Objective:To evaluate the basic appearance and variation of the venous sinuses and veins in healthy individuals.Methods:Prospectively-recruited healthy volunteers completed a questionnaire and underwent magnetic reson...Objective:To evaluate the basic appearance and variation of the venous sinuses and veins in healthy individuals.Methods:Prospectively-recruited healthy volunteers completed a questionnaire and underwent magnetic resonance imaging plus contrast-enhanced magnetic resonance venography(CE-MRV)to measure their sinus diameters.Anatomical variations of cerebral venous sinuses were evaluated.Results:Fifty-eight individuals were included.The mean diameter of the left transverse sinus(LTS)(5.37±1.35 mm)was significantly smaller than that of the right transverse sinus(RTS)(6.65±1.57 mm)(P<0.001),and the average discrepancy was 19.2%.RTS dominance was noted in 55.1%of cases.Four superior sagittal sinus(SSS)anatomical variations were found.Type A was the most common and was present in 43 participants(74.1%).The SSS preferentially drained into the RTS in 32 patients(55.2%),and arachnoid granulation was observed in the transverse sinus(TS)and SSS in patients.According to our reclassification combined with Osborn’s previous research,we found that the SSS commonly drained into the RTS and that the straight sinus(StS)branched into both TSs.Conclusions:A 19%difference between the LTS and RTS provides a threshold for TS lateral dominance instead of a TS abnormality.Clinicians and radiologists should not ignore the influence of acquired pathology when the SSS drains in a non-RTS-dominant manner.Anatomical variations of the torcular herophili are frequent;the most commonly observed was the StS branching into both TSs,with the SSS draining into the RTS.展开更多
Diabetes mellitus(DM)is a pressing global public health issue with a high incidence of morbidity and mortality due to its complications.Although there are many medicines available for the treatment of DM,long-term use...Diabetes mellitus(DM)is a pressing global public health issue with a high incidence of morbidity and mortality due to its complications.Although there are many medicines available for the treatment of DM,long-term use causes various adverse effects,such as diarrhea,vomiting,and nausea.Tea,owing to its richness of diverse bioactive components including tea polyphenols,tea polysaccharides,and alkaloids,has displayed promising antidiabetic properties.Screening antidiabetic bioactive compounds derived from teas is receiving increasing attention.Epidemiological and clinical investigations have demonstrated an inverse relationship between tea consumption and the incidence of DM.Both in vitro and in vivo experiments have substantiated the hypoglycemic effects of tea and its bioactive components through several possible mechanisms,including improvement of insulin resistance,inhibition of carbohydrates digestion and absorption(inhibitα-amylase andα-glucosidase activity),regulations of gut microbiota,inflammatory cytokines,and gene and protein expressions in the insulin signaling pathway,as well as amelioration of DM complications.This comprehensive review provides an up-to-date overview of the hypoglycemic properties associated with tea and its bioactive components.It also delves into their potential mechanisms,offering a theoretical foundation for further research into tea's antidiabetic properties and for the development of innovative antidiabetic functional products.展开更多
The hydrogen evolution reaction(HER) through electrocatalysis is promising for the production of clean hydrogen fuel. However,designing the structure of catalysts,controlling their electronic properties,and manipulati...The hydrogen evolution reaction(HER) through electrocatalysis is promising for the production of clean hydrogen fuel. However,designing the structure of catalysts,controlling their electronic properties,and manipulating their catalytic sites are a significant challenge in this field. Here,we propose an electrochemical surface restructuring strategy to design synergistically interactive phosphorus-doped carbon@MoP electrocatalysts for the HER. A simple electrochemical cycling method is developed to tune the thickness of the carbon layers that cover on MoP core,which significantly influences HER performance. Experimental investigations and theoretical calculations indicate that the inactive surface carbon layers can be removed through electrochemical cycling,leading to a close bond between the MoP and a few layers of coated graphene. The electronsdonated by the MoP core enhance the adhesion and electronegativity of the carbon layers;the negatively charged carbon layers act as an active surface. The electrochemically induced optimization of the surface/interface electronic structures in the electrocatalysts significantly promotes the HER. Using this strategy endows the catalyst with excellent activity in terms of the HER in both acidic and alkaline environments(current density of 10 mA cm^(-2) at low overpotentials,of 68 mV in 0.5 M H_(2)SO_(4) and 67 mV in 1.0 M KOH).展开更多
Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocy...Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstrated that protein kinase B(AKT) activation,as well as reduced CCAAT enhancer-binding protein beta(C/EBPβ) and increased CBP/p300-interacting transactivators with E(glutamic acid)/D(aspartic acid)-rich-carboxylterminal domain 4(CITED4),contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation.Conclusion:Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation,and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis.These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.展开更多
The present study examined 24 children with acute Guillain-Barre syndrome using magnetic resonance imaging (MRI) plain scans and fat-suppressed enhanced Tl-weighted imaging (T1WI) scans. Axial MRI plain scans cent...The present study examined 24 children with acute Guillain-Barre syndrome using magnetic resonance imaging (MRI) plain scans and fat-suppressed enhanced Tl-weighted imaging (T1WI) scans. Axial MRI plain scans centering on the medullary conus were positive in nine patients (38%). These displayed variable thickening involving the cauda equina with isointensity on T1WI and isointensity or slight hyperintensity on T2WI. False negatives were obtained in patients with cervical and cranial nerve symptoms. Contrast enhancement of T1WI with fat suppression was positive in all patients in the cauda equina with varied thickening and enhancement centering on the medullary conus. Five patients (36%) were positive in the cervical nerves and 3 patients (50%) were positive in the cranial nerves. These patients had corresponding cervical and cranial nerve symptoms, respectively. Patients with serious clinical symptoms in the lower limbs exhibited obvious involvement of the cauda equina by MRI. Statistical analysis revealed a positive correlation between the extent of enlargement of the cauda equina, centering on the medullary conus, and cerebrospinal fluid protein concentration.展开更多
Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disea...Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective inter...Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.展开更多
The coronavirus disease 2019(COVID-19)epidemic has triggered a huge impact on healthcare,socioeconomics,and other aspects of the world over the past three years.An increasing number of studies have identified a comple...The coronavirus disease 2019(COVID-19)epidemic has triggered a huge impact on healthcare,socioeconomics,and other aspects of the world over the past three years.An increasing number of studies have identified a complex relationship between COVID-19 and stroke,although active measures are being implemented to prevent disease transmission.Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality,posing a serious challenge to acute stroke diagnosis,treatment,and care.This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke,including arterial stroke(ischemic stroke and hemorrhagic stroke)and venous stroke(cerebral venous thrombosis).Additionally,the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented.Evidence on vaccinations,potential therapeutic approaches,and effective strategies for stroke management has been highlighted.展开更多
氨是一种很有前途的能源载体,由于其高氢含量和无碳的特点,可用于燃料电池,并可作为电解水制氢装置中水的替代氧化底物.然而,人们对氨电氧化反应(AOR)的机理认识不足,且缺乏廉价、高效的AOR催化剂,因而阻碍了氨基能源系统的发展.在这项...氨是一种很有前途的能源载体,由于其高氢含量和无碳的特点,可用于燃料电池,并可作为电解水制氢装置中水的替代氧化底物.然而,人们对氨电氧化反应(AOR)的机理认识不足,且缺乏廉价、高效的AOR催化剂,因而阻碍了氨基能源系统的发展.在这项工作中,我们通过光诱导化学沉淀法合成的新型Ni和Cu共掺杂的多孔FeOOH纳米棒(NiCu-FeOOH)可以作为AOR催化剂,其具有高效的催化活性(阳极电流密度达到10 mA cm^(-2)时执行电压为1.41 V)和在氨碱溶液中优异的稳定性.实验数据和理论计算结果表明,异质的Ni和Cu原子的协同作用使得NiCu-FeOOH表面的Ni和Fe位点表现出更合适的电子结构,他们可以共同吸附含氮中间产物和羟基,并使其吸附自由能位于火山形曲线的顶部,从而加速AOR脱氢.决速步骤的后移(*NH_(2)+*OH形成步骤移至*N_(2)H_(3)+*OH形成步骤)和决速步骤较低的能垒(0.86 eV)揭示了Ni和Cu的共掺策略使FeOOH晶体对催化AOR更具活性.本文创新地提出了涉及含氮中间物和羟基的共吸附反应途径,以更好地描述和模拟AOR过程,这为设计低成本和稳定的AOR催化剂开辟了新的路径.展开更多
