Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-...Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis.Methods: Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno-associated virus serotype 8 vector(AAV8) were used to overexpress the truncated β-chain(βΔ) of LRP1 both in vitro and in vivo.Results: On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose-and time-dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase(GYS), and diminished glycogen synthesis in insulin-stimulated HepG2 cells, which was restored by exogenous expression of the βΔ-chain. By contrast, AAV8-mediated hepatic βΔ-chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high-fat diet(HFD)-fed mice.Conclusion: Our data revealed that LRP1, especially its β-chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance-related diseases.展开更多
A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capa...A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capacitance fabricated via one-step carbonization/activation of dense bacterial cellulose(BC)precursor followed by nitrogen/sulfur dual doping is reported.The microporous carbon possesses highly concentrated micropores(~2 nm)and a considerable amount of sub-micropores(<1 nm).The unique porous structure provides high specific surface area(1554 m^2 g^-1)and packing density(1.18 g cm^-3).The synergistic effects from the particular porous structure and optimal doping effectively enhance ion storage and ion/electron transport.As a result,the remarkable specific capacitances,including ultrahigh gravimetric and volumetric capacitances(430 F g^-1 and 507 F cm^-3 at 0.5 A g^-1),and excellent cycling and rate stability even at a high current density of 10 A g^-1(327 F g^-1 and 385 F cm^-3)are realized.Via compositing the porous carbon and BC skeleton,a robust all-solid-state cellulose-based supercapacitor presents super high areal energy density(~0.77 mWh cm^-2),volumetric energy density(~17.8 W L^-1),and excellent cyclic stability.展开更多
In the interaction between a tumor and the immune system,immune checkpoints play an important role,and in tumor immune escape,co-inhibitory immune checkpoints are important.Immune checkpoint inhibitors(ICIs)can enhanc...In the interaction between a tumor and the immune system,immune checkpoints play an important role,and in tumor immune escape,co-inhibitory immune checkpoints are important.Immune checkpoint inhibitors(ICIs)can enhance the immune system's killing effect on tumors.To date,impressive progress has been made in a variety of tumor treatments;PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors.However,glioblastoma(GBM)still lacks an effective treatment.Recently,a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab.Therefore,the use of immune checkpoints in the treatment of GBM still faces many challenges.First,to clarify the mechanism of action,how different immune checkpoints play roles in tumor escape needs to be determined;which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined.Second,to optimize combination therapies,how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed.All of these concerns require extensive basic research and clinical trials.In this study,we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments,summarized the state of ICIs in preclinical studies and clinical trials involving GBM,and speculated on the therapeutic prospects of ICIs in the treatment of GBM.展开更多
Objective:Long noncoding RNAs(lncRNAs)play an important role in regulating the occurrence and development of cardiovascular diseases.However,the role of lncRNAs in heart aging remains poorly understood.The objective o...Objective:Long noncoding RNAs(lncRNAs)play an important role in regulating the occurrence and development of cardiovascular diseases.However,the role of lncRNAs in heart aging remains poorly understood.The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging.Materials and methods:Echocardiography was used to detect the cardiac function of 18-months(aged)and 3-months(young)old C57BL/6 mice.Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs,and qRT-PCR to verify the highly dysregulated lncRNAs.Results:Our results demonstrated that the heart function in aged mice was impaired relative to young ones.Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated,and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts.Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function,cell proliferation,copper ion response,and cellular cation homeostasis.KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction,inflammatory mediator regulation of TRP channels,and the NF-kappa B signaling pathway.Conclusion:These results imply that the differentially expressed lncRNAs may regulate the development of heart aging.This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.展开更多
Structural colors originated from Mie scattering of dielectric spheres can be regulated by the coupling effect between them and substrates.Here a rapid visual identification method of silver ornaments was proposed by ...Structural colors originated from Mie scattering of dielectric spheres can be regulated by the coupling effect between them and substrates.Here a rapid visual identification method of silver ornaments was proposed by the coupling effect of Zn O spheres with them.Both simulation and experimental results proved that,by coupling with different metal substrates,the Mie resonance scattering peaks of ZnO spheres with dimeter of 700 nm showed different degrees of redshift,which lead to different structural color appeared when ZnO spheres deposited on different metal surfaces with a similar appearance.A red structural color was displayed on the surface of the real silver ornament and a yellow-green structural color was shown on the surface of the cupronickel ornament.This method is quite simple and low-cost because it only needs to spray the dispersion of ZnO spheres on the ornament surface.Due to the mild chemical properties of the ZnO,covering and erasing ZnO spheres on the surface of silver would not corrode the silver ornament.Finally,an atomizer method was used for portable and daily testing.This work opens new perspectives on the visual identification of silver.展开更多
