Wedelolactone attenuates sepsis-associated acute liver injury by regulating the macrophage M1/M2 polarization balance through the PI3K/AKT/NF-κB signalling pathway

Background:Liver injury caused by sepsis seriously impairs the normal physiology of the liver.Wedelactone(WED)has an obvious anti-inflammatory effect against liver damage caused by various factors.Nevertheless,further research is needed to determine if WED might mitigate acute liver damage linked to sepsis by influencing macrophage polarization.Methods:We first assessed the effect of WED on lipopolysaccharides-triggered liver injury by biochemistry assay and tissue staining.Inflammatory factors were assessed using the ELISA kits.The expression of Cluster of Differentiation 86(CD86)and Cluster of Differentiation 206(CD206)was measured by immunofluorescence assay.The protein levels of inducible nitric oxide sythase(iNOS),Arginase 1(Arg-1),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),PI3K phosphorylation(p-PI3K),AKT phosphorylation(p-AKT),inhibitor of kappa B kinase(IKK),inhibitor of kappa B(IκB),and nuclear factor kappa-B(NF-κB)p65 were quantified by western blot analysis.Results:WED decreased the level of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and malondialdehyde,and increased the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-PX).Moreover,WED exerted effective anti-inflammatory effects by decreasing the level of Tumor necrosis factor-α(TNF-α)and Interleukin 6(IL-6)and increasing the level of Interleukin 10(IL-10)in serum and cells.WED not only decreased CD86 and iNOS expression but also increased CD206 and Arg-1 expression.WED also downregulated the increased expression of PI3K,AKT,p-PI3K,p-AKT,IKK,and NF-κB p65 induced by lipopolysaccharides,while up-regulated the decreased expression of IκB.Besides,LY294002 with WED decreased the expression of protein PI3K,AKT,p-PI3K,p-AKT,IKK and NF-κB p65,and raised the expression of IκBα.Conclusion:Wedelolactone could attenuate sepsis-associated acute liver injury,and its mechanism may be associated with balancing pro-inflammatory and anti-inflammatory by the regulation of M1/M2 macrophage polarization via the PI3K/AKT/NF-κB signaling pathway.

Can ChatGPT Boost Artistic Creation:The Need of Imaginative Intelligence for Parallel Art

CHATGPT,one of the leading Large Language Models(LLMs),has acquired linguistic capabilities such as text comprehension and logical reasoning,enabling it to engage in natural conversations with humans.

In vitro bio-corrosion behaviors of biodegradable AZ31B magnesium alloy under static stresses of different forms and magnitudes

Biomedical degradable materials would be subjected to different degrees and forms of static stress after being implanted in the human body.In this work,the biocorrosion behaviors of AZ31B magnesium alloy under different stress forms with different magnitudes(20~150MPa)were studied.It was found that the corrosion behaviors at stressed conditions were severer than those at unstressed conditions and corrosion rates were obviously accelerated.The biocorrosion behaviors are more sensitive to the effects of tensile loads than to compressive loads.A biocorrosion numerical model on the degradation process of Mg alloy under static loads was established.The corrosion current density(i_(corr))of Mg alloy and the applied static stress(σ)matches a linear relationship of ln i_(corr)~σwell during the early stage(within 24 hrs)while deviated gradually in the latter period of corrosion.This work could provide a guidance and theoretical reference for further researches on the biocorrosion behaviors and practical clinical applications of the biomedical materials subjected to physiological loads.

Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths.The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism,including mitochondrial stress response.Mitokines,soluble proteins produced and secreted in response to mitochondrial stress,play an essential immunomodulatory role.Immunotherapy has emerged as a crucial treatment option for HCC.However,a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment.Therefore,exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy.This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function.In addition,a systematic review of mitokines-mediated immunomodulation in HCC is presented.Finally,the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized.Recent progress in mitokine research represents a new prospect for mitochondrial therapy.Considering the potential of mitokines to regulate immune function,investigating them as a relevant mole cular target holds great promise for the diagnosis and treatment of HCC.

