非生长因子依赖的MDS细胞系的建立及其生物学特性研究

本研究的目的是从骨髓增生异常综合征-慢性粒-单核细胞白血病(MDS-CMML)病人获取骨髓细胞,建立 非生长因子依赖的细胞株。该细胞株在不添加任何生长因子的含15％胎牛血清的RPMI 1640和DMEM混合培养 液中进行了培养,并分别从细胞株的形态、细胞表面抗原分子、细胞增殖、分化、凋亡等方面检测其生物学特性。结 果表明:在不添加任何生长因子的培养条件下该细胞株可以长期存活和生长,并能向单核及巨核细胞分化。结论: 成功建立了一株非生长因子依赖的MDS-JSN04(MDS-江苏南京04)细胞株,并阐明了其部分生物学特性。

MDS发病分子机制、预后和表观遗传学治疗进展——第12届骨髓增生异常综合征(MDS)国际研讨会采撷

1MDS基因突变 MDS是一组克隆性造血千细胞疾病，其特征是血细胞减少，髓系细胞一系或多系发育异常（dysplasia），无效造血（ineffective haematopoiesis）及演变为急性髓系白血病（AML）的风险增高。MDS主要病理生理本质是：（1）起源于造血干细胞的克隆性疾病；（2）粒系、

福氏志贺菌mdoC基因对其在洗菜水中生长及生物膜形成的影响

【目的】研究福氏志贺菌mdoC基因对细菌在不同洗菜水中生长及生物膜形成的影响。【方法】以福氏志贺菌野生型和敲除mdoC基因的opgC突变体为出发菌株,采用生长曲线法和结晶紫染色法,在低渗透压及正常渗透压的菠菜、芹菜、生菜及白菜洗菜水中,研究福氏志贺菌野生型和opgC突变体生长及生物膜的产生能力。【结果】在不同洗菜水中,福氏志贺菌opgC突变体生长速率明显较野生型慢,加盐提高渗透压之后,野生型和opgC突变体稳定生长期均提前。野生型和opgC突变体的生物膜产量在菠菜水、生菜水和白菜水中有显著区别;提高渗透压之后,福氏志贺菌野生型在菠菜水中的生物膜产量显著提高,而在生菜水和白菜水中生物膜产量显著下降,opgC突变体在菠菜水、生菜水和白菜水中生物膜产量均显著提高。【结论】低渗条件下,福氏志贺菌mdoC基因的缺失显著地延缓了细菌生长。提高渗透压后,在菠菜、生菜和白菜洗菜水中,mdoC基因的缺失促进了生物膜的形成。

Prevalence of unsuspected thyroid nodules in adults on contrast enhanced 16-and 64-MDCT of the chest

AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.

EEMD and bidimensional RLS to suppress physiological interference for heterogeneous distribution in fNIRS study

Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.

MDR1基因多态性与儿童难治性癫痫的相关性研究

目的探讨多药耐药基因1(multidrug resistance gene 1,MDR1)单核苷酸多态性与儿童难治性癫痫的相关性.方法2014年12月至2017年3月本院小儿神经门诊就诊的200例癫痫患儿及100名体检正常儿,提取DNA、PCR扩增、琼脂糖凝胶电泳,目标位点测序对rs1922242、rs2235048、rs10808072、rs868755、rs1202184单核苷酸位点进行基因分型.结果耐药组与药物敏感组rs1922242、rs2235048、rs10808072、rs868755位点基因型分布和等位基因频率及rs1202184等位基因频率的差异均无统计学意义,而rs1202184位点基因型分布差异有统计学意义(P=0.008),两组不同单倍型频率差异无统计学意义.结论MDR1基因rs1202184位点基因型与难治性癫痫相关,且以AA基因型为主.