The near-infrared(NIR)persistent luminescence materials(PLMs)can remain long-lasting luminescence after removal of the excitation light,which permits bioimaging with high sensitivity owing to the absence of background...The near-infrared(NIR)persistent luminescence materials(PLMs)can remain long-lasting luminescence after removal of the excitation light,which permits bioimaging with high sensitivity owing to the absence of background fluorescence interference from in situ excitation.Recently,the NIR PLMs have aroused intensive research interest in bioimaging.However,the optimal excitation wavelength of current NIR PLMs is located in the ultraviolet region with shallow tissue penetration,making it difficult to activate effectively in vivo,and seriously hindering their further application in bioimaging.Herein,we report a novel kind of Cr^(3+)ions and Y^(3+)ions co-doped NIR PLM,Zn_(1.3)Ga_(1.4)Sn_(0.3)O_(4):Cr^(3+),Y^(3+)(ZGSCY),which emits NIR persistent luminescence at 696 nm.Compared with Zn_(1.3)Ga_(1.4)Sn_(0.3)O_(4):Cr^(3+)(ZGSC)excited by the light with a wavelength in the biological window(>650 nm),after being co-doped with Y^(3+)ions,the NIR persistent luminescence performance of ZGSCY is significantly improved because of the increase of trap concentration in the matrix.In addition,we synthesized ZGSCY nanoparticles(NPs)by the combustion method,which exhibit excellent optical properties after being excited by the light with a wavelength in the biological window.After surface modification with PEG,the ZGSCY NPs present low cytotoxicity.Notably,due to the co-doping of Y^(3+)ions,the signal-to-noise ratio(SNR)of ZGSCY NPs in vivo imaging is about 1.8 times higher than that of the ZGSC NPs.Furthermore,the rechargeable in vivo imaging and passive tumor-targeted imaging are successfully achieved by activating with a lightemitting diode(LED,659 nm)after intravenous injection of ZGSCY.Thus,this kind of NIR PLM with high excitation efficiency performance in the biological window is expected to promote its biomedical application in deep tissues.展开更多
The responses of sulfur (S) uptake assimilation-related genes' expression in roots of two rice cultivars to cadmium (Cd), bensulfuron-methyl (BSM) and their co-contamination (Cd+BSM) were investigated by gen...The responses of sulfur (S) uptake assimilation-related genes' expression in roots of two rice cultivars to cadmium (Cd), bensulfuron-methyl (BSM) and their co-contamination (Cd+BSM) were investigated by gene-chip microarray analysis and quantitative real-time PCR (QRT-PCR) technology. Treatments of Cd and Cd+BSM induced expression of sulfate transporter and permease genes, and promoted sulfate uptake in rice roots. Cd+BSM could alleviate Cd toxicity to cv. Fengmeizhan seedlings, probably due to Cd+BSM promoting greater S absorption by seedlings. Cd and Cd+BSM induced expression of sulfate assimilation-related genes, and thus activated the sulfur assimilation pathway. Cd and Cd+BSM induced expression of phytochelatin synthase and metallothionein genes, and induced expression of glutathione S-transferases (GSTs), glutathione synthase (GS) and S- containing antioxidation enzyme genes, which detoxified Cd2+. It is suggested that (to cope with the toxicity of Cd, BSM and their co-contamination) the S uptake and assimilation pathway was activated in rice roots by increased expression of related genes, thus enhancing the supply of organic S for synthesis of Cd or BSM resistance-related substances.展开更多
Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are signi...Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are significant for understanding cell metabolism and their related diseases. Herein, a multisitebinding fluorescent probe(MCP) was developed for simultaneous sensing of mitochondrial Cys, GSH and Hcy from three fluorescence channels for the first time. This novel probe exhibited rapid fluorescence turn-on, good water-solubility, high selectivity and large spectral separation for discriminating Cys, GSH and Hcy with 131-, 96-, 748-fold fluorescence increasement at 471, 520, 567 nm through different excitation wavelengths, respectively. Importantly, this probe was successfully applied to simultaneous monitoring of mitochondrial Cys, GSH, and Hcy in live cells and zebrafish from three fluorescence channels,promoting the understanding of the functions of Hcy, Cys and GSH.展开更多
基金supported by the National Natural Science Foundation of China(82027802)the Pharmaceutical Collaboration Project of the Beijing Science and Technology Commission(Z181100001918026)the Talents Gathering Project of Xuanwu Hospital,Capital Medical University.
