基于灰色关联分析的支持向量机的铁路货运量预测研究

采用基于灰色关联分析的支持向量机对铁路货运量进行预测.首先利用灰色关联分析法对影响铁路货运量的因素进行分析处理,然后利用基于高斯核函数的支持向量回归机建立了铁路货运量预测模型.通过分析预测结果可以发现,经过灰色关联分析后的支持向量机模型对复杂的铁路货运量数据有较好地处理能力,且预测相对误差较小.特别地,由于支持向量机的适应性,该模型具有较高的泛化能力,对影响因素较为复杂,样本数量小的预测问题可以提供一定参考.

前列腺癌可能存在多克隆起源

目的 :探寻人类前列腺癌发生和多发的细胞克隆来源。方法 :采用病理切片上病灶显微切割、P5 3基因突变的PCR SSCP分析及DNA测序测定 3例患者前列腺癌根治切除术标本中癌灶和高分级PIN灶组织 ;同时还采用免疫组织化学方法检测了p2 1WAF1/CIP1蛋白的表达。结果 :在人前列腺癌灶和高分级PIN灶组织中均发现有p5 3基因的点突变 ,同 1例患者标本中癌灶和高分级PIN灶所含点突变均在不同位点上。含p5 3基因的点突变的癌灶和高分级PIN灶组织中均未见有p2 1WAF1/CIP1蛋白的表达。结论 :人前列腺癌发生和多发可能有多细胞克隆来源 ,其p2 1WAF1/CIP1蛋白的表达系P5

中西医结合分子配伍治疗肿瘤协同增效及逆转耐药的研究进展

增效减毒是中西医结合治疗肿瘤的特色和优势,如何有效增强抗肿瘤药物的敏感性或逆转其耐药性已成为当今肿瘤治疗亟待解决的问题。传统中医药主要通过发挥多组分、多靶点、多阶段的优势而具有增强抗肿瘤药物敏感性或逆转肿瘤耐药的功效,但其成分复杂,具体机制尚未明确。现代医学克服肿瘤耐药的主要策略为更换新一代药物,但这些药物靶点相对单一、不良反应较多,且容易诱发多药耐药,因而限制了其在肿瘤治疗中的广泛应用。本课题组在传统中医药配伍理论“君臣佐使”“七情和合”的基础上,研究了具有化疗增敏和逆转耐药作用的中药,挖掘出其发挥药效的有效成分,阐明了其发挥作用的分子机理,进一步将成分、结构、药效、机理清楚的多个活性分子与抗肿瘤药物优化配伍,组成新的“分子配伍”复方,形成药效叠加、不良反应减小的“分子配伍”药物,为增强抗肿瘤药物的疗效提供了一种中西医结合“分子配伍”的治疗策略。本文将系统性阐述中西医结合“分子配伍”的科学内涵,分析其在治疗肿瘤协同增效和抑制耐药方面的研究现状,以期为肿瘤治疗提供一种新的方法和策略。

An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.

Epigenetics of epithelial Na^+ channel-dependent sodium uptake and blood pressure regulation

The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.

A Real-time Cutting Model Based on Finite Element and Order Reduction

Telemedicine plays an important role in Corona Virus Disease 2019(COVID-19).The virtual surgery simulation system,as a key component in telemedicine,requires to compute in real-time.Therefore,this paper proposes a realtime cutting model based on finite element and order reduction method,which improves the computational speed and ensure the real-time performance.The proposed model uses the finite element model to construct a deformation model of the virtual lung.Meanwhile,a model order reduction method combining proper orthogonal decomposition and Galerkin projection is employed to reduce the amount of deformation computation.In addition,the cutting path is formed according to the collision intersection position of the surgical instrument and the lesion area of the virtual lung.Then,the Bezier curve is adopted to draw the incision outline after the virtual lung has been cut.Finally,the simulation system is set up on the PHANTOM OMNI force haptic feedback device to realize the cutting simulation of the virtual lung.Experimental results show that the proposed model can enhance the real-time performance of telemedicine,reduce the complexity of the cutting simulation and make the incision smoother and more natural.

