Interference of Hepatitis B Virus with Cellular Signaling

The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis.

Cellular signaling pathways of T cells in giant cell arteritis

Giant cell arteritis(GCA)is a commonly occurring large vacuities characterized by angiopathy of medium and large-sized vessels.GCA granulomatous formation plays an important role in the pathogenesis of GCA.Analysis of T cell lineages and signaling pathways in GCA have revealed the essential role of T cells in the pathology of GCA.T cells are the dominant population present in GCA lesions.CD4+T cell subtypes that are present include Th1,Th2,Th9,Th17,follicular helper T(Tfh)cells,and regulatory T(Treg)cells.CD8 T cells can primarily differentiate into cytotoxic CD8+T lymphocytes and Treg cells.The instrumental part of GCA is the interplay between dendritic cells,macrophages and endothelial cells,which can result in the vascular injury and the characteristics granulomatous infiltrates formation.During the inflammatory loop of GCA,several signaling pathways have been reported to play an essential role in recruiting,activating and differentiating T cells,including T-cell receptor(TCR)signaling,vascular endothelial growth factor(VEGF)-Jagged-Notch signaling and the Janus kinase and signal transducer and activator of transcription(STAT)pathway(JAK-STAT)pathway.In this review,we have focused on the role of T cells and their potential signaling mechanism(s)that are involved in the pathogenesis of GCA.A better understanding of the role of T cells mediated complicated orchestration during the homeostasis and the changes could possibly favor developments of novel treatment strategies against immunological disorders associated with GCA.

Stability Analysis for the Cellular Signaling Systems Composed of Two Phosphorylation-Dephosphorylation Cyclic Reactions

The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.

SELF-ADAPTIVE CONTROLS OF A COMPLEX CELLULAR SIGNALING TRANSDUCTION SYSTEM

In cells, the interactions of distinct signaling transduction pathways originating from cross-talkings between signaling molecules give rise to the formation of signaling transduction networks, which contributes to the changes (emergency) of kinetic behaviors of signaling system compared with single molecule or pathway. Depending on the known experimental data, we have constructed a model for complex cellular signaling transduction system, which is derived from signaling transduction of epidermal growth factor receptor in neuron. By the computational simulating methods, the self-adaptive controls of this system have been investigated. We find that this model exhibits a relatively stable selfadaptive system, especially to over-stimulation of agonist, and the amplitude and duration of signaling intermediates in it could be controlled by multiple self-adaptive effects, such as 'signal scattering', 'positive feedback', 'negative feedback' and 'B-Raf shunt'. Our results provide an approach to understanding the dynamic behaviors of complex biological systems.

A new cellular automaton for signal controlled traffic flow based on driving behaviors

The complexity of signal controlled traffic largely stems from the various driving behaviors developed in response to the traffic signal. However, the existing models take a few driving behaviors into account and consequently the traffic dynamics has not been completely explored. Therefore, a new cellular automaton model, which incorporates the driving behaviors typically manifesting during the different stages when the vehicles are moving toward a traffic light, is proposed in this paper. Numerical simulations have demonstrated that the proposed model can produce the spontaneous traffic breakdown and the dissolution of the over-saturated traffic phenomena. Furthermore, the simulation results indicate that the slow-to-start behavior and the inch-forward behavior can foster the traffic breakdown. Particularly, it has been discovered that the over-saturated traffic can be revised to be an under-saturated state when the slow-down behavior is activated after the spontaneous breakdown. Finally, the contributions of the driving behaviors on the traffic breakdown have been examined.

