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。

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.

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.

Experimental and numerical study regarding H-steel all-bolted connection steel frame with composite wall boards

H-steel all-bolted connection steel frame structures with heat preservation and decoration composite wall boards were investigated and the seismic performances of three scaled specimens were studied.The failure modes,hysteresis curves,bearing capacity,ductility,energy dissipation capacity,stiffness degradation and strain distribution were discussed.The calculation method of structural theoretical internal force was presented.The results showed that the overall structural seismic performance was better,and the structural ductility met the demands of elastic-plastic inter-story drift angle for seismic design.The H-steel weak-axis connection structure obtained better energy dissipation capacity,and its bearing capacity and stiffness were slightly different from the strong-axis connection.The heat preservation and decoration performance of composite wallboard and the all-bolted connection of the steel frame realized prefabrication during the whole construction period.The plastic hinge of the steel beam can be moved outwards because of the L-angles,which effectively avoids stress concentration in joint areas and expands the plastic hinge range.The errors between the theoretical structural capacity calculated by the plastic analysis method and the test results were within 2.44%.In addition,structural failure mechanisms and bearing capacities were verified by the finite element(FE)analysis,and the effects of the main parameters on the structures were investigated.The FE verification results were the same as in the test.The research results provide theoretical support and technical guidance for the application of thermal insulation and decorative composite wall panels in H-shaped steel all-bolted steel frames.

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.

Effect of copper content on the pyrolysis process of organic components in waste printed circuit boards:Based on experimental and quantum chemical DFT simulations

In recent years,scientists have become increasingly concerned in recycling electronic trash,particularly waste printed circuit boards(WPCBs).Previous research has indicated that the presence of Cu impacts the pyrolysis of WPCBs.However,there may be errors in the experimental results,as printed circuit boards(PCBs)with copper and those without copper are produced differently.For this experiment,we blended copper powder with PCB nonmetallic resin powder in various ratios to create the samples.The apparent kinetics and pyrolysis properties of four resin powders with varying copper concentrations were compared using nonisothermal thermogravimetric analysis(TG)and thermal pyrolysis-gas chromatography mass spectrometry(Py-GC/MS).From the perspective of kinetics,the apparent activation energy of the resin powder in the pyrolysis reaction shows a rise(0.1<a<0.2)-stable(0.2<a<0.4)-accelerated increase(0.4<a<0.8)-decrease(0.8<a<0.9)process.After adding copper powder,the apparent activation energy changes more obviously when(0.2<a<0.4).In the early stage of the pyrolysis reaction(0.1<a<0.6),the apparent activation energy is reduced,but when a?0.8,it is much higher than that of the resin sample without copper.Additionally,it is discovered using thermogravimetric analysis and Py-GC/MS that copper shortens the temperature range of the primary pyrolysis reaction and prevents the creation of compounds containing bromine.This inhibition will raise the temperature at which compounds containing bromine first form,and it will keep rising as the copper level rises.The majority of the circuit board molecules have lower bond energies when copper is present,according to calculations performed using the Gaussian09 software,which promotes the pyrolysis reaction.

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.

Effect of Low pH on Forming Process of Desulfurization Gypsum Composite Boards Strengthened by Melamine-formaldehyde Resin

Through exploring the effects of low pH on the composite system of desulfurization gypsum(DG)enhanced by melamine-formaldehyde resin(MF),it is found that the inducing of sulfate-ion,in contrast to chloride and oxalate ions,favors the longitudinal growth of the crystalline form of the hydration product,which was relatively simple and had the highest length to width(L/D)ratio.At the same time,MF can also improve L/D ratio of gypsum hydration products,which favors the formation of hydrated whiskers.Finally,in a composite system composed of hemihydrate gypsum,MF,and glass fibers,when dilute sulfuric acid was used to regulate pH=3-4,the tight binding formed among the components of the composite system compared to pH=5-6.The hydration product of gypsum adheres tightly to glass fiber surface and produces a good cross-linking and binding effect with MF.The flexural strength,compressive strength,elastic modulus,and water absorption of the desulphurized gypsum composite board is 22.7 MPa,39.8 MPa,5608 MPa,and 1.8%,respectively.