Effect of Straw Mulching on Vineyard Ecology and Fruit Quality of Southern Jiangsu Province

[Objectives] The ecological environment of orchard has a direct impact on fruit quality,and straw mulching can effectively improve the physicochemical indicators of orchard soil,so as to achieve environmental protection and yield increase.[Methods]Tests were carried out for 3 consecutive years of mulching straw in vineyard of southern Jiangsu Province.[Results]The results showed that mulching straw continuously could effectively improve soil physicochemical properties,weed controlling effect,and the photosynthetic rate of leaves,as well as the yield and quality of grapes.The contents of total nitrogen,available phosphorus,quickacting potassium and organic matter increased up to 91.67%,259.76%,442.39% and 34.30%,respectively.Soil bulk density decreased by 7.15%,and the weed plant control effect reached 87.45%.The increased of fresh weight was up to 93.55%,and the increase of the leaf parenthetical rate was up to 18.24%.The increases of soluble solids content and single grain weight reached up to 8.82% and 12.75%.The rate of dehiscent fruit was decreased by 50.89%.The grape could pick for sale 3 days ahead,and the increase of unit area yield reached up to 13.16%.[Conclusions]Straw mulching cultivation in vineyard is a good model for efficient recycling of crop straw and safe production of quality grape,and it provides a new technical approach for straw utilization,promising with good economic and ecological benefits.

温和光热疗法在肿瘤治疗中的研究进展

癌症是目前世界上发病率和死亡率最高的疾病之一.光热疗法(photothermal therapy,PTT)是一种无创的癌症治疗新策略,即把具有较高光热转化效率的材料(photothermal agent,PTA)注入人体内部,利用靶向性聚集在肿瘤组织附近,再在近红外(near-infrared,NIR)等外部光源的照射下,将光能转化为热能来杀死癌细胞.然而,光热治疗所需要达到的高温可能对正常组织损伤较大,因此,相对低温的温和光热疗法(mild photothermal therapy,MPTT)备受关注.温和光热疗法本身的抗肿瘤作用有限,通常需与其他疗法联合以构建协同治疗体系,达到治疗肿瘤的目的.近期,本团队合成了一种二维锗量子点光热转换材料,突破了既往无法得到二维材料以及传统材料光热转换效率低的重大难题.本文从温和光热疗法常用光热转换剂的类型及特点、主要障碍及其解决策略、抗肿瘤作用机制、与其他疗法联合的效果等方面对温和光热疗法在肿瘤治疗中的研究现状进行系统性总结,并对未来的发展方向进行展望和讨论,旨在为肿瘤治疗提供一种新思路和新方法.

中西医结合防治肿瘤耐药的研究进展

化疗和靶向治疗是晚期恶性肿瘤的主要治疗方法之一,而其耐药性是导致肿瘤治疗失败的重要原因.引起肿瘤耐药的原因有肿瘤细胞的异质性、药物外排及代谢失活、肿瘤微环境变化、DNA损伤修复失调、表观遗传改变等多种因素.当前,临床上主要采取更换联合化疗用药或更换新的抗肿瘤药物的策略来克服肿瘤耐药,但由于该方法作用靶点单一,且治疗耐药过程中容易产生新的耐药甚至多药耐药,导致肿瘤治疗的难度增大.因此,寻找高效、低毒、广谱的逆转肿瘤耐药方法或药物已成为当今肿瘤领域的研究热点及难点.中医药由于成分复杂,可以通过多组分、多靶点呈现多方面抗肿瘤作用,因而在增强抗肿瘤药物敏感性或克服肿瘤耐药方面具有巨大潜能.本文系统阐述了肿瘤耐药的发生机制,分析了现代医学和传统中医学在克服肿瘤耐药方面的最新研究进展,旨在为增强抗肿瘤药物的敏感性或克服肿瘤耐药提供一种新的思路和策略.

Erianin,a novel dibenzyl compound in Dendrobium extract,inhibits lung cancer cell growth and migration via calcium/calmodulin-dependent ferroptosis

Ferroptosis,a novel form of programmed cell death,is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases,including cancer.Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy.Therefore,ferroptosis-inducing drugs are attracting more attention for cancer treatment.Here,we showed that erianin,a natural product isolated from Dendrobium chrysotoxum Lindl,exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells.Subsequently,we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells,which was accompanied by ROS accumulation,lipid peroxidation,and GSH depletion.The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK,CQ,or necrostatin-1 rescued erianin-induced cell death,indicating that ferroptosis contributed to erianin-induced cell death.Furthermore,we demonstrated that Ca^(2+)/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis.Taken together,our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca^(2+)/CaMdependent ferroptosis and inhibiting cell migration,and erianin will hopefully serve as a prospective compound for lung cancer treatment.