FUNDAMENTAL COMMUNICATIONS THEORIES AND SIGNAL PROCESSING TECHNIQUES FOR AMORPHOUS CELLULAR SYSTEMS

The rapid developing of the fourth generation(4G)wireless communications has aroused tremendous demands for high speed data transmission due to the dissemination of various types of the intelligent user terminals as well as the wireless multi-media services.It is predicted that the network throughput will increase

富血小板血浆促进创面愈合的细胞和分子机制

背景:尽管富血小板血浆在促进创面愈合方面显示出治疗潜力,但其临床应用仍需要进一步的研究和验证。此外,对于富血小板血浆作用的机制仍存在一些争议和不确定性。目的:通过对富血小板血浆促进创面愈合的机制进行概述和分析,以增进对该治疗方法的理解,为未来的基础研究和临床应用提供有益的指导。方法:在中国知网、PubMed数据库检索2000年1月至2023年12月发表的相关文献。英文检索词为“platelet rich plasma,PRP,wound,wound healing,refractory wounds,chronic wounds,cellular and molecular mechanisms,signaling pathways,regenerative medicine”,中文检索词为“富血小板血浆,PRP,创面,伤口,创面愈合,难愈性创面,慢性创面,细胞和分子机制,信号通路,再生医学”。根据纳入和排除标准,最终对80篇文献进行综述。结果与结论:①富血小板血浆在创面愈合中具有许多潜在的优势,它能够提供丰富的生长因子和细胞因子等生物活性物质;②富血小板血浆可以调节参与创面愈合的各种细胞类型的功能,包括表皮细胞、血管内皮细胞、成纤维细胞、干细胞和炎症细胞等;③在富血小板血浆疗法中,细胞外囊泡、线粒体对于创面愈合可能扮演着重要角色;④负载富血小板血浆水凝胶可广泛用于增强组织再生和作为药物传递的功能性载体;⑤富血小板血浆对创面细胞外基质合成和降解起调节作用,从而影响伤口愈合过程中基质重建;⑥富血小板血浆可能通过动态调节多种信号通路和上皮间质转化来影响组织修复与再生,从而为创面愈合的研究提供了全新的视角。

Small Peptide Interacting with Pollen Calmodulinand their Effects on Cellular Functions

The interaction between dansyl-labeled pollen calmodulin (D-pCaM) and synthesized peptides was studied in the presence of Ca2+ by fluorescence spectra. It is Found that Gly/L-Ala --> D-Ala substitution in peptide chains caused great changes in their affinity for pCaM. Besides. our data provided evidence on the dissimilarity of different CaMs although they have highly-conserved structures. A preliminary study was carried out on the effects of CaM-binding peptides on cellular signal transduction, cell proliferation, showing the participation of CaM in cell functions mentioned above.

Mechanisms of resistance to sorafenib and the corresponding strategies in hepatocellular carcinoma

Sorafenib, the unique drug as first-line treatment for advanced hepatocellular carcinoma (HCC), has opened a window of hope after searching for effective agents to combat HCC for decades. However, the overall outcomes are far from satisfactory. One of the explanations is the genetic heterogeneity of HCC, which has led to identifying predictive biomarkers for primary resistance to sorafenib, and then applying the concept of personalized medicine, or seeking therapeutic strategies such as combining sorafenib with other anticancer agents. Some of the combinations have demonstrated a better effectiveness than sorafenib alone, with good tolerance. The acquired resistance to sorafenib has also drawn attention. As a multikinase inhibitor, sorafenib targets several cellular signaling pathways but simultaneously or sequentially the addiction switches and compensatory pathways are activated. Several mechanisms are involved in the acquired resistance to sorafenib, such as crosstalks involving PI3K/Akt and JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition, etc . Based on the investigated mechanisms,some other molecular targeted drugs have been applied as second-line treatment for treat HCC after the failure of sorafenib therapy and more are under evaluation in clinical trials. However, the exact mechanisms accounting for sorafenib resistance remains unclear. Further investigation on the crosstalk and relationship of associated pathways will better our understanding of the mechanisms and help to find effective strategies for overcoming sorafenib resistance in HCC.

