Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in Chin...Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in China have been increasing,gradually exceeding the global levels[2].Due to the fact that most CRC patients are diagnosed at the advanced stage,the treatment of this disease is challenging and often ineffective.Therefore,prevention and early diagnosis of CRC are crucial.展开更多
Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2...Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2023,our hospital admitted a total of 58 patients with NAFLD.These patients were split into two groups at random:one for experimentation and the other for control.There were 27 patients in the experimental group at the end,compared to 26 in the control group,reasonable exercise,weight management,lipid regulation,and oral polyene phosphatidylcholine capsules(PPC).The experimental group received JGXZ in addition to the above treatments for 12 consecutive weeks.Changes in Traditional Chinese Medicine(TCM)syndrome scores,blood lipids,liver function indicators,the levels of oxidative stress markers,such as malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and superoxide dismutase(SOD),as well as serum inflammatory factors,such as interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α),were measured both before and after treatment.Results:After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)and improvements in blood lipids,liver function indicators,inflammatory factors,and oxidative stress markers(P<0.05).Improvements were noticeably better in the experimental group than in the control group.(P<0.05).Conclusion:JGXZ can significantly improve clinical symptoms,regulate blood lipids,and protect liver function in patients with NAFLD.Its mechanism may be related to inhibiting inflammatory responses and regulating the balance of the oxidation-antioxidation system.展开更多
MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 wer...MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phosphatase and tensin homology deleted on chromosome ten(PTEN),at 10 μM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC_(50) value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G_(0)/G_(1) phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.展开更多
Two new compounds, gonioquinone (1) and goniofufurone acetonide (2), have been isolated from the roots of Goniothalamus cheliensis Hu. Their structures were determined on the basis of spectral and chemical evidence.
Two new styryllactones, iso-goniopypyrone and 8-acetyl-9-deoxygoniopypyrone, were isolated from the roots of Goniothalamus cheliensis. Their structure were elucidated on the basis of spectroscopic and chemical eviden...Two new styryllactones, iso-goniopypyrone and 8-acetyl-9-deoxygoniopypyrone, were isolated from the roots of Goniothalamus cheliensis. Their structure were elucidated on the basis of spectroscopic and chemical evidences.展开更多
Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ...Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.展开更多
The YOLOx-s network does not sufficiently meet the accuracy demand of equipment detection in the autonomous inspection of distribution lines by Unmanned Aerial Vehicle(UAV)due to the complex background of distribution...The YOLOx-s network does not sufficiently meet the accuracy demand of equipment detection in the autonomous inspection of distribution lines by Unmanned Aerial Vehicle(UAV)due to the complex background of distribution lines,variable morphology of equipment,and large differences in equipment sizes.Therefore,aiming at the difficult detection of power equipment in UAV inspection images,we propose a multi-equipment detection method for inspection of distribution lines based on the YOLOx-s.Based on the YOLOx-s network,we make the following improvements:1)The Receptive Field Block(RFB)module is added after the shallow feature layer of the backbone network to expand the receptive field of the network.2)The Coordinate Attention(CA)module is added to obtain the spatial direction information of the targets and improve the accuracy of target localization.3)After the first fusion of features in the Path Aggregation Network(PANet),the Adaptively Spatial Feature Fusion(ASFF)module is added to achieve efficient re-fusion of multi-scale deep and shallow feature maps by assigning adaptive weight parameters to features at different scales.4)The loss function Binary Cross Entropy(BCE)Loss in YOLOx-s is replaced by Focal Loss to alleviate the difficulty of network convergence caused by the imbalance between positive and negative samples of small-sized targets.The experiments take a private dataset consisting of four types of power equipment:Transformers,Isolators,Drop Fuses,and Lightning Arrestors.On average,the mean Average Precision(mAP)of the proposed method can reach 93.64%,an increase of 3.27%.The experimental results show that the proposed method can better identify multiple types of power equipment of different scales at the same time,which helps to improve the intelligence of UAV autonomous inspection in distribution lines.展开更多
