miR-125b reverses cisplatin resistance by regulating autophagy via targeting RORA/BNIP3L axis in lung adenocarcinoma

The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma(LUAD),and chemoresistance,however,usually results in treatment failure and limits its application in the clinic.It has been shown that microRNAs(miRNAs)play a significant role in tumor chemoresistance.In this study,miR-125b was identified as a specific cisplatin(DDP)-resistant gene in LUAD,as indicated by the bioinformatics analysis and the real-time quantitative PCR assay.The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time.MiR-125b decreased the A549/DDP proliferation,and the multiple drug resistance-and autophagy-related protein expression levels,which were all reversed by the inhibition of miR-125b.In addition,xenografts of human tumors in nude mice were suppressed by miR-125b,demonstrating that through autophagy regulation,miR-125b could reverse the DDP resistance in LUAD cells,both in vitro and in vivo.Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L,which in turn inhibited autophagy and reversed chemoresistance.Based on these findings,miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.

CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma

Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

儿童维生素AD滴剂,这样吃才对

众所周知,维生素A、D对孩子的生长发育至关重要。而补充维生素A、D,最好选择专门的维生素AD制剂,比如维生素AD滴剂。但许多家长对其又不甚了解,有诸多疑问。以下,笔者将一一进行解答。

ADS-B信号在对流层大气波导中的传播性能

对流层大气环境存在特殊大气结构“大气波导”,可形成电波超视距传播或产生雷达盲区等。目前,通过雷达、GNSS信号等可以对大气波导进行一定程度的反演探测,但均存在一定的不足。ADS-B信号具有应用范围广、信号密度大、实时性高等特点,为此提出利用ADS-B信号受到不同大气环境影响后能量损耗不同的特点对ADS-B信号与对流层大气环境关联性进行分析研究。以武汉地区ADS-B信号数据为例,基于抛物方程传播理论对路径损耗进行仿真分析,并进行了实验验证。结果表明:ADS-B接收信号与仿真结果存在线性相关性并给出线性表述,为后续利用ADS-B信号反演大气波导提供参考依据。

星基ADS-B系统空天链路的建模与仿真

星基广播式自动相关监视(ADS-B,automatic dependent surveillance-broadcast)系统是一种新型的航空器监视技术,在未来空中交通管理系统中具有广阔的应用前景。为了深入研究星基ADS-B系统中航空器到卫星的空天链路通信性能,将专业软件Matlab和STK(system tool kit)有效联合,构建符合国际标准的星基ADS-B空天链路完整模型;通过离散事件动态交互模拟ADS-B消息的发送与接收全过程,最后统计得出体现星基ADS-B空天链路通信性能的消息识别概率(POI,possibility of identify)、消息检测概率(POD,possibility of detective)、信号接收功率、信号冲突概率、卫星覆盖范围等指标。仿真结果表明,随着区域内航空器数量上升,POI、POD下降,消息冲突概率上升。

基于迁移学习-元学习的ADS-B攻击分类研究

准确分类通航领域ADS-B攻击类型,采取预防攻击措施,对保障通航运行安全性具有重要意义。针对通航领域ADS-B攻击数据样本少,提出一种基于迁移学习-元学习的ADS-B攻击分类模型。该模型将迁移学习与深度卷积自编码器相结合,建立ADS-B攻击特征提取模型,提取数据样本的攻击有效特征表示,并运用元学习策略在特征空间中实现ADS-B攻击准确分类。实例研究表明,基于迁移学习-元学习的攻击分类模型可有效分类小样本ADS-B攻击,且正确率在95%以上。

基于多时间特征融合网络的ADS-B实采信号分离

不同于以往单天线广播式自动相关监视(Automatic Dependent Surveillance-Broadcast,ADS-B)信号分离中利用仿真的ADS-B信号制作数据集,将单天线接收的真实飞机发射的ADS-B原始信号通过调整信号起始时间以及功率并人为增加噪声来制作数据集。为了提高信号分离的时域波形精度,提出一种多分辨率多时间特征融合重采样(Multi-Temporal fusion Resampling of Multi-Resolution Features,MTRM-RF)网络,通过卷积将信号转化成不同采样率的信号并分别使用多层堆叠逐渐膨胀的一维卷积提取不同时间间隔的特征,以获得更多的时间信息。对多种基于深度学习的语音分离网络进行比较发现,MTRM-RF网络能够有效地融合ADS-B信号的不同采样率、不同时间间隔采样点的特征进行训练。并且随着训练集数据量的增加,分离信号的平均解码正确率达到88.39%,证明该网络可有效分离单天线实采的ADS-B交织信号。

