Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

Microscopic growth mechanism and edge states of monolayer 1T'-MoTe_(2)

Transition metal ditellurides(TMTDs)have versatile physical properties,including non-trivial topology,Weyl semimetal states and unique spin texture.Controlled growth of high-quality and large-scale monolayer TMTDs with preferred crystal phases is crucial for their applications.Here,we demonstrate the epitaxial growth of 1T'-MoTe_(2) on Au(111)and graphitized silicon carbide(Gr/SiC)by molecular beam epitaxy(MBE).We investigate the morphology of the grown1T'-MoTe_(2) at the atomic level by scanning tunnelling microscopy(STM)and reveal the corresponding microscopic growth mechanism.It is found that the unique ordered Te structures preferentially deposited on Au(111)regulate the growth of monolayer single crystal 1T'-MoTe_(2),while the Mo clusters were preferentially deposited on the Gr/SiC substrate,which impedes the ordered growth of monolayer MoTe_(2).We confirm that the size of single crystal 1T'-MoTe_(2) grown on Au(111)is nearly two orders of magnitude larger than that on Gr/SiC.By scanning tunnelling spectroscopy(STS),we observe that the STS spectrum of the monolayer 1T'-MoTe_(2) nano-island at the edge is different from that at the interior,which exhibits enhanced conductivity.

Expression of the B7 - related molecule B7 - H1 by glioma cells: a potential mechanism of immune paralysis

Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities.B7-homologue l(B7-H 1),a recently identified homologue of B7.1/2(CD80/86),has been described to exert costimulatoryand immune regulatory functions.We investigated the expression and the functional activity of B7-H 1 in humanglioma cells in vitro and in vivo.Although lacking B7.1/2(CD80/86),all 12 glioma cel1 1ines constitutivelyexpressed B7-H1 mRNA and protein.Exposure to IFN-gamma strongly enhanced B7-H 1 expression.Im-

Inhibition of epidermal growth factor receptor signaling protects human malignant glioma cells from hypoxia - induced cell death

Epidermal growth factor receptor(EGFR)signaling has become an importanttarget for drug development becauseEGFR signaling enhances tumor cell proliferation,migration,and invasion and inhibits apoptosis.However,theresults of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing.Here,wereport a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hy-poxia,which contrasts with their proapoptotic effects under normoxia.Under hypoxic conditions,both agents re-

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.

Shared Ideas,Divergent Approaches:The Hydromethods of the Great West(Taixi shuifa泰西水法)and the Question on Tides

One of the questions about natural phenomena asked in the Hydromethods of the Great West(Taixi shuifa泰西水法;1612)(hereafter TXSF),composed by the Italian Jesuit Sabatino de Ursis with the support of the Chinese official Xu Guangqi徐光啟,concerns the causes of sea tides.The idiosyncratic answer given in the TXSF serves as an example for the Jesuit missionaries,strategically motivated approach to the transfer of knowledge through the translation of Western scientific thought into Chinese.From a chronological overview of the attempts made both in the East and in the West to theoretically conceptualize the causes of the cyclical occurrence of ebb and flow,the comparison reveals that despite being based on totally different cosmologies,the related insights were virtually on a par.The aim to nevertheless convince the audience of the TXSF of the superiority of Western sciences resulted in a particular rhetoric and a division of tasks in the composition of the tides paragraph.In order to verify the success of this joint effort of de Ursis and Xu Guangqi,a change of perspective from the transmitter to the receiver side is necessary.Thus,the paper also explores the work's reception in later Chinese works dealing with this topic.