Material and mechanical factors:new strategy in cellular neurogenesis

Since damaged neural circuits are not generally self-recovered, developing methods to stimulate neurogenesis is critically required. Most studies have examined the effects of soluble pharma- cological factors on the cellular neurogenesis. On the other hand, it is now recognized that the other extracellular factors, including material and mechanical cues, also have a strong potential to induce cellular neurogenesis. This article will review recent data on the material （chemical patterning, micro/nano-topography, carbon nanotube, graphene） and mechanical （static cue from substrate stiffness, dynamic cue from stretch and flow shear） stimulations of cellular neuro- genesis. These approaches may provide new neural regenerative medicine protocols. Scaffolding material templates capable of triggering cellular neurogenesis can be explored in the presence of neurogenesis-stimulatory mechanical environments, and also with conventional soluble factors, to enhance axonal growth and neural network formation in neural tissue engineering.

己酮可可碱腹腔注射对1型糖尿病小鼠足溃疡的改善作用及其机制

目的观察己酮可可碱腹腔注射对1型糖尿病(T1DM)小鼠足溃疡的改善作用,并探讨其作用机制。方法18只健康雄性SPF级小鼠随机分成3组:模型组、己酮可可碱组和贝复济组,每组6只。3组小鼠均制备T1DM足溃疡模型。制备成功后,己酮可可碱组小鼠腹腔注射己酮可可碱连续14 d,贝复济组小鼠外喷贝复济连续14 d,模型组小鼠外用50%乙醇溶液连续14 d。取各组小鼠,在制备T1DM足溃疡模型当天和药物干预14 d时分别拍摄足溃疡创面处照片,计算创面愈合率。取各组小鼠,用血糖仪与医用血糖试纸检测尾静脉血FPG。取各组小鼠足溃疡处皮损组织,采用免疫荧光法测算皮损组织中中性粒细胞数量(以MPO阳性细胞数表示),采用免疫组化法测算皮损组织中NETs形成标志物Cit-H3阳性细胞占比,采用免疫荧光法评估皮损组织中NETs释放情况(以MPO+NE双阳性细胞数表示),采用ELISA法检测皮损组织中NETs相关标志物MPO、NE、LL37,采用流式细胞法检测皮损组织中ROS,采用Western blot法检测皮损组织中p38 MAPK、p-p38 MAPK、ERK1/2、p-ERK1/2蛋白。结果己酮可可碱组和贝复济组小鼠,足溃疡创面愈合率均高于模型组(P均<0.05)FPG水平、皮损组织中中性粒细胞数均低于模型组。己酮可可碱组和贝复济组小鼠皮损组织中Cit-H3阳性细胞占比、MPO+NE双阳性细胞数、ROS荧光强度和皮损组织中MPO、NE、LL37水平均低于模型组,且己酮可可碱组低于贝复济组(P均<0.05)。己酮可可碱组皮损组织中p38 MAPK、p-p38 MAPK、ERK1/2、p-ERK1/2蛋白相对表达量均高于模型组(P均<0.05),贝复济组皮损组织中p-p38 MAPK、p-ERK1/2蛋白相对表达量均高于模型组(P均<0.05),且己酮可可碱组皮损组织中p-p38 MAPK、ERK1/2、p-ERK1/2蛋白相对表达量均高于贝复济组(P均<0.05)。结论己酮可可碱腹腔注射可显著改善T1DM小鼠的足溃疡,其作用机制可能与降低FPG水平和中性粒细胞数、抑制NETs形成和释放、抑制ROS生成、激活p38MAPK/ERK信号通路有关。

