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BET inhibitors enhance the anti-cancer effect of etoposide by suppressing the MrN-ATM axis in the dNA damage response

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Genes & diseases 2024年第1期11卷 19-22页

作者： Zhenhai Li Wenchao Xu Feng Chen Jun Zhang Wei-Guo Zhu Guangdong Key Laboratory of Genome Instability and Human disease Prevention Department of Biochemistry and Molecular BiologyShenzhen University School of MedicineShenzhenGuangdong 518055China School of Pharmaceutical Sciences Shenzhen University Health Science CenterShenzhenGuangdong 518055China Base for International Science and Technology Cooperation:Carson Cancer Stem Cell Vaccines r&d center International Cancer CenterShenzhen University Health Science CenterShenzhenGuangdong 518055China shenzhen Bay Laboratory Shenzhen University School of MedicineShenzhenGuangdong 518055China Marshall Laboratory of Biomedical Engineering Shenzhen University School of MedicineShenzhenGuangdong 518055China

Etoposide is widely used for cancer chemotherapy in the clinic.However,long-term etoposide treatment can lead to adverse effects or drug resistance.To improve the situation,we evaluated the therapeutic efficiency of etoposide combined with inhibitors of bromodomain and extraterminal(BET)family proteins,which have recently emerged as novel anti-cancer targets due to their critical roles in cancer development.Firstly,we showed Brd4,one of the main targets of BET inhibitors,was involved in dNA damage response(ddr)via the homologous recombination(Hr)repair pathway.

关键词： etoposide damage cancer

Three-channel CMOS transimpedance amplifier for LidAr sensor receiver

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Journal of Systems Engineering and Electronics 2024年第1期35卷 74-80页

作者： LIU ruqing ZHU Jingguo JIANG Yan LI Feng JIANG Chenghao MENG Zhe Photoelectric r&d center Academy of Opto-ElectronicsChinese Academy of SciencesBeijing 100094China

For time-of-flight(TOF)light detection and ranging(LidAr),a three-channel high-performance transimpedance amplifier(TIA)with high immunity to input load capacitance is presented.A regulated cascade(rGC)as the input stage is at the core of the complementary metal oxide semiconductor(CMOS)circuit chip,giving it more immunity to input photodiode detectors.A simple smart output interface acting as a feedback structure,which is rarely found in other designs,reduces the chip size and power consumption simultaneously.The circuit is designed using a 0.5μm CMOS process technology to achieve low cost.The device delivers a 33.87 dB?transimpedance gain at 350 MHz.With a higher input load capacitance,it shows a-3 dB bandwidth of 461 MHz,indicating a better detector tolerance at the front end of the system.Under a 3.3 V supply voltage,the device consumes 5.2 mW,and the total chip area with three channels is 402.8×597.0μm2(including the test pads).

关键词： transimpedance amplifier(TIA) three-channel regulated cascade(rGC) light detection and ranging(LidAr)

mtdNA-triggered pH response signal-amplified fluorescent probe for multiple cell discrimination

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Chinese Chemical Letters 2024年第3期35卷 363-368页

作者： Tianping Xia Yanxian Hou Zhuoran Xia Gengwen Chen Peichen Tang Jiangli Fan Xiaojun Peng State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical EngineeringDalian University of TechnologyDalian 116024China Hematology reagent r&d department Mindray Bio-medical Electronics Co.Ltd.Shenzhen 518132China research Institute of dalian University of Technology in shenzhen Shenzhen 518057China

developing fluorescence probes with multiple responses has vital significance but remains challenging.Herein,for the first time,we present a mitochondrial dNA(mtdNA)-triggered pH response signalamplified fluorescent probe(QCY-dBT)for multiple cell detection.The probe exhibited a large stokes shift(229 nm),excellent dNA selectivity over rNA,and ultrasensitivity of detection limit(dL;74.0 ng/mL).Thus,QCY-dBT was successfully applied to analyze multiple human peripheral blood cells and visualize mtdNA in healthy and apoptotic cells.In the tumor acidic environment(pH 6.0–7.0),the absorbance of QCY-dBT at 436 nm increased,and the fluorescence signal(665 nm)was amplified by mtdNA,which enabled the direct observation of tumor cells.Our study provides help in designing smart probes with multiple responses for efficient abnormal cell detection.

