Timosaponin AⅢ induces drug-metabolizing enzymes by activating constitutive androstane receptor (CAR) via dephosphorylation of the EGFR signaling pathway

The current study aimed to assess the effect of timosaponin AⅢ(T-AⅢ)on drug-metabolizing enzymes during anticancer therapy.The in vivo experiments were conducted on nude and ICR mice.Following a 24-day administration of T-AⅢ,the nude mice exhibited an induction of CYP2B10,MDR1,and CYP3A11 expression in the liver tissues.In the ICR mice,the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration.The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6,MDR1,and CYP3A4,along with constitutive androstane receptor(CAR)activation.Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression.Furthermore,other CAR target genes also showed a significant increase in the expression.The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice.Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation,with this effect being partially reversed by the ERK activator t-BHQ.Inhibition of the ERK1/2 signaling pathway was also observed in vivo.Additionally,T-AⅢ inhibited the phosphorylation of EGFR at Tyr1173 and Tyr845,and suppressed EGF-induced phosphorylation of EGFR,ERK,and CAR.In the nude mice,T-AⅢ also inhibited EGFR phosphorylation.These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

Multi-Strategy-Driven Salp Swarm Algorithm for Global Optimization

In response to the shortcomings of the Salp Swarm Algorithm (SSA) such as low convergence accuracy and slow convergence speed, a Multi-Strategy-Driven Salp Swarm Algorithm (MSD-SSA) was proposed. First, food sources or random leaders were associated with the current bottle sea squirt at the beginning of the iteration, to which Levy flight random walk and crossover operators with small probability were added to improve the global search and ability to jump out of local optimum. Secondly, the position mean of the leader was used to establish a link with the followers, which effectively avoided the blind following of the followers and greatly improved the convergence speed of the algorithm. Finally, Brownian motion stochastic steps were introduced to improve the convergence accuracy of populations near food sources. The improved method switched under changes in the adaptive parameters, balancing the exploration and development of SSA. In the simulation experiments, the performance of the algorithm was examined using SSA and MSD-SSA on the commonly used CEC benchmark test functions and CEC2017-constrained optimization problems, and the effectiveness of MSD-SSA was verified by solving three real engineering problems. The results showed that MSD-SSA improved the convergence speed and convergence accuracy of the algorithm, and achieved good results in practical engineering problems.

Constitutive modelling of fabric effect on sand liquefaction

Sand liquefaction under static and dynamic loading can cause failure of embankments,slopes,bridges and other important infrastructure.Sand liquefaction in the seabed can also cause submarine landslides and tsunamis.Fabric anisotropy related to the internal soil structure such as particle orientation,force network and void space is found to have profound influence on sand liquefaction.A constitutive model accounting for the effect of anisotropy on sand liquefaction is proposed.Evolution of fabric anisotropy during loading is considered according to the anisotropic critical state theory for sand.The model has been validated by extensive test results on Toyoura sand with different initial densities and stress states.The effect of sample preparation method on sand liquefaction is qualitatively analysed.The model has been used to investigate the response of a sand ground under earthquake loading.It is shown that sand with horizontal bedding plane has the highest resistance to liquefaction when the sand deposit is anisotropic,which is consistent with the centrifuge test results.The initial degree of fabric anisotropy has a more significant influence on the liquefaction resistance.Sand with more anisotropic fabric that can be caused by previous loading history or compaction methods has lower liquefaction resistance.

Carbenoxolone pretreatment and treatment of posttraumatic epilepsy

Gap junction blocking agents can inhibit spontaneous discharge frequency in cells. We established a rat model of posttraumatic epilepsy induced using ferric ions. Rats were intraperitoneally injected with carbenoxolone, 20 mg/kg, prior to and 30 minutes after model establishment, once a day for 14 consecutive days. Immunohistochemistry showed glial cell proliferation around a cortical focus and significantly increased connexin expression in posttraumatic epilepsy. However, carbenoxolone pretreatment or treatment significantly reduced connexin expression in the cortex, inhibited glial fibdllary acidic protein expression and ameliorated seizure degree in rats. These findings indicate that large amounts of glial cell proliferation and abnormal gap junction generation play a role in posttraumatic epilepsy, and that carbenoxolone may prevent and treat this disease.

