Natural regulatory T cells and bifunctional regulatory T cells:potential targets of traditional Chinese medicine in treating colitis-associated colon cancer

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.

The effect of Jiangan Xiaozhi Formula on oxidative stress and inflammatory factors in patients with non-alcoholic fatty liver disease

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.

Design,synthesis,and evaluation of fluoroquinolone derivatives as microRNA-21 small-molecule inhibitors

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.

Two New Compounds from Goniothalamus Cheliensis Hu

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 from Goniothalamus cheliensis

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.

A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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.

Multi-Equipment Detection Method for Distribution Lines Based on Improved YOLOx-s

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.

Identification of FOXO1 as a geroprotector in human synovium through single-nucleus transcriptomic profiling

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.

Repairing mitochondrial dysfunction:potential mechanisms of natural products in the treatment of NAFLD

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].

Feasibility of condensate water recycle of split air handling unit in Chinese University buildings

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.

Research on Ubiquitous Map Visualization for Ternary Space

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.

Research on Ubiquitous Map Information Organization Oriented to Location-Based Aggregation

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.

乳腺癌雌激素受体、孕激素受体、人类表皮生长因子受体-2及血清肿瘤标志物水平与骨转移的关系

目的探讨乳腺癌雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体-2(HER2)的表达及血清肿瘤标志物水平与骨转移的关系。方法收集从2013年1月-2015年10月锦州医科大学附属第一医院经病理确诊为乳腺癌并经全身骨显像结合临床表现及其他影像学方法确诊的骨转移患者52例和无骨转移患者111例。对患者进行血清肿瘤标志物癌胚抗原(CEA)、糖类抗原(CA)153的测定,并对乳腺癌标本进行ER、PR、HER2的免疫组织化学检测。结果不同分子分型乳腺癌患者骨转移与无骨转移差异有统计学意义(P<0.05)。单发骨转移、多发骨转移及无转移组ER、PR、HER2差异有统计学意义(P<0.05)。乳腺癌患者单发骨转移及多发骨转移组血清CEA、CA153水平均高于无骨转移组(P<0.05)。结论乳腺癌骨转移与无骨转移患者间分子分型、ER、PR和HER2表达水平及血清CEA、CA153水平有差异,骨转移越严重,血清CEA、CA153水平越高。

A New Isoprenylated flavonol from the Leaves of Broussonetia kazinoki

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.

Immunogenicity and immunizing protection effect of GAMA gene DNA vaccine on Plasmodium berghei

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.

Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system

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.

A Novel Dihydroflavone from the Roots of Uvaria Macrophylla

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.

Single-nucleus transcriptomics reveals a gatekeeper role for FoxP1 in primate cardiac aging

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.

4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis

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.