CHIP相关基因与MPN患者心脑血管事件的风险分析

目的:分析骨髓增殖性肿瘤(MPN)患者不确定潜能的克隆性造血(CHIP)相关基因突变谱和临床特征,探讨CHIP相关基因与其心脑血管事件(CCE)的相关性及可能作用机制。方法:回顾性分析2019年8月-2022年7月首都医科大学附属北京安贞医院血液科收治的73例MPN患者的临床资料和二代测序结果,采用Logistic回归分析CHIP相关基因、炎症细胞因子对MPN患者CCE的影响。结果:55例(75.3%)MPN患者检出CHIP相关基因,原发性血小板增多症(ET)和真性红细胞增多症(PV)患者CHIP相关基因各突变频率差异无统计学意义。CHIP相关基因突变以单基因形式为主,检出率从高至低依次为JAK2V617F(63.0%,46/73)、ASXL1(16.4%,12/73)、TET2(11.0%,8/73)、DNMT3A(9.6%,7/73)、SRSF2(6.9%,5/73)、SF3B1(4.1%,3/73)、TP53(1.4%,1/73)和PPMID(1.4%,1/73)。年龄>60岁患者CHIP相关基因检出率明显高于≤60岁者[91.7%(33/36)vs 59.5%(22/37)]。27例(37.0%)MPN患者伴CCE(MPN/CCE),2次CCE者5例,均为动脉事件。CCE组患者年龄(62.8±12.8 vs 53.9±15.8岁,P=0.015)、IL-1β水平(17.7±26.0vs 4.3±8.6,P=0.012)、IL-8水平(360.7±598.6 vs 108.3±317.0,P=0.045)、血栓形成史(29.6%vs 2.2%,P=0.020)和CHIP相关基因检出率(88.9%vs 67.4%,P=0.040)高于无CCE组。多因素Logistic回归分析结果显示,年龄(OR=0.917,95%CI:0.843-0.999,P=0.047)、血栓形成史(OR=34.148,95%CI:2.392-487.535,P=0.009)、任何1个CHIP相关基因突变(OR=16.065,95%CI:1.217-212.024,P=0.035)和IL-1β水平升高(OR=0.929,95%CI:0.870-0.992,P=0.027)均是MPN/CCE的独立危险因素;CHIP相关单基因突变与MPN/CCE无关,但DNMT3A(OR=88.717,95%CI:2.690-292.482,P=0.012)、ASXL1(OR=7.941,95%CI:1.045-60.353,P=0.045)突变是PV/CCE的独立危险因素。结论:MPN患者CHIP相关基因突变率高,尤其是60岁以上患者;高龄、血栓形成史、CHIP相关基因突变和IL-1β水平升高是MPN发生CCE的独立危险因素。DNMT3A、ASXL1单基因突变是PV患者CCE的独立危险因素。CHIP相关基因突变及炎症细胞因子IL-1β升高是MPN新的CCE危险因素。