体育设施多维度时空供需匹配与优化——以北京市石景山区为例

体育设施的时间属性较强,时空供需失配较严重,需从时空间行为角度对其时空供需匹配进行分析。构建包含总量、时间、空间、项目“1+3”层面的体育设施时空供需匹配程度分析与优化研究框架,提出基于多源数据的体育设施时空供应量测度方法、基于居民体育生活方式的体育运动总量和分项目需求测度与供需匹配分析方法、基于手机信令活动特征的分时段需求测度与供需匹配分析方法、基于循环两步移动搜索法的分空间单元供需匹配分析方法、开放内部体育设施的潜在收益模拟测算方法。使用上述方法对北京市石景山区的体育设施供需匹配进行分析。分析结果显示,该区的人均公共体育用地指标虽已高于《北京城市总体规划(2016年—2035年)》目标,但体育设施时空供需总量,以及分时间段、分空间单元、分项目类型的时空供需间均存在缺口,缺口分别为需求总量的10.3%、16.7%、31.7%、38.3%。在分时间层面,缺口分布在一早一晚,且晨间缺口大于晚间缺口;在分空间层面,新开发区域供给缺口较大;在分项目层面,“三小球”的缺口最大,“三大球”次之。不同程度地开放学校体育设施可弥补总量33%~85%的缺口。

Performance of joint dual links dynamic power control and smart antenna for TDMA/TDD cellular mobile communications

Interference cancellation is made available by using smart antenna at cellular base stations. Well distributed cumulative probability of signal to interference plus noise power ratio appears to be vital for cellular mobile multimedia communications. A scenario of dual links dynamic power control combined to a solution of smart antenna is proposed to adjust the instant transmission power in terms of the disparity from the favorite range. Simulation results show that this method is quite effective to improve the cumulative distribution probability performance. Meanwhile, accompanying low power consumption is also obtained at both base stations and mobile stations.

混合式教学在《细胞信号转导的分子机理》教学中的实践研究

目的探讨线上线下混合式教学模式对《细胞信号转导的分子机理》课程教学效果的影响。方法选择采取混合式和线上两种教学方式的2022级博士生(n=697)为研究对象,分别采取线下或线上教学方式的2021级博士生(n=692)为对照,对学生的期末成绩和调查问卷满意度进行分析和统计,评估教学效果。结果2022级线上线下混合教学效果优于2021级线下教学;在采用混合式教学改革的班级中,约90%的博士生对课程的目标、内容的应用性和添加最新研究进展方面满意,认为该课程有助于学生科研思维的培养和课题研究的开展。结论混合式教学模式能够提高本课程的教学效果,促进学生对理论知识的深入理解和应用,得到了学生们的认可。

线粒体自噬影响胰岛素抵抗的作用及机制

胰岛素抵抗(IR)是诱发许多代谢疾病的关键因素,包括代谢综合征、非酒精性脂肪性肝病、动脉粥样硬化和2型糖尿病(T2DM)。随着相关代谢疾病日益增多,寻找新的治疗靶点迫在眉睫。线粒体自噬是一种选择性自噬,其通过清除受损和功能失调的线粒体以维持正常线粒体功能和能量代谢。研究发现,线粒体自噬在代谢疾病中有积极作用,线粒体自噬受到各种信号通路与信号分子调控而改善代谢疾病,如AMPK/ULK1、PINK1/Parkin信号通路以及BNIP3/Nix和FUNDC1等信号分子。本文阐述了线粒体自噬在胰岛素抵抗中的作用及调控机制,综述了近年的相关研究进展。

基于元胞自动机的Brugada综合征患者心电信号研究

针对Brugada综合征(Brugada syndrome,BrS)患者的症状发展与其异常CV(conduction velocity,CV)恢复和异常APD(action potential duration,APD)恢复之间的联系仍未明确问题,本文采用元胞自动机模型对其进行研究。首先根据BrS患者心电信号的特点对元胞自动机模型进行量纲化处理,并在模型中考虑CV恢复和APD恢复;然后使用该模型数值模拟不同CV恢复及APD恢复下与心动过速对应的心电信号螺旋波态的演化行为。结果表明:只存在CV恢复时,心动过速只会维持,不会恶化;在CV恢复和无记忆APD恢复共同影响下,心动过速可能消失,也可能转化为心室颤动,其中转化为心室颤动的概率为54%,明显高于临床数据;在CV恢复和带记忆APD恢复共同影响下,心动过速可能消失、维持或转化为心室颤动,其中转化为心室颤动的概率约为35%,与临床数据一致。跟踪观察波头附近的心电信号传导情况,发现BrS患者的症状发展与CV恢复或APD恢复导致的电信号传导阻滞有关,传导阻滞的程度越严重,BrS患者就越容易由心动过速发展为心室颤动。记忆性APD恢复因其记忆效应能降低APD的振荡幅度,所以能降低心室颤动的发生率。

