This study employed Mendelian randomization(MR)analysis to confirm the association between breast cancer and the risk of anxiety and depression,and to explore the molecular mechanisms by which lipid nanoparticles of k...This study employed Mendelian randomization(MR)analysis to confirm the association between breast cancer and the risk of anxiety and depression,and to explore the molecular mechanisms by which lipid nanoparticles of ketamine(LNP@Ket)modulate these behaviors in a mouse model of breast cancer.Through single-cell transcriptomic analysis,the study aimed to clarify nuclear factor erythroid 2-related factor 2(Nrf2)’s role in the development of anxiety and depression in these mice.Analysis of patient data from genome-wide association study(GWAS)databases supported the link between breast cancer,anxiety,and depression.In vivo experiments demonstrated that treating breast cancer mice with LNP@Ket significantly reduced anxiety and depression behaviors.The synthesis of LNP@Ket and its subsequent analysis highlighted its inhibitory effects on these behaviors.Single-cell transcriptomic sequencing identified key cells and genes affected by LNP@Ket treatment,particularly emphasizing Nrf2.Upregulation of Nrf2 in astrocytes increased the expression of antioxidant enzymes and reduced pro-inflammatory cytokines,alleviating anxiety and depression symptoms by inhibiting neuroinflammation and neurodegeneration.This comprehensive study highlights the pivotal role of Nrf2 in the therapeutic efficacy of LNP@Ket for treating anxiety and depression in breast cancer mice.展开更多
An efficient strategy has been developed to reconstruct chain folding and traversing of poly(L-lactide)(PLLA)during melt crystallization based on the selective hydrolysis of its amorphous regions.The molecular weights...An efficient strategy has been developed to reconstruct chain folding and traversing of poly(L-lactide)(PLLA)during melt crystallization based on the selective hydrolysis of its amorphous regions.The molecular weights of the pristine PLLA(crystalline part),single stem,and single cluster were determined by gel permeation chromatography(GPC)according to their evolution during alkali hydrolysis.The maximum-folding-number(in a single cluster)and minimum-cluster-number(in one polymer chain)were obtained using these molecular weights.With the help of two numbers,the chain folding and traversing during the melt crystallization process(at 120℃)of PLLA can be described as follows.Statistically,in a single polymer chain,there are at least 2 clusters consisting of up to 6.5 stems in each of them,while the rest of the polymer chain contributes to amorphous regions.Our results provide a new strategy for the investigation and fundamental understanding of the melt crystallization of PLLA.展开更多
A tri-quaternary ammonium salt cationic surfactant was synthesized.Its structure was confirmed by using Fourier-transform infrared spectroscopy,^(1)H nuclear magnetic resonance spectroscopy,and X-ray photoelectron spe...A tri-quaternary ammonium salt cationic surfactant was synthesized.Its structure was confirmed by using Fourier-transform infrared spectroscopy,^(1)H nuclear magnetic resonance spectroscopy,and X-ray photoelectron spectroscopy analyses.Three model surfaces,including Au-CH_(3),Au-OH and Au-COOH,were fabricated.Adsorptions of surfactant on the three model surfaces and subsequent plasma proteins adsorption were investigated by quartz crystal microbalance with dissipation(QCM-D).The mass of surfactant on the Au-COOH surface was the largest,followed by that on the Au-CH_(3)surface,and that on the Au-OH surface.These results suggested that the main driving force of surfactant immobilization was electrostatic interaction followed by hydrophobic interaction.Based on the results obtained,we concluded that the protein mass adsorbed on Au-CH_(3)-S,Au-OH-S,and Au-COOH-S surfaces depended on the protein size and orientation.The mass and thickness of S on the Au-COOH surface is the largest and the protein adsorption capacity of Au-COOH-S surface is inferior to that of Au-CH_(3)-S.The Au-COOH-S surface could inhibit lysozyme adsorption,maintain the adsorption balance of bovine serum albumin,and induce fibrinogen-binding protein adsorption.展开更多