替普瑞酮通过E3泛素连接酶CHIP减轻LPS引起的心肌炎症反应和心功能障碍

目的:探究替普瑞酮又称香叶基香叶基丙酮,GGA)对脂多糖(LPS)诱导的心功能障碍的治疗作用及机制。方法:(1)取8周龄C57BL/6雄性野生型小鼠和热休克蛋白70(HSP70)羧基末端相互作用蛋白(CHIP)基因敲除小鼠,随机分为对照组、LPS组、LPS+GGA组和GGA组,每组8只。用腹腔注射LPS(25 mg/kg)的方法建立模型,于LPS刺激后1 h给予小鼠腹腔注射GGA(100 mg/kg)。利用小动物超声系统评估小鼠心脏功能;采集各组小鼠血清,检测血清肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平;HE染色观察病理学改变;ELISA检测心脏组织中炎症因子肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的水平;Western blot检测各组心脏组织HSP70、CHIP、核转运蛋白α2(KPNA2)、髓过氧化物酶(MPO)、血管细胞黏附分子(VCAM)和细胞间黏附分子(ICAM)的蛋白表达以及细胞核NF-κB的水平。(2)利用小鼠心肌细胞HL-1,建立LPS刺激的离体细胞炎症模型。ELISA检测细胞上清中TNF-α和IL-6的水平;Western blot检测心肌细胞中HSP70、CHIP和KPNA2蛋白表达;免疫荧光染色观察细胞核NF-κB的表达。结果:(1)GGA有效改善LPS刺激小鼠的心脏功能,显著提高射血分数和左室短轴缩短率(P<0.01),减少血清CK-MB和LDH含量(P<0.01),减轻心肌损伤。(2)GGA显著减少LPS引起的TNF-α和IL-6炎症因子的释放(P<0.01),以及NF-κB的入核,降低心肌组织中KPNA2、MPO、VCAM和ICAM蛋白表达,增加心肌组织和细胞HSP70的水平(P<0.01)。(3)在CHIP基因敲除的心肌细胞和小鼠中,GGA不能抑制LPS引起的炎症反应,失去了改善LPS刺激小鼠心脏功能的作用。结论:GGA能够减轻LPS引起的心功能障碍,其作用机制与升高HSP70的表达,促进CHIP的活化,减少NF-κB的入核,抑制炎症因子的释放有关。CHIP的敲除使GGA丧失了减轻LPS诱导的炎症反应和心肌损伤的作用。

Ultrasensitive quantification of trace amines based on N-phosphorylation labeling chip 2D LC-QQQ/MS

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neurological disorders.Comprehensive measurement of TAs is essential for understanding pathological processes and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simultaneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

基于Lab色彩空间的沙尘降质图像增强方法

针对沙尘天气导致的数字图像质量大幅下降问题,提出一种基于Lab色彩空间的沙尘降质图像增强方法。将沙尘图像增强分解为偏色校正与细节增强两个步骤处理。偏色校正部分包括去除色偏与亮度拉伸。首先对Lab与YUV色彩空间中的沙尘图像直方图偏移特点进行了分析,然后提出一种Lab空间偏色校正算法修正直方图偏移,并对初步去除偏色的图像进行亮度拉伸,提升图像对比度。在细节增强部分,引入一种基于饱和度估计透射率的去雾方法进一步增强图像细节信息。实验结果表明,相较于各对比算法,所提算法可以去除不同程度沙尘带来的色偏,且在面对中小型图像时具有最佳的时间性能表现。在量化指标方面,基于无参考感知的图像质量评估标准和基于熵的无参考图像质量评价标准分别提升了3.2%和10.7%。本文方法可以有效去除色偏,还原清晰图像。

Efficient stochastic parallel gradient descent training for on-chip optical processor

In recent years,space-division multiplexing(SDM)technology,which involves transmitting data information on multiple parallel channels for efficient capacity scaling,has been widely used in fiber and free-space optical communication sys-tems.To enable flexible data management and cope with the mixing between different channels,the integrated reconfig-urable optical processor is used for optical switching and mitigating the channel crosstalk.However,efficient online train-ing becomes intricate and challenging,particularly when dealing with a significant number of channels.Here we use the stochastic parallel gradient descent(SPGD)algorithm to configure the integrated optical processor,which has less com-putation than the traditional gradient descent(GD)algorithm.We design and fabricate a 6×6 on-chip optical processor on silicon platform to implement optical switching and descrambling assisted by the online training with the SPDG algorithm.Moreover,we apply the on-chip processor configured by the SPGD algorithm to optical communications for optical switching and efficiently mitigating the channel crosstalk in SDM systems.In comparison with the traditional GD al-gorithm,it is found that the SPGD algorithm features better performance especially when the scale of matrix is large,which means it has the potential to optimize large-scale optical matrix computation acceleration chips.

基于单片机和LabVIEW的无线温度监测与控制系统设计

本文设计了一个基于STC89C52单片机和LabVIEW的无线温度监测与控制系统.该系统采用上下位机的结构,其中下位机通过STC89C52单片机控制DS18B20采集实时温度,并利用控制模块实现加热或降温,同时,通过蓝牙模块实现与上位机的无线通信;上位机以LabVIEW作为开发平台,实现对温度的实时显示、处理、存储、阈值设定和温度控制等功能.该系统电路设计简单、成本低、扩展性强、人机界面友好,可用于智能大棚的温度控制等需要温度检测的场所,具有广阔的应用前景.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