放射外科在MD安德森肿瘤中心的实践及进展

非小细胞肺癌（NSCLC）是我国最常见的恶性肿瘤之一.立体放射外科（SABR）,也称立体定向放疗（SBRT）,是一种无创性治疗,在现代精确的影像引导技术下给予局部肿瘤以高剂量、低分割的放射治疗,可获得超过90％的肿瘤局部控制率,已成为不可切除早期NSCLC的标准治疗,也是可手术早期NSCLC的治疗选择之一.美国德州大学MD安德森肿瘤中心（MDACC）作为全美肿瘤治疗排名第一的机构,对NSCLC的放射治疗进行了一系列颇具影响力的SABR临床试验和研究,促进了SABR在早期和晚期NSCLC中的应用.本文将MDACC对SABR的临床应用、研究结果和进展做一总结.

乳腺大体标本取材：美国MD安德森癌症中心乳腺癌标本取材介绍

随着医学的发展,精准医疗逐渐成为现代医疗的发展方向.为了给患者制定有效的个体化治疗方案,临床医师对病理诊断的精准性提出了更高的要求.规范化的取材是精准病理诊断的基础,也是精准治疗的前提[1].近几年来,随着乳腺B超引导下粗针穿刺活检已经逐渐取代手术活检,多数患者在手术切除时已经有了明确诊断.为了更精准测量肿瘤的位置,客观地评判手术范围,准确地评估肿瘤分期和治疗反应,乳腺标本的大体取材受到临床与病理的共同重视,取材方法也在逐渐改进[1-5].准确的大体检查往往依赖于病理医师、放射医师及外科医师的合作.我们旨在介绍乳腺癌手术切除标本和前哨淋巴结的大体取材方法,其主要内容来自于美国MD安德森癌症中心（MD Anderson Cancer Center,MDACC） 行之有效的多年实践.

Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Comparison of Optical Transport Schemes for LMDS with Optical Fiber Backbone

We investigate and compare the performance of four optical transport schemes for distributing Local Multipoint Distribution Service (LMDS) signals using an optical fiber backbone.

Design of ultrahigh-affinity and dual-specificity peptide antagonists of MDM2 and MDMX for P53 activation and tumor suppression

Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo,representing a viable therapeutic strategy for cancer treatment.Using phage display techniques,we previously identified a potent peptide activator of P53,termed PMI(TSFAEYWNLLSP),with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range.Here we report an ultrahigh affinity,dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivitybased molecular design.Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3(LTFLEYWAQLMQ)that bound to MDM2 and MDMX with K_(d)values in the low picomolar concentration range as verified by isothermal titration calorimetry.Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 A resolution,respectively.Similar to PMI,PMI-M3 occupied the P53-binding pocket of MDM2/MDMX,which was dominated energetically by intermolecular interactions involving Phe3,Tyr6,Trp7,and Leu 10.Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2,and Leu1 and Met11 with MDMX,collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins.By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake,we obtained modified peptides termed PMI-2K(KTSFAEYWNLLSPK)and M3-2K(KLTFLEYWAQLMQK).Compared with PMI-2K,M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner.This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become,in its own right,a powerful lead compound for anticancer drug development,and can aid molecular design of other classes of P53 activators as well for anticancer therapy.

约束Green函数与非线性地基梁模态分析

在生物和医学领域,微机电系统(MEMS)中的微梁结构在植入人体的使用时,由于体内的细胞环境类似于水凝胶,在这种环境下工作,设备和仪器的精度和稳定性很大程度上受到细胞弹性的影响.为了分析此类地基梁的动力学问题,本文建立了非线性基础上的梁振动模型,研究了任意位置弹簧和非线性弹簧基础上的梁模态.通过Laplace变换和线性叠加原理,得到了一种约束Green函数,利用数值计算验证方案的有效性,并研究了各种重要物理参数的影响,发现弹簧位置向跨中移动时,模态对称性被打破,弹簧刚度增加,模态阶数改变.

