Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-t...Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide(GICP), was previously reported as a ligand for the VAV3 protein(a Rho-GTPase guanine nucleotide exchange factor),which is mainly expressed on glioma cells; the stabilized heptapeptide ~DA7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1), and has demonstrated good neovasculature-targeting ability. By linking ~DA7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood–tumor barrier(BTB) was also determined. The results indicate that the coupled Y-shaped peptide ~DA7R–GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.展开更多
Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathoge...Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathogenic role in diseases such as inflammatory bowel disease(IBD)and celiac disease,and functional bowel disorders such as irritable bowel syndrome.Therefore,clarification of the inflammatory responses,the defense pathway and the corresponding regulatory system is essential and may lead to the development of new therapies.MicroRNAs(miRNAs)are small(19-22nt)noncoding RNA molecules that regulate genes at the post-transcriptional level by base-pairing to specific messenger RNAs for degradation to repress translation.Recent studies suggested that miRNAs are important in the immune response and mediate a critical role in multiple immune response-related disorders.Based on these discoveries,attention has been focused on understanding the role of miRNAs in regulating intestinal barrier dysfunction,especially in IBD.Here,we provide a review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction.展开更多
The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(...The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)channel and the ^(12)C(^(12)C,3a)^(12)C channel could be measured down to the level of a few milibarns.The ^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)reaction channel was determined to be 10_(-8)^(+24) mb at E_(c.m.)=11.1 MeV,supporting the direct a transfer reaction mechanism.The ^(12)C(^(12)C,3α)^(12)C reaction channel was studied for the first time using an exclusive measurement.Our result does not confirm the anomaly behavior reported in the previous inclusive measurement by Kolata et al.[Phys.Rev.C 21,579(1980)].Our comparisons with statistical model calculations suggest that the 3 a channel is dominated by the fusion evaporation process at E_(c.m.)>19 MeV.The additional contribution of the 3 a channel increases the fusion reaction cross section by 10% at energies above 20 MeV.We also find that an additional reaction mechanism is needed to explain the measured cross section at E_(c.m.)<15 MeV at which point the statistical model prediction vanishes.展开更多
Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investiga...Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.展开更多
The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery.Elevated intraspinal pressure(ISP)likely plays an important ...The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery.Elevated intraspinal pressure(ISP)likely plays an important role in the processes involved in secondary spinal cord injury,and should not be overlooked.However,the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature.Here,we review the etiology and progression of elevated ISP,as well as potential therapeutic measures that target elevated ISP.Elevated ISP is a time-dependent process that is mainly caused by hemorrhage,edema,and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury.Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window.Other potential treatments such as decompression,spinal cord incision,hemostasis,and methylprednisolone treatment require further validation.展开更多
Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several as...Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.展开更多
Bloodebrain barrier(BBB)damage after ischemia significantly influences stroke outcome.Compound LFHP-1 c was previously discovered with neuroprotective role in stroke model,but its mechanism of action on protection of ...Bloodebrain barrier(BBB)damage after ischemia significantly influences stroke outcome.Compound LFHP-1 c was previously discovered with neuroprotective role in stroke model,but its mechanism of action on protection of BBB disruption after stroke remains unknown.Here,we show that LFHP-1 c,as a direct PGAM5 inhibitor,prevented BBB disruption after transient middle cerebral artery occlusion(tMCAO)in rats.Mechanistically,LFHP-1 c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity,but also reduced the interaction of PGAM5 with NRF2,which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia.Furthermore,LFHP-1 c administration by targeting PGAM5 shows a trend toward reduced infarct volume,brain edema and neurological deficits in nonhuman primate Macaca fascicularis model with t MCAO.Thus,our study identifies compound LFHP-1 c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption in vitro and in vivo,and provides a potentially therapeutics for brain ischemic stroke.展开更多
With the increasing demand for security,building strong barrier coverage in directional sensor networks is important for effectively detecting un-authorized intrusions.In this paper,we propose an efficient scheme to f...With the increasing demand for security,building strong barrier coverage in directional sensor networks is important for effectively detecting un-authorized intrusions.In this paper,we propose an efficient scheme to form the strong barrier coverage by adding the mobile nodes one by one into the barrier.We first present the concept of target circle which determines the appropriate residence region and working direction of any candidate node to be added.Then we select the optimal relay sensor to be added into the current barrier based on its input-output ratio(barrier weight)which reflects the extension of barrier coverage.This strategy looses the demand of minimal required sensor nodes(maximal gain of each sensor)or maximal lifetime of one single barrier,leading to an augmentation of sensors to be used.Numerical simulation results show that,compared with the available schemes,the proposed method significantly reduces the minimal deploy density required to establish k-barrier,and increases the total service lifetime with a high deploy efficiency.展开更多
This paper examines the function of mother tongue in second or foreign language teaching and learning, focusing on the case of Chinese learners of English. The use of L1 in L2 vocabulary teaching is studied by summari...This paper examines the function of mother tongue in second or foreign language teaching and learning, focusing on the case of Chinese learners of English. The use of L1 in L2 vocabulary teaching is studied by summarizing relevant theories and by analyzing an example of how Chinese teachers introduce new words to students. The influence of L1 in L2 vocabulary learning is explored through studying three major negative transfers of Chinese learners of English with abundant common and typical examples.Seven implications for L2 teachers are listed as the result of my study.展开更多
基金supported by National Basic Research Program of China (973 Program, No. 2013CB932500)National Natural Science Foundation of China (Nos. 81773657, 81690263 and 81473149)+1 种基金Shanghai Education Commission Major Project (No. 2017-01-07-00-07-E00052)Shanghai International Science and Technology Cooperation Project (No.16430723800)
文摘Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide(GICP), was previously reported as a ligand for the VAV3 protein(a Rho-GTPase guanine nucleotide exchange factor),which is mainly expressed on glioma cells; the stabilized heptapeptide ~DA7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1), and has demonstrated good neovasculature-targeting ability. By linking ~DA7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood–tumor barrier(BTB) was also determined. The results indicate that the coupled Y-shaped peptide ~DA7R–GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.