Staurosporine-Induced Cell Death in Trypanosoma brucei and the Role of Endonuclease G during Apoptosis

Apoptosis in single-cell organisms like Trypanosoma or Leishmania was characterized in several studies in the last few years [1]-[4]. Cell death in these caspase lacking protozoa is still poorly understood and a conclusive apoptotic pathway has not been identified so far. In the work presented here, we studied the effects of prostaglandin D2 and staurosporine induced cell death in blood-forms of Trypanosoma brucei in a time dependent manner and focused on the role of a nuclease similar to endonuclease G of higher eukaryotes. We found that these parasites undergo apoptotic cell death as demonstrated by the appearance of several canonical hallmarks of apoptosis in higher eukaryotes, but that different stimuli induce remarkable differences in the way these cells die. We compared the effects of prostaglandin D2 and staurosporine in trypanosomes with and without endonuclease G overexpression by flow cytometric and electron microscopic methods with the result that endonuclease G overexpression led to a significant modification of intracellular organelles and accelerated apoptotic cell death in prostaglandin D2 or staurosporine treated cells. Our results demonstrate that different stimuli induce apoptosis even in these ancient organisms in different caspase-independent ways. Whereas central processes of apoptosis like ROS formation, loss of mitochondrial membrane potential, endonuclease G release, phosphatidylserine exposure and DNA fragmentation appeared in the same chronology during treatment with either one of both drugs, other effects like cell cycle arrest or change of cell shape occurred only in the case of prostaglandin D2 or staurosporine treatment. We conclude from these results that trypanosomes react to stimuli of apoptosis with the concerted action of cellular responses but cannot control the final outcome if additional stress, as in the case of staurosporine, is superimposed.

卵巢组织冻存与移植对宫颈癌患者卵巢内分泌功能的影响

国际生育力保护保存专家强烈建议所有年轻癌症患者当诊断为癌症时,应立即得到医生关于生育力保护保存的建议。宫颈癌是女性最常见的妇科恶性肿瘤,放化疗会导致卵巢功能不同程度的减退或衰竭,本文主要评述卵巢组织冻存与移植对宫颈癌患者卵巢内分泌功能的保护作用。

医院就诊女性患者性功能障碍调查(附420例资料分析)

目的总结在我院就诊的女性患者性功能障碍的患病率和患病类型,探讨其影响因素。方法选取420例就诊于北京妇产医院内分泌科的围绝经期女性及女性家属,采用女性性功能指数量表(female sexual function in-dex,FSFI)和自制量表进行问卷调查,并进行统计学分析。结果本组女性患者性功能障碍总体发病率为84.1%,性欲障碍、性唤起障碍、阴道润滑、性高潮、性交痛和性满意度发生率分别为95.5%,69.4%,57.9%,66.9%,68.5%和69.1%。不同年龄、月经情况、收入及是否有合并症/激素补充治疗女性性功能FSD发生率差异均有统计学意义(P<0.05)。结论影响女性性功能的主要因素有年龄、绝经、激素补充、经济水平和身体健康状况。

有孔虫分子生物学研究进展

传统的微体古生物学研究中,有孔虫是生活于海洋环境中以具有膜状、胶结质或钙质壳为特征的丝网状肉足虫类原生动物.最近对底栖有孔虫rDNA序列的分析研究,揭示了有孔虫还有无壳(裸露)种类以及生活于陆地淡水环境的类型. 同时分子系统学研究表明有孔虫位于真核生物系统树的基部,在双滴虫类与绿眼虫类之间.对浮游有孔虫大量基因型及其与环境关系的研究, 揭示了传统研究低估了有孔虫的多样性.有孔虫基因型与生物地理分布、海洋环境有关研究表明利用rDNA序列分析识别出的同一物种的不同基因型可以为古环境研究提供更加精确的替代性指标.

AGNP精神科治疗药物监测共识指南：2011

治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从"强烈推荐"到"可能有用"的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的"治疗参考浓度范围"和"剂量相关参考浓度范围"呈现给大家。本共识指南引入了"实验室警戒浓度"的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中获益。