关键词： Fluorescence probe Mitochondrial dNA pH response Peripheral blood cells Multiple cell detection

Activation redistribution Based Hybrid Asymmetric Quantization Method of Neural Networks

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工程与科学中的计算机建模(英文) 2024年第1期138卷 981-1000页

作者： Lu Wei Zhong Ma Chaojie Yang r&d Innovation center Xi’an Microelectronics Technology InstituteXi’an710065China

The demand for adopting neural networks in resource-constrained embedded devices is continuously increasing.Quantization is one of the most promising solutions to reduce computational cost and memory storage on embedded devices.In order to reduce the complexity and overhead of deploying neural networks on Integeronly hardware,most current quantization methods use a symmetric quantization mapping strategy to quantize a floating-point neural network into an integer network.However,although symmetric quantization has the advantage of easier implementation,it is sub-optimal for cases where the range could be skewed and not symmetric.This often comes at the cost of lower accuracy.This paper proposed an activation redistribution-based hybrid asymmetric quantizationmethod for neural networks.The proposedmethod takes data distribution into consideration and can resolve the contradiction between the quantization accuracy and the ease of implementation,balance the trade-off between clipping range and quantization resolution,and thus improve the accuracy of the quantized neural network.The experimental results indicate that the accuracy of the proposed method is 2.02%and 5.52%higher than the traditional symmetric quantization method for classification and detection tasks,respectively.The proposed method paves the way for computationally intensive neural network models to be deployed on devices with limited computing resources.Codes will be available on https://***/ycjcy/Hybrid-Asymmetric-Quantization.

关键词： Quantization neural network hybrid asymmetric accuracy

LdAS&ET-Ad:Learnable distillation Attack Strategies and Evolvable Teachers Adversarial distillation

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Computers, Materials & Continua 2024年第5期79卷 2331-2359页

作者： Shuyi Li Hongchao Hu Xiaohan Yang Guozhen Cheng Wenyan Liu Wei Guo National digital Switching System Engineering&Technological r&d center The PLA Information Engineering UniversityZhengzhou450000China

Adversarial distillation(Ad)has emerged as a potential solution to tackle the challenging optimization problem of loss with hard labels in adversarial training.However,fixed sample-agnostic and student-egocentric attack strategies are unsuitable for distillation.Additionally,the reliability of guidance from static teachers diminishes as target models become more robust.This paper proposes an Ad method called Learnable distillation Attack Strategies and Evolvable Teachers Adversarial distillation(LdAS&ET-Ad).Firstly,a learnable distillation attack strategies generating mechanism is developed to automatically generate sample-dependent attack strategies tailored for distillation.A strategy model is introduced to produce attack strategies that enable adversarial examples(AEs)to be created in areas where the target model significantly diverges from the teachers by competing with the target model in minimizing or maximizing the Ad loss.Secondly,a teacher evolution strategy is introduced to enhance the reliability and effectiveness of knowledge in improving the generalization performance of the target model.By calculating the experimentally updated target model’s validation performance on both clean samples and AEs,the impact of distillation from each training sample and AE on the target model’s generalization and robustness abilities is assessed to serve as feedback to fine-tune standard and robust teachers accordingly.Experiments evaluate the performance of LdAS&ET-Ad against different adversarial attacks on the CIFAr-10 and CIFAr-100 datasets.The experimental results demonstrate that the proposed method achieves a robust precision of 45.39%and 42.63%against AutoAttack(AA)on the CIFAr-10 dataset for resNet-18 and MobileNet-V2,respectively,marking an improvement of 2.31%and 3.49%over the baseline method.In comparison to state-of-the-art adversarial defense techniques,our method surpasses Introspective Adversarial distillation,the top-performing method in terms of robustness under AA attack for the CIFAr-10 dataset,with