Modeling and Analysis the Effects of EMP on the Balise System

Balise system is one kind of high-rate point-mode data transmission equipment.It plays an indispensable role in Chinese Train Control System(CTCS),and it has been immigrated and widely used for passenger dedicated lines and high-speed lines.Thus,its working conditions directly affect train operation safety.However,the balise information transmission system(BITS)is based on the principle of electromagnetic induction,and the communication process is susceptible to external electromagnetic interference.Therefore,it is vital to study the influence of transient signal interference on the balise system.This paper builds the up-link model between the vehicle antena and the balise,and verifies the model’s correctness using finite-difference time-domain method and electromagnetic field theory.This paper analyzes the effect of electromagnetic pulses on the transponder’s uplink and simulates the coupled current under irradiation.The spectral distribution of the three types of pulse interference is analyzed according to relevant standards.Strong electromagnetic pulses have a strong energy distribution in the working frequency band of the up-link,which will generate in-band interference and bit errors.It will affect the balise communication and threaten the safety of train operation.As we know we are the first to analyze the effects of EMP on Chinese BITS,which will lay a foundation for the research of electromagnetic anti-interference or protection to highspeed railway.

真核生物起源研究进展

作为重大进化谜题,真核生物起源的研究对于解码真核基因组、阐释真核细胞内部结构之间的关系有重要启示作用。在1977年美国微生物学家Carl Woese发现古细菌并提出三域生命之树之后,大量研究显示古细菌与真核生物在进化上存在着密切联系。21世纪以来,系统发育分析方法不断改进,泉古菌门(Crenarchaeota)、广古菌门(Euryarchaeota)之外与真核生物更加相似的新古细菌门类也相继被发现,这些证据更加支持将真核生物与古细菌合并为一域,形成二域生命之树。目前,通过宏基因组技术发现的Asgard古细菌是与真核生物进化距离最近的原核生物。然而,真核生物祖先的身份以及线粒体起源的时间等核心问题仍是学术界争论的焦点。本文结合近年来国内外研究成果,从生命之树的形态变化与真核生物演变的具体机制两个角度梳理了目前对真核生物起源的认知过程、现有水平和研究前景,以期为揭示真核生物起源进程的后续研究提供参考与指引。

Experimental testing of low-energy rockfall catch fence meshes

Flexible catch fences are widely used to protect infrastructure like railways, roads and buildings from rockfall damage. The wire meshes are the most critical components for catch fences as they dissipate most of the impact energy. Understanding their mechanical response is crucial for a catch fence design. This paper presents a new method for testing the wire meshes under rock impact. Wire meshes with different lengths can be used and the supporting cables can be readily installed in the tests. It is found that a smaller boulder causes more deformation localisation in the mesh. Longer mesh length makes the fence more flexible. Under the same impact condition, the longer mesh deforms more along the impact direction and shrinks more laterally. Supporting cables can reduce the lateral shrinkage of the mesh effectively. Most of the impact energy is dissipated by stretching of the wires.Wire breakage has not been observed.

Composition design and performance evaluation of rubber-particle cement-stabilized gravel

To improve the mechanical properties and durability of the cement-stabilized base,rubber particles of three different sizes and with three different contents were optimally selected,the evolution laws of the mechanical strength and toughness of rubber-particle cement-stabilized gravel(RCSG)under different schemes were determined,and the optimal particle size and content of rubber particles were obtained.On this basis,the durability of the RCSG base was clarified.The results show that with an increase in the rubber particle size and content,the mechanical strength of RCSG gradually decreased,whereas the toughness and transverse deformation ability gradually increased.1%content and 2–4 mm sized RCSG can better balance the relationship between mechanical strength and toughness.The 7 d unconfined compressive strength was 17.7%higher than that of the 4–8 mm RCSG.The 28 d toughness index and ultimate splitting strain can be increased by 9.8%and 6.3 times,respectively,compared with ordinary cement-stabilized gravel(CSG).In terms of durability,compared with CSG,RCSG showed a 3.7%increase in the water stability property of cement-stabilized base with 1%content and 2–4 mm rubber particles,5.5%increase in the frozen coefficient,and 80.6%and 37.9%increase in the fatigue life at 0.70 and 0.85 stress ratio levels,respectively.