基于深度强化学习的无人机切换管理研究

为无人机提供网络连接是未来蜂窝网络系统的一个主要应用,无人机在蜂窝网络中作为移动基站或移动用户设备时,需要在不同的基站之间切换,以保持高速可靠的网络连接。针对无人机移动性强、飞行环境复杂造成无人机在蜂窝基站间发生频繁切换、切换失败等问题,提出了一种基于深度强化学习的无人机连接蜂窝网络切换优化方法。基于深度强化学习框架,实现无人机自适应基站切换的在线学习和决策,克服了以往算法中当状态空间过大而导致训练时间长、泛化能力差的缺点;融合参考信号接收功率和切换次数两项指标作为联合奖励函数,保证无人机在稳定蜂窝网络连接的前提下,减少了无人机在蜂窝基站间的无效切换次数。实验结果表明,所提出的算法经过1000轮训练,无人机的平均切换次数显著降低,有效避免了不必要的切换,降低了切换失败的概率,提升了无人机连接蜂窝网络时的信号接收功率。

高架出口匝道下游交叉口信号控制方法研究

城市高架快速路与地面道路,主要通过出口匝道及其下游交叉口进行交通转换,高峰时段出口匝道及下游交叉口交通拥堵频发。以元胞传输模型为基础,构建出口匝道及下游交叉口交通预测模型;采用动态调整周期时长和信号相位的控制策略,建立基于元胞传输模型的交叉口信号控制模型。以排队长度、绿灯和周期时长为约束条件,以各进口道加权平均延误为目标函数,进行信号配时动态优化。以成都市实例匝道和交叉口进行验证,表明本文提出信号控制策略可有效降低此类交叉口的饱和度、延误和排队长度,提升其通行效率。

考虑排队长度的高速公路施工区动态信号控制策略

针对高速公路施工区车辆汇合引发的交通冲突,提出考虑排队长度的高速公路施工区动态信号控制策略来降低冲突频率,提升交通效率与安全.利用元胞自动机仿真模型对比动态信号控制策略与早汇合、晚汇合以及固定信号控制等策略在不同交通条件下的功效,通过分析交通量、交通延误、排队车辆数和冒进换道发生频次等交通指标后发现:晚汇合策略下冒进换道频次超出普通策略15.8%,实际应用中存在较高冲突风险;早汇合策略与普通策略的指标变化特征相似,但该策略降低交通延误方面功效显著,较普通策略低7.6%;在信号控制策略下路段的交通延误降低了10%,冒进换道减少了20%;相较于固定信号配时,动态信号控制策略可实现对施工区上游车辆排队长度的控制,并能使不同车道上的车辆排队更加均衡,并且在低交通密度下动态信号控制策略具有更良好的适用性.研究结论可为高速公路施工区路段的换道汇合管理提供借鉴.

广州市新城职住演变分析及反思

新城规划建设是中心城区功能疏解的重要手段,其职住发展在不同时期具有不同的问题及特征。在总结新城类型及典型特征基础上,基于广州市20余年交通模型维护获取的丰富历史数据,从职住发展视角探讨新城的建设周期,解析发展规律。广州市11个主要新城(区)发展经验表明,居住功能在新城区具有更快的发展速度,而靠近中心城区的产业新城具有更快的发展速度,从而导致外住内职的现象,加剧进出城通勤交通压力;新城产业发展速度明显滞后于居住,居住功能完全发育成熟需14.9年,就业功能完全发育成熟需32.2年。据此提出发展建议:新城开发建设保持适度规模,在产业布局上发挥比较优势;注重产业要素导入,避免形成卧城;加强合理的用地配置,实现职住平衡;充分利用轨道交通设施,分阶段导入不同新城发展要素。