基金Supported by Grant for Key Clinical Discipline Construction of Shanghai Municipality,China,No.ZK2012B20Phase Ⅱ Outstanding Young Medical Personnel Training Fund of Jinshan District Health Systems,Shanghai,China,No.JWKJ-RCYQ-201207
文摘Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation.Growing evidence has shown that an increase in intestinal permeability has a pathogenic role in diseases such as inflammatory bowel disease(IBD)and celiac disease,and functional bowel disorders such as irritable bowel syndrome.Therefore,clarification of the inflammatory responses,the defense pathway and the corresponding regulatory system is essential and may lead to the development of new therapies.MicroRNAs(miRNAs)are small(19-22nt)noncoding RNA molecules that regulate genes at the post-transcriptional level by base-pairing to specific messenger RNAs for degradation to repress translation.Recent studies suggested that miRNAs are important in the immune response and mediate a critical role in multiple immune response-related disorders.Based on these discoveries,attention has been focused on understanding the role of miRNAs in regulating intestinal barrier dysfunction,especially in IBD.Here,we provide a review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction.
基金Supported in part by the Strategic Priority Research Program of Chinese Academy of Sciences(XDB34020200)the National Key Research and Development program(MOST 2016YFA0400501)from the Ministry of Science and Technology of China+2 种基金the State Key Laboratory of Nuclear Physics and Technology,PKU(NPT2020KFY06)the National Natural Science Foundation of China(U1632142,12175156),the National Natural Science Foundation of China(11905260)the Western Light Project of Chinese Academy of Sciences。
文摘The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)channel and the ^(12)C(^(12)C,3a)^(12)C channel could be measured down to the level of a few milibarns.The ^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)reaction channel was determined to be 10_(-8)^(+24) mb at E_(c.m.)=11.1 MeV,supporting the direct a transfer reaction mechanism.The ^(12)C(^(12)C,3α)^(12)C reaction channel was studied for the first time using an exclusive measurement.Our result does not confirm the anomaly behavior reported in the previous inclusive measurement by Kolata et al.[Phys.Rev.C 21,579(1980)].Our comparisons with statistical model calculations suggest that the 3 a channel is dominated by the fusion evaporation process at E_(c.m.)>19 MeV.The additional contribution of the 3 a channel increases the fusion reaction cross section by 10% at energies above 20 MeV.We also find that an additional reaction mechanism is needed to explain the measured cross section at E_(c.m.)<15 MeV at which point the statistical model prediction vanishes.
基金supported by National Science Foundation of China(Grant Nos.30825045 and 81273465).
文摘Liposomes,as one of the most successful nanotherapeutics,have a major impact on many biomedical areas.In this study,we performed laser scanning confocal microscope(LSCM)and immunohistochemistry(IHC)assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptideconjugated active targeting liposomes(GE11-TLs)in SMMC7721 xenograft model.According to classification of individual cell types in high resolution images,biodistribution of macrophages,tumor cells,cells with high epidermal growth factor receptor(EGFR)expres sion and interstitial matrix in tumor microenvironment,in addition,their impacts on intra-tumor penetration of GE11-TLs were estimated.Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts.Tumor angiogenesis was of great heterogeneity from the periphery to the center region.However,the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs.We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drag delivery.
基金supported by a grant from Chongqing Yingcai Plan Project,No.cstc2021ycjh-bgzxm0041(to ZXQ).