文摘Objective:To evaluate the basic appearance and variation of the venous sinuses and veins in healthy individuals.Methods:Prospectively-recruited healthy volunteers completed a questionnaire and underwent magnetic resonance imaging plus contrast-enhanced magnetic resonance venography(CE-MRV)to measure their sinus diameters.Anatomical variations of cerebral venous sinuses were evaluated.Results:Fifty-eight individuals were included.The mean diameter of the left transverse sinus(LTS)(5.37±1.35 mm)was significantly smaller than that of the right transverse sinus(RTS)(6.65±1.57 mm)(P<0.001),and the average discrepancy was 19.2%.RTS dominance was noted in 55.1%of cases.Four superior sagittal sinus(SSS)anatomical variations were found.Type A was the most common and was present in 43 participants(74.1%).The SSS preferentially drained into the RTS in 32 patients(55.2%),and arachnoid granulation was observed in the transverse sinus(TS)and SSS in patients.According to our reclassification combined with Osborn’s previous research,we found that the SSS commonly drained into the RTS and that the straight sinus(StS)branched into both TSs.Conclusions:A 19%difference between the LTS and RTS provides a threshold for TS lateral dominance instead of a TS abnormality.Clinicians and radiologists should not ignore the influence of acquired pathology when the SSS drains in a non-RTS-dominant manner.Anatomical variations of the torcular herophili are frequent;the most commonly observed was the StS branching into both TSs,with the SSS draining into the RTS.
基金supported by the Zhejiang Province Natural Science Foundation(LR23C160002)the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2023-TRICAAS)the National Natural Science Foundation(32172630 and 31972467).
文摘Diabetes mellitus(DM)is a pressing global public health issue with a high incidence of morbidity and mortality due to its complications.Although there are many medicines available for the treatment of DM,long-term use causes various adverse effects,such as diarrhea,vomiting,and nausea.Tea,owing to its richness of diverse bioactive components including tea polyphenols,tea polysaccharides,and alkaloids,has displayed promising antidiabetic properties.Screening antidiabetic bioactive compounds derived from teas is receiving increasing attention.Epidemiological and clinical investigations have demonstrated an inverse relationship between tea consumption and the incidence of DM.Both in vitro and in vivo experiments have substantiated the hypoglycemic effects of tea and its bioactive components through several possible mechanisms,including improvement of insulin resistance,inhibition of carbohydrates digestion and absorption(inhibitα-amylase andα-glucosidase activity),regulations of gut microbiota,inflammatory cytokines,and gene and protein expressions in the insulin signaling pathway,as well as amelioration of DM complications.This comprehensive review provides an up-to-date overview of the hypoglycemic properties associated with tea and its bioactive components.It also delves into their potential mechanisms,offering a theoretical foundation for further research into tea's antidiabetic properties and for the development of innovative antidiabetic functional products.