Polyvinyl alcohol fiber cement-stabilized macadam:A review and performance evaluation

This review evaluated research results on polyvinyl alcohol fiber cement-stabilized macadam(PVA-FCSM)to further improve the long-term durability of road structures and promote its in-depth study and high-quality application.The suitable PVA fiber technical indexes for ordinary cement-stabilized macadam(CSM)were recommended.The difference in the mechanical properties between CSM and PVA-FCSM was described.The extent to which PVA fibers enhance the durability of CSM were clarified.Additionally,the mechanism of enhancement of CSM by PVA fibers was revealed.Finally,the performance of each type of fiber cement-stabilized macadam(FCSM)was compared and evaluated.The results indicated that the suggested PVA fiber length and content for CSM were 12-30 mm and 0.6-1.2 kg/m^(3),respectively.At different ages,the mean degree of improvement in the unconfined compressive strength was 14%,20%,and 14%,that in the compressive resilience modulus was 8%,11%,and 6%,and that in the splitting strength was 29%,15%,and 22%,respectively.At different ages,the mean degree of decreased in the dry shrinkage coefficient was 21%,16%,and 15%and that in the temperature shrinkage coefficient(20℃-30℃)was 23%,23%,and 18%,respectively.The coefficients increased with extended curing age.Moreover,at the same stress level,PVA-FCSM has a higher fatigue life compared to CSM.The bridging effect,high strength,and high modulus of PVA fiber enhance the strength and anti-cracking of CSM.The recommended fiber type for CSM is PVA fiber.

Failure-Informed Adaptive Sampling for PINNs,Part II:Combining with Re-sampling and Subset Simulation

This is the second part of our series works on failure-informed adaptive sampling for physic-informed neural networks(PINNs).In our previous work(SIAM J.Sci.Comput.45:A1971–A1994),we have presented an adaptive sampling framework by using the failure probability as the posterior error indicator,where the truncated Gaussian model has been adopted for estimating the indicator.Here,we present two extensions of that work.The first extension consists in combining with a re-sampling technique,so that the new algorithm can maintain a constant training size.This is achieved through a cosine-annealing,which gradually transforms the sampling of collocation points from uniform to adaptive via the training progress.The second extension is to present the subset simulation(SS)algorithm as the posterior model(instead of the truncated Gaussian model)for estimating the error indicator,which can more effectively estimate the failure probability and generate new effective training points in the failure region.We investigate the performance of the new approach using several challenging problems,and numerical experiments demonstrate a significant improvement over the original algorithm.

湖南省两栖、爬行动物物种多样性及其地理分布

物种多样性及其地理分布是制定野生动物保护对策的重要依据。两栖、爬行动物在生物演化的历史上占据着重要地位,又是脊椎动物分类体系变动较大的类群。为了掌握湖南省两栖、爬行动物物种多样性现状,促进湖南省生物多样性保护和野生动物管理工作,我们参考分类学及分子生物系统学的最新研究成果,系统地收集了近10多年来有关湖南省两栖、爬行动物分类的文献资料,结合团队长期以来的野外调查数据,对湖南省两栖、爬行动物名录进行了整理与更新(截止到2021年10月31日)。结果表明:湖南省已记录两栖动物2目10科30属86种(含亚种),爬行动物2目22科55属105种(含亚种),其中中国特有种分别有62种和30种,湖南省特有种分别有10种和4种。列入《国家重点保护野生动物名录》(2021)的两栖动物有11种,爬行动物有10种;列为《中国生物多样性红色名录》(2021)受威胁等级的两栖动物有20种,爬行动物有30种。此外,湖南省两栖、爬行动物区系特征明显,以东洋界种类为主(81.2%),广布种较少(18.8%),无古北界种。在地理分布上,湘南山地丘陵区、湘西北山地区是湖南省两栖、爬行动物物种丰富度较高的地区。