Construction of human monoclonal single-chain Fv antibodies against small-cell lung cancer by phage display libraries derived from cell-immunized SCID mice engrafted with human peripheral blood lymphocytes

In this study, we describe a phage display strategy to obtain human monoclonal single-chain Fv (scFv) antibodies binding target cancer cell surface proteins. By developing a cancer cell immunization protocol for SCID mice engrafted with human peripheral blood lymphocytes in combination with an antibody phage display method, we have isolated phage antibodies binding small-cell lung cancer cell line H889 by subtractive selection. One of the isolated scFv antibodies, 12EAb, recognized the E2 component of pyruvate dehydrogenase complex (PDC-E2) by immunoprecipitation according to MALDI-TOF MS analysis. Furthermore, we have confirmed the plasma membrane localization of PDC-E2 in small-cell lung cancer cells by immunocytochemistry and cell surface protein biotinylation, although PDC-E2 is usually located in the mitochondrial matrix. These results, including unique localization of identified antigens, were obtained by proteomic approaches. The present methods can be applied to generate human monoclonal scFv antibodies against tumor cells and to identify new molecular targets for immunotherapy and markers for diagnosis.     

A novel method for three-dimensional observation of the vascular networks in the whole mouse brain

A novel method for acquiring serial images suitable for three-dimensional reconstruction of vascular networks in the whole brain of mouse was developed. The brain infused with a White India ink-gelatin solution was fixed and embedded in paraffin containing Sudan Black B through xylene also containing Sudan Black B. Each sliced surface of the paraffin block was coated with liquid paraffin and its image was serially acquired. Coating with liquid paraffin extremely improved the quality of the image. The series of serial images was free of distortion and a three-dimensional image was reconstructed without the problem of the alignment and registration of adjacent images. The volume-rendered image indicated three-dimensional distribution of blood vessels in a whole brain. No ghost or shadow was observed on a volume-rendered image of the White India ink-gelatin infused brain. The z-axial resolution examined on the orthogonal sections reconstituted from serial images obtained at an interval of 5 mum showed no cross talk, indicating that the z-axial resolution was no larger than 5 mum. A proper understanding of the vascular system in a whole brain is indispensable to reveal the development of the vascular system in the brain of normal and genetically manipulated mouse and vascular alterations in pathological situation, such as stroke and neurodegenerative disease. Although simple and inexpensive, this method will provide fundamental information on the vascular system in a whole brain.     

基于整体退火遗传算法的低功耗最佳极性搜索

针对n变量逻辑函数在不同极性下所对应的XNOR/OR电路功耗和面积不同的特点,首先用信号概率传递算法和多输入XNOR/OR(同或/或)门的低功耗分解算法建立了XNOR/OR电路的功耗估计模型.在此基础上,将基于列表技术的极性转换算法和整体退火遗传算法相结合,提出了一种针对大规模XNOR/OR电路的低功耗最佳极性搜索算法.对8个较大规模MCNC Benchmark电路测试表明,该算法搜索到的最佳极性所对应的XNOR/OR电路与极性0时的XNOR/OR电路相比,平均节省功耗和面积分别达到了84.4%和65.2%.     

Promote Intratumoral Drug Release and Penetration to Counteract Docetaxel-Induced Metastasis by Photosensitizer-Modified Red Blood Cell Membrane-Coated Nanoparticle

The red blood cell membrane (RBCm) provides tight protection, lowers the immunogenicity, and prolongs the circulation time of drugs in vivo when acting as the coating of drug delivery systems. However, the cellular uptake and release of drugs are hindered by RBCm. Docetaxel (DTX) is the first-line medicine for treating triple-negative breast cancer (TNBC), but it induces tumor metastasis. To solve these dilemmas, in this study, the photosensitizer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-modified RBCm (DM) is prepared, which is coated onto a hybrid micelle consisting of the prodrugs of DTX and the anti-metastasis agent calcitriol (CTL), obtaining a nanoparticle, named HDC-DM. In a 4T1 tumor-bearing mouse model, after injecting HDC-DM, the intratumoral DTX and CTL concentrations are increased by 1.7 and 2.5 times compared with the free drug groups. After irradiating tumors with near-infrared laser, DiR elicits the photothermal effect, triggering the rupture of RBCm and drug release, promoting drug penetration in tumors, and inducing immunogenic cell death. The tumor growth inhibition rate is 77%, and the formation of lung metastases is reduced by 82%, with good biocompatibility. It is suggested that the combination of phototherapy, chemotherapy, and anti-metastatic therapy using HDC-DM is expected to be a powerful strategy for treating TNBC.     