Hybrid-Vlasov simulation of soft X-ray emissions at the Earth’s dayside magnetospheric boundaries

Solar wind charge exchange produces emissions in the soft X-ray energy range which can enable the study of near-Earth space regions such as the magnetopause,the magnetosheath and the polar cusps by remote sensing techniques.The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)and Lunar Environment heliospheric X-ray Imager(LEXI)missions aim to obtain soft Xray images of near-Earth space thanks to their Soft X-ray Imager(SXI)instruments.While earlier modeling works have already simulated soft X-ray images as might be obtained by SMILE SXI during its mission,the numerical models used so far are all based on the magnetohydrodynamics description of the space plasma.To investigate the possible signatures of ion-kinetic-scale processes in soft Xray images,we use for the first time a global hybrid-Vlasov simulation of the geospace from the Vlasiator model.The simulation is driven by fast and tenuous solar wind conditions and purely southward interplanetary magnetic field.We first produce global X-ray images of the dayside near-Earth space by placing a virtual imaging satellite at two different locations,providing meridional and equatorial views.We then analyze regional features present in the images and show that they correspond to signatures in soft X-ray emissions of mirrormode wave structures in the magnetosheath and flux transfer events(FTEs)at the magnetopause.Our results suggest that,although the time scales associated with the motion of those transient phenomena will likely be significantly smaller than the integration time of the SMILE and LEXI imagers,mirror-mode structures and FTEs can cumulatively produce detectable signatures in the soft X-ray images.For instance,a local increase by 30%in the proton density at the dayside magnetopause resulting from the transit of multiple FTEs leads to a 12%enhancement in the line-of-sight-and time-integrated soft X-ray emissivity originating from this region.Likewise,a proton density increase by 14%in the magnetosheath associated with mirror-mode structures can result in an enhancement in the soft X-ray signal by 4%.These are likely conservative estimates,given that the solar wind conditions used in the Vlasiator run can be expected to generate weaker soft X-ray emissions than the more common denser solar wind.These results will contribute to the preparatory work for the SMILE and LEXI missions by providing the community with quantitative estimates of the effects of small-scale,transient phenomena occurring on the dayside.

Finding the magnetopause location using soft X-ray observations and a statistical inverse method

Variability in the location and shape of the dayside magnetopause is attributed to magnetic reconnection,a fundamental process that enables the transfer of mass,energy,and momentum from the solar wind into the magnetosphere.The spatial and temporal properties of the magnetopause,under varying solar and magnetospheric conditions,remain largely unknown because empirical studies using in-situ observations are challenging to interpret.Global wide field-of-view(FOV)imaging is the only means to simultaneously observe the spatial distribution of the plasma properties over the vast dayside magnetospheric region and,subsequently,quantify the energy transport from the interplanetary medium into the terrestrial magnetosphere.Two upcoming missions,ESA/CAS SMILE and NASA’s LEXI will provide wide-field imagery of the dayside magnetosheath in soft X-rays,an emission generated by charge exchange interactions between high charge-state heavy ions of solar wind origin and exospheric neutral atoms.High-cadence two-dimensional observations of the magnetosheath will allow the estimation of dynamic properties of its inner boundary,the magnetopause,and enable studies of its response to changes in the solar wind dynamic pressure and interplanetary magnetic field orientation.This work introduces a statistically-based estimation approach based on inverse theory to estimate the spatial distribution of magnetosheath soft X-ray emissivities and,with this,identify the location of the magnetopause over the Sun−Earth line.To do so,we simulate the magnetosheath structure using the MHD-based OpenGGCM model and generate synthetic soft X-ray images using LEXI’s orbit and attitude information.Our results show that 3-D estimations using the described statistically-based technique are robust against Poisson-distributed shot noise inherent to soft X-ray images.Also,our proposed methodology shows that the accuracy of both three-dimensional(3-D)estimation and the magnetopause standoff distance calculation highly depends on the observational point.

