Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in mainta...Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.展开更多
目的观察阿利沙坦酯联合硝苯地平缓释片对中重度原发性高血压伴心绞痛疗效和安全性。方法选取2021年1月至2022年1月佛山市中医院禅城高新区医院老年医学科收治的符合纳入标准的120例中重度原发性高血压伴心绞痛患者,根据随机数表法分为...目的观察阿利沙坦酯联合硝苯地平缓释片对中重度原发性高血压伴心绞痛疗效和安全性。方法选取2021年1月至2022年1月佛山市中医院禅城高新区医院老年医学科收治的符合纳入标准的120例中重度原发性高血压伴心绞痛患者,根据随机数表法分为研究组和对照组,每组各60例。对照组使用硝苯地平缓释片Ⅰ治疗,研究组在对照组基础上联合阿利沙坦酯片治疗,疗程为12周。治疗前后测量诊室血压并进行动态血压监测,评估降压效果,计算血压达标率。记录治疗期间两组心绞痛发作持续时间、发作频率、硝酸甘油用量,评估心绞痛改善情况。测量治疗前后患者生命体征,并行血尿常规、血糖、胆固醇、三酰甘油、尿素氮、肌酐、尿酸、血电解质、转氨酶、血清肌酐等实验室检查,记录治疗期间不良反应发生情况。结果治疗后,两组诊室收缩压(SBP)和舒张压(DBP)均较治疗前降低,且研究组低于对照组(P<0.05)。治疗后,两组24 h SBP、24 h DBP、白昼SBP(dSBP)、白昼DBP(dDBP)、夜间SBP(nSBP)和夜间DBP(nDBP)均降低,且研究组低于对照组(P<0.05)。研究组降压总有效率高于对照组(P<0.05)。两组与同组治疗2周后和治疗4周后比较,治疗8周后和治疗12周后两组血压达标率均增加(P<0.05)。治疗后,两组心绞痛发作持续时间、发作频率、硝酸甘油用量均较治疗前减少,且研究组低于对照组(P<0.05)。研究组心绞痛改善总有效率高于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论阿利沙坦酯联合硝苯地平缓释片治疗中重度原发性高血压伴心绞痛疗效显著,有效降压并维持血压稳定的同时,还可改善心绞痛症状,且安全性较高,具有临床应用价值。展开更多
Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and phagosomes.Therefore,artificially man...Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and phagosomes.Therefore,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and treatment.Herein,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEG)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ADA.Subsequently,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic vesicles.As a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.展开更多
Enhancing the lifetime of perovskite solar cells(PSCs)is one of the essential challenges for their industrialization.Although the external encapsulation protects the perovskite device from the erosion of moisture and ...Enhancing the lifetime of perovskite solar cells(PSCs)is one of the essential challenges for their industrialization.Although the external encapsulation protects the perovskite device from the erosion of moisture and oxygen under various harsh conditions.However,the perovskite devices still undergo static and dynamic thermal stress during thermal and thermal cycling aging,respectively,resulting in irreversible damage to the morphology,component,and phase of stacked materials.Herein,the viscoelastic polymer polyvinyl butyral(PVB)material is designed onto the surface of perovskite films to form flexible interface encapsulation.After PVB interface encapsulation,the surface modulus of perovskite films decreases by nearly 50%,and the interface stress range under the dynamic temperature field(−40 to 85°C)drops from−42.5 to 64.8 MPa to−14.8 to 5.0 MPa.Besides,PVB forms chemical interactions with FA+cations and Pb^(2+),and the macroscopic residual stress is regulated and defects are reduced of the PVB encapsulated perovskite film.As a result,the optimized device's efficiency increases from 22.21%to 23.11%.Additionally,after 1500 h of thermal treatment(85°C),1000 h of damp heat test(85°C&85%RH),and 250 cycles of thermal cycling test(−40 to 85°C),the devices maintain 92.6%,85.8%,and 96.1%of their initial efficiencies,respectively.展开更多
在级联H桥多电平静止无功发生器(Static Var Generator,SVG)中,H桥固有的结构特性使得角形级联SVG直流侧电容电压存在二倍频纹波,电压波动影响电能质量补偿效果甚至导致系统失调。为抑制角形级联SVG的H桥直流侧二倍频电压纹波,文中提出...在级联H桥多电平静止无功发生器(Static Var Generator,SVG)中,H桥固有的结构特性使得角形级联SVG直流侧电容电压存在二倍频纹波,电压波动影响电能质量补偿效果甚至导致系统失调。为抑制角形级联SVG的H桥直流侧二倍频电压纹波,文中提出了基于Boost型有源功率解耦(Active Power Decoupling,APD)的角形级联H桥多电平SVG的设计方案。有源功率解耦电路将波动功率和稳定功率相互分离,采用储能元件吸收波动功率,从而削弱了H桥直流侧电压波动。利用MATLAB/Simulink搭建仿真平台进行仿真,结果表明基于Boost型有源功率解耦的角形级联H桥多电平SVG能够有效抑制直流侧电容电压的二倍频纹波。展开更多