Design of Online Vitals Monitor by Integrating Big Data and IoT

In this work, we design a multisensory IoT-based online vitals monitor (hereinafter referred to as the VITALS) to sense four bedside physiological parameters including pulse (heart) rate, body temperature, blood pressure, and peripheral oxygen saturation. Then, the proposed system constantly transfers these signals to the analytics system which aids in enhancing diagnostics at an earlier stage as well as monitoring after recovery. The core hardware of the VITALS includes commercial off-the-shelf sensing devices/medical equipment, a powerful microcontroller, a reliable wireless communication module, and a big data analytics system. It extracts human vital signs in a pre-programmed interval of 30 min and sends them to big data analytics system through the WiFi module for further analysis. We use Apache Kafka (to gather live data streams from connected sensors), Apache Spark (to categorize the patient vitals and notify the medical professionals while identifying abnormalities in physiological parameters), Hadoop Distributed File System (HDFS) (to archive data streams for further analysis and long-term storage), Spark SQL, Hive and Matplotlib (to support caregivers to access/visualize appropriate information from collected data streams and to explore/understand the health status of the individuals). In addition, we develop a mobile application to send statistical graphs to doctors and patients to enable them to monitor health conditions remotely. Our proposed system is implemented on three patients for 7 days to check the effectiveness of sensing, data processing, and data transmission mechanisms. To validate the system accuracy, we compare the data values collected from established sensors with the measured readouts using a commercial healthcare monitor, the Welch Allyn® Spot Check. Our proposed system provides improved care solutions, especially for those whose access to care services is limited.     

基于深度学习的心脏图像分割研究现状

面对严重的医学影像分析缺口,深度学习的发展能够满足国内医疗行业的需求。心脏图像的处理方法可大致分为传统的图像处理技术、基于图谱的方法（atlas-based methods）、基于模型的方法（model-based methods）以及目前热门的采用机器学习和深度学习的方法。在深度学习兴起之前,传统的机器学习技术如模型法和图集法在心脏图像分割中有良好表现,但通常需要大量的特征工程知识或先验知识才能获得令人满意的精度。而基于深度学习的算法能从数据中自动发现复杂的特征以进行对象检测和分割。得益于先进的计算机硬件以及更多可用于训练的数据集,基于深度学习的分割算法已超越了以往的传统方法。本文回顾了2012—2022年有关心室、心外膜和心包脂肪的图像处理的各项方法、衡量指标及其目前的研究现状,并结合分割技术的发展,讨论了心脏分割的发展趋势。     

Drug self-assembly: A phenomenon at the nanometer scale with major impact in the structure–biological properties relationship and the treatment of disease

Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed.     

Non-Contact Physiological Measurement System for Wearing Masks During the Epidemic

Physiological signals indicate a person’s physical and mental state at any given time. Accordingly, many studies extract physiological signals from the human body with non-contact methods, and most of them require facial feature points. However, under COVID-19, wearing a mask has become a must in many places, so how non-contact physiological information measurements can still be performed correctly even when a mask covers the facial information has become a focus of research. In this study, RGB and thermal infrared cameras were used to execute non-contact physiological information measurement systems for heart rate, blood pressure, respiratory rate, and forehead temperature for people wearing masks due to the pandemic. Using the green (G) minus red (R) signal in the RGB image, the region of interest (ROI) is established in the forehead and nose bridge regions. The photoplethysmography (PPG) waveforms of the two regions are obtained after the acquired PPG signal is subjected to the optical flow method, baseline drift calibration, normalization, and bandpass filtering. The relevant parameters in Deep Neural Networks (DNN) for the regression model can correctly predict the heartbeat and blood pressure. In addition, the temperature change in the ROI of the mask after thermal image processing and filtering can be used to correctly determine the number of breaths. Meanwhile, the thermal image can be used to read the temperature average of the ROI of the forehead, and the forehead temperature can be obtained smoothly. The experimental results show that the above-mentioned physiological signals of a subject can be obtained in 6-s images with the error for both heart rate and blood pressure within 2%~3% and the error of forehead temperature within ±0.5°C.