Mshpy23:a user-friendly,parameterized model of magnetosheath conditions

Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind−Magnetosphere−Ionosphere Link Explorer(SMILE)will observe magnetosheath and its boundary motion in soft X-rays for understanding magnetopause reconnection modes under various solar wind conditions after their respective launches in 2024 and 2025.Magnetosheath conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE missions.We developed a userfriendly model of magnetosheath that parameterizes number density,velocity,temperature,and magnetic field by utilizing the global Magnetohydrodynamics(MHD)model as well as the pre-existing gas-dynamic and analytic models.Using this parameterized magnetosheath model,scientists can easily reconstruct expected soft X-ray images and utilize them for analysis of observed images of LEXI and SMILE without simulating the complicated global magnetosphere models.First,we created an MHD-based magnetosheath model by running a total of 14 OpenGGCM global MHD simulations under 7 solar wind densities(1,5,10,15,20,25,and 30 cm)and 2 interplanetary magnetic field Bz components(±4 nT),and then parameterizing the results in new magnetosheath conditions.We compared the magnetosheath model result with THEMIS statistical data and it showed good agreement with a weighted Pearson correlation coefficient greater than 0.77,especially for plasma density and plasma velocity.Second,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the performance.The MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath parameters.Third,we constructed a tool to calculate a soft X-ray image from any given vantage point,which can support the planning and data analysis of the aforementioned LEXI and SMILE missions.A release of the code has been uploaded to a Github repository.

Simulation of the SMILE Soft X-ray Imager response to a southward interplanetary magnetic field turning

The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)Soft X-ray Imager(SXI)will shine a spotlight on magnetopause dynamics during magnetic reconnection.We simulate an event with a southward interplanetary magnetic field turning and produce SXI count maps with a 5-minute integration time.By making assumptions about the magnetopause shape,we find the magnetopause standoff distance from the count maps and compare it with the one obtained directly from the magnetohydrodynamic(MHD)simulation.The root mean square deviations between the reconstructed and MHD standoff distances do not exceed 0.2 RE(Earth radius)and the maximal difference equals 0.24 RE during the 25-minute interval around the southward turning.

The magnetosheath at high spectral resolution

While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems appropriate to look ahead to the abilities of the next generation of astrophysics missions.Of these,the Line Emission Mapper(LEM),a large aperture micro-calorimeter based mission,is currently planned to be able to observe the magnetosheath at high spectral resolution(~2 eV).With a field of view of~30′,LEM will allow higher spatial resolution and higher cadence measurement of the motion of a very small portion of the magnetopause over relatively short periods of time(multiple hours),complementing SMILE’s global mapping.LEM’s strength is its spectral resolution.It will be able to measure the abundance of a broad range of elements and ionization states,many of which are inaccessible to current in situ instruments,and will be able to separate the emission from the magnetosheath from the emission from the cosmic X-ray background using the difference in their relative velocities.

偏倚抽样问题的选择性评论及其在现代统计学中的应用

偏倚抽样是一个普遍存在的问题,跨越各个学科领域,影响着计量经济学、流行病学、医学、调查研究,以及最近的机器学习和人工智能(AI)等领域.当选择用于分析或研究的数据点引入系统性偏倚时,这种无处不在的挑战可能会影响研究结果的准确性和可靠性.本文的目标是全面介绍与偏倚抽样问题相关的基础概念和推理方法.此外,我们还旨在建立偏倚抽样问题与机器学习中关于分布转移问题的最新讨论之间的联系.我们还将深入探讨偏倚抽样的最新进展,特别是在转移学习和预测置信区间的符合推理方面.我们的最终目标是以一种对研究生易于理解的方式呈现这些材料,使他们能够在自己的研究工作中识别偏倚抽样问题的应用.我们怀着深深的敬意和感激之情,将本文献给已故的茆诗松教授,他多年来的指导和智慧对我们至关重要.

Erratum to “Plant Defense against Necrotrophic Pathogens” [American Journal of Plant Sciences 11(12) (2020) 2122-2138]

The original online version of this article (Ghozlan, M.H., EL-Argawy, E., Tokgöz, S., Lakshman, D.K. and Mitra, A. (2020) Plant Defense against Necrotrophic Pathogens. American Journal of Plant Sciences, 11, 2122-2138. https://doi.org/10.4236/ajps.2020.1112149) was published mistakenly without another co-author, Nikita Gambhir. In this regard, we revise authors and “how to cite” sections by adding her name.

Mechanism of Cu entry into the brain:many unanswered questions

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.