仓鼠头部切片在自身免疫性内耳病中的实验观察

目的含有组织抗体的内耳病患者血清与未固定及未脱钙的仓鼠头部冰冻切片反应可避免抗原性的改变,而且在同一张切片上耳蜗以外的组织可以用来对照。方法66份前庭听觉功能障碍或听力正常的患者血清和一份正常人的血清与仓鼠头部切片进行反应,结果抗血管内皮抗体、抗核抗体以及抗线粒体抗体阳性的血清和仓鼠头部切片上的内耳以及其它组织呈现阳性反应。表明患者血清中的这些抗体对内耳来说不是器官特异性的。50例前庭听觉功能障碍的患者血清中只有2例有耳硬化的患者血清在免疫发病机理上可以看作是半器官特异性的。抗内膜抗体和抗平滑肌抗体阳性的血清对内耳组织反应阴性。对头皮肌和镫骨动脉壁及内耳动脉壁有反应。Corti氏器的盖膜显示出非特异性的自身绿色荧光。结论头部切片对于区分器官特异性抗体以及诊断自身免疫性内耳病是一种新的、方便的且安全的技术。单纯的免疫组化测定并没有对内耳疾病的单因素病因学给出一个提示。在使用患者血清中的组织抗体时,其它的额外因素也应该被考虑在内,因为前庭听觉功能障碍在病因学可能是多因素的。

前庭神经鞘瘤手术进展：漫长的成功之路

20世纪前庭神经鞘瘤（vestibular schwannoma）手术疗效的显著提高伴随着神经外科的整体进展。这段历史是与前庭神经鞘瘤高病死率和高病残率艰难抗争的历史。

Could non-invasive brain-stimulation prevent neuronal degeneration upon ion channel re-distribution and ion accumulation after demyelination?

Fast and efficient transmission of electrical signals in the nervous system is mediated through myelinated nerve fibers.In neuronal diseases such as multiple sclerosis,the conduction properties of axons are disturbed by the removal of the myelin sheath,leaving nerve cells at a higher risk of degenerating.In some cases,the protective myelin sheath of axons can be rebuilt by remyelination through oligodendroglial cells.In any case,however,changes in the ion channel organization occur and may help to restore impulse conduction after demyelination.On the other hand,changes in ion channel distribution may increase the energy demand of axons,thereby increasing the probability of axonal degeneration.Many attempts have been made or discussed in recent years to increase remyelination of affected axons in demyelinating diseases such as multiple sclerosis.These approaches range from pharmacological treatments that reduce inflammatory processes or block ion channels to the modulation of neuronal activity through electrical cortical stimulation.However,these treatments either affect the entire organism(pharmacological)or exert a very local effect(electrodes).Current results show that neuronal activity is a strong regulator of oligodendroglial development.To bridge the gap between global and very local treatments,non-invasive transcranial magnetic stimulation could be considered.Transcranial magnetic stimulation is externally applied to brain areas and experiments with repetitive transcranial magnetic stimulation show that the neuronal activity can be modulated depending on the stimulation parameters in both humans and animals.In this review,we discuss the possibilities of influencing ion channel distribution and increasing neuronal activity by transcranial magnetic stimulation as well as the effect of this modulation on oligodendroglial cells and their capacity to remyelinate previously demyelinated axons.Although the physiological mechanisms underlying the effects of transcranial magnetic stimulation clearly need further investigations,repetitive transcranial magnetic stimulation may be a promising approach for non-invasive neuronal modulation aiming at enhancing remyelination and thus reducing neurodegeneration.

应用双能CT显示泌尿系统结石的特征:低剂量扫描方案的体外和在体评估

评价双能CT评估泌尿系统结石的低剂量方案的辐射剂量和效能。双能CT低剂量肾结石检查方案（140kV，46mAs：80kV，210mas）衍生于我院检查肾结石的单能CT检查方案（120kV，75mAs）。采用上述2种检查方案分别对配置热释光剂量仪的Alderson—Rando模型进行扫描。计算有效剂量。51例怀疑或确诊的泌尿系结石病人行双能CT扫描。检测到结石后用专用软件包进行双能分析，将结果与术后取出结石的化学分析进行对比。双能扫描时，

Applying Methods from Differential Geometry to Devise Stable and Persistent Air Layers Attached to Objects Immersed in Water