基金supported by the National Natural Science Foundation of China (Grant Nos. 21975286 and 21473254)the Special Project Fund of “Taishan Scholar” of Shandong Province (Grant No. ts201511017)+2 种基金the QLUT Special Funding for Distinguished Scholars (Grant No. 2419010420)the project ZR2020QE058 supported by Shandong Provincial Natural Science Foundationthe Fundamental Research Funds for the Central Universities (Grant Nos. YCX2020050,18CX06030A,and 17CX02039A)。
文摘The hydrogen evolution reaction(HER) through electrocatalysis is promising for the production of clean hydrogen fuel. However,designing the structure of catalysts,controlling their electronic properties,and manipulating their catalytic sites are a significant challenge in this field. Here,we propose an electrochemical surface restructuring strategy to design synergistically interactive phosphorus-doped carbon@MoP electrocatalysts for the HER. A simple electrochemical cycling method is developed to tune the thickness of the carbon layers that cover on MoP core,which significantly influences HER performance. Experimental investigations and theoretical calculations indicate that the inactive surface carbon layers can be removed through electrochemical cycling,leading to a close bond between the MoP and a few layers of coated graphene. The electronsdonated by the MoP core enhance the adhesion and electronegativity of the carbon layers;the negatively charged carbon layers act as an active surface. The electrochemically induced optimization of the surface/interface electronic structures in the electrocatalysts significantly promotes the HER. Using this strategy endows the catalyst with excellent activity in terms of the HER in both acidic and alkaline environments(current density of 10 mA cm^(-2) at low overpotentials,of 68 mV in 0.5 M H_(2)SO_(4) and 67 mV in 1.0 M KOH).
基金supported by the grants from National Key Research and Development Project(2018YFE0113500 to JX)National Natural Science Foundation of China(82020108002 and 81911540486 to JX,81970335 and 82170285 to YB)+4 种基金Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX)Science and Technology Commission of Shanghai Municipality(20DZ2255400 and 18410722200 to JX)the“Dawn”Program of Shanghai Education Commission(19SG34 to JX)the Shanghai Rising-Star Program(19QA1403900 to YB)the Science and Technology Commission of Shanghai Municipality(21SQBS00100 to YB).
文摘Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstrated that protein kinase B(AKT) activation,as well as reduced CCAAT enhancer-binding protein beta(C/EBPβ) and increased CBP/p300-interacting transactivators with E(glutamic acid)/D(aspartic acid)-rich-carboxylterminal domain 4(CITED4),contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation.Conclusion:Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation,and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis.These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.
文摘The present study examined 24 children with acute Guillain-Barre syndrome using magnetic resonance imaging (MRI) plain scans and fat-suppressed enhanced Tl-weighted imaging (T1WI) scans. Axial MRI plain scans centering on the medullary conus were positive in nine patients (38%). These displayed variable thickening involving the cauda equina with isointensity on T1WI and isointensity or slight hyperintensity on T2WI. False negatives were obtained in patients with cervical and cranial nerve symptoms. Contrast enhancement of T1WI with fat suppression was positive in all patients in the cauda equina with varied thickening and enhancement centering on the medullary conus. Five patients (36%) were positive in the cervical nerves and 3 patients (50%) were positive in the cranial nerves. These patients had corresponding cervical and cranial nerve symptoms, respectively. Patients with serious clinical symptoms in the lower limbs exhibited obvious involvement of the cauda equina by MRI. Statistical analysis revealed a positive correlation between the extent of enlargement of the cauda equina, centering on the medullary conus, and cerebrospinal fluid protein concentration.
基金funded by the China National Natural Science Foundation(No.81970618,82170720,82200788)China National Clinical Research Centre Foundation(No.NCRC-2019-GP-02)+2 种基金Science and Technology Research Project of Chongqing Education Commission of China(No.KJZDM201900401)Chongqing Science and Health Joint Medical Research Project(China)(No.2023GGXM001)National Key R&D Program of China(No.2022YFC2705101).
文摘Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.