Managing Editor:Peng Lyu Macrofocal multiple myeloma(MFMM)is a distinct entity within multiple myeloma(MM)characterized by the presence of multiple lytic bone lesions,with clonal plasma cells in the bone marrow accoun...Managing Editor:Peng Lyu Macrofocal multiple myeloma(MFMM)is a distinct entity within multiple myeloma(MM)characterized by the presence of multiple lytic bone lesions,with clonal plasma cells in the bone marrow accounting for<10%.1,2 The revised 2022 Chinese guidelines for the diagnosis and treatment of MM state:in patients with<10%clonal plasma cells in multi-site bone marrow aspirates,attention should be given to MFMM,characterized by single or multiple bone destructive lesions,often accompanied by involvement of surrounding soft tissues or lymph nodes.3 Research is limited regarding the long-term use of adoptive immunotherapy for the treatment of MFMM;as such,we report herein the case of an elderly patient diagnosed with MFMM who experienced severe chemotherapy side effects and subsequently underwent adoptive immunotherapy.Remarkably,the patient benefited from 14 years of treatment[Figure 1A].展开更多
Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae...Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood. This article focuses on the relationship between caveolin proteins and human diseases and reviews the molecular mechanisms of caveolins in disease networks.展开更多
Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patien...Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.展开更多
Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is dete...Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is detectable at nanomolar levels in human serum worldwide.The pregnancy associated doses of 17b-estradiol(E2)plus tumor-necrosis factor-a(TNF-a)induce distorted maturation of human dendritic cells(DCs)that result in an increased capacity to induce T helper(Th)2 responses.The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs,thereby polarizing the subsequent Th response.In the presence of TNF-a,BPA treatment enhanced the expression of CC chemokine ligand 1(CCL1)in DCs.In addition,DCs exposed to BPA/TNF-a produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation,and preferentially induced Th2 deviation.BPA exerts the same effect with E2 at the same dose(0.01–0.1 mM)with regard to DC-mediated Th2 polarization.These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions.展开更多
With the high morbidity and mortality rates,cardiovascular diseases have become one of the most concerning diseases worldwide.The heart of adult mammals can hardly regenerate naturally after injury because adult cardi...With the high morbidity and mortality rates,cardiovascular diseases have become one of the most concerning diseases worldwide.The heart of adult mammals can hardly regenerate naturally after injury because adult cardiomyocytes have already exited the cell cycle,which subseqently triggers cardiac remodeling and heart failure.Although a series of pharmacological treatments and surgical methods have been utilized to improve heart functions,they cannot replenish the massive loss of beating cardiomyocytes after injury.Here,we summarize the latest research progress in cardiac regeneration and heart repair through altering cardiomyocyte fate plasticity,which is emerging as an effective strategy to compensate for the loss of functional cardiomyocytes and improve the impaired heart functions.First,residual cardiomyocytes in damaged hearts re-enter the cell cycle to acquire the proliferative capacity by the modifications of cell cycle-related genes or regulation of growth-related signals.Additionally,non-cardiomyocytes such as cardiac fbroblasts,were shown to be reprogrammed into cardiomyocytes and thus favor the repair of damaged hearts.Moreover,pluripotent stem cells have been shown to transform into cardiomyocytes to promote heart healing after myocardial infarction(MI).Furthermore,in vitro and in vivo studies demonstrated that environmental oxygen,energy metabolism,extracellular factors,nerves,non-coding RNAs,etc.play the key regulatory functions in cardiac regeneration.These fndings provide the theoretical basis of targeting cellular fate plasticity to induce cardiomyocyte proliferation or formation,and also provide the clues for stimulating heart repair after injury.展开更多
β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human cancers.Previously,we showed that in vivo targeted ablation ofβ-catenin ...β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human cancers.Previously,we showed that in vivo targeted ablation ofβ-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth.However,when the expression ofβ-catenin was ablated in melanoma-associated fibroblasts before tumor initiation,melanoma development was surprisingly accelerated.How stromalβ-catenin deficiency leads to opposite biological effects in melanoma progression is not completely understood.Here,we report thatβ-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell interactions.Using coimmunoprecipitation and proximity ligation assays,we identified Yes-associated protein(YAP)as an importantβ-catenin-interacting partner in stromal fibroblasts.YAP is highly expressed in the nuclei of cancer-associated fibroblasts(CAFs)in both human and murine melanomas.Mechanistic investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in fibroblasts.Blocking Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear translocation.In the absence of YAP,the ability of stromal fibroblasts to remodel the extracellular matrix(ECM)was inhibited,which is consistent with the phenotype observed in cells withβ-catenin deficiency.Further studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ablation.Collectively,our data provide a new paradigm in which theβ-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.展开更多