We describe a few mathematical tools which allow to investigate whether air-water interfaces exist(under prescribed conditions)and are mechanically stable and temporally persistent.In terms of physics,air-water interfaces are governed by the Young-Laplace equation.Mathematically they are surfaces of constant mean curvature which represent solutions of a nonlinear elliptic partial differential equation.Although explicit solutions of this equation can be obtained only in very special cases,it is -under moderately special circumstances-possible to establish the existence of a solution without actually solving the differential equation.We also derive criteria for mechanical stability and temporal persistence of an air layer.Furthermore we calculate the lifetime of a non-persistent air layer.Finally,we apply these tools to two examples which exhibit the symmetries of 2D lattices.These examples can be viewed as abstractions of the biological model represented by the aquatic fern Salvinia.

Polarized photoluminescence spectroscopy in WS_(2),WSe_(2) atomic layers and heterostructures by cylindrical vector beams

Due to the large exciton binding energy,two-dimensional(2D)transition metal dichalcogenides(TMDCs)provide an ideal platform for studying excitonic states and related photonics and optoelectronics.Polarization states lead to distinct light-matter interactions which are of great importance for device applications.In this work,we study polarized photoluminescence spectra from intralayer exciton and indirect exciton in WS_(2) and WSe_(2) atomic layers,and interlayer exciton in WS_(2)/WSe_(2) heterostructures by radially and azimuthally polarized cylindrical vector laser beams.We demonstrated the same in-plane and out-of-plane polarization behavior from the intralayer and indirect exciton.Moreover,with these two laser modes,we obtained interlayer exciton in WS_(2)/WSe_(2) heterostructures with stronger out-of-plane polarization,due to the formation of vertical electric dipole moment.

模拟岩溶含水系统演化的耦合网络模型

提出一个数学模型以研究碳酸盐岩含水层由其原始状态到成熟岩溶含水系统的发育过程。模型由3个模块组成:(a)二维连续空隙水渗流模块,表示裂隙系统(“分散流”系统),即岩溶空管道之间透水性差而贮水性强的那部分岩体;(b)非连续管道网络模块,模拟岩溶管道内发生的层流、紊流运动和溶质运移过程;(c)碳酸盐岩溶蚀模块。管道-裂隙系统模型的模拟结果表明,模拟那种复杂的、具有多种地下水补给方式的岩溶含水盆地的演化是可能的。模拟显示岩溶含水系统发端于泉口,向上游方向扩展,这与其他一些作者基于野外观察、溶蚀实验和电法比拟研究所提出的假说一致。此外,通过检验某些参数对溶蚀过程的影响发现 Ca 的平衡浓度是一个岩溶系统发育极为敏感的因子。

Optimized Antiretroviral Therapy with Darunavir/Ritonavir, Etravirine and/or Raltegarvir: A Salvage Therapy Option in HIV-1 Infected Patients with Long-Term Therapeutic Failures, about 23 Cases

Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.

Chitinase 10 controls chitin amounts and organization in the wing cuticle of Drosophila

Wings are essential for insect fitness.A number of proteins and enzymes have been identified to be involved in wing terminal differentiation,which is characterized by the formation of the wing cuticle.Here,we addressed the question whether chitinase 10(Cht10)may play an important role in chitin organization in the wings of the fruit fly Drosophila melanogaster.Initially,we first found that Cht10 expression coincides with the expression of the chitin synthase coding gene kkv.This suggests that the respective proteins may cooperate during wing differentiation.In tissue-specific RNA interference experiments,we demonstrate that suppression of Cht10 causes an excess in chitin amounts in the wing cuticle.Chitin organization is severely disrupted in these wings.Based on these data,we hypothesize that Cht10 restricts chitin amounts produced by Kkv in order to ensure normal chitin organization and wing cuticle formation.In addition,we found by scanning electron microscopy that Cht10 suppression also affects the cuticle surface.In turn,cuticle inward permeability is enhanced in Cht10 Aess wings.Moreover,flies with reduced Cht 10 function are unable to fly.In conclusion,Cht10 is essential for wing terminal differentiation and function.