The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underly...The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.展开更多
Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of phy...Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of physical activity reduction and nutritional imbalance are becoming increasingly prominent.The prevalence of NAFLD has reached 25%globally[2],and it is also showing a trend of continuous growth and younger onset ag[3].Although numerous studies have confirmed that the pathogenesis of NAFLD may be related to genetic susceptibility,gene polymorphism,intestinal microenvironment disorder,insulin resistance,and other factors[4],the"two-hit"theory also reveals the mechanism of the occurrence of some NAFLD,there is still a lack of effective and stable drugs that can inhibit the progression of NAFLD to liver fibrosis and even liver cancer in the treatment of NAFLD[5].展开更多
Recycling the condensate water of the air conditioner could be explored as an alternative water source to con-tribute to building the green campus.This paper explored the condensate water production through actual mea...Recycling the condensate water of the air conditioner could be explored as an alternative water source to con-tribute to building the green campus.This paper explored the condensate water production through actual mea-surement based on a split air handling unit(SAHU)in a university building.Then,the statistical analysis was used to analyze the recycling feasibility and the impact factors of the condensate water production in 31 Chinese provincial capital cities to obtain the recycling potential map of the condensate water generated from a SAHU.Results showed that:(1)In the measurement,the amount of condensate water produced by a single split air conditioner was 1.6 kg from 12:40 to 13:40.Therefore,the daily output of condensate water of the air condi-tioner with the university operation schedule could reach 52.99 kg during the main air-conditioning season.(2)Among the 31 provincial capital cities in China,the largest condensate water outputs could be found in the Hot Summer and Warm Winter zone and the Hot Summer and Cold Winter zone,with an average monthly output of 1600 kg and 1100 kg,respectively.(3)Regression analysis showed that the dry-bulb temperature and dew point temperature of outdoor air had the highest positive and significant influence on condensate water production.The objective of this study is to provide theoretical guidance for the design and energy conservation evaluation of the feasibility of SAHU condensate water recycling in universities.展开更多
In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” with the extension of its object space, expression space an...In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” with the extension of its object space, expression space and information source, which challenges the theory of cartographic visualization. This paper discusses the ubiquitous map visualization from the object content and expression form. Oriented to the ternary space, it divides the object dimension of ubiquitous map visualization and analyzes the expression characteristics of ubiquitous map visualization. Based on that, it constructs the variable system, symbol system and method system of ubiquitous map visualization. With three cases of the metro roadmap, the tag map, and the three-dimensional (3D) city map, the application of the proposed content is explained to illustrate its effectiveness. The research in this paper is expected to further enrich the theoretical basis of cartographic visualization and provide theoretical support for the expression and application of ubiquitous map visualization.展开更多
<div style="text-align:justify;"> In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” due to th...<div style="text-align:justify;"> In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” due to the extension of its object space and the geographic information it contains, which brings new challenges to map information organization. This paper analyzes the concept and information characteristics of the ubiquitous map. Based on that, it proposes a ubiquitous map information organization model oriented to location-based aggregation. This new model includes three parts as “ubiquitous map instance”, “location-based aggregation mode” and “map scene”. This paper focuses on the “map scene” part which is the core of the model and contains two mutually mapped aspects as “content scene” and “representation scene”. And both aspects are divided into three levels as “features” ←→ “elements” ←→ “scenes” according to ubiquitous map information characteristics and location-based aggregation mode. With cases of map decomposition, the application of the model is explained to illustrate its effectiveness. The model is expected to provide powerful data organization and management capabilities for ubiquitous map production and use. </div>展开更多
A new isoprenylated flavonol, named broussonol A (1) was isolated from the leaves of Broussonetia kazinoki Sieb. The structure of broussonol A was characterized by chemical and spectral methods.
Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR...Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR technique and eukaryotic expression vector(containing immunostimulatory sequence) was built. BALB/c mice were divided into PBS control group, empty vector control group and study group and were immunized at week 0, 3 and 6 respectively. Blood was collected 2 weeks after each immunization and serum was separated to detect the Ig G, Ig G1 and Ig G2 a levels. Spleen of mice was obtained for preparation of splenic mononuclear cell and the cytokine IL-4 and IFN-αlevels were detected. Indirect immunofluorescence and western blot were employed to verify the specificity of antiserum. Sporozoite and merozoite invasion were used respectively to detect the immune protective effect 2 weeks after the third immunization. Ookinete conversion rate in vitro and oocyst numbers of mosquito stomach were observed to evaluate the transmission-blocking levels. Results: In GAMA DNA vaccine group: antiserum could be combined with recombinant protein specifically and green fluorescence signals of merozoite, ookinete and sporozoite were observable, while specific fragments and fluorescence signals were not observable in empty vector group. Compared with control group, specific Ig G in DNA vaccine immunity group significantly increased(P<0.01), and Ig G1 and Ig G2 a all increased(P<0.01). IL-4, IFN-αcontent in study group significantly increased, compared with control group(P<0.01). GAMA DNA vaccine immunity could not obviously block the erythrocyte-stage infection(caused by sporozoite invasion); compared with control group, liver worm load was slightly reduced(P<0.05), and antiserum ookinete numbers(cultured in vitro) had no significant difference with oocyst numbers of mosquito stomach in DNA vaccine group. Conclusions:GAMA has good antigenicity, which could stimulate the body to produce specific immune responses; while DNA vaccine immunity could not play a good protective effect, the effect of which is only limited to the slight reduction of liver worm load, and has no obvious erythrocytestage protective effect and transmission-blocking effect. Therefore, trying other immunization strategies for further research on the value of GAMA(as multi-stage antigen vaccine and multistage combined vaccine components of the life-cycle of plasmodium) is necessary.展开更多
Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is...Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.展开更多
A new dihydroflavone (1), named macrophyllol A, was isolated from the roots of Uvaria macrophylla. Its structure was elucidated on the basis of spectroscopic evidence.
Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed ...Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.展开更多
Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of ...Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.展开更多
基金This study is supported by National Natural Science Foundation of China(82374320,82060864).
文摘Colon cancer(CRC)is one of the most common malignancies globally,ranking third in terms of new cancer cases and second as a cause of cancer deaths[1].In recent 30 years,the incidence and mortality rates of CRC in China have been increasing,gradually exceeding the global levels[2].Due to the fact that most CRC patients are diagnosed at the advanced stage,the treatment of this disease is challenging and often ineffective.Therefore,prevention and early diagnosis of CRC are crucial.
基金supported by National Natural Science Foundation of China,Youth Science Fund Project(82104820)Zhejiang Natural Science Foundation Project(LTGY23H270009)+1 种基金Applied Basic Research Project of Jiaxing Science and Technology Bureau(2023AY11035)Applied Basic Research Project of Jiaxing Science and Technology Bureau(2023AD11047).
文摘Objective:To investigate the effects of Jiangan Xiaozhi Formula(JGXZ)on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease(NAFLD).Methods:Between September 2022 and December 2023,our hospital admitted a total of 58 patients with NAFLD.These patients were split into two groups at random:one for experimentation and the other for control.There were 27 patients in the experimental group at the end,compared to 26 in the control group,reasonable exercise,weight management,lipid regulation,and oral polyene phosphatidylcholine capsules(PPC).The experimental group received JGXZ in addition to the above treatments for 12 consecutive weeks.Changes in Traditional Chinese Medicine(TCM)syndrome scores,blood lipids,liver function indicators,the levels of oxidative stress markers,such as malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and superoxide dismutase(SOD),as well as serum inflammatory factors,such as interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α),were measured both before and after treatment.Results:After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)and improvements in blood lipids,liver function indicators,inflammatory factors,and oxidative stress markers(P<0.05).Improvements were noticeably better in the experimental group than in the control group.(P<0.05).Conclusion:JGXZ can significantly improve clinical symptoms,regulate blood lipids,and protect liver function in patients with NAFLD.Its mechanism may be related to inhibiting inflammatory responses and regulating the balance of the oxidation-antioxidation system.
基金Financial support from the National Natural Science Foundation of China(Grant No.:81673354)is gratefully acknowledged.
文摘MicroRNA-21(miRNA-21)is highly expressed in various tumors.Small-molecule inhibition of miRNA-21 is considered to be an attractive novel cancer therapeutic strategy.In this study,fluoroquinolone derivatives A1eA43 were synthesized and used as miRNA-21 inhibitors.Compound A36 showed the most potent inhibitory activity and specificity for miRNA-21 in a dual-luciferase reporter assay in HeLa cells.Compound A36 significantly reduced the expression of mature miRNA-21 and increased the protein expression of miRNA-21 target genes,including programmed cell death protein 4(PDCD4)and phosphatase and tensin homology deleted on chromosome ten(PTEN),at 10 μM in HeLa cells.The Cell Counting Kit-8 assay(CCK-8)was used to evaluate the antiproliferative activity of A36;the results showed that the IC_(50) value range of A36 against six tumor cell lines was between 1.76 and 13.0 μM.Meanwhile,A36 did not display cytotoxicity in BEAS-2B cells(lung epithelial cells from a healthy human donor).Furthermore,A36 significantly induced apoptosis,arrested cells at the G_(0)/G_(1) phase,and inhibited cell-colony formation in HeLa cells.In addition,mRNA deep sequencing showed that treatment with A36 could generate 171 dysregulated mRNAs in HeLa cells,while the expression of miRNA-21 target gene dual-specificity phosphatase 5(DUSP5)was significantly upregulated at both the mRNA and protein levels.Collectively,these findings demonstrated that A36 is a novel miRNA-21 inhibitor.
