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  • Editorial
    Song Li, Lisa X. Xu
  • Review
    Jiayu Liao
    Med-X. 2023, 1(1): 13-13. https://doi.org/10.1007/s44258-023-00014-y

    Protein-protein interactions and enzyme-catalyzed reactions are the fundamental processes in life, and the quantification and manipulation, kinetics determination, and ether activation or inhibition of these processes are critical for fully understanding physiological processes and discovering new medicine. Various methodologies and technologies have been developed to determine the parameters of these biological and medical processes. However, due to the extreme complexity of these processes, current methods and technologies can only determine one or a few parameters. The recent development of quantitative Forster resonance energy transfer (qFRET) methodology combined with technology aims to establish a high-throughput assay platform to determine protein interaction affinity, enzymatic kinetics, high-throughput screening, and pharmacological parameters using one assay platform. The FRET assay is widely used in biological and biomedical research in vitro and in vivo and provides high-sensitivity measurement in real time. Extensive efforts have been made to develop the FRET assay into a quantitative assay to determine protein-protein interaction affinity and enzymatic kinetics in the past. However, the progress has been challenging due to complicated FRET signal analysis and translational hurdles. The recent qFRET analysis utilizes cross-wavelength correlation coefficiency to dissect the sensitized FRET signal from the total fluorescence signal, which then is used for various biochemical and pharmacological parameter determination, such as KD, Kcat, KM, Ki, IC50, and product inhibition kinetics parameters. The qFRET-based biochemical and pharmacological parameter assays and qFRET-based screenings are conducted in 384-well plates in a high-throughput assay mode. Therefore, the qFRET assay platform can provide a universal high-throughput assay platform for future large-scale protein characterizations and therapeutics development.

  • Research article
    Zhi Zhang, Han Wang, Lei Chen, Chensi Cao, Tengwen Liu, Ruifang Ren, Ruixing Zhou, Rudan Huang, Dan Hu, Chenxing Zhu, Chong Lu, Yunsheng Xu, Zhaohui Fang, Fuer Lu, Huimin Pan, Yanjin Su, Nanlin Fu, Huixia Zhan, Qin Si, Chenze Bai