Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we...Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.展开更多
These rational solutions which can be described a kind of algebraic solitary waves which have great potential in applied value in atmosphere and ocean. It has attracted more and more attention recently. In this paper,...These rational solutions which can be described a kind of algebraic solitary waves which have great potential in applied value in atmosphere and ocean. It has attracted more and more attention recently. In this paper, the generalized bilinear method instead of the Hirota bilinear method is used to obtain the rational solutions to the (2 + 1)-dimensional Boiti-Leon-Manna-Pempinelli-like equation (hereinafter referred to as BLMP equation). Meanwhile, the (2 + 1)-dimensional BLMP-like equation is derived on the basis of the generalized bilinear operators D3,x D3,y and D3,t. And the rational solutions to the (2 + 1)-dimensional BLMP-like equation are obtained successively. Finally, with the help of the N-soliton solutions of the (2 + 1)-dimensional BLMP equation, the interactions of the N-soliton solutions can be derived. The results show that the two soliton still maintained the original waveform after happened collision.展开更多
Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,an...Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.展开更多
The metabolic state of a cell is closely related to its structure and function in adult mammalian cardiomyocytes.These adult cardiomyocytes primarily use fatty acids as an energy substrate to support heart contraction...The metabolic state of a cell is closely related to its structure and function in adult mammalian cardiomyocytes.These adult cardiomyocytes primarily use fatty acids as an energy substrate to support heart contraction.Recently,Li and his colleagues reported that inhibiting fatty acid oxidation in cardiomyocytes keeps them in an immature state.This influences epigenomic modifications and ultimately increases the proliferation capacity of the cardiomyocytes.展开更多
基金The authors gratefully acknowledge financial support from National Natural Science Foundation of China(81872818)National Key R&D Program of China(2021YFE0115200).
文摘Exosomes,as promising vehicles,have been widely used in the research of oral drug delivery,but the generally low drug loading efficiency of exosomes seriously limits its application and transformation.In this study,we systematically investigated the effects of drug loading methods and physicochemical properties(lipophilicity and molecular weight)on drug loading efficiency of milk-derived exosomes to explore the most appropriate loading conditions.Our finding revealed that the drug loading efficiency of exosomes was closely related to the drug loading method,drug lipophilicity,drug molecular weight and exosome/drug proportions.Of note,we demonstrated the universality that hydrophilic biomacromolecule drugs were the most appropriate loading drugs for milk-derived exosomes,which was attributed to the efficient loading capacity and sustained release behavior.Furthermore,milk-derived exosomes could significantly improve the transepithelial transport and oral bioavailability of model hydrophilic biomacromolecule drugs(octreotide,exendin-4 and salmon calcitonin).Collectively,our results suggested that the encapsulation of hydrophilic biomacromolecule drugs might be the most promising direction for milk exosomes as oral drug delivery vehicles.
文摘These rational solutions which can be described a kind of algebraic solitary waves which have great potential in applied value in atmosphere and ocean. It has attracted more and more attention recently. In this paper, the generalized bilinear method instead of the Hirota bilinear method is used to obtain the rational solutions to the (2 + 1)-dimensional Boiti-Leon-Manna-Pempinelli-like equation (hereinafter referred to as BLMP equation). Meanwhile, the (2 + 1)-dimensional BLMP-like equation is derived on the basis of the generalized bilinear operators D3,x D3,y and D3,t. And the rational solutions to the (2 + 1)-dimensional BLMP-like equation are obtained successively. Finally, with the help of the N-soliton solutions of the (2 + 1)-dimensional BLMP equation, the interactions of the N-soliton solutions can be derived. The results show that the two soliton still maintained the original waveform after happened collision.
基金supported by the National Key Research and Development Program of China(81930103)the National Natural Science Foundations of China(82104162)the Natural Science Foundation of Jiangsu Province(BK20210539).
文摘Epilepsy is a multifaceted neurological syndrome characterized by recurrent,spontaneous,and synchronous seizures.The pathogenesis of epilepsy,known as epileptogenesis,involves intricate changes in neurons,neuroglia,and endothelium,leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy.Although current research on epilepsy treatments primarily centers around anti-seizure drugs,it is imperative to seek effective interventions capable of disrupting epileptogenesis.To this end,a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets.Emphasizing early diagnosis and timely intervention is paramount,as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden.In this review,we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.
文摘The metabolic state of a cell is closely related to its structure and function in adult mammalian cardiomyocytes.These adult cardiomyocytes primarily use fatty acids as an energy substrate to support heart contraction.Recently,Li and his colleagues reported that inhibiting fatty acid oxidation in cardiomyocytes keeps them in an immature state.This influences epigenomic modifications and ultimately increases the proliferation capacity of the cardiomyocytes.