The electronic structures and optical properties of the monoclinic ZrO2 (m-ZrO2) are investigated by means of first-principles local density approximation (LDA) + U approach.Without on-site Coulomb interactions,the ba...The electronic structures and optical properties of the monoclinic ZrO2 (m-ZrO2) are investigated by means of first-principles local density approximation (LDA) + U approach.Without on-site Coulomb interactions,the band gap of m-ZrO2 is 3.60 eV,much lower than the experimental value (5.8 eV).By introducing the Coulomb interactions of 4d orbitals on Zr atom (Ud) and of 2p orbitals on O atom (Up),we can reproduce the experimental value of the band gap.The calculated dielectric function of m-ZrO2 exhibits a small shoulder at the edge of the band gap in its imaginary part,while in the tetragonal ZrO2 and cubic ZrO2 it is absent,which is consistent with the experimental observations.The origin of the shoulder is attributed to the difference of electronic structures near the edge of the valence and conduction bands.展开更多
Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles,aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment.Activation of auto...Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles,aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment.Activation of autophagy can be observed during myocardial injury,during which inflammatory responses are strongly triggered.Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria.In addition,autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue.In this paper,we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions,including myocardial ischemia,ischemia/reperfusion injury and sepsis cardiomyopathy.展开更多
Traumatic brain injury(TBI)disrupts normal brain function and is associated with high morbidity and fatality rates.TBI is characterized as mild,moderate or severe depending on its severity.The damage may be transient ...Traumatic brain injury(TBI)disrupts normal brain function and is associated with high morbidity and fatality rates.TBI is characterized as mild,moderate or severe depending on its severity.The damage may be transient and limited to the dura matter,with only subtle changes in cerebral parenchyma,or life-threatening with obvious focal contusions,hematomas and edema.Blood vessels are often injured in TBI.Even in mild TBI,dysfunctional cerebral vascular repair may result in prolonged symptoms and poor outcomes.Various distinct types of cells participate in vascular repair after TBI.A better understanding of the cellular response and function in vascular repair can facilitate the development of new therapeutic strategies.In this review,we analyzed the mechanism of cerebrovascular impairment and the repercussions following various forms of TBI.We then discussed the role of distinct cell types in the repair of meningeal and parenchyma vasculature following TBI,including endothelial cells,endothelial progenitor cells,pericytes,glial cells(astrocytes and microglia),neurons,myeloid cells(macrophages and monocytes)and meningeal lymphatic endothelial cells.Finally,possible treatment techniques targeting these unique cell types for vascular repair after TBI are discussed.展开更多
基金the Macao Science and Technology Development Fund(No.0086/2021/A2)Shenzhen Fundamental Research Program(No.SGDX20210823103804030)+1 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012416).
文摘Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.