Progress in the research of cuproptosis and possible targets for cancer therapy

Developing novel cancer therapies that exploit programmed cell death pathways holds promise for advancing cancer treatment.According to a recently published study in Science,copper death(cuproptosis)occurs when intracellular copper is overloaded,triggering aggregation of lipidated mitochondrial proteins and Fe–S cluster proteins.This intriguing phenomenon is triggered by the instability of copper ions.Understanding the molecular mechanisms behind cuproptosis and its associated genes,as identified by Tsvetkov,including ferredoxin 1,lipoic acid synthase,lipoyltransferase 1,dihydrolipid amide dehydrogenase,dihydrolipoamide transacetylase,pyruvate dehydrogenaseα1,pyruvate dehydrogenaseβ,metallothionein,glutaminase,and cyclin-dependent kinase inhibitor 2A,may open new avenues for cancer therapy.Here,we provide a new understanding of the role of copper death and related genes in cancer.

术前恶性不除外手术病理确诊肺部良性病变297例患者临床-放射-病理特征分析:一项中国单中心回顾性队列研究

背景与目的随着癌症早筛意识的提高,低剂量计算机断层扫描(low-dose computed tomography,LDCT)用于肺癌筛查在中国广泛开展。尽管有部分胸部LDCT筛查所见的肺部病灶是肿瘤病灶,但大多数的肺部结节是良性病变。如何有效的对肺部病灶进行术前鉴别,如何降低部分可避免手术的良性疾病的手术切除比例,是需要关注的问题。方法本研究纳入2017年1月1日-2018年12月31日期间北京协和医院诊治的,术前考虑肺部恶性病变不能除外,经手术病理确认为良性病变的患者,回顾性分析患者临床信息。结果 297例患者纳入本研究,占我院肺部病灶行肺部手术治疗患者的9.8%。197例(66.3%)患者因体检行LDCT筛查发现肺部病灶。肺部病变胸部CT影像学评估情况,可评估的323个病灶,平均长径为(17.9±12.1)mm,直径≥8 mm的占91.0%,实性最多见(212/323, 65.6%),此类肺部病灶可有毛刺征(71/323, 22.0%)、分叶征(94/323, 29.1%)、胸膜牵拉征(81/323, 25.1%)、血管集束征(130/323, 40.2%)、空泡征(23/323, 7.1%)等,提示恶性病变的影像学特征。292例(98.3%)行电视辅助胸腔镜手术(video-assisted thoracoscopic surgery, VATS),232例(78.1%)患者行肺楔形切除术,13例(4.4%)行肺段切除术,51例(17.2%)患者行肺叶切除术。4例(1.3%)患者出现手术并发症。术后病理类型前3位的是感染性疾病98例(33.0%)、炎性结节96例(32.3%)和错构瘤64例(21.5%)。结论因术前不能排除恶性而行手术切除的肺部良性病灶,影像学表现以实性病灶多见,但多具有提示恶性的影像学特征。VATS可作为一种明确病原病理的重要活检方式。此类病灶病理结果以感染性疾病和炎性结节最为常见,错构瘤第三。

电磁导航支气管镜在胸外科中的应用及进展

肺癌是目前我国癌症发病率和死亡率最高的肿瘤。随着影像学技术的发展与普及,肺周围小结节(small pulmonary peripheral nodules, SPPNs)的检出率越来越高,而SPPNs的精确定位及定性一直是胸外科临床诊治过程中的难题。电磁导航支气管镜(electromagnetic navigation bronchoscopy, ENB)的问世,为肺外周病灶的诊治提供了新的微创手段。本文将对ENB在外科手术前定位、诊断和局部治疗中的应用及进展,以及ENB在一体化杂交手术室的临床应用情况进行综述。

microRNA-125b在舌鳞状细胞癌中的表达及意义

目的检测舌鳞状细胞癌(TSCC)中microRNA-125b的表达,分析与TSCC患者临床病理特征的关系。方法采用实时荧光定量聚合酶链反应(RT-qPCR)检测35例TSCC组织及对应的癌旁正常组织中microRNA-125b的表达情况,并分析microRNA-125b在TSCC组织中的表达与临床特征的关系。采用原位杂交技术(ISH)检测35例TSCC组织及对应的癌旁正常组织切片中microRNA-125b基因的表达水平。结果RT-qPCR结果显示,TSCC组织和癌旁正常组织中microRNA-125b的相对表达量分别为2.32±0.69和0.87±0.32,TSCC组织中microRNA-125b的表达显著高于癌旁正常组织,差异有统计学意义(P<0.001);35例TSCC组织中microRNA-125b的表达水平与年龄、性别、病理分级和淋巴结转移无明显相关性,而与TNM分期有明显相关性,分期越高microRNA-125b的表达水平越高(P<0.05)。经过microRNA-125b探针杂交染色结果显示,35例患者的TSCC组织和癌旁正常组织的染色平均密度分别为0.010±0.003和0.004±0.001,癌组织高于癌旁组织,差异有统计学意义(P<0.05)。结论microRNA-125b在35例TSCC患者中高表达,并与临床分期相关,提示microRNA-125b表达上调可能参与TSCC的发生发展。