基金This research was supported by National 973 Project(G1998051120).
文摘Two new compounds, gonioquinone (1) and goniofufurone acetonide (2), have been isolated from the roots of Goniothalamus cheliensis Hu. Their structures were determined on the basis of spectral and chemical evidence.
文摘Two new styryllactones, iso-goniopypyrone and 8-acetyl-9-deoxygoniopypyrone, were isolated from the roots of Goniothalamus cheliensis. Their structure were elucidated on the basis of spectroscopic and chemical evidences.
基金supported by the National Natural Science Foundation of China(Grant No51079043)the Special Fund for Public Welfare Industry of Ministry of Water Resources of China(Grants No200901064 and 201001020)the Research Innovation Program for College Graduates of Jiangsu Province(Grant No CXZZ11_0450)
基金supported by the National Key Research and Development Program of China (Grant Nos.2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,2022YFA1103800,2021YFA1101401,the STI2030-Major Projects-2021ZD0202400)the National Natural Science Foundation of China (Grant Nos.92049116,81921006,82125011,92149301,92168201,91949209,92049304,32121001,82192863,82122024,82071588,32000500,82271600)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000)CAS Project for Young Scientists in Basic Research (YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation (Z190019)the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes (No.11000022T000000461062)Youth Innovation Promotion Association of CAS (E1CAZW0401,2023092,2022083)Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cormerstone Science Foundation through the XPLORER PRIZE (2021-1045)Excellent Young Talents Program of Capital Medical University (No.12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105).
文摘Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.
基金supported by the National Natural Science Foundation of China under Grants 62362040,61662033supported by the Science and Technology Project of the State Grid Jiangxi Electric Power Co.,Ltd.of China under Grant 521820210006.
文摘The YOLOx-s network does not sufficiently meet the accuracy demand of equipment detection in the autonomous inspection of distribution lines by Unmanned Aerial Vehicle(UAV)due to the complex background of distribution lines,variable morphology of equipment,and large differences in equipment sizes.Therefore,aiming at the difficult detection of power equipment in UAV inspection images,we propose a multi-equipment detection method for inspection of distribution lines based on the YOLOx-s.Based on the YOLOx-s network,we make the following improvements:1)The Receptive Field Block(RFB)module is added after the shallow feature layer of the backbone network to expand the receptive field of the network.2)The Coordinate Attention(CA)module is added to obtain the spatial direction information of the targets and improve the accuracy of target localization.3)After the first fusion of features in the Path Aggregation Network(PANet),the Adaptively Spatial Feature Fusion(ASFF)module is added to achieve efficient re-fusion of multi-scale deep and shallow feature maps by assigning adaptive weight parameters to features at different scales.4)The loss function Binary Cross Entropy(BCE)Loss in YOLOx-s is replaced by Focal Loss to alleviate the difficulty of network convergence caused by the imbalance between positive and negative samples of small-sized targets.The experiments take a private dataset consisting of four types of power equipment:Transformers,Isolators,Drop Fuses,and Lightning Arrestors.On average,the mean Average Precision(mAP)of the proposed method can reach 93.64%,an increase of 3.27%.The experimental results show that the proposed method can better identify multiple types of power equipment of different scales at the same time,which helps to improve the intelligence of UAV autonomous inspection in distribution lines.
基金supported by the National Natural Science Foundation of China(92149301,81921006,82125011)the National Key Research and Development Program of China(2022YFA1103700,2022YFA1103800,2020YFA0804000,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400)+8 种基金the National Natural Science Foundation of China(92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,32000500,82271600)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310)Youth Innovation Promotion Association of CAS(E1CAZW0401,2023092,2022083)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Excellent Young Talents Program of Capital Medical University(12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001).