文摘目的观察阿利沙坦酯联合硝苯地平缓释片对中重度原发性高血压伴心绞痛疗效和安全性。方法选取2021年1月至2022年1月佛山市中医院禅城高新区医院老年医学科收治的符合纳入标准的120例中重度原发性高血压伴心绞痛患者,根据随机数表法分为研究组和对照组,每组各60例。对照组使用硝苯地平缓释片Ⅰ治疗,研究组在对照组基础上联合阿利沙坦酯片治疗,疗程为12周。治疗前后测量诊室血压并进行动态血压监测,评估降压效果,计算血压达标率。记录治疗期间两组心绞痛发作持续时间、发作频率、硝酸甘油用量,评估心绞痛改善情况。测量治疗前后患者生命体征,并行血尿常规、血糖、胆固醇、三酰甘油、尿素氮、肌酐、尿酸、血电解质、转氨酶、血清肌酐等实验室检查,记录治疗期间不良反应发生情况。结果治疗后,两组诊室收缩压(SBP)和舒张压(DBP)均较治疗前降低,且研究组低于对照组(P<0.05)。治疗后,两组24 h SBP、24 h DBP、白昼SBP(dSBP)、白昼DBP(dDBP)、夜间SBP(nSBP)和夜间DBP(nDBP)均降低,且研究组低于对照组(P<0.05)。研究组降压总有效率高于对照组(P<0.05)。两组与同组治疗2周后和治疗4周后比较,治疗8周后和治疗12周后两组血压达标率均增加(P<0.05)。治疗后,两组心绞痛发作持续时间、发作频率、硝酸甘油用量均较治疗前减少,且研究组低于对照组(P<0.05)。研究组心绞痛改善总有效率高于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论阿利沙坦酯联合硝苯地平缓释片治疗中重度原发性高血压伴心绞痛疗效显著,有效降压并维持血压稳定的同时,还可改善心绞痛症状,且安全性较高,具有临床应用价值。
基金The National Natural Science Foundation of China(grant nos.21871301,22071275,and 22201056)is gratefully acknowledged for providing financial support for this work。
文摘Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and phagosomes.Therefore,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and treatment.Herein,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEG)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ADA.Subsequently,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic vesicles.As a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.
基金the National Natural Science Foundation of China(U21A20172,21975028)the China Postdoctoral Science Foundation under Grant Number 2023 M740167.
文摘Enhancing the lifetime of perovskite solar cells(PSCs)is one of the essential challenges for their industrialization.Although the external encapsulation protects the perovskite device from the erosion of moisture and oxygen under various harsh conditions.However,the perovskite devices still undergo static and dynamic thermal stress during thermal and thermal cycling aging,respectively,resulting in irreversible damage to the morphology,component,and phase of stacked materials.Herein,the viscoelastic polymer polyvinyl butyral(PVB)material is designed onto the surface of perovskite films to form flexible interface encapsulation.After PVB interface encapsulation,the surface modulus of perovskite films decreases by nearly 50%,and the interface stress range under the dynamic temperature field(−40 to 85°C)drops from−42.5 to 64.8 MPa to−14.8 to 5.0 MPa.Besides,PVB forms chemical interactions with FA+cations and Pb^(2+),and the macroscopic residual stress is regulated and defects are reduced of the PVB encapsulated perovskite film.As a result,the optimized device's efficiency increases from 22.21%to 23.11%.Additionally,after 1500 h of thermal treatment(85°C),1000 h of damp heat test(85°C&85%RH),and 250 cycles of thermal cycling test(−40 to 85°C),the devices maintain 92.6%,85.8%,and 96.1%of their initial efficiencies,respectively.