文摘The currently recommended management for acute traumatic spinal cord injury aims to reduce the incidence of secondary injury and promote functional recovery.Elevated intraspinal pressure(ISP)likely plays an important role in the processes involved in secondary spinal cord injury,and should not be overlooked.However,the factors and detailed time course contributing to elevated ISP and its impact on pathophysiology after traumatic spinal cord injury have not been reviewed in the literature.Here,we review the etiology and progression of elevated ISP,as well as potential therapeutic measures that target elevated ISP.Elevated ISP is a time-dependent process that is mainly caused by hemorrhage,edema,and blood-spinal cord barrier destruction and peaks at 3 days after traumatic spinal cord injury.Duraplasty and hypertonic saline may be promising treatments for reducing ISP within this time window.Other potential treatments such as decompression,spinal cord incision,hemostasis,and methylprednisolone treatment require further validation.
基金supported by the National Natural Science Foundation of China (Grants No.82270011 and 81960513)the Scientific Research Foundation of the Affiliated Hospital of Xuzhou Medical University (Grant No.2020KA010)+2 种基金the Priority Academic Program Development of jiangsu Higher Education Institutions (PAPD),and Postgraduate Research&Practice Innovation Program of Jiangsu Province (Grant No.KYCX22_2815)the Natural Science Foundation of Guizhou Provincial Scientific and Technology Department Grant (Grant No. (2022)626)Scientific Research Foundation of Wenzhou Institute,University of Chinese Academy of Sciences.
文摘Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.
基金supported by the National Natural Science Foundation of China(81973512,81822041,21977116,and 81673305)National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”(No.2018ZX09711002006-013,China)+7 种基金Science&Technology Major Project of Zhongshan City(No.2019A4020,China)Double First-Class Project of China Pharmaceutical University(CPU2018GY06,CPU2018GY18,and CPU2018GY20,China)the Open Project of State Key Laboratory of Natural Medicines(SKLNMZZCX 201824 and SKLNMZZ202029,China)the Open Project Program of the State Key Laboratory of Drug Research(SIMM2004KF-08,China)the Open Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University(Traditional Chinese Pharmacology,China)Zhejiang Chinese Medical University(No.ZYAOX2018001,China)State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia Fund(SKL-HIDCA-2018-1,China)supported by the Six Talent Peaks Project of Jiangsu Province to Tao Pang
文摘Bloodebrain barrier(BBB)damage after ischemia significantly influences stroke outcome.Compound LFHP-1 c was previously discovered with neuroprotective role in stroke model,but its mechanism of action on protection of BBB disruption after stroke remains unknown.Here,we show that LFHP-1 c,as a direct PGAM5 inhibitor,prevented BBB disruption after transient middle cerebral artery occlusion(tMCAO)in rats.Mechanistically,LFHP-1 c binding with endothelial PGAM5 not only inhibited the PGAM5 phosphatase activity,but also reduced the interaction of PGAM5 with NRF2,which facilitated nuclear translocation of NRF2 to prevent BBB disruption from ischemia.Furthermore,LFHP-1 c administration by targeting PGAM5 shows a trend toward reduced infarct volume,brain edema and neurological deficits in nonhuman primate Macaca fascicularis model with t MCAO.Thus,our study identifies compound LFHP-1 c as a firstly direct PGAM5 inhibitor showing amelioration of ischemia-induced BBB disruption in vitro and in vivo,and provides a potentially therapeutics for brain ischemic stroke.
基金This research was supported in part by the National Natural Science Foundation of China under Grant Nos.11405145,40241461,61374152,and 61876168Zhejiang Provincial Natural Science Foundation of China under Grant Nos.LY20F020024 and LY17F030016.
文摘With the increasing demand for security,building strong barrier coverage in directional sensor networks is important for effectively detecting un-authorized intrusions.In this paper,we propose an efficient scheme to form the strong barrier coverage by adding the mobile nodes one by one into the barrier.We first present the concept of target circle which determines the appropriate residence region and working direction of any candidate node to be added.Then we select the optimal relay sensor to be added into the current barrier based on its input-output ratio(barrier weight)which reflects the extension of barrier coverage.This strategy looses the demand of minimal required sensor nodes(maximal gain of each sensor)or maximal lifetime of one single barrier,leading to an augmentation of sensors to be used.Numerical simulation results show that,compared with the available schemes,the proposed method significantly reduces the minimal deploy density required to establish k-barrier,and increases the total service lifetime with a high deploy efficiency.
文摘This paper examines the function of mother tongue in second or foreign language teaching and learning, focusing on the case of Chinese learners of English. The use of L1 in L2 vocabulary teaching is studied by summarizing relevant theories and by analyzing an example of how Chinese teachers introduce new words to students. The influence of L1 in L2 vocabulary learning is explored through studying three major negative transfers of Chinese learners of English with abundant common and typical examples.Seven implications for L2 teachers are listed as the result of my study.