文摘The synovium,a thin layer of tissue that is adjacent to the joints and secretes synovial fluid,undergoes changes in aging that contribute to intense shoulder pain and other joint diseases.However,the mechanism underlying human synovial aging remains poorly characterized.Here,we generated a comprehensive transcriptomic profile of synovial cells present in the subacromial synovium from young and aged individuals.By delineating aging-related transcriptomic changes across different cell types and their associated regulatory networks,we identified two subsets of mesenchymal stromal cells(MSCs)in human synovium,which are lining and sublining MSCs,and found that angiogenesis and fibrosis-associated genes were upregulated whereas genes associated with cell adhesion and cartilage development were downregulated in aged MSCs.Moreover,the specific cell-cell communications in aged synovium mirrors that of aging-related inflammation and tissue remodeling,including vascular hyperplasia and tissue fibrosis.In particular,we identified forkhead box O1(FOXO1)as one of the major regulons for aging differentially expressed genes(DEGs)in synovial MSCs,and validated its downregulation in both lining and sublining MSC populations of the aged synovium.In human FOXO1-depleted MSCs derived from human embryonic stem cells,we recapitulated the senescent phenotype observed in the subacromial synovium of aged donors.These data indicate an important role of FOXO1 in the regulation of human synovial aging.Overall,our study improves our understanding of synovial aging during joint degeneration,thereby informing the development of novel intervention strategies aimed at rejuvenating the aged joint.
文摘Non-alcoholic fatty liver disease(NAFLD),also known as MAFLD,is a chronic liver disease characterized by dyslipidemia and excessive steatosis in hepatocytes[1].With the acceleration of urbanization,the problems of physical activity reduction and nutritional imbalance are becoming increasingly prominent.The prevalence of NAFLD has reached 25%globally[2],and it is also showing a trend of continuous growth and younger onset ag[3].Although numerous studies have confirmed that the pathogenesis of NAFLD may be related to genetic susceptibility,gene polymorphism,intestinal microenvironment disorder,insulin resistance,and other factors[4],the"two-hit"theory also reveals the mechanism of the occurrence of some NAFLD,there is still a lack of effective and stable drugs that can inhibit the progression of NAFLD to liver fibrosis and even liver cancer in the treatment of NAFLD[5].
基金funded by Sichuan Agriculture University,and is supported in part by the scholarship from China Scholarship Council(CSC)under the Grant CSC 202006915024.
文摘Recycling the condensate water of the air conditioner could be explored as an alternative water source to con-tribute to building the green campus.This paper explored the condensate water production through actual mea-surement based on a split air handling unit(SAHU)in a university building.Then,the statistical analysis was used to analyze the recycling feasibility and the impact factors of the condensate water production in 31 Chinese provincial capital cities to obtain the recycling potential map of the condensate water generated from a SAHU.Results showed that:(1)In the measurement,the amount of condensate water produced by a single split air conditioner was 1.6 kg from 12:40 to 13:40.Therefore,the daily output of condensate water of the air condi-tioner with the university operation schedule could reach 52.99 kg during the main air-conditioning season.(2)Among the 31 provincial capital cities in China,the largest condensate water outputs could be found in the Hot Summer and Warm Winter zone and the Hot Summer and Cold Winter zone,with an average monthly output of 1600 kg and 1100 kg,respectively.(3)Regression analysis showed that the dry-bulb temperature and dew point temperature of outdoor air had the highest positive and significant influence on condensate water production.The objective of this study is to provide theoretical guidance for the design and energy conservation evaluation of the feasibility of SAHU condensate water recycling in universities.
文摘In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” with the extension of its object space, expression space and information source, which challenges the theory of cartographic visualization. This paper discusses the ubiquitous map visualization from the object content and expression form. Oriented to the ternary space, it divides the object dimension of ubiquitous map visualization and analyzes the expression characteristics of ubiquitous map visualization. Based on that, it constructs the variable system, symbol system and method system of ubiquitous map visualization. With three cases of the metro roadmap, the tag map, and the three-dimensional (3D) city map, the application of the proposed content is explained to illustrate its effectiveness. The research in this paper is expected to further enrich the theoretical basis of cartographic visualization and provide theoretical support for the expression and application of ubiquitous map visualization.
