and RNA release ability which are highly concerned issues of the formulation.This would benefit the design and research of RNA-LNP in the future.