On-chip quantum NOON state sensing for temperature and humidity

A maximal photon number entangled state,namely NOON state,can be adopted for sensing with a quantum enhancedprecision.In this work,we designed silicon quantum photonic chips containing two types of Mach-Zehnder interferometerswherein the two-photon NOON state,sensing element for temperature or humidity,is generated.Compared with classicallight or single photon case,two-photon NOON state sensing shows a solid enhancement in the sensing resolution andprecision.As the first demonstration of on-chip quantum photonic sensing,it reveals the advantages of photonic chips forhigh integration density,small-size,stability for multiple-parameter sensing serviceability.A higher sensing precision isexpected to beat the standard quantum limit with a higher photon number NOON state.

A Fully-Integrated Memristor Chip for Edge Learning

It is still challenging to fully integrate computing in memory chip as edge learning devices.In recent work published on Science,a fully-integrated chip based on neuromorphic memristors was developed for edge learning as artificial neural networks with functionality of synapses,dendrites,and somas.A crossbar-array memristor chip facilitated edge learning including hardware realization,learning algorithm,and cycle-parallel sign-and threshold-based learning(STELLAR)scheme.The motion control and demonstration platforms were executed to improve the edge learning ability for adapting to new scenarios.

Simplified quantitative analysis method and its application in the insitu synthesized copper-based azide chips

Copper-based azide(Cu(N_(3))2 or CuN_(3),CA)chips synthesized by in-situ azide reaction and utilized in miniaturized explosive systems has become a hot research topic in recent years.However,the advantages of in-situ synthesis method,including small size and low dosage,bring about difficulties in quantitative analysis and differences in ignition capabilities of CA chips.The aim of present work is to develop a simplified quantitative analysis method for accurate and safe analysis of components in CA chips to evaluate and investigate the corresponding ignition ability.In this work,Cu(N_(3))2 and CuN_(3)components in CA chips were separated through dissolution and distillation by utilizing the difference in solubility and corresponding content was obtained by measuring N_(3)-concentration through spectrophotometry.The spectrophotometry method was optimized by studying influencing factors and the recovery rate of different separation methods was studied,ensuring the accuracy and reproducibility of test results.The optimized method is linear in range from 1.0-25.0 mg/L,with a correlation coefficient R^(2)=0.9998,which meets the requirements of CA chips with a milligram-level content test.Compared with the existing ICP method,component analysis results of CA chips obtained by spectrophotometry are closer to real component content in samples and have satisfactory accuracy.Moreover,as its application in miniaturized explosive systems,the ignition ability of CA chips with different component contents for direct ink writing CL-20 and the corresponding mechanism was studied.This study provided a basis and idea for the design and performance evaluation of CA chips in miniaturized explosive systems.

A novel integrated microfluidic chip for on-demand electrostatic droplet charging and sorting

On-demand droplet sorting is extensively applied for the efficient manipulation and genome-wide analysis of individual cells.However,state-of-the-art microfluidic chips for droplet sorting still suffer from low sorting speeds,sample loss,and labor-intensive preparation procedures.Here,we demonstrate the development of a novel microfluidic chip that integrates droplet generation,on-demand electrostatic droplet charging,and high-throughput sorting.The charging electrode is a copper wire buried above the nozzle of the microchannel,and the deflecting electrode is the phosphate buffered saline in the microchannel,which greatly simplifies the structure and fabrication process of the chip.Moreover,this chip is capable of high-frequency droplet generation and sorting,with a frequency of 11.757 kHz in the drop state.The chip completes the selective charging process via electrostatic induction during droplet generation.On-demand charged microdroplets can arbitrarilymove to specific exit channels in a three-dimensional(3D)-deflected electric field,which can be controlled according to user requirements,and the flux of droplet deflection is thereby significantly enhanced.Furthermore,a lossless modification strategy is presented to improve the accuracy of droplet deflection or harvest rate from 97.49% to 99.38% by monitoring the frequency of droplet generation in real time and feeding it back to the charging signal.This chip has great potential for quantitative processing and analysis of single cells for elucidating cell-to-cell variations.

