Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
Rechargeable lithium-carbon dioxide(Li-CO_(2))batteries have emerged as a highly promising approach to simultaneously address energy shortages and the greenhouse effect.However,certain limitations exist in Li-CO_(2)ba...Rechargeable lithium-carbon dioxide(Li-CO_(2))batteries have emerged as a highly promising approach to simultaneously address energy shortages and the greenhouse effect.However,certain limitations exist in Li-CO_(2)batteries like high charge overpotential and unstable Li metal interface,which adversely affect the energy efficiency and cycling life.The incorporation of soluble redox mediators(RMs)has proven effective in enhancing the charge transfer between lithium carbonate(Li_(2)CO_(3))and cathode,thereby substantially reducing the charge overpotential.Nevertheless,the severe shuttle effect of RMs results in the reactions with Li anode,not only exacerbating the corrosion of Li anode but also leading to the depletion of RMs and electrical energy efficiency.In this work,an organic compound containing large cation group,1-ethyl-3-methylimidazole bromide(EMIBr)is proposed as the defense donor RM for Li anode in Li-CO_(2)batteries to address the above problems simultaneously.During charging,Li_(2)CO_(3)oxidation kinetics can be accelerated by bromide anion pair(Br_(3)^(−)/Br^(−)).Meanwhile,the cations(EMI^(+))are preferentially adsorbed around the protruding tips of Li anode through electrostatic interaction driven by surface free energy,forming protective layers that effectively inhibit further Li deposition at these tips,which is verified by DFT calculations.Additionally,Li dendrites growth is inhibited by the electrostatic repulsion of polar groups in EMIBr,resulting in uniform Li deposition.Consequently,a lower overpotential(∼1.17 V)and a longer cycle life(∼200 cycles)have been obtained for Li-CO_(2)battery incorporating EMIBr.展开更多
Oxygen(O_(2))is an abundant material with its highly positive redox potential,making it a cost-effective choice for the cathodic active material of aqueous flow batteries(AFBs).However,utilizing O_(2)as an active mate...Oxygen(O_(2))is an abundant material with its highly positive redox potential,making it a cost-effective choice for the cathodic active material of aqueous flow batteries(AFBs).However,utilizing O_(2)as an active material may induce a high overpotential issue for oxygen reduction reaction(ORR).To address this problem,this study proposes a new AFB system employing iron-2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol complex(Fe(BIS-TRIS))and O_(2)as redox couple and cobalt(triisopropanolamine)complex(Co(TiPA))as the redox mediator.Co(TiPA)can mitigate ORR overpotential through a mediated electron transfer(MET)mechanism.More specifically,during the charging step,in the catholyte,Co(II)(TiPA)s are oxidized to Co(III)(TiPA)s at the cathode,while HO_(2)-s are oxidized in the electrolyte tank,producing O_(2).During the discharging step,Co(III)(TiPA)s are reduced to Co(II)(TiPA)s.The resulting Co(II)(TiPA)then chemically reacts with O_(2)in the electrolyte tank,regenerating Co(III)(TiPA).Namely,this cycle ensures that Co(III)(TiPA)is electrochemically reduced to Co(II)(TiPA)at the cathode,while the reduced Co(II)(TiPA)is chemically re-oxidized in the electrolyte tank,effectively mediating electron transfer between electrode and oxygen.This process facilitates ORR without direct electrochemical reaction at the cathode,thereby alleviating its overpotential.UV-Vis spectroscopic analysis verifies that Co(TiPA)spontaneously reacts with O₂and mediates ORR.Fe(BIS-TRIS)-O_(2)AFB maintains 79.1%of its initial capacity over 170 h,demonstrating the feasibility of Co(TiPA)as the redox mediator.However,its structural degradation under oxygen evolution reaction is observed,limiting the long-term stability of Fe(BIS-TRIS)-O_(2)AFB.Thus,its structural modifications or development of alternative redox mediators are required.展开更多
Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water spl...Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water splitting.In this study,we constructed a superior Ti-doped hematite photoanode(TiFeO)by employing SnOx as an electron transfer mediator,partially oxidized graphene(pGO)as a hole transfer mediator,and molecular Co cubane as a water oxidation catalyst.The Co/pGO/TiFeO/SnO_(x)integrated system achieves a photocurrent density of 2.52 mA cm^(-2) at 1.23 VRHE,which is 2.4 times higher than bare photoanode(1.04 mA cm^(-2)),with operational stability up to 100 h.Kinetic measurements indicate that pGO can promote charge transfer from TiFeO to the Co cubane catalyst.In contrast,SnOx reduces charge recombination at the interface between TiFeO and the fluorinated tin oxide substrate.In-situ infrared spectroscopy shows the formation of an O–O bonded intermediate during water oxidation.This study highlights the crucial role of incorporating dual charge-transfer mediators into photoelectrodes for efficient solar energy conversion.展开更多
All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide s...All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide shuttle problem.While the volume expansion(~80%)that occurs during the initial transformation of sulfur to lithium sulfide induces mechanical stress,this can be avoided by using Li_(2)S as a cathode,which also permits the anode-free cell design.However,the high oxidation energy barrier of Li_(2)S cathode during the charging step limits its application in commercial devices.Redox mediators have been extensively used to reduce the oxidation energy barrier of Li_(2)S to the sulfur conversation and boost the reversible kinetics of the conversion reaction.In this review,we have summarized the available redox mediators for Li_(2)S cathode in ASSLSBs and its working mechanism.Moreover,we have proposed novel strategies and guidelines for designing effective redox mediators to boost the reversible conversion reaction.展开更多
This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study pr...This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study provides com-pelling evidence that overweight mediates approximately 61%of this relationship,suggesting that depression may contribute to diabetes by influencing behaviors that lead to weight gain.This aligns with the understanding that depression can impact appetite regulation and physical activity.While the study employs a longitudinal design and robust statistical methods,limitations such as reliance on self-reported data and body mass index measurements warrant consideration.This analysis emphasizes the need for integrated interventions that address both mental and metabolic health for effective diabetes prevention.Future research should further explore the interplay of lifestyle factors,biological pathways,and social determinants in the development of this complex relationship.Ultimately,an integrated approach targeting both behavioral and biological components is crucial for the prevention and management of new-onset diabetes.展开更多
Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast canc...Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer.About 75%of breast cancer cases are diagnosed as ER-positive;however,nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies.Recent studies have identified an ER coactivator,Mediator Subunit 1(MED1),as a unique,tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance.MED1 is overexpressed in over 50%of human breast cancer cases and co-amplifies with another important breast cancer gene,receptor tyrosine kinase HER2.Clinically,MED1 expression highly correlates with poor disease-free survival of breast cancer patients,and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment.In this review,we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex,its crosstalk with HER2 in anti-estrogen resistance,breast cancer stem cell formation,and metastasis both in vitro and in vivo.Furthermore,we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.展开更多
人机交互语言工具是电信网管的重要组成部分,是网管系统中使用频率最高的模块之一,命令参数的显示控制是它的实现难点.基于Mediator模式的参数控制法分离了参数表示和逻辑控制,它让每个参数专心处理自身表示,由中介者控制显示逻辑,解除...人机交互语言工具是电信网管的重要组成部分,是网管系统中使用频率最高的模块之一,命令参数的显示控制是它的实现难点.基于Mediator模式的参数控制法分离了参数表示和逻辑控制,它让每个参数专心处理自身表示,由中介者控制显示逻辑,解除了参数间的耦合关系.这种实现方法,集中了对参数的控制,减少了耦合,有利于各参数的复用,易于逻辑关系扩展,提高了命令解析效率.实际测试表明,在PIII 1.0 G CPU环境下,解析一条命令的平均时间只需0.14 s.该方法为开发网管人机交互语言工具或处理对象强耦合问题提供了一种有参考价值的实现方法.展开更多
AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and tre...AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.展开更多
BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, li...BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.展开更多
Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated tha...Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金financially supported by National Natural Science Foundation of China(No.22075171).