Comparative Proteomic Analysis of Arabidopsis Mature Pollen and Germinated Pollen

Proteomic analysis was applied to generating the map of Arabidopsis mature pollen proteins and analyzing the differentially expressed proteins that are potentially involved in the regulation of Arabidopsis pollen germination. By applying 2-D electrophoresis and silver staining, we resolved 499 and 494 protein spots from protein samples extracted from pollen grains and pollen tubes, respectively. Using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry method, we identified 189 distinct proteins from 213 protein spots expressed in mature pollen or pollen tubes, and 75 new identified proteins that had not been reported before in research into the Arabidopsis pollen proteome. Comparative analysis revealed that 40 protein spots exhibit reproducible significant changes between mature pollen and pollen tubes. And 21 proteins from 17 downregulated and six upregulated protein spots were identified. Functional category analysis indicated that these differentially expressed proteins mainly involved in signaling, cellular structure, transport, defense/stress responses, transcription, metabolism, and energy production. The patterns of changes at protein level suggested the important roles for energy metabolism-related proteins in pollen tube growth, accompanied by the activation of the stress response pathway and modifications to the cell wall.

Pre-chamber turbulent jet ignition of methane/air mixtures with multiple orifices in a large bore constant volume chamber: effect of air-fuel equivalence ratio and pre-mixed pressure

Liquefied natural gas (LNG), mainly composed of methane, is in progress to substitute diesel fuel in heavyduty marine engine for practical, economic, and environmental considerations. However, natural gas is relatively difficult to be ignited in a large bore combustion chamber. A combustion enhancement technique called prechamber turbulent jet ignition (TJI) can permit combustion and flame propagation in a largebore volume. To investigate the effect of air-fuel equivalence ratio and pre-mixed pressure on pre-chamber TJI of methane/air mixtures with multiple orifices in a large bore volume, experimental tests and computational simulations were implemented to study the discharge of hot turbulent jets from six orifices of the pre-chamber. Different initial pressures and air-fuel equivalence ratios were considered to analyze the characteristics of TJI. The asymmetry of the turbulent jet actuated from six different orifices were found due to the asymmetric orientation of the spark plug, resulting in the inhomogeneous distribution of combustion in the constant volume chamber, which should be considered seriously in the marine engine design. Besides,as the premixed pressure increases, it has more effect on the flame propagation and plays a more important role, as it further increases.

PCDH17 increases the sensitivity of colorectal cancer to 5-fluorouracil treatment by inducing apoptosis and autophagic cell death

5-Fluorouracil(5-FU)is known as a first-line chemotherapeutic agent against colorectal cancer(CRC),but drug resistance occurs frequently and significantly limits its clinical success.Our previous study showed that the protocadherin 17(PCDH17)gene was frequently methylated and functioned as a tumor suppressor in CRC.However,the relationship between PCDH17 and 5-FU resistance in CRC remains unclear.Here,we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues,and high expression of PCDH17 was correlated with high BECN1 expression.Moreover,this expression profile contributed to superior prognosis and increased survival in CRC patients.Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death.Furthermore,autophagy played a dominant role in PCDH17-induced cell death,as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK.PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity.Mechanistically,we showed that c-Jun NH2-terminal kinase(JNK)activation was a key determinant in PCDH17-induced autophagy.The compound SP600125,an inhibitor of JNK,suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells.Taken together,our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death.PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients.

Nonlinear Vibration Analyses of Cylindrical Shells Composed of Hyperelastic Materials

The nonlinear vibration problem is studied for a thin-walled rubber cylindrical shell composed of the classical incompressible Mooney-Rivlin material and subjected to a radial harmonic excitation. With the KirchhofF-Love hypothesis, DonnelFs nonlinear shallow shell theory, hyperelastic constitutive relation, Lagrange equations and small strain hypothesis, a system of nonlinear differential equations describing the large-deflection vibration of the shell is derived. First, the natural frequencies of radial, circumferential and axial vibrations axe studied. Then, based on the bifurcation diagrams and the Poincare sections, the nonlinear behaviors describing the radial vibration of the shell are illustrated. Examining the influences of structural and material parameters on radial vibration of the shell shows that the vibration modes are highly sensitive to the thickness-radius ratio when the ratio is less than a certain critical value. Moreover, in terms of the results of multimodal expansion, it is found that the response of the shell to radial motion is more regular than that without considering the coupling between modes, while there are more phenomena for the uncoupled case.

Threshold public key encryption scheme resilient against continual leakage without random oracles

Threshold public key encryption allows a set of servers to decrypt a ciphertext if a given threshold of authorized servers cooperate. In the setting of threshold public key encryption, we consider the question of how to correctly decrypt a ciphertext where all servers continually leak information about their secret keys to an external attacker. Dodis et al. and Akavia et al. show two concrete schemes on how to store secrets on continually leaky servers. However, their construc- tions are only interactive between two servers. To achieve continual leakage security among more than two servers, we give the first threshold public key encryption scheme against adaptively chosen ciphertext attack in the continual leak- age model under three static assumptions. In our model, the servers update their keys individually and asynchronously, without any communication between two servers. Moreover, the update procedure is re-randomized and the randomness can leak as well.