Bioinformatics Identification of ZNFs/LINC00520/miR-181d/BCL2 Axis as a Novel Network in Cisplatin-Resistant Lung Adenocarcinoma Cells

Background: Resistance to cisplatin (DDP) leads to poor prognosis in patients with Lung Adenocarcinoma (LUAD) and limits its clinical application. It has been confirmed that autophagy promotes chemoresistance and, therefore, novel strategies to reverse chemoresistance by regulating autophagy are desperately needed. Methods: The differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) between A549 and A549/DDP cell lines were identified using the limma package in R, after gene expression profiles were obtained from Gene Expression Omnibus (GEO) database. By combining Autophagy-Related Genes (ARGs) from Human Autophagy Database (HADb), the interactions lncRNA-miRNAs and the interactions miRNAs-mRNAs respectively predicted by miRcode and miRDB/Targetscan database, the autophagy-related ceRNA network was constructed. Then, extraction of ceRNA subnetwork and Cox regression analyses were performed. A prognosis-related ceRNA subnetwork was constructed, and the upstream Transcription Factors (TFs) regulating lncRNAs were predicted by the JASPAR database. Finally, the expression patterns of candidate genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR) experiments. Results: A total of 3179 DEmRNAs, 180 DEmiRNAs, and 160 DElncRNAs were identified, and 35 DEmRNAs were contained in the HADb. Based on the ceRNA hypothesis, we established a ceRNA network, including 10 autophagy-related DEmRNAs, 9 DEmiRNAs, and 14 DElncRNAs. Then, LINC00520, miR-181d, and BCL2 were identified to construct a risk score model, which was confirmed to be a well-predicting prognostic factor. Furthermore, 5 TF ZNF family members were predicted to regulate LINC00520, whereas the RT-PCR results showed that the 5 ZNFs were consistent with the bioinformatics analysis. Finally, a ZNF regulatory LINC00520/miR-181d/BCL2 ceRNA subnetwork was constructed. Conclusions: An ZNFs/LINC00520/miR-181d/BCL2 axis as a novel network in DDP-resistant LUAD has been constructed successfully, which may provide potential therapeutic targets for LUAD.

Erratum to:ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer

The original version of this article was revised due to production error by the vendor.The author“Hua-min DING”is one of the co-authors,and the name should be labeled correctly as appears on PDF.The affiliation of“Yu-jun SHUAI”and“Chao HUANG”is“Department of Urology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China”,and both of them should be labeled as 1,as correctively appears on PDF.

基于AD与TRIZ的加工中心主轴松拉刀机构优化设计

数控加工中心在加工过程中常出现主轴松刀力不足或无法松刀的现象。针对此问题,通过TRIZ系统组件分析明确现有松拉刀机构各组件间作用关系,利用因果链分析得出影响松刀的根本原因,最终应用TRIZ理论中的物场模型分析方法和AD独立性原理提出优化设计方案。根据新方案计算出实际工况下的主轴松刀力和螺杆强度,并对松刀杆进行建模和仿真。结果表明:最大位移量为6.995μm,最大应力为45.24 MPa,符合结构设计要求。最后,经过现场实物测试,当液压力为5 MPa时,松刀行程、松刀力以及打刀量均符合生产要求,验证了优化设计方案的合理性。

白菜型冬油菜BrADS2基因的克隆、表达分析与亚细胞定位

【目的】探究白菜型冬油菜(Brassica rapa L.)脂肪酸去饱和酶ADS2(Δ9 fatty acid desaturase)基因与抗寒性的关系。【方法】基于前期转录组结果,采用一步定向克隆法得到BrADS2基因;构建GFP融合表达载体,通过注射法在烟草下表皮细胞进行瞬时转化,同时采用农杆菌侵染法侵染‘中双11号’;利用qRT-PCR技术,检测抗寒性不同的白菜型冬油菜品种叶片中ADS2基因的表达模式,并对低温下冬油菜的形态变化和抗氧化酶活性、电导率含量进行分析。【结果】白菜型冬油菜BrADS2基因可编码307个氨基酸,该基因编码的蛋白具有亲水性特性;qRT-PCR结果显示,BrADS2基因的表达量呈先升后降的单峰型变化,且在-4℃时表达量达到峰值;亚细胞定位结果显示BrADS2蛋白在细胞质和细胞膜上表达;低温处理下3个品种叶片的相对电导率、抗氧化物酶活性均显著上升,强抗寒品种抗氧化酶活性高于弱抗寒品种,电导率却相反;农杆菌介导侵染‘中双11号’下胚轴后获得15株转基因阳性苗,且转基因油菜阳性植株叶中的BrADS2基因表达量均显著高于野生型。【结论】推测BrADS2基因在白菜型冬油菜膜脂不饱和调节中起重要作用,揭示了ADS2基因与冬油菜抗低温胁迫的关系。

