Dry eye disease(DED)is a prevalent inflammatory condition significantly impacting quality of life,yet lacks effective pharmacological therapies.Herein,we proposed a novel approach to modulate the inflammation through ...Dry eye disease(DED)is a prevalent inflammatory condition significantly impacting quality of life,yet lacks effective pharmacological therapies.Herein,we proposed a novel approach to modulate the inflammation through metabolic remodeling,thus promoting dry eye recovery.Our study demonstrated that co-treatment with mesenchymal stem cells(MSCs)and thymosin beta-4(Tβ4)yielded the best therapeutic outcome against dry eye,surpassing monotherapy outcomes.In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)revealed increased glutamine levels in cornea following MSC+Tβ4 combined therapy.Inhibition of glutamine reversed the anti-inflammatory,anti-apoptotic,and homeostasis-preserving effects observed with combined therapy,highlighting the critical role of glutamine in dry eye therapy.Clinical cases and rodent model showed elevated expression of glutaminase(GLS1),an upstream enzyme in glutamine metabolism,following dry eye injury.Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced,respectively,the anti-inflammatory effects of combined therapy,underscoring GLS1’s pivotal role in regulating glutamine metabolism.Furthermore,single-cell sequencing revealed a distinct subset of pro-inflammatory and pro-fibrotic corneal epithelial cells in the dry eye model,while glutamine treatment downregulated those subclusters,thereby reducing their inflammatory cytokine secretion.In summary,glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling.The present study suggests that glutamine metabolism plays a critical,previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.展开更多
Calcium bismuth niobate(CBN)ceramic,as a core element of high-temperature piezoelectric sensors,has attracted widespread attention due to its high Curie temperature within the class of Aurivillius compounds.However,CB...Calcium bismuth niobate(CBN)ceramic,as a core element of high-temperature piezoelectric sensors,has attracted widespread attention due to its high Curie temperature within the class of Aurivillius compounds.However,CBN usually faces two shortcomings.poor piezoelectric constant and low resistivity.In this work,CBN-based ceramics with donor–acceptor ions(W/Co)co-substituted at B-site were prepared by solid-state reaction method,and structure–property relationship of ceramics was studied in detail.Co-substitution of W/Co ions effectively improved the electrical property and hardness of CBN ceramics.CaBi_(2)Nb_(1.91)(W_(2/3)Co_(1/3)T_(0.09)O_(9))exhibits enhanced electrical and mechanical properties including high resistivity of-10^(7)Ω·cm at 500℃,piezoelectric constant of-15.3 pC/N and hardness value of-3.57 GPa.These values are two orders of magnitude,over two times,and 1.36 times higher than those of pure CBN ceramic,respectively.This work provides a reference for exploring other bismuth-layered structural ceramics.展开更多
基金supported by grants from National Natural Science Foundation of China(32371035,32000530)Beijing Nova Program(20230484246)+2 种基金the National Key R&D Program of China(2022YFA1105502)Young Elite Scientists Sponsorship Program by CAST(2023QNRC001)The authors appreciate the kind support from Dr.Wei Chen(Beijing Institute of Biotechnology)and Dr.Rui Yu(Beijing Institute of Biotechnology).
文摘Dry eye disease(DED)is a prevalent inflammatory condition significantly impacting quality of life,yet lacks effective pharmacological therapies.Herein,we proposed a novel approach to modulate the inflammation through metabolic remodeling,thus promoting dry eye recovery.Our study demonstrated that co-treatment with mesenchymal stem cells(MSCs)and thymosin beta-4(Tβ4)yielded the best therapeutic outcome against dry eye,surpassing monotherapy outcomes.In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)revealed increased glutamine levels in cornea following MSC+Tβ4 combined therapy.Inhibition of glutamine reversed the anti-inflammatory,anti-apoptotic,and homeostasis-preserving effects observed with combined therapy,highlighting the critical role of glutamine in dry eye therapy.Clinical cases and rodent model showed elevated expression of glutaminase(GLS1),an upstream enzyme in glutamine metabolism,following dry eye injury.Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced,respectively,the anti-inflammatory effects of combined therapy,underscoring GLS1’s pivotal role in regulating glutamine metabolism.Furthermore,single-cell sequencing revealed a distinct subset of pro-inflammatory and pro-fibrotic corneal epithelial cells in the dry eye model,while glutamine treatment downregulated those subclusters,thereby reducing their inflammatory cytokine secretion.In summary,glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling.The present study suggests that glutamine metabolism plays a critical,previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.
基金supported by the National Natural Science Foundation of China[51932010,12004267]Natural Science Foundation Project of Chongqing Science&Technology Commission[CSTB2024NSCQ-MSX2081]+3 种基金Scientific and Technological Research Program of Chongqing Municipal Education Commission[KJQN202401132]Open Project Fund of Key Laboratory of Inorganic Functional Materials and Devices,ChineseAcademy of Sciences[KLIFMD202311]Sichuan Science and Technology Program[23ZDYF0173]the Cultivation Project of CQUT for Research and Innovation Group.
文摘Calcium bismuth niobate(CBN)ceramic,as a core element of high-temperature piezoelectric sensors,has attracted widespread attention due to its high Curie temperature within the class of Aurivillius compounds.However,CBN usually faces two shortcomings.poor piezoelectric constant and low resistivity.In this work,CBN-based ceramics with donor–acceptor ions(W/Co)co-substituted at B-site were prepared by solid-state reaction method,and structure–property relationship of ceramics was studied in detail.Co-substitution of W/Co ions effectively improved the electrical property and hardness of CBN ceramics.CaBi_(2)Nb_(1.91)(W_(2/3)Co_(1/3)T_(0.09)O_(9))exhibits enhanced electrical and mechanical properties including high resistivity of-10^(7)Ω·cm at 500℃,piezoelectric constant of-15.3 pC/N and hardness value of-3.57 GPa.These values are two orders of magnitude,over two times,and 1.36 times higher than those of pure CBN ceramic,respectively.This work provides a reference for exploring other bismuth-layered structural ceramics.