Currently,increasing users are using MOOC platforms to choose courses and leave text comments with emotional overtones.The traditional words vector representationmethod uses static method to extract text information,w...Currently,increasing users are using MOOC platforms to choose courses and leave text comments with emotional overtones.The traditional words vector representationmethod uses static method to extract text information,which ignores the text position information.The traditional convolutional neural network fails to make full use of the semantic features and association information of the text between channels,which will cause inaccurate text sentiment classification.In order to solve the problems,a text classification model based on Albert and Capsule Network and attention mechanism is proposed.The model was verified on the MOOC comment data set,and compared with the traditional user comment sentiment analysis model.The results show the accuracy of the model was improved to a certain extent.展开更多
With the development of the Internet in various fields,the combination of education and the Internet is close.Many users choose courses they are interested in to study on the MOOC platform and leave text reviews with ...With the development of the Internet in various fields,the combination of education and the Internet is close.Many users choose courses they are interested in to study on the MOOC platform and leave text reviews with emotional colors.However,the traditional word vector representation method extracts text information in a static way,which ignores text location information.The convolutional neural network cannot fully utilize the semantic features and correlation information,so the results of text sentiment analysis are inaccurate.To solve the above problems,this paper proposes a sentiment analysis method based on BGCaps MOOC text review.The ALBERT pretraining model was used to obtain the dynamic feature of the text.Combined with the BiGRU and capsule network model,the features were trained to obtain deep semantic features.We evaluated our mode on theMOOCreviewdataset.The results showthat the proposed method achieved effective improvement in accuracy.展开更多
基金financially supported by the National Natural Science Foundation of China (Grant No. 82270854)the Natural Science Foundation of Chongqing+2 种基金China (No. cstc2020jcyj-msxm X0408)the Program for Youth Innovation in Future MedicineChongqing Medical University (No. W0162) to Yinyuan Ding。
文摘Background: LDL receptor-related protein-1(LRP1) is a cell-surface receptor that functions in diverse physiological pathways. We previously demonstrated that hepatocyte-specific LRP1 deficiency(hLRP1KO) promotes diet-induced insulin resistance and increases hepatic gluconeogenesis in mice. However, it remains unclear whether LRP1 regulates hepatic glycogenesis.Methods: Insulin signaling, glycogenic gene expression, and glycogen content were assessed in mice and HepG2 cells. The pcDNA 3.1 plasmid and adeno-associated virus serotype 8 vector(AAV8) were used to overexpress the truncated β-chain(βΔ) of LRP1 both in vitro and in vivo.Results: On a normal chow diet, hLRP1KO mice exhibited impaired insulin signaling and decreased glycogen content. Moreover, LRP1 expression in HepG2 cells was significantly repressed by palmitate in a dose-and time-dependent manner. Both LRP1 knockdown and palmitate treatment led to reduced phosphorylation of Akt and GSK3β, increased levels of phosphorylated glycogen synthase(GYS), and diminished glycogen synthesis in insulin-stimulated HepG2 cells, which was restored by exogenous expression of the βΔ-chain. By contrast, AAV8-mediated hepatic βΔ-chain overexpression significantly improved the insulin signaling pathway, thus activating glycogenesis and enhancing glycogen storage in the livers of high-fat diet(HFD)-fed mice.Conclusion: Our data revealed that LRP1, especially its β-chain, facilitates hepatic glycogenesis by improving the insulin signaling pathway, suggesting a new therapeutic strategy for hepatic insulin resistance-related diseases.
文摘A breakthrough in advancing power density and stability of carbon-based supercapacitors is trapped by inefficient pore structures of electrode materials.Herein,an ultramicroporous carbon with ultrahigh integrated capacitance fabricated via one-step carbonization/activation of dense bacterial cellulose(BC)precursor followed by nitrogen/sulfur dual doping is reported.The microporous carbon possesses highly concentrated micropores(~2 nm)and a considerable amount of sub-micropores(<1 nm).The unique porous structure provides high specific surface area(1554 m^2 g^-1)and packing density(1.18 g cm^-3).The synergistic effects from the particular porous structure and optimal doping effectively enhance ion storage and ion/electron transport.As a result,the remarkable specific capacitances,including ultrahigh gravimetric and volumetric capacitances(430 F g^-1 and 507 F cm^-3 at 0.5 A g^-1),and excellent cycling and rate stability even at a high current density of 10 A g^-1(327 F g^-1 and 385 F cm^-3)are realized.Via compositing the porous carbon and BC skeleton,a robust all-solid-state cellulose-based supercapacitor presents super high areal energy density(~0.77 mWh cm^-2),volumetric energy density(~17.8 W L^-1),and excellent cyclic stability.