文摘<div style="text-align:justify;"> In the era of information and communication technology (ICT) and big data, the map gradually shows a new qualitative feature of “spatiotemporal ubiquitous” due to the extension of its object space and the geographic information it contains, which brings new challenges to map information organization. This paper analyzes the concept and information characteristics of the ubiquitous map. Based on that, it proposes a ubiquitous map information organization model oriented to location-based aggregation. This new model includes three parts as “ubiquitous map instance”, “location-based aggregation mode” and “map scene”. This paper focuses on the “map scene” part which is the core of the model and contains two mutually mapped aspects as “content scene” and “representation scene”. And both aspects are divided into three levels as “features” ←→ “elements” ←→ “scenes” according to ubiquitous map information characteristics and location-based aggregation mode. With cases of map decomposition, the application of the model is explained to illustrate its effectiveness. The model is expected to provide powerful data organization and management capabilities for ubiquitous map production and use. </div>
文摘A new isoprenylated flavonol, named broussonol A (1) was isolated from the leaves of Broussonetia kazinoki Sieb. The structure of broussonol A was characterized by chemical and spectral methods.
基金supported by National Natural Science Foundation of China(NSFC)(No.81471978)
文摘Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR technique and eukaryotic expression vector(containing immunostimulatory sequence) was built. BALB/c mice were divided into PBS control group, empty vector control group and study group and were immunized at week 0, 3 and 6 respectively. Blood was collected 2 weeks after each immunization and serum was separated to detect the Ig G, Ig G1 and Ig G2 a levels. Spleen of mice was obtained for preparation of splenic mononuclear cell and the cytokine IL-4 and IFN-αlevels were detected. Indirect immunofluorescence and western blot were employed to verify the specificity of antiserum. Sporozoite and merozoite invasion were used respectively to detect the immune protective effect 2 weeks after the third immunization. Ookinete conversion rate in vitro and oocyst numbers of mosquito stomach were observed to evaluate the transmission-blocking levels. Results: In GAMA DNA vaccine group: antiserum could be combined with recombinant protein specifically and green fluorescence signals of merozoite, ookinete and sporozoite were observable, while specific fragments and fluorescence signals were not observable in empty vector group. Compared with control group, specific Ig G in DNA vaccine immunity group significantly increased(P<0.01), and Ig G1 and Ig G2 a all increased(P<0.01). IL-4, IFN-αcontent in study group significantly increased, compared with control group(P<0.01). GAMA DNA vaccine immunity could not obviously block the erythrocyte-stage infection(caused by sporozoite invasion); compared with control group, liver worm load was slightly reduced(P<0.05), and antiserum ookinete numbers(cultured in vitro) had no significant difference with oocyst numbers of mosquito stomach in DNA vaccine group. Conclusions:GAMA has good antigenicity, which could stimulate the body to produce specific immune responses; while DNA vaccine immunity could not play a good protective effect, the effect of which is only limited to the slight reduction of liver worm load, and has no obvious erythrocytestage protective effect and transmission-blocking effect. Therefore, trying other immunization strategies for further research on the value of GAMA(as multi-stage antigen vaccine and multistage combined vaccine components of the life-cycle of plasmodium) is necessary.
基金supported by the National Natural Science Foundation of China (31971282 and 32071362)2019 Chongqing Graduate Tutor Team Construction Project (dstd201903)Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN201900415)。
文摘Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.
文摘A new dihydroflavone (1), named macrophyllol A, was isolated from the roots of Uvaria macrophylla. Its structure was elucidated on the basis of spectroscopic evidence.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+6 种基金the National Natural Science Foundation of China(81921006,92149301,92168201,82125011,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81901432,32000510,81861168034,32000500,81901433,81870228,81922027)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Young Elite Scientists Sponsorship Program by CAST(YESS20200012,YESS20210002)The Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)CAS Project for Young Scientists in Basic Research(YSBR-012),Youth Innovation Promotion Association of CAS(E1CAZW0401,2022083)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14),the Tencent Foundation(2021-1045).
文摘Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+9 种基金the National Natural Science Foundation of China(8190143281921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81861168034,81922027,81870228,32100937,31900524,82201727)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2020YFA0112200,2018YFA0107203,the STI2030-Major Projects-2021ZD0202400,2021YFF1201005,2022YFA1103700,2022YFA1103800)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08)Young Elite Scientists Sponsorship Program by CAST(YESS20200012)Youth Innovation Promotion Association of CAS(EiCAZW0401)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14)CAS Special Research Assistant(SRA)Program,and the Tencent Foundation(2021-1045).
文摘Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.