文摘Rechargeable lithium-carbon dioxide(Li-CO_(2))batteries have emerged as a highly promising approach to simultaneously address energy shortages and the greenhouse effect.However,certain limitations exist in Li-CO_(2)batteries like high charge overpotential and unstable Li metal interface,which adversely affect the energy efficiency and cycling life.The incorporation of soluble redox mediators(RMs)has proven effective in enhancing the charge transfer between lithium carbonate(Li_(2)CO_(3))and cathode,thereby substantially reducing the charge overpotential.Nevertheless,the severe shuttle effect of RMs results in the reactions with Li anode,not only exacerbating the corrosion of Li anode but also leading to the depletion of RMs and electrical energy efficiency.In this work,an organic compound containing large cation group,1-ethyl-3-methylimidazole bromide(EMIBr)is proposed as the defense donor RM for Li anode in Li-CO_(2)batteries to address the above problems simultaneously.During charging,Li_(2)CO_(3)oxidation kinetics can be accelerated by bromide anion pair(Br_(3)^(−)/Br^(−)).Meanwhile,the cations(EMI^(+))are preferentially adsorbed around the protruding tips of Li anode through electrostatic interaction driven by surface free energy,forming protective layers that effectively inhibit further Li deposition at these tips,which is verified by DFT calculations.Additionally,Li dendrites growth is inhibited by the electrostatic repulsion of polar groups in EMIBr,resulting in uniform Li deposition.Consequently,a lower overpotential(∼1.17 V)and a longer cycle life(∼200 cycles)have been obtained for Li-CO_(2)battery incorporating EMIBr.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.2023R1A2C2002444).
文摘Oxygen(O_(2))is an abundant material with its highly positive redox potential,making it a cost-effective choice for the cathodic active material of aqueous flow batteries(AFBs).However,utilizing O_(2)as an active material may induce a high overpotential issue for oxygen reduction reaction(ORR).To address this problem,this study proposes a new AFB system employing iron-2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol complex(Fe(BIS-TRIS))and O_(2)as redox couple and cobalt(triisopropanolamine)complex(Co(TiPA))as the redox mediator.Co(TiPA)can mitigate ORR overpotential through a mediated electron transfer(MET)mechanism.More specifically,during the charging step,in the catholyte,Co(II)(TiPA)s are oxidized to Co(III)(TiPA)s at the cathode,while HO_(2)-s are oxidized in the electrolyte tank,producing O_(2).During the discharging step,Co(III)(TiPA)s are reduced to Co(II)(TiPA)s.The resulting Co(II)(TiPA)then chemically reacts with O_(2)in the electrolyte tank,regenerating Co(III)(TiPA).Namely,this cycle ensures that Co(III)(TiPA)is electrochemically reduced to Co(II)(TiPA)at the cathode,while the reduced Co(II)(TiPA)is chemically re-oxidized in the electrolyte tank,effectively mediating electron transfer between electrode and oxygen.This process facilitates ORR without direct electrochemical reaction at the cathode,thereby alleviating its overpotential.UV-Vis spectroscopic analysis verifies that Co(TiPA)spontaneously reacts with O₂and mediates ORR.Fe(BIS-TRIS)-O_(2)AFB maintains 79.1%of its initial capacity over 170 h,demonstrating the feasibility of Co(TiPA)as the redox mediator.However,its structural degradation under oxygen evolution reaction is observed,limiting the long-term stability of Fe(BIS-TRIS)-O_(2)AFB.Thus,its structural modifications or development of alternative redox mediators are required.
文摘Regulating the interfacial charge transfer is pivotal for elucidating the kinetics of engineering the interface between the light-harvesting semiconductor and the substrate/catalyst for photoelectrocatalytic water splitting.In this study,we constructed a superior Ti-doped hematite photoanode(TiFeO)by employing SnOx as an electron transfer mediator,partially oxidized graphene(pGO)as a hole transfer mediator,and molecular Co cubane as a water oxidation catalyst.The Co/pGO/TiFeO/SnO_(x)integrated system achieves a photocurrent density of 2.52 mA cm^(-2) at 1.23 VRHE,which is 2.4 times higher than bare photoanode(1.04 mA cm^(-2)),with operational stability up to 100 h.Kinetic measurements indicate that pGO can promote charge transfer from TiFeO to the Co cubane catalyst.In contrast,SnOx reduces charge recombination at the interface between TiFeO and the fluorinated tin oxide substrate.In-situ infrared spectroscopy shows the formation of an O–O bonded intermediate during water oxidation.This study highlights the crucial role of incorporating dual charge-transfer mediators into photoelectrodes for efficient solar energy conversion.