文摘In the interaction between a tumor and the immune system,immune checkpoints play an important role,and in tumor immune escape,co-inhibitory immune checkpoints are important.Immune checkpoint inhibitors(ICIs)can enhance the immune system's killing effect on tumors.To date,impressive progress has been made in a variety of tumor treatments;PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors.However,glioblastoma(GBM)still lacks an effective treatment.Recently,a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab.Therefore,the use of immune checkpoints in the treatment of GBM still faces many challenges.First,to clarify the mechanism of action,how different immune checkpoints play roles in tumor escape needs to be determined;which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined.Second,to optimize combination therapies,how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed.All of these concerns require extensive basic research and clinical trials.In this study,we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments,summarized the state of ICIs in preclinical studies and clinical trials involving GBM,and speculated on the therapeutic prospects of ICIs in the treatment of GBM.
基金This work was supported by the National Natural Science Fund of China(81573434/81872857)the Program for New Century Excellent Talents in Heilongjiang Provincial University(grant number 1252-NCET-013).
文摘Objective:Long noncoding RNAs(lncRNAs)play an important role in regulating the occurrence and development of cardiovascular diseases.However,the role of lncRNAs in heart aging remains poorly understood.The objective of this study was to identify differentially expressed lncRNAs in the heart of aging mice and elucidate the relevant regulatory pathways of cardiac aging.Materials and methods:Echocardiography was used to detect the cardiac function of 18-months(aged)and 3-months(young)old C57BL/6 mice.Microarray analysis was performed to unravel the expression profiles of lncRNAs and mRNAs,and qRT-PCR to verify the highly dysregulated lncRNAs.Results:Our results demonstrated that the heart function in aged mice was impaired relative to young ones.Microarray results showed that 155 lncRNAs were upregulated and 37 were downregulated,and 170 mRNAs were significantly upregulated and 44 were remarkably downregulated in aging hearts.Gene ontology analysis indicated that differentially expressed genes are mainly related to immune function,cell proliferation,copper ion response,and cellular cation homeostasis.KEGG pathway analysis showed that the differentially expressed mRNAs are related to cytokine-cytokine receptor interaction,inflammatory mediator regulation of TRP channels,and the NF-kappa B signaling pathway.Conclusion:These results imply that the differentially expressed lncRNAs may regulate the development of heart aging.This study provides a new perspective on the potential effects and mechanisms of lncRNAs in heart aging.
基金supported by the National Natural Science Foundation of China(Nos.22178047 and 21878042)the Dalian Science and Technology Innovation Fund(No.2020JJ26GX046)the Fundamental Research Funds for the Central Universities(Nos.DUT22LAB610 and DUT2022TB10)。
文摘Structural colors originated from Mie scattering of dielectric spheres can be regulated by the coupling effect between them and substrates.Here a rapid visual identification method of silver ornaments was proposed by the coupling effect of Zn O spheres with them.Both simulation and experimental results proved that,by coupling with different metal substrates,the Mie resonance scattering peaks of ZnO spheres with dimeter of 700 nm showed different degrees of redshift,which lead to different structural color appeared when ZnO spheres deposited on different metal surfaces with a similar appearance.A red structural color was displayed on the surface of the real silver ornament and a yellow-green structural color was shown on the surface of the cupronickel ornament.This method is quite simple and low-cost because it only needs to spray the dispersion of ZnO spheres on the ornament surface.Due to the mild chemical properties of the ZnO,covering and erasing ZnO spheres on the surface of silver would not corrode the silver ornament.Finally,an atomizer method was used for portable and daily testing.This work opens new perspectives on the visual identification of silver.
基金supported by the National Key Research and Development Program of China(No.2021YFC2701700)the National Key Research and Development Program of China(No.2021YFC2701704)the Military Logistics Research Project Health Special Project(No.NCRCG-PLAGH-20230010).