非小细胞肺癌新辅助免疫治疗进展

非小细胞肺癌新辅助免疫治疗发展迅速,包括新辅助单药/双药免疫治疗、新辅助化疗/放疗联合免疫治疗等;部分临床试验结果显示,在经过选择的非小细胞肺癌患者中,新辅助免疫治疗具有可观的病理缓解率并产生可观察到的临床获益,而且毒副作用可耐受。Nivolumab联合化疗已于近期被美国食品药物监督管理局(Food and Drug Administration,FDA)批准用于非小细胞肺癌新辅助治疗。非小细胞肺癌新辅助免疫治疗的长期疗效、副作用以及手术相关问题需要进一步关注。

人非小细胞肺癌NCI-H1299细胞特异性结合肽的筛选及鉴定

背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)是最常见的肺癌组织学类型,也是病死率最高的恶性肿瘤之一。多肽作为光学分子成像探针的主体可以实现肿瘤的早期筛查及诊断,提高患者存活率。本研究旨在利用体内噬菌体展示技术筛选与人NSCLC细胞NCI-H1299高度结合的小分子多肽并通过体外实验鉴定其结合特异性。方法制备NCI-H1299细胞荷瘤裸鼠模型,用噬菌体展示环七肽库进行3轮体内筛选后随机挑取噬菌体克隆,免疫组织化学法及酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)鉴定噬菌体克隆对NCI-H1299细胞的亲和力。提取阳性单克隆噬菌体DNA测序获得外源多肽氨基酸序列,将重复率最高的序列化学合成多肽并进行异硫氰酸荧光素(fluorescein,FITC)标记,制备光学分子探针,初步鉴定其对NCI-H1299细胞的特异性。结果经3轮体内筛选后噬菌体富集率是首轮的341.3倍;免疫组织化学染色显示随着筛选次数增加,肿瘤组织中结合的噬菌体不断增加,且结合量明显高于正常组织;ELISA结果显示随机挑取的30个噬菌体克隆中20个为阳性克隆,经测序后将重复率最高的序列合成多肽并命名为NSP1;四甲基偶氮唑盐比色法(methyl thiazolyl tetrazolium assay,MTT)、细胞划痕实验表明NSP1不会影响细胞增殖、迁移;流式细胞术、细胞免疫荧光结果表明NSP1可与NCI-H1299细胞特异性结合。结论利用体内噬菌体展示技术成功得到了与肺癌NCI-H1299细胞特异性结合的多肽NSP1,为NSCLC的早期诊断及靶向治疗奠定了研究基础。

淋巴管生成与非小细胞肺癌淋巴转移的机制研究进展

肺癌在我国的发病率和死亡率均排名第一,肿瘤发生转移往往预示患者预后不良。其中,非小细胞肺癌(non-small cell lung cancer, NSCLC)的淋巴转移是导致患者预后不良的重要因素。淋巴管生成是促进肿瘤淋巴转移的重要环节。本文综述肿瘤相关淋巴管生成的分子机制,探讨肿瘤微环境与淋巴管内皮细胞间的相互作用,并总结了目前关于非编码RNA对于肿瘤相关淋巴管生成调控机制的研究及进展,以期为NSCLC相关淋巴管生成的研究与诊疗提供新的思路。

Dual-Material Electron Beam Selective Melting:Hardware Development and Validation Studies

Electron beam selective melting(EBSM) is an additive manufacturing technique that directly fabricates three-dimensional parts in a layerwise fashion by using an electron beam to scan and melt metal powder. In recent years, EBSM has been successfully used in the additive manufacturing of a variety of materials. Previous research focused on the EBSM process of a single material. In this study, a novel EBSM process capable of building a gradient structure with dual metal materials was developed, and a powder-supplying method based on vibration was put forward. Two different powders can be supplied individually and then mixed. Two materials were used in this study: Ti6Al4 V powder and Ti47Al2Cr2 Nb powder. Ti6Al4 V has excellent strength and plasticity at room temperature, while Ti47Al2Cr2 Nb has excellent performance at high temperature, but is very brittle. A Ti6Al4V/Ti47Al2Cr2 Nb gradient material was successfully fabricated by the developed system. The microstructures and chemical compositions were characterized by optical microscopy, scanning microscopy, and electron microprobe analysis. Results showed that the interface thickness was about 300 μm. The interface was free of cracks, and the chemical compositions exhibited a staircase-like change within the interface.