基金supported by National Key Research&Development Program from the Ministry of Science and Technology of the PRC(No.2019YFE0111800,China)National Natural Science Foundation of China(No.81872923,China)+1 种基金Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2021-JKCS-016,China)The Science and Technology Development Fund,Macao SAR(No.0074/2019/AMJ,China).
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive lung disease with unclear etiology and limited treatment options.The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation.As important components of lung tissue,endothelial cells(ECs)are associated with pulmonary diseases.However,the role of endothelial dysfunction in pulmonary fibrosis(PF)is incompletely understood.Sphingosine-1-phosphate receptor 1(S1PR1)is a G protein-coupled receptor highly expressed in lung ECs.Its expression is markedly reduced in patients with IPF.Herein,we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin(BLM)challenge.Selective activation of S1PR1 with an S1PR1 agonist,IMMH002,exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier.These results suggest that S1PR1 might be a promising drug target for IPF therapy.
基金supported by the National Natural Science Foundation of China(No.882027802)Pharmaceutical Collaboration Project of the Beijing Science and Technology Commission(No.Z181100001918026)Talents Gathering Project of Xuanwu Hospital,Capital Medical University.
文摘The coronavirus disease 2019(COVID-19)epidemic has triggered a huge impact on healthcare,socioeconomics,and other aspects of the world over the past three years.An increasing number of studies have identified a complex relationship between COVID-19 and stroke,although active measures are being implemented to prevent disease transmission.Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality,posing a serious challenge to acute stroke diagnosis,treatment,and care.This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke,including arterial stroke(ischemic stroke and hemorrhagic stroke)and venous stroke(cerebral venous thrombosis).Additionally,the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented.Evidence on vaccinations,potential therapeutic approaches,and effective strategies for stroke management has been highlighted.
基金supported by the National Natural Science Foundation of China(21975286)Shandong Provincial Natural Science Foundation(ZR2020QE058)+1 种基金the Colleges and Universities Twenty Terms Foundation of Jinan(202228053)the QLUT Special Funding for Distinguished Scholars(2419010420)。
文摘氨是一种很有前途的能源载体,由于其高氢含量和无碳的特点,可用于燃料电池,并可作为电解水制氢装置中水的替代氧化底物.然而,人们对氨电氧化反应(AOR)的机理认识不足,且缺乏廉价、高效的AOR催化剂,因而阻碍了氨基能源系统的发展.在这项工作中,我们通过光诱导化学沉淀法合成的新型Ni和Cu共掺杂的多孔FeOOH纳米棒(NiCu-FeOOH)可以作为AOR催化剂,其具有高效的催化活性(阳极电流密度达到10 mA cm^(-2)时执行电压为1.41 V)和在氨碱溶液中优异的稳定性.实验数据和理论计算结果表明,异质的Ni和Cu原子的协同作用使得NiCu-FeOOH表面的Ni和Fe位点表现出更合适的电子结构,他们可以共同吸附含氮中间产物和羟基,并使其吸附自由能位于火山形曲线的顶部,从而加速AOR脱氢.决速步骤的后移(*NH_(2)+*OH形成步骤移至*N_(2)H_(3)+*OH形成步骤)和决速步骤较低的能垒(0.86 eV)揭示了Ni和Cu的共掺策略使FeOOH晶体对催化AOR更具活性.本文创新地提出了涉及含氮中间物和羟基的共吸附反应途径,以更好地描述和模拟AOR过程,这为设计低成本和稳定的AOR催化剂开辟了新的路径.