文摘Managing Editor:Peng Lyu Macrofocal multiple myeloma(MFMM)is a distinct entity within multiple myeloma(MM)characterized by the presence of multiple lytic bone lesions,with clonal plasma cells in the bone marrow accounting for<10%.1,2 The revised 2022 Chinese guidelines for the diagnosis and treatment of MM state:in patients with<10%clonal plasma cells in multi-site bone marrow aspirates,attention should be given to MFMM,characterized by single or multiple bone destructive lesions,often accompanied by involvement of surrounding soft tissues or lymph nodes.3 Research is limited regarding the long-term use of adoptive immunotherapy for the treatment of MFMM;as such,we report herein the case of an elderly patient diagnosed with MFMM who experienced severe chemotherapy side effects and subsequently underwent adoptive immunotherapy.Remarkably,the patient benefited from 14 years of treatment[Figure 1A].
基金This work was supported by the National Natural Science Foundation of China （Nos. 81470490 and 81670238）.
文摘Caveolae are a kind of specific cystic structures of lipid rafts in the cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent years, many researchers have found that both caveolins and caveolae play a role in the development of various human diseases, including coronary heart disease, hypertension, and nervous system disorders. The specific mechanisms by which caveolins induce diseases have been a topic of interest. However, a number of detailed molecular mechanisms remain poorly understood. This article focuses on the relationship between caveolin proteins and human diseases and reviews the molecular mechanisms of caveolins in disease networks.
基金Funded by The National Key R&D Program of China and others.ClinicalTrials.gov number,NCT04288102supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000,2020YFC08860900)+1 种基金The Innovation Groups of the National Natural Science Foundation of China(81721002)The National Science and Technology Major Project(2017YFA0105703).
文摘Treatment of severe Coronavirus Disease 2019(COVID-19)is challenging.We performed a phase 2 trial to assess the efficacy andsafety of human umbilical cord-mesenchymal stem cells(UC-MScs)to treat severe coViD-19 patients with lung damage,based onour phase 1 data.In this randomized,double-blind,and placebo-controlled trial,we recruited 101 severe coVID-19 patients withlung damage.They were randomly assigned at a 2:1 ratio to receive either UC-MSCs(4×10^(7)cells per infusion)or placebo on day 0,3,and 6.The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28.Other imagingoutcomes,6-minute walk test(6-MWT),maximum vital capacity,diffusing capacity,and adverse events were recorded and analyzed.In all,100 COVID-19 patients were finally received either UC-MSCs in=65)or placebo(n=35).UC-MSCs administrationexerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo(the mediandifference was-13.31%,95%Cl-29.14%,2.13%,P=0.08).UC-MSCs significanty reduced the proportions of solid componentlesion volume compared with the placebo(median difference:-15.45%;95%CI-30.82%,-0.39%;P=0.043).The 6-MWT showedan increased distance in patients treated with UC-MSCs(difference:27.00 m;95%CI 0.00,57.00;P=0.057).The incidence of adverseevents was similar in the two groups.These results suggest that UC-MSCs treatment is a safe and potentially effective therapeuticapproach for COVID-19 patients with lung damage.A phase 3 trial is required to evaluate effects on reducing mortality andpreventing long-term pulmonary disability.
基金This work was supported in part by the Nursing Foundation for Science Development and Innovation 09KMM06 from Chinese PLA General Hospital,Grants-in-Aid 21791572,21791473 and 20591190 from the Ministry of Education,Culture,Sports,Science and Technology(MEXT),Japan,and research grants from the Kansai Medical University(Research grant C)the Osaka Cancer Research Foundation(2010)and the Princess Takamatsu Cancer Research Fund(09-24104).
文摘Bisphenol A(BPA)is a monomer used in manufacturing a wide range of chemical products,including epoxy resins and polycarbonate.BPA,an important endocrine disrupting chemical that exerts estrogen-like activities,is detectable at nanomolar levels in human serum worldwide.The pregnancy associated doses of 17b-estradiol(E2)plus tumor-necrosis factor-a(TNF-a)induce distorted maturation of human dendritic cells(DCs)that result in an increased capacity to induce T helper(Th)2 responses.The current study demonstrated that the presence of BPA during DC maturation influences the function of human DCs,thereby polarizing the subsequent Th response.In the presence of TNF-a,BPA treatment enhanced the expression of CC chemokine ligand 1(CCL1)in DCs.In addition,DCs exposed to BPA/TNF-a produced higher levels of IL-10 relative to those of IL-12p70 on CD40 ligation,and preferentially induced Th2 deviation.BPA exerts the same effect with E2 at the same dose(0.01–0.1 mM)with regard to DC-mediated Th2 polarization.These findings imply that DCs exposed to BPA will provide one of the initial signals driving the development and perpetuation of Th2-dominated immune response in allergic reactions.