文摘This study employed Mendelian randomization(MR)analysis to confirm the association between breast cancer and the risk of anxiety and depression,and to explore the molecular mechanisms by which lipid nanoparticles of ketamine(LNP@Ket)modulate these behaviors in a mouse model of breast cancer.Through single-cell transcriptomic analysis,the study aimed to clarify nuclear factor erythroid 2-related factor 2(Nrf2)’s role in the development of anxiety and depression in these mice.Analysis of patient data from genome-wide association study(GWAS)databases supported the link between breast cancer,anxiety,and depression.In vivo experiments demonstrated that treating breast cancer mice with LNP@Ket significantly reduced anxiety and depression behaviors.The synthesis of LNP@Ket and its subsequent analysis highlighted its inhibitory effects on these behaviors.Single-cell transcriptomic sequencing identified key cells and genes affected by LNP@Ket treatment,particularly emphasizing Nrf2.Upregulation of Nrf2 in astrocytes increased the expression of antioxidant enzymes and reduced pro-inflammatory cytokines,alleviating anxiety and depression symptoms by inhibiting neuroinflammation and neurodegeneration.This comprehensive study highlights the pivotal role of Nrf2 in the therapeutic efficacy of LNP@Ket for treating anxiety and depression in breast cancer mice.
基金financially supported by"Pioneer"and"Leading Goose"R&D Program of Zhejiang(No.2023C03130)the National Natural Science Foundation of China(No.22373029)+1 种基金Interdisciplinary Research Project of Hangzhou Normal University(No.2024JCXK02)Open Project Program of Key Laboratory of Yarn Materials Forming and Composite Processing Technology of Zhejiang Province(No.MTC2022-09)。
文摘An efficient strategy has been developed to reconstruct chain folding and traversing of poly(L-lactide)(PLLA)during melt crystallization based on the selective hydrolysis of its amorphous regions.The molecular weights of the pristine PLLA(crystalline part),single stem,and single cluster were determined by gel permeation chromatography(GPC)according to their evolution during alkali hydrolysis.The maximum-folding-number(in a single cluster)and minimum-cluster-number(in one polymer chain)were obtained using these molecular weights.With the help of two numbers,the chain folding and traversing during the melt crystallization process(at 120℃)of PLLA can be described as follows.Statistically,in a single polymer chain,there are at least 2 clusters consisting of up to 6.5 stems in each of them,while the rest of the polymer chain contributes to amorphous regions.Our results provide a new strategy for the investigation and fundamental understanding of the melt crystallization of PLLA.
基金the National Natural Science Fundamental Committee of China and HI-Tech Research and the Development Program(863,No.2006AA02Z291)of China.
文摘A tri-quaternary ammonium salt cationic surfactant was synthesized.Its structure was confirmed by using Fourier-transform infrared spectroscopy,^(1)H nuclear magnetic resonance spectroscopy,and X-ray photoelectron spectroscopy analyses.Three model surfaces,including Au-CH_(3),Au-OH and Au-COOH,were fabricated.Adsorptions of surfactant on the three model surfaces and subsequent plasma proteins adsorption were investigated by quartz crystal microbalance with dissipation(QCM-D).The mass of surfactant on the Au-COOH surface was the largest,followed by that on the Au-CH_(3)surface,and that on the Au-OH surface.These results suggested that the main driving force of surfactant immobilization was electrostatic interaction followed by hydrophobic interaction.Based on the results obtained,we concluded that the protein mass adsorbed on Au-CH_(3)-S,Au-OH-S,and Au-COOH-S surfaces depended on the protein size and orientation.The mass and thickness of S on the Au-COOH surface is the largest and the protein adsorption capacity of Au-COOH-S surface is inferior to that of Au-CH_(3)-S.The Au-COOH-S surface could inhibit lysozyme adsorption,maintain the adsorption balance of bovine serum albumin,and induce fibrinogen-binding protein adsorption.