基金Project supported by the National Natural Science Foundation of China(61705228,21507129)the Natural Science Foundation of Fujian ProvinceChina(2019J05159)。
文摘The near-infrared(NIR)persistent luminescence materials(PLMs)can remain long-lasting luminescence after removal of the excitation light,which permits bioimaging with high sensitivity owing to the absence of background fluorescence interference from in situ excitation.Recently,the NIR PLMs have aroused intensive research interest in bioimaging.However,the optimal excitation wavelength of current NIR PLMs is located in the ultraviolet region with shallow tissue penetration,making it difficult to activate effectively in vivo,and seriously hindering their further application in bioimaging.Herein,we report a novel kind of Cr^(3+)ions and Y^(3+)ions co-doped NIR PLM,Zn_(1.3)Ga_(1.4)Sn_(0.3)O_(4):Cr^(3+),Y^(3+)(ZGSCY),which emits NIR persistent luminescence at 696 nm.Compared with Zn_(1.3)Ga_(1.4)Sn_(0.3)O_(4):Cr^(3+)(ZGSC)excited by the light with a wavelength in the biological window(>650 nm),after being co-doped with Y^(3+)ions,the NIR persistent luminescence performance of ZGSCY is significantly improved because of the increase of trap concentration in the matrix.In addition,we synthesized ZGSCY nanoparticles(NPs)by the combustion method,which exhibit excellent optical properties after being excited by the light with a wavelength in the biological window.After surface modification with PEG,the ZGSCY NPs present low cytotoxicity.Notably,due to the co-doping of Y^(3+)ions,the signal-to-noise ratio(SNR)of ZGSCY NPs in vivo imaging is about 1.8 times higher than that of the ZGSC NPs.Furthermore,the rechargeable in vivo imaging and passive tumor-targeted imaging are successfully achieved by activating with a lightemitting diode(LED,659 nm)after intravenous injection of ZGSCY.Thus,this kind of NIR PLM with high excitation efficiency performance in the biological window is expected to promote its biomedical application in deep tissues.
基金supported by the National Natural Science Foundation of China(No.20877101)the Special Fund for Agro-Scientific Research in the Public Interest(No.201103007)
文摘The responses of sulfur (S) uptake assimilation-related genes' expression in roots of two rice cultivars to cadmium (Cd), bensulfuron-methyl (BSM) and their co-contamination (Cd+BSM) were investigated by gene-chip microarray analysis and quantitative real-time PCR (QRT-PCR) technology. Treatments of Cd and Cd+BSM induced expression of sulfate transporter and permease genes, and promoted sulfate uptake in rice roots. Cd+BSM could alleviate Cd toxicity to cv. Fengmeizhan seedlings, probably due to Cd+BSM promoting greater S absorption by seedlings. Cd and Cd+BSM induced expression of sulfate assimilation-related genes, and thus activated the sulfur assimilation pathway. Cd and Cd+BSM induced expression of phytochelatin synthase and metallothionein genes, and induced expression of glutathione S-transferases (GSTs), glutathione synthase (GS) and S- containing antioxidation enzyme genes, which detoxified Cd2+. It is suggested that (to cope with the toxicity of Cd, BSM and their co-contamination) the S uptake and assimilation pathway was activated in rice roots by increased expression of related genes, thus enhancing the supply of organic S for synthesis of Cd or BSM resistance-related substances.
基金supported by the National Natural Science Foundation of China (Nos. 21877035 and 21977028)Research Foundation of Education Bureau of Hunan Province (No. 18B004)。
文摘Homocysteine(Hcy), cysteine(Cys) and glutathione(GSH) play crucial roles in redox homeostasis during mitochondria functions. Simultaneous differentiation and visualization of mitochondrial biothiols dynamics are significant for understanding cell metabolism and their related diseases. Herein, a multisitebinding fluorescent probe(MCP) was developed for simultaneous sensing of mitochondrial Cys, GSH and Hcy from three fluorescence channels for the first time. This novel probe exhibited rapid fluorescence turn-on, good water-solubility, high selectivity and large spectral separation for discriminating Cys, GSH and Hcy with 131-, 96-, 748-fold fluorescence increasement at 471, 520, 567 nm through different excitation wavelengths, respectively. Importantly, this probe was successfully applied to simultaneous monitoring of mitochondrial Cys, GSH, and Hcy in live cells and zebrafish from three fluorescence channels,promoting the understanding of the functions of Hcy, Cys and GSH.