From Mind to Products:Towards Social Manufacturing and Service

After reviewing the development of industrial manufacturing, a novel concept called social manufacturing(SM) and service are proposed as an innovative manufacturing solution for the coming personalized customization era. SM can realize a customer's requirements of "from mind to products", and fulfill tangible and intangible needs of a prosumer, i.e., producer and consumer at the same time. It represents a manufacturing trend,and is expected to become popular in more and more industries.First, a comparison between mass customization and SM is given out, and the basis and motivation from social network to SM is analyzed. Then, its basic theories and supporting technologies,like Internet of Things(Io T), social networks, cloud computing,3 D printing, and intelligent systems, are introduced and analyzed,and an SM platform prototype is developed. Finally, three transformation modes towards SM and 3 D printing are suggested for different user cases.

Social Manufacturing for High-end Apparel Customization

Social manufacturing(SM), a novel distributed,collaborative and intelligent manufacturing mode, is proposed and developed for high-end apparel customization. The main components of SM cloud are designed, and its research topics are summarized. Then, SM's key technologies are studied. 3D technologies for apparel customization, like 3D modeling, 3D fitting mirror and 3D customization, are developed to improve the customization precision and user experience. Information based collaborative management is realized to share, communicate,and handle the information efficiently among all groups and individuals of SM cloud. Suppliers' evaluation mechanism is designed to support the optimal decisions making. Next, SM cloud is constructed in five layers for high-end apparel customization.By using SM cloud based crowd-sourcing, social resources can be allocated rationally and utilized efficiently, consumer can customize the product in any processes like innovation, design,making, marketing and service, and traditional apparel enterprise can be upgraded into SM mode for keeping it competitive in the future customization markets.

Throughput Analysis of Dynamic Spectrum Anti-Jamming Multiple-Access in HF Communication Systems

A multiple-access networking scheme based on the new dynamic spectrum anti-jamming system is proposed in this paper. The network consists of a center node and multiple user nodes. The center node detects spectrum holes in the operation band periodically according to the user performance target. Detected spectrum holes are allocated to users who request communication. Throughput of this networking scheme is analyzed over a high-frequency(HF) interference channel. The effect of error correction coding and spectrum hole information transmission error is discussed. Throughput of this scheme and conventional frequency-hopping multiple-access(FHMA) scheme are compared. Results show that user performance increase leads to throughput decrease, which can be offset by error correction coding. If spectrum hole information transmission is in error, the throughput is not affected much as long as the bit error rate is below 10-2. Furthermore, throughput of this scheme is obviously superior to the throughput of FHMA scheme.

趋化因子IL-8、MCP-1和MIP-1α在胆囊癌中表达的临床病理学意义(英文)

Objective: Gallbladder carcinoma was one of the malignant tumors in the digestive system, characterized by high recurrence and invasion. Recent research indicates that chemotactic factors such as IL-8, MCP-1 and MIP-1α have played an important role in such aspects as formulation, growth, shifting of the tumor. The aim of this study was to investigate expressions of IL-8, MCP-1 and MIP-1α in gallbladder adenocarcinoma tissues. Methods: Gallbladder adenocarcinoma and noncancerous tissues were routinely formalin-fixed and paraffin-embedded, and in situ hybridization assay for IL-8, MCP-1and MIP-1α mRNA. Results:(1) The positive rates or the scorings of IL-8, MCP-1 and MIP-1α mRNA were significantly higher in human gallbladder adenocarcinoma than those in human chronic cholecystitis(P < 0.01). The positive rates or the scorings of three factors were lower in well-differentiatiated gallbladder adenocarcinoma than in poorly-differenfiatted ones, whereas there was only one significant difference between MCP-1 mRNA(P < 0.05). The closely positive correlation were found among IL-8, MCP-1 and MIP-1α mRNA.(2) Both the positive rates of IL-8 mRNA and MCP-1 mRNA as well as their scorings were tightly related to their invasion of the common bile duct and the occurrence of lymph node transfer, moreover, the positive rates of MIP-1α mRNA and its scorings were tightly related to its invasion of liver.(3) Close positive correlation exists not only in IL-8 mRNA and MCP-1 mRNA(r = 0.528), but also in MIP-1α mRNA and IL-8 mRNA(r = 0.422), so does in MCP-1mRNA and MIP-1α mRNA(r = 0.638). Conclusion: The positive rates or the scorings of IL-8, MCP-1 and MIP-1α mRNA are significantly higher in human gallbladder adenocarcinoma than those in human chronic cholecystitis, and the closely positive correlation are found among them, which suggests that IL-8, MCP-1 and MIP-1α regulate and influence the development and transformation of the gallbladder adencarcinoma together.