Protective benefits of HDPE board sand fences in an environment with variable wind directions on Gobi surfaces:wind tunnel study

The Golmud-Korla Railway in the Gobi area faces operational challenges due to sand hazards,caused by strong and variable winds.This study addresses these challenges by conducting wind tunnel tests to evaluate the protective benefits of High Density Polyethylene(HDPE)board sand fences,focusing on their orientation relative to various wind directions(referred to as'wind angle').This study found that the size of the low-velocity zone on the leeward side of the sand fences(LSF)expanded with an increase in the wind angle(WA).At 1H(the height of the sand fence)and 2H positions on the LSF,the wind speed profiles(WSP)exhibited a segmented logarithmic growth,constrained by Z=H at varying WAs.The efficacy of the sand fence in obstructing airflow escalated as WA increased.The size of the WA has a significant impact on the protective efficiency of HDPE board sand fences.Furthermore,compared to typical sandy surfaces,the rate of sand transport across the Gobi surface diminishes more slowly with height,attributed to the gravel's rebound effect.This phenomenon allows some sand particles to bypass the fences,rendering them less effective at blocking wind and trapping sand than in sandy environments.This paper offers scientific evidence supporting the practical use and enhancement of HDPE board sand fences in varied wind conditions.

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.

Protective benefit of folded linear HDPE board sand fences along the Golmud-Korla Railway,China:Field observation and wind tunnel study

The Milan Gobi area of the Golmud-Korla Railway in northwest China is located in the lower dispersal area of the mountain pass and has strong winds with evident double wind direction characteristics.This study introduced a novel sand fence deployment technique,termed‘folded linear deployment',designed to position the sand fence orthogonally to the two predominant wind directions for optimal protection.This study used wind tunnel and field tests to evaluate the wind and sand flow characteristics,as well as the windproof and sandresistant performance of folded linear HDPE(Highdensity polyethylene)board sand fences.The results suggest that the airflow around the fence creates clear zoning characteristics.The deceleration area on the BSF(backwind side of the sand fence)is much larger than that on the DSF(downwind side of the sand fence).Thus,sand particles are primarily deposited on the BSF.At different wind speeds,the airflow at 2 and 5 h on the DSF is not disturbed.The WSP(wind speed profile)presents a logarithmic distribution.The airflow is disturbed at 1-20 h on the BSF,and the WSP gradually deviates from the logarithmic law.However,as the airflow moves away from the fence,the WSP gradually approaches a logarithmic distribution.Meanwhile,the WPE(windproof efficiency)and SRE(sand-resistant efficiency)of the sand fence exceed 80%.In addition,the results of wind tunnel tests are compared with those of field tests.The overall dispersion is good,and the best dispersion is found at z/H=2.00,indicating good agreement between the two test results.This study provides a scientific basis for the design of sand hazard control measures,similar to the railway project in the Gobi Gale area.

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.

Women on Boards of Directors

This research aims to measure the current gender representation in membership of boards of directors,and to study the factors affecting the presence of women on boards.The results of the study will support the decision makers and policy makers at all levels by providing knowledge that contributes to bridging the current gap in participation of women boards.The methodology used in this research is the descriptive analytical approach,which relies on quantitative methods in the process of collecting and analyzing data.This study represents the boards of directors in the three sectors(public,private,and non-profit)in the Kingdom of Saudi Arabia,The study sample contained 350 targets,where a random sample of 150 people in the public sector,100 people in the private sector,and 100 people in the non-profit sector were selected.The research result found that the majority of the responses believe that the lack of experience and training,and social factors,are the most impact areas of explaining the reasons for the existence of a gap in women’s membership in boards of directors in the three sectors.And the most important reasons for the existence of a gender gap in board membership are:there is no statutory minimum percentage for women’s representation on boards of directors,and scarcity of female competencies in general,and the lack of women occupying leadership positions.

BOB(Bosa On Board)设计研究

采用bosa on board的方式,将光通信电路直接铺设在PCB板上,替代传统的光模块独立器件,实现GPON/EPON产品的低成本高性能。

Development and Characterization of Particle Boards Based on Sorghum Husk

This study tackles current environmental challenges by developing innovative and eco-friendly particle boards utilizing sorghum husk, combined with recycled expanded polystyrene (EPS). This dual eco-responsible approach valorizes sorghum husk, often deemed agricultural waste, and repurposes EPS, a plastic waste, thus contributing to CO2 emission reduction and effective waste management. The manufacturing process involves dissolving recycled polystyrene within a solvent to create a binder, which is then mixed with sorghum husk and cold-pressed into composite boards. The study explores the impact of two particle sizes (fine and coarse) and two different concentrations of the recycled EPS binder. Results demonstrate significant variations in the boards’ mechanical properties, displaying a range of Modulus of Rupture (MOR) from 0.84 MPa to 3.85 MPa, and Modulus of Elasticity (MOE) spanning from 658.13 MPa to 1313.25 MPa, influenced by the binder concentration and particle size. These characteristics suggest that the boards can be effectively used in various construction applications, including interior decoration, false ceilings, and potentially for furniture and door manufacturing when combined with appropriate coatings. This study not only exemplifies the valorization of plastic and agricultural wastes but also offers a practical, localized solution to global climate change challenges by promoting sustainable construction materials.

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.

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。