基金supported by the National Natural Science Fund of China(81170096/81573434/81872857)the Program for New Century Excellent Talents in Heilongjiang Provincial University(1252-NCET-013).
文摘With the high morbidity and mortality rates,cardiovascular diseases have become one of the most concerning diseases worldwide.The heart of adult mammals can hardly regenerate naturally after injury because adult cardiomyocytes have already exited the cell cycle,which subseqently triggers cardiac remodeling and heart failure.Although a series of pharmacological treatments and surgical methods have been utilized to improve heart functions,they cannot replenish the massive loss of beating cardiomyocytes after injury.Here,we summarize the latest research progress in cardiac regeneration and heart repair through altering cardiomyocyte fate plasticity,which is emerging as an effective strategy to compensate for the loss of functional cardiomyocytes and improve the impaired heart functions.First,residual cardiomyocytes in damaged hearts re-enter the cell cycle to acquire the proliferative capacity by the modifications of cell cycle-related genes or regulation of growth-related signals.Additionally,non-cardiomyocytes such as cardiac fbroblasts,were shown to be reprogrammed into cardiomyocytes and thus favor the repair of damaged hearts.Moreover,pluripotent stem cells have been shown to transform into cardiomyocytes to promote heart healing after myocardial infarction(MI).Furthermore,in vitro and in vivo studies demonstrated that environmental oxygen,energy metabolism,extracellular factors,nerves,non-coding RNAs,etc.play the key regulatory functions in cardiac regeneration.These fndings provide the theoretical basis of targeting cellular fate plasticity to induce cardiomyocyte proliferation or formation,and also provide the clues for stimulating heart repair after injury.
基金This work was supported by NIH R15CA228014(YZ),the Cincinnati Cancer Center-Mentor-Mentee Award(YZ),the Harry J Lloyd Trust Research Award(Y.Z.)and the CCTST Pilot Translational Research&Innovative Core Grant(Y.Z.).
文摘β-catenin is a multifunctional protein that plays crucial roles in embryonic development,physiological homeostasis,and a wide variety of human cancers.Previously,we showed that in vivo targeted ablation ofβ-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth.However,when the expression ofβ-catenin was ablated in melanoma-associated fibroblasts before tumor initiation,melanoma development was surprisingly accelerated.How stromalβ-catenin deficiency leads to opposite biological effects in melanoma progression is not completely understood.Here,we report thatβ-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell interactions.Using coimmunoprecipitation and proximity ligation assays,we identified Yes-associated protein(YAP)as an importantβ-catenin-interacting partner in stromal fibroblasts.YAP is highly expressed in the nuclei of cancer-associated fibroblasts(CAFs)in both human and murine melanomas.Mechanistic investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in fibroblasts.Blocking Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear translocation.In the absence of YAP,the ability of stromal fibroblasts to remodel the extracellular matrix(ECM)was inhibited,which is consistent with the phenotype observed in cells withβ-catenin deficiency.Further studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ablation.Collectively,our data provide a new paradigm in which theβ-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.
文摘Currently,increasing users are using MOOC platforms to choose courses and leave text comments with emotional overtones.The traditional words vector representationmethod uses static method to extract text information,which ignores the text position information.The traditional convolutional neural network fails to make full use of the semantic features and association information of the text between channels,which will cause inaccurate text sentiment classification.In order to solve the problems,a text classification model based on Albert and Capsule Network and attention mechanism is proposed.The model was verified on the MOOC comment data set,and compared with the traditional user comment sentiment analysis model.The results show the accuracy of the model was improved to a certain extent.
文摘With the development of the Internet in various fields,the combination of education and the Internet is close.Many users choose courses they are interested in to study on the MOOC platform and leave text reviews with emotional colors.However,the traditional word vector representation method extracts text information in a static way,which ignores text location information.The convolutional neural network cannot fully utilize the semantic features and correlation information,so the results of text sentiment analysis are inaccurate.To solve the above problems,this paper proposes a sentiment analysis method based on BGCaps MOOC text review.The ALBERT pretraining model was used to obtain the dynamic feature of the text.Combined with the BiGRU and capsule network model,the features were trained to obtain deep semantic features.We evaluated our mode on theMOOCreviewdataset.The results showthat the proposed method achieved effective improvement in accuracy.