Single event effects evaluation on convolution neural network in Xilinx 28 nm system on chip

Convolutional neural networks(CNNs) exhibit excellent performance in the areas of image recognition and object detection, which can enhance the intelligence level of spacecraft. However, in aerospace, energetic particles, such as heavy ions, protons, and alpha particles, can induce single event effects(SEEs) that lead CNNs to malfunction and can significantly impact the reliability of a CNN system. In this paper, the MNIST CNN system was constructed based on a 28 nm systemon-chip(SoC), and then an alpha particle irradiation experiment and fault injection were applied to evaluate the SEE of the CNN system. Various types of soft errors in the CNN system have been detected, and the SEE cross sections have been calculated. Furthermore, the mechanisms behind some soft errors have been explained. This research will provide technical support for the design of radiation-resistant artificial intelligence chips.

Rapid fabrication of modular 3D paper-basedmicrofluidic chips using projection-based 3D printing

Paper-based microchips have different advantages,such as better biocompatibility,simple production,and easy handling,making them promising candidates for clinical diagnosis and other fields.This study describes amethod developed to fabricate modular three-dimensional(3D)paper-based microfluidic chips based on projection-based 3D printing(PBP)technology.A series of two-dimensional(2D)paper-based microfluidic modules was designed and fabricated.After evaluating the effect of exposure time on the accuracy of the flow channel,the resolution of this channel was experimentally analyzed.Furthermore,several 3D paper-based microfluidic chips were assembled based on the 2D ones using different methods,with good channel connectivity.Scaffold-based 2D and hydrogel-based 3D cell culture systems based on 3D paper-based microfluidic chips were verified to be feasible.Furthermore,by combining extrusion 3D bioprinting technology and the proposed 3D paper-based microfluidic chips,multiorgan microfluidic chips were established by directly printing 3D hydrogel structures on 3D paperbased microfluidic chips,confirming that the prepared modular 3D paper-based microfluidic chip is potentially applicable in various biomedical applications.

Effects of Using Softwood Pellet Biochar Prepared at Different Temperatures with Grass Chippings on Retention of Heavy Metals in Contaminated Soils

Heavy metals have been viewed as hazardous environmental pollutants, and anthropogenic activities due to their high toxicity and persistent nature in the environment. Anthropogenic activities such as artisanal mining, industrial activities, improper usage of fertilizers and pesticides, and indiscriminate open waste disposal bring about an increase in the presence of heavy metals in the environment. In the Keffi Metropolis, different elements lead to land contamination which debilitates soil quality, plant survival, human well-being, and the environment as a result of extensive dispersion or quantity of heavy metals in the soil and water. In recent years, biochar has emerged as a promising soil amendment for mitigating heavy metal pollution due to its unique physicochemical properties. This paper provides the effects of softwood pellet biochar on the retention of heavy metals in contaminated soils. A microcosm experiment was carried out to investigate the effects of biochar on the retention of heavy metals in contaminated soils. This research aimed to give an overview of the effects of softwood biochar at different temperatures (550˚C and 700˚C) on the retention of heavy metals and metalloids released from the soil during water inundation. The results show that the addition of organic matter (grass chippings) minimizes heavy metal mobilization. Also, biochar at high temperatures is more effective than those at low temperatures. The expected outcome of the research analysis includes providing insights into the role of biochar in retaining heavy metal contamination and further understanding the use of biochar as a sorbent for the management of contaminated soil.

基于Living Lab理念的体验式教学设计与应用研究——以“高等数学”课程为例

针对传统“高等数学”课程教学存在抽象理论难以理解、实践应用环节欠缺、学习兴趣普遍不高和教学质量效果不佳等问题,提出采用Living Lab理念的体验式教学方法作为课堂教学的补充和改进方案。Living Lab理念强调在真实环境中进行学习和研究,以实地考察、实践操作和数学建模等活动为载体,将抽象的数学理论与实际生活和工程问题相结合,促进学生对数学知识的理解和应用。Living Lab理念的体验式教学为改进高等数学课程教学提供了新思路和新方法,有助于提高教学质量和激发学生的学习动力。

Flip Chip技术在集成电路封装中的应用

阐述从集成电路封装发展现状、Flip Chip技术内涵、Flip Chip技术在集成电路封装中的应用剖析、市场发展展望等多个角度,探讨在集成电路封装中,应用Flip Chip技术的必要性和重要性。