基于改进型多斜Ⅲ技术的7位半AD转换器设计

高精度测试仪器在环境试验中扮演着重要角色,而积分型AD转换器被广泛的应用在高精度测试仪器中。针对传统型积分型AD转换器转换速率较低的问题,提出了一种提高转换速率的改进型多斜ⅢAD转换器,详细的介绍了其原理和设计思路。该转换器以单片机与CPLD一同控制积分型ADC,在积分末尾利用单片机片内ADC测量积分器的残留电压,以达到提高转换速率的目的。经理论分析该AD转换器比传统型转换速率快836倍,分辨率可达到31位,在±10V直流电压测量中可实现7位半分辨率。

Flavonoids in safflower extract reduce cisplatin-induced damage to human follicle dermal papilla cells by inhibiting DNA damage and Rad17/Chk1/Cdc25C signaling

Background:Cisplatin is a chemotherapeutic agent commonly used clinically for the treatment of various human cancers.Patients often reduce the use of cisplatin due to its side effects,which in turn affects its treatment.This study explored the mechanism of action of safflower extract as an adjuvant traditional Chinese medicine for chemotherapy.Methods:Primary human follicle dermal papilla cells(HFDPCs)were used as target cells for cisplatininduced damage to hair cells.Western blotting was used to investigate the molecular targets of cisplatin and safflower extract in causing HFDPCs damage.Cell survival and cell cycle were analyzed by mitochondrial staining reagent WST-1 and propidium iodide.Results:Cisplatin could reduce the viability of HFDPCs without causing cell death.Cisplatin increased the level of phospho-Rad17 in HFDPCs and activated the Chk1/Cdc25C signaling to reduce the expression of Cdc2 protein,thereby arresting the cells in the G2/M phase.The combination of safflower extract and the flavonoids could effectively inhibit the signal transduction of Rad17/Chk1/Cdc25 in cisplatin-treated cells and reduce the cell population in the G2/M phase.Finally,we also confirmed that safflower extract could effectively inhibit the damage to HFDPCs caused by cisplatin,mainly at the level of reducing the DNA damage caused by cisplatin.Conclusions:Safflower extract can be used as an adjuvant Chinese medicine for chemotherapy to reduce the damage caused by chemotherapy to normal hair follicle cells.

基于FPGA与AD9786的调制解调电路的设计

谐振式光学陀螺因其高理论精度、小型化以及高稳定性受到了国内外的强烈关注。针对于谐振式光学陀螺检测信号微弱的特点,需要对该信号进行调制解调,以实现陀螺的稳定输出,设计了一种基于FPGA和AD9786的高精度模拟信号源,该信号以FPGA作为核心控制单元,AD9786作为数模转换器,实现16位的高精度DA转换,通过上位机实现指令的通信过程,可实现不同频率的交流信号。该实验结果表明,该系统符合陀螺测试系统调制解调要求,通过上位机对不同输出信号进行测试,且测试结果无纹波时输出噪声Vrms269μV,交流信号精度达到0.01%,最高频率可达到2M,稳定性高。

基于AD7616的16通道数据采集系统设计

针对传统数据采集系统因通道不足或数据量过大,无法满足多通道同步采集的问题,设计了一种基于AD7616的16通道数据采集系统。系统以Xilinx系列FPGA作为主控芯片,ADI公司的AD7616作为模数转换芯片,DDR3 SDRAM作为缓存单元。介绍了各个模块硬件的设计思路,重点介绍了FPGA控制AD7616模数转换模块、DDR3 SDRAM缓存模块的软件程序设计,并对系统的多通道采样功能、同步性能以及实际水下超声信号的采集能力进行了实验验证,结果表明,系统可以完成水下超声信号的多通道同步采集。

ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer

Objective Cisplatin(CDDP)-based chemotherapy is a first-line,drug regimen for muscle-invasive bladder cancer(BC)and metastatic bladder cancer.Clinically,resistance to CDDP restricts the clinical benefit of some bladder cancer patients.AT-rich interaction domain 1A(ARID1A)gene mutation occurs frequently in bladder cancer;however,the role of CDDP sensitivity in BC has not been studied.Methods We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology.IC50 determination,flow cytometry analysis of apoptosis,and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A.qRT-PCR,Western blotting,RNA interference,bioinformatic analysis,and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC.Results It was found that ARID1A inactivation was associated with CDDP resistance in BC cells.Mechanically,loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3(EIF4A3)through epigenetic regulation.Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399(circ0008399),a novel circular RNA(circRNA)identified in our previous study,which,to some extent,showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells.Importantly,EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP.Conclusion Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.

脉冲电流对轧辊用AD180高碳半钢材料力学性能及组织的影响

为分析电流处理对轧辊材料的影响规律,通过改变电流密度和处理时间来调整AD180高碳半钢的微观组织和力学性能。使用万能拉伸试验机对电流处理后的试样进行单轴拉伸实验,并对试样进行SEM断口截面分析和EBSD微观表征,研究其力学性能和微观组织的变化规律。拉伸结果表明,在电流密度11.88 A·mm-2、通电5 min时,试样的综合性能最好,屈服强度提高6.5%,抗拉强度提高12.1%,伸长率提高了25.4%。通过断口截面分析发现,拉伸试样均为脆性断裂,未通电试样存在大量孔洞缺陷,而合适的电流密度和通电时间可以促进试样内部孔洞缺陷的“愈合”,其中,电流密度为11.88 A·mm^(-2)、通电5 min时,试样断口上的缺陷最少。EBSD微观表征结果表明,脉冲电流使试样在较低温度下发生了再结晶,细化了晶粒。由此可见,脉冲电流可以改善试样内部的组织结构和治愈微缺陷,提高其综合力学性能。

基于动态离散模型的机场ADS-B攻击威胁影响研究

随着航空业信息技术的发展,空中交通管制系统面临着多种网络攻击的威胁。广播式自动相关监视(ADS-B)系统因其明文广播的数据传输方式,存在着被网络攻击的安全问题。依据“等待降落-降落-停泊-排队起飞-起飞”的航班运行全流程,建立了WLPQD动态离散模型,研究机场流量和航班延误。模型引入了系统冗余能力、处理速率等参数,模拟了攻击场景;通过受影响飞机数量和延误时间等指标研究了机场航班延误的传播影响。模型展示了ADS-B消息注入攻击对降落、起飞航班造成的延误,提出了两种攻击缓解方法。结果表明,延误规模的大小与攻击强度呈现正相关,且攻击对起飞航班的延误影响更大;提升对“幽灵飞机”和合法飞机的处理速率都可提升机场系统的抗毁性,但前者对提升机场系统冗余能力的效果更加显著。所做研究为机场系统抵御网络攻击、增强抗毁性提供了决策分析的参考依据。

Cisplatin-induced activation of TGF-βsignaling contributes to drug resistance

Growing evidence suggests an association between epithelial-mesenchymal transition(EMT),a hallmark of tumor malignancy,and chemoresistance to a number of anti-cancer drugs.However,the mechanism of EMT induction in the process of acquiring anti-cancer drug resistance remains unclear.To address this issue,we obtained a number of cisplatin-resistant clones from LoVo cells and found that almost all of them lost cell-cell contacts.In these clones,the epithelial marker E-cadherin was downregulated,whereas the mesenchymal marker N-cadherin was upregulated.Moreover,the expression of EMT-related transcription factors,including Slug,was elevated.On the other hand,the upregulation of other mesenchymal marker Vimentin was weak,suggesting that the mesenchymal-like phenotypic changes occurred in these cisplatin-resistant clones.These mesenchymal-like features of cisplatin-resistant clones were partially reversed to parental epithelial-like features by treatment with transforming growth factor-β(TGF-β)receptor kinase inhibitors,indicating that TGF-βsignaling is involved in cisplatin-induced the mesenchymallike phenotypic changes.Moreover,cisplatin was observed to enhance the secretion of TGF-βinto the culture media without influencing TGF-βgene transcription.These results suggest that cisplatin may induce the mesenchymal-like phenotypic changes by enhancing TGF-βsecretion,ultimately resulting in drug resistance.