基金supported by the“Regional Innovation Strategy(RIS)”through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(MOE)(2021RIS-003),South Koreasupported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2023-00241916),South Korea+4 种基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(IRIS RS-2024-00352303),South Koreathe results of a study on the“Leaders in Industry-university Cooperation 3.0”project,supported by the Ministry of Education and National Research Foundation of Korea,South Koreasupported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(2020R1A6A03038697),South Koreasupported by Learning&Academic research institution for Master’s PhD students,and Postdocs(LAMP)Program of the National Research Foundation of Korea(NRF)grant funded by the Ministry of Education(No.RS-2023-00301974),South Koreasupported by the Technology Innovation Program(RS-2024-00432013)funded By the Ministry of Trade,Industry&Energy(MOTIE,South Korea)。
文摘All-solid-state Li-S batteries(ASSLSBs)are more attractive owing to their achievable superior energy density at a reasonable cost and the solid electrolyte(SE)utilization mitigating the widely recognized polysulfide shuttle problem.While the volume expansion(~80%)that occurs during the initial transformation of sulfur to lithium sulfide induces mechanical stress,this can be avoided by using Li_(2)S as a cathode,which also permits the anode-free cell design.However,the high oxidation energy barrier of Li_(2)S cathode during the charging step limits its application in commercial devices.Redox mediators have been extensively used to reduce the oxidation energy barrier of Li_(2)S to the sulfur conversation and boost the reversible kinetics of the conversion reaction.In this review,we have summarized the available redox mediators for Li_(2)S cathode in ASSLSBs and its working mechanism.Moreover,we have proposed novel strategies and guidelines for designing effective redox mediators to boost the reversible conversion reaction.
基金Supported by the New Professor Research Program of KOREATECH,No.202501930001.
文摘This letter critically examines a recent study by Zhang et al investigating the mediating role of overweight in the association between depression and new-onset diabetes among middle-aged and older adults.The study provides com-pelling evidence that overweight mediates approximately 61%of this relationship,suggesting that depression may contribute to diabetes by influencing behaviors that lead to weight gain.This aligns with the understanding that depression can impact appetite regulation and physical activity.While the study employs a longitudinal design and robust statistical methods,limitations such as reliance on self-reported data and body mass index measurements warrant consideration.This analysis emphasizes the need for integrated interventions that address both mental and metabolic health for effective diabetes prevention.Future research should further explore the interplay of lifestyle factors,biological pathways,and social determinants in the development of this complex relationship.Ultimately,an integrated approach targeting both behavioral and biological components is crucial for the prevention and management of new-onset diabetes.
基金Project supported by the National Cancer Institute(No.R01CA197865),the Ride Cincinnati Awardthe National Center for Advancing Translation Science of the National Institutes of Health(No.UL1TR001425),USA
文摘Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer.About 75%of breast cancer cases are diagnosed as ER-positive;however,nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies.Recent studies have identified an ER coactivator,Mediator Subunit 1(MED1),as a unique,tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance.MED1 is overexpressed in over 50%of human breast cancer cases and co-amplifies with another important breast cancer gene,receptor tyrosine kinase HER2.Clinically,MED1 expression highly correlates with poor disease-free survival of breast cancer patients,and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment.In this review,we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex,its crosstalk with HER2 in anti-estrogen resistance,breast cancer stem cell formation,and metastasis both in vitro and in vivo.Furthermore,we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.
文摘人机交互语言工具是电信网管的重要组成部分,是网管系统中使用频率最高的模块之一,命令参数的显示控制是它的实现难点.基于Mediator模式的参数控制法分离了参数表示和逻辑控制,它让每个参数专心处理自身表示,由中介者控制显示逻辑,解除了参数间的耦合关系.这种实现方法,集中了对参数的控制,减少了耦合,有利于各参数的复用,易于逻辑关系扩展,提高了命令解析效率.实际测试表明,在PIII 1.0 G CPU环境下,解析一条命令的平均时间只需0.14 s.该方法为开发网管人机交互语言工具或处理对象强耦合问题提供了一种有参考价值的实现方法.
基金Supported by Grants for Traditional Chinese Medicine Science of Zhejiang Province,and Medical Science and Technology of Zhejiang Province and Hangzhou
文摘AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.
基金supported by grants from the Technological Foundation Project of Traditional Chinese Medical Science of Zhejiang Province(No.2003C130No.2004C142)the Foundation Project for Medical Science and Technology of Zhejiang Province(No.2003B134).
文摘BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.
基金supported by the National Basic Research Development Program of China (2013CB966900)the National Natural Science Foundation of China (81241144, 81371372)the National Key Clinical Specialty Construction Program of China
文摘Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.