A Safe and Reliable Routing Mechanism of LEO Satellite Based on SDN

Satellite networks have high requirements for security and data processing speed.In order to improve the reliability of the network,software-defined network(SDN)technology is introduced and a central controller is set in the network.Due to the characteristics of global perspective,control data separation,and centralized control of SDN,the idea of SDN is introduced to the design of the satellite network model.As a result,satellite nodes are only responsible for data transmission,while the maintenance of the links and the calculation of routes are implemented by the controller.For the massive LEO satellite network based on SDN,a state evaluation decision routing mechanism is proposed.The designed mechanism monitors the status of the entire network effectively and reduces the on-board load on the satellite network.The best routing decision is made under the comprehensive consideration of the current and historical status of each inter-satellite link between Low Earth Orbit(LEO)satellite network nodes.The calculation and storage requirements are controlled within a reasonable range.Based on the curve parameter transmission fuzzy encryption algorithm,a safe and reliable condition assessment decision routing mechanism(CADRM)is designed.It ensures that the personal information of the LEO satellite network can be transmitted safely and effectively.The experimental simulation results show the improvement of network throughput,the reduction of packet loss rate and the enhancing of network reliability.

Software-Defined Space-Air-Ground Integrated Network Architecture with the Multi-Layer Satellite Backbone Network

Under the background of the rapid development of ground mobile communication,the advantages of high coverage,survivability,and flexibility of satellite communication provide air support to the construction of space information network.According to the requirements of the future space information communication,a software-defined Space-Air-Ground Integrated network architecture was proposed.It consisted of layered structure satellite backbone network,deep space communication network,the stratosphere communication network and the ground network.The Space-Air-Ground Integrated network was supported by the satellite backbone network.It provided data relay for the missions such as deep space exploration and controlled the deep-space spacecraft when needed.In addition,it safeguarded the anti-destructibility of stratospheric communication and assisted the stratosphere to supplement ground network communication.In this paper,algorithm requirements of the congestion control and routing of satellite backbone protocols for heterogeneous users’services were proposed.The algorithm requirements of distinguishing different service objects for the deep space communication and stratospheric communication network protocols were described.Considering the realistic demand for the dynamic coverage of the satellite backbone network and node cost,the multi-layer satellite backbone network architecture was constructed.On this basis,the proposed Software-defined Space-Air-Ground Integrated network architecture could be built as a large,scalable and efficient communication network that could be integrated into space,air,and ground.

Optimal Mixture Ratios of Biodiesel Ethanol Diesel for Diesel Engines

In this paper, we study the best-mixture ratio of biodiesel-ethanol-diesel for diesel engines. The simulation results show that the integrated indexes including engine power, cost-effectiveness and emission properties are rather better with different optimizing index when the ratio of bio-diesel, ethanol and diesel are 71.58:2.72:25.70 and 50:2.4127:47.5873.

Magnetic Field and Operating Performance Analysisof Conical-rotor Permanent Magnet Synchronous Motor

In order to accurately analyze the magnetic field of conical-rotor permanent magnet synchronous motor(CR-PMSM),the effectiveness of two methods was studied on handling of problems concerned with non-uniform distribution of magnetic field along axial direction in CR-PMSM,which were sectional calculation(SC)method and three-dimensional finite element(3-D FE)method.On this basis,the influence of the axial displacement and dq-axis currents on the operating characteristics of axial magnetic force and torque is analyzed by using the 3-D FE model.Analysis results show that the axial magnetic force and torque decrease with the increase of axial displacement of the rotor,and the amplitude regularity of the axial magnetic force is affected by the d-axis current.A prototype machine is fabricated and tested,in order to validate the design theory.