关键词： Adversarial training adversarial distillation learnable distillation attack strategies teacher evolution strategy

A new type of lipophilic hydrophobic self-repairing cellulose insulating paper developed with ST-110/FAS/PTFE ternary system as coating substrate

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High Voltage 2024年第2期9卷 474-483页

作者： Zhenglin Zeng Jinshan Qin Zuhao Wang Weimin Tan Chao Tang College of Engineering and Technology Southwest UniversityChongqingChina International r&d center for New Technologies of Smart Grid and Equipment ChongqingChina

The moisture generated by the ageing of the oil-paper insulating system can easily lead to the deterioration of the performance of the insulating paper.In order to alleviate the impact of moisture on the performance of the insulating paper,we developed a kind of lipophilic hydrophobic self-repairing cellulose insulating paper(new insulating paper)based on the ternary system of polytetrafluoroethylene,fluorocarbon surfactant and fluorinated alkyl silane,and accelerated thermal ageing test for 45 days at 130°C was carried out.The experimental results show that the new insulating paper with excellent lipophilic property can realise hydrophobic self-repairing through heat treatment after physical damage.The tensile strength and elongation at break of the new insulating paper increased by 5%–8%and 6.25%–27%respectively compared with the original cellulose insulating paper.At the end of ageing,the relative dielectric constant and dielectric loss factor of new insulating paper are 10.4%and 9.9%lower than that of the original cel-lulose insulating paper,while the breakdown voltage is 6.8%higher.The acid and moisture content produced during the ageing process of the insulating oil impregnated with new insulating paper are also less,indicating that the coating can delay the ageing of the insulating paper.

关键词： coating moisture cellulose

3-Epi-betulinic acid 3-O-β-d-glucopyranoside(eBAG)induces autophagy by activation of AMP-activated protein kinase in hepatocellular carcinoma

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Food Science and Human Wellness 2024年第3期13卷 1453-1464页

作者： Mengjie Liu Xuqiang Liu Kaiyue He Yongping Jian Yujia Li Jinrong Guo Jingyu Yang Zhixiang Xu Wenyi Kang School of Life Sciences Henan UniversityKaifeng 475004China National r&d center for Edible Fungus Processing Technology Henan UniversityKaifeng 475004China Joint International research Laboratory of Food&Medicine resource Function Kaifeng 475004China shenzhen research Institute of Henan University Shenzhen 518000China

3-Epi-betulinic acid 3-O-β-d-glucopyranoside(eBAG)is a pentacyclic triterpene mainly distributed in food and medicinal plants,which exhibits various pharmacological properties.However,whether these functions are attributed to eBAG or additional components in these plants remain unknown.Herein,we report that eBAG exerted an inhibitory activity against hepatocellular carcinoma and esophageal cancer cells.EBAG induced non-apoptotic cell death in hepatocellular carcinoma cells.The eBAG-induced cell death was inhibited by knock-down of autophagy related gene(ATG)5 and ATG7,by administration of 3-methyladenine,a selective autophagy inhibitor that suppresses phosphoinositide 3-kinase(PI3K),and by chloroquine,a classic autophagy flux inhibitor.We demonstrated that eBAG induced an autophagy-mediated cell death.Application of eBAG mimicked cellular bioenergetics depletion leading to the reduction of intracellular ATP,activation of AMP-activated protein kinase(AMPK),and inhibition of mTOr.Co-treatment with compound C,an AMPK inhibitor,abrogated cell death induced by eBAG.We further validated the anti-tumor effect of eBAG in the murine xenograft model of hepatocellular carcinoma and found that eBAG treatment promoted the induction of autophagy and reduction of tumor growth in mice.As a functional food ingredient,eBAG is a potential therapeutic agent for the treatment of hepatocellular carcinoma and esophageal cancer.