FINITE DEFORMATION OF A CLASS OF RECTANGULAR RUBBER RINGS SUBJECTED TO END AXIAL LOADS

The problem of finite deformation of an incompressible rectangular rubber ring with an internal rigid body, where the ring is subjected to equal axial loads at its two ends, is examined. A reasonable mathematical model is formulated by using the nonlinear field theory and the implicit analytical solutions are derived. Then numerical simulations are implemented to further illustrate the results and obtain some meaningful conclusions. The deformation of the lateral surface of the ring becomes larger with the increasing axial loads, the decreasing ratio of the inner and outer radii and the increasing height of the ring.

Crystal structure of human Gadd45 reveals an active dimer

The human Gadd45 protein family plays critical roles in DNA repair,negative growth control,genomic stability,cell cycle checkpoints and apoptosis.Here we report the crystal structure of human Gadd45,revealing a unique dimer formed via a bundle of four parallel helices,involving the most conserved residues among the Gadd45 isoforms.Mutational analysis of human Gadd45 identified a conserved,highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen(PCNA),p21 and cdc2,suggesting that the parallel dimer is the active form for the interaction.Cellular assays indicate that:(1)dimerization of Gadd45 is necessary for apoptosis as well as growth inhibition,and that cell growth inhibition is caused by both cell cycle arrest and apoptosis;(2)a conserved and highly acidic patch on the dimer surface,including the important residues Glu87 and Asp89,is a putative interface for binding proteins related to the cell cycle,DNA repair and apoptosis.These results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.

Dislocation-mediated migration of interphase boundaries

Faceted interphase boundaries(IPBs)are commonly observed in lath-shaped precipitates in alloys consisting of simple face-centred cubic(fcc),body centred-cubic(bcc)or hexagonal closed packed(hcp)phases,which normally contain one or two sets of parallel dislocations.The influence of these dislocations on interface migration and possible accompanying long-range strain field remain unclear.To elucidate this,we carried out atomistic simulations to investigate the dislocation-mediated migration processes of IPBs in a pure-iron system.Our results show that the migration of these IPBs is accompanied with the slip of interfacial dislocations,even in high-index slip planes,with two migration modes were observed:the first mode is the uniform migration mode that occurs only when all of the dislocations slip in a common slip plane.A shear-coupled interface migration was observed for this mode.The other interfaces propagate in the stick-slip migration mode that occurs when the dislocations glide on different slip planes,involving dislocation reaction or tangling.A quantitative relationship was established to link the atomic displacements with the dislocation structure,slip plane,and interface normal.The macroscopic shear deformation due to the effect of overall atomic displacement shows a good agreement with the results obtained based on the phenomenological theory of martensite crystallography.Our findings have general implications for the understanding of phase transformations and the surface relief effect at the atomic scale.

The inflammatory microenvironment and the urinary microbiome in the initiation and progression of bladder cancer

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies,including bladder cancer.This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment.Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of in-flammatory molecules and signals.Recently,it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer,which can be mediated through the stimulation of chronic inflammation.In effect,the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer.In other words,chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer.Here,we provide a detailed and comprehensive account of the link between chronic inflammation,the microbiome and bladder cancer.Finally,we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.

Large-Amplitude Oscillations of Hyperelastic Cylindrical Membrane Under Thermal-Mechanical Fields

In this paper,the nonlinear dynamic behaviors of a hyperelastic cylindrical membrane composed of the incompressible Ogden material are examined,where the membrane is subjected to uniformly distributed radial periodic loads at the internal surface and surrounded by a thermal field.A second-order nonlinear differential equation describing the radially symmetric motion of the membrane is obtained.Then,the dynamic characteristics of the system are qualitatively analyzed in terms of different material parameter spaces and ambient tem-peratures.Particularly,for a given constant load,the bifurcation phenomenon of equilibrium points is examined.It is shown that there exists a critical load,and the phase orbits may be the asymmetrie homoclinic orbits of the“oo”type.Moreover,for the system with two centers and one saddle point,the dynamic behaviors of the system show softening phenomena at both centers,but the temperature has opposite effects on the stiffness of the structure.For a given periodically perturbed load superposed on the constant term,some complex dynamic behaviors such as quasiperiodic and chaotic oscillations are analyzed.With the Poincare section and the maximum Lyapunov characteristic exponent,it is found that the ambient temperature could lead to the irregularity and unpredictability of the nonlinear system,and also changes the threshold of chaos.