文摘在级联H桥多电平静止无功发生器(Static Var Generator,SVG)中,H桥固有的结构特性使得角形级联SVG直流侧电容电压存在二倍频纹波,电压波动影响电能质量补偿效果甚至导致系统失调。为抑制角形级联SVG的H桥直流侧二倍频电压纹波,文中提出了基于Boost型有源功率解耦(Active Power Decoupling,APD)的角形级联H桥多电平SVG的设计方案。有源功率解耦电路将波动功率和稳定功率相互分离,采用储能元件吸收波动功率,从而削弱了H桥直流侧电压波动。利用MATLAB/Simulink搭建仿真平台进行仿真,结果表明基于Boost型有源功率解耦的角形级联H桥多电平SVG能够有效抑制直流侧电容电压的二倍频纹波。
基金the National Natural Science Foundation of China，the Strategic Programs for Innovative Research，the Computational Materials Science Initiative，the Yukawa International Program for Quark-Hadron Sciences at YITP,Kyoto University
文摘The electronic structures and optical properties of the monoclinic ZrO2 (m-ZrO2) are investigated by means of first-principles local density approximation (LDA) + U approach.Without on-site Coulomb interactions,the band gap of m-ZrO2 is 3.60 eV,much lower than the experimental value (5.8 eV).By introducing the Coulomb interactions of 4d orbitals on Zr atom (Ud) and of 2p orbitals on O atom (Up),we can reproduce the experimental value of the band gap.The calculated dielectric function of m-ZrO2 exhibits a small shoulder at the edge of the band gap in its imaginary part,while in the tetragonal ZrO2 and cubic ZrO2 it is absent,which is consistent with the experimental observations.The origin of the shoulder is attributed to the difference of electronic structures near the edge of the valence and conduction bands.
基金supported by the National Natural Science Foundation of China(82104495 and 82174161)Shenzhen Fundamental Research Program(No.SGDX20210823103804030)+8 种基金Science and Technology Development Fund,Macao SAR(No.0025/2022/A1)University of Macao grants(No.MYRG2019-00129-ICMS)Macao Youth Scholars Program(AM2021023)Guangdong Basic and Applied Basic Research Foundation(2022A1515010395 and 2021A1515012573)Science and Technology Foundation of Guangzhou City(202102010257)State Key Laboratory of Dampness Syndrome of Chinese Medicine Research Foundation(SZ2021ZZ21 and SZ2022QN02)Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine(Nos.20212088)TCM Research Fund of Guangdong Provincial Hospital of Chinese Medicine(YN2020MS13)The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006 and MY2022KF05).
文摘Autophagy is a highly conserved bulk degradation mechanism that degrades damaged organelles,aged proteins and intracellular contents to maintain the homeostasis of the intracellular microenvironment.Activation of autophagy can be observed during myocardial injury,during which inflammatory responses are strongly triggered.Autophagy can inhibit the inflammatory response and regulate the inflammatory microenvironment by removing invading pathogens and damaged mitochondria.In addition,autophagy may enhance the clearance of apoptotic and necrotic cells to promote the repair of damaged tissue.In this paper,we briefly review the role of autophagy in different cell types in the inflammatory microenvironment of myocardial injury and discuss the molecular mechanism of autophagy in regulating the inflammatory response in a series of myocardial injury conditions,including myocardial ischemia,ischemia/reperfusion injury and sepsis cardiomyopathy.
基金supported by Macao Young Scholars Program(AM2020032)Macao Science and Technology Development Fund(0061/2021/A2)and(EF026/ICMS-SHX/2022/SZSTIC).
文摘Traumatic brain injury(TBI)disrupts normal brain function and is associated with high morbidity and fatality rates.TBI is characterized as mild,moderate or severe depending on its severity.The damage may be transient and limited to the dura matter,with only subtle changes in cerebral parenchyma,or life-threatening with obvious focal contusions,hematomas and edema.Blood vessels are often injured in TBI.Even in mild TBI,dysfunctional cerebral vascular repair may result in prolonged symptoms and poor outcomes.Various distinct types of cells participate in vascular repair after TBI.A better understanding of the cellular response and function in vascular repair can facilitate the development of new therapeutic strategies.In this review,we analyzed the mechanism of cerebrovascular impairment and the repercussions following various forms of TBI.We then discussed the role of distinct cell types in the repair of meningeal and parenchyma vasculature following TBI,including endothelial cells,endothelial progenitor cells,pericytes,glial cells(astrocytes and microglia),neurons,myeloid cells(macrophages and monocytes)and meningeal lymphatic endothelial cells.Finally,possible treatment techniques targeting these unique cell types for vascular repair after TBI are discussed.