关键词： eBAG Autophagy ATP AMPK Hepatocellular carcinoma

development of rPA-Cas12a-fluorescence assay for rapid and reliable detection of human bocavirus 1

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Animal Models and Experimental Medicine 2024年第2期7卷 179-188页

作者： Weidong Qian Xuefei Wang Ting Wang Jie Huang Qian Zhang Yongdong Li Si Chen School of Food and Biological Engineering Shaanxi University of Science and TechnologyXi'anP.R.China department of dermatology Huazhong University of Science and Technology Union Shenzhen HospitalShenzhenP.R.China Ningbo Municipal center for disease Control and Prevention NingboP.R.China Medical College of shenzhen University ShenzhenP.R.China

Human bocavirus(HBoV)1 is considered an important pathogen that mainly affects infants aged 6–24 months,but preventing viral transmission in resource-limited regions through rapid and affordable on-site diagnosis of individuals with early infection of HBoV1 remains somewhat challenging.Herein,we present a novel faster,lower cost,reliable method for the detection of HBoV1,which integrates a recombinase polymerase amplification(rPA)assay with the CrISPr/Cas12a system,designated the rPA-Cas12a-fluorescence assay.The rPA-Cas12a-fluorescence system can specifically detect target gene levels as low as 0.5 copies of HBoV1 plasmid dNA per microliter within 40 min at 37℃without the need for sophisticated instruments.The method also demonstrates excellent specificity without cross-reactivity to non-target pathogens.Furthermore,the method was appraised using 28 clinical samples,and displayed high accuracy with positive and negative predictive agreement of 90.9%and 100%,respectively.Therefore,our proposed rapid and sensitive HBoV1 detection method,the rPA-Cas12a-fluorescence assay,shows promising potential for early on-site diagnosis of HBoV1 infection in the fields of public health and health care.The established rPA-Cas12a-fluorescence assay is rapid and reliable method for human bocavirus 1 detection.The rPA-Cas12a-fluorescence assay can be completed within 40 min with robust specificity and sensitivity of 0.5 copies/μl.

关键词： CrISPr-Cas12a detection human bocavirus 1 on-site diagnosis recombinase polymerase amplification

Combined Promoting Effects of Specific Organic Functional Groups and Alumina Surface Characteristics for the design of a Highly Efficient NiMo/Al_(2)O_(3) Hydrodesulfurization Catalyst

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China Petroleum Processing & Petrochemical Technology 2024年第1期26卷 1-11页

作者： Li Huifeng Li Mingfeng Zhang Le Wang Wei Nie Hong National Energy r&d center of Petroleum refining Technology SINOPEC Research Institute of Petroleum Processing Co.Ltd.Beijing 100083China

To prepare a highly efficient NiMo/Al_(2)O_(3) hydrodesulfurization catalyst,the combined effects of specific organic functional groups and alumina surface characteristics were investigated.First,the correlation between the surface characteristics of four different alumina and the existing Mo species states was established.It was found that the Mo equilibrium adsorption capacity can be used as a specific descriptor to quantitatively evaluate the changes in surface characteristics of different alumina.A lower Mo equilibrium adsorption capacity for alumina means weaker metal-support interaction and the loaded Mo species are easier to transform into MoS2.However,the Mo-O-Al bonds still exist at the metal-support interface.The introduction of cationic surfactant hecadecyl trimethyl ammonium bromide(CTAB)can further improve Mo species dispersion through electrostatic attraction with Mo anions and interaction of its alkyl chain with the alumina surface;meanwhile,the introduction of ethylenediamine tetraacetic acid(EdTA)can complex with Ni ions to enhance the Ni-promoting effect on Mo.Therefore,the NiMo catalyst designed using alumina with lower Mo equilibrium adsorption capacity and the simultaneous addition of EdTA and CTAB exhibits the highest hydrodesulfurization activity for 4,6-dimethyl dibenzothiophene because of its proper metal-support interaction and more well-dispersed Ni-Mo-S active phases.

关键词： alumina Mo equilibrium adsorption capacity organic functional groups metal-support interaction hydrodesulfurization