An electrochemiluminescent magneto-immunosensor for ultrasensitive detection of hs-cTnI on a microfluidic chip

Sensitive detection and precise quantitation of trace-level crucial biomarkers in a complex sample matrix has become an important area of research.For example,the detection of high-sensitivity cardiac troponin I (hs-cTnI) is strongly recommended in clinical guidelines for early diagnosis of acute myocardial infarction.Based on the use of an electrode modified by single-walled carbon nanotubes (SWCNTs) and a Ru(bpy)32+-doped silica nanoparticle (Ru@SiO2)/tripropylamine (TPA) system,a novel type of electrochemiluminescent (ECL) magnetoimmunosensor is developed for ultrasensitive detection of hs-cTnI.In this approach,a large amount of[Ru(bpy)3]2+is loaded in SiO2(silica nanoparticles) as luminophores with high luminescent efficiency and SWCNTs as electrode surface modification material with excellent electrooxidation ability for TPA.Subsequently,a hierarchical micropillar array of microstructures is fabricated with a magnet placed at each end to efficiently confine a single layer of immunomagnetic microbeads on the surface of the electrode and enable 7.5-fold signal enhancement In particular,the use of transparent SWCNTs to modify a transparent ITO electrode provides a two-order-of-magnitude ECL signal amplification.A good linear calibration curve is developed for hs-cTnI concentrations over a wide range from 10 fg/ml to 10 ng/ml,with the limit of detection calculated as 8.720 fg/ml (S/N=3).This ultrasensitive immunosensor exhibits superior detection performance with remarkable stability,reproducibility,and selectivity.Satisfactory recoveries are obtained in the detection of hs-cTnI in human serum,providing a potentia analysis protocol for clinical applications.

E-Lab手术示教系统在神经介入医生规范化培训中的应用

目的分析在神经介入医生培训中基于E-Lab手术示教系统开展脑血管造影的培训效果。方法对2022年9月至2023年3月在海军军医大学第一附属医院脑血管病中心进修的45名医生进行入组筛选,将14名符合入组条件的进修医生分为试验组和对照组,每组7人,试验组采取理论授课+基于E-Lab系统的录播案例开展培训,对照组按照传统理论授课+临床带教操作模式进行培训,比较试验组和对照组在不同培训模式下理论知识和操作技能的学习效果。结果学员的平均年龄、职称,以及培训期间造影例数、疾病类别、主动脉弓解剖类型、经桡动脉入路例数等基线指标比较,差异无统计学意义(P>0.05)。最终考核中的技能考核成绩和总成绩,2组比较差异有统计学意义(P<0.05)。其中2组的理论考核成绩差异无统计学意义(P>0.05);而技能考核中,2组导丝控制、导管控制、血管超选、操作时间、熟练程度技能得分比较,差异有统计学意义(P<0.05)。结论将E-Lab系统应用于脑血管造影术的进修学员教学培训中,对其操作技能培养有效果和优势,为神经介入的人才培养提供了新思路。

基于Neptune Lab智能实验系统综合测试平台助力教学创新策略

Neptune Lab智能实验系统的综合测试平台对教学创新策略具有一定的助力作用。通过Neptune Lab系统,教师可以收集学生的实验数据、实验报告和成绩等信息,全面评估学生的实验操作能力和学习效果。本文首先介绍Neptune Lab系统的特点和优势,其次探讨该系统在教学创新中的应用,包括教学效果评估、智能化教学辅助、虚拟实验环境等方面。最后,总结Neptune Lab系统在教学创新中的潜在发展方向。

敦煌文化在数字领域中的设计研究——以Team Lab为例

敦煌壁画在中国古代艺术中占据着至关重要的地位,其独特的艺术风格和丰富的文化内涵使其成为中国古代文化的瑰宝之一。而提及对敦煌壁画的保护和传承,“数字敦煌”居功至伟。在此基础上,敦煌壁画的数字艺术设计得以蓬勃发展。本文旨在探究敦煌壁画在数字领域下的设计研究,通过对日本Team Lab及其作品的分析,探索敦煌文化在数字领域中的设计创新实践及其所面临的挑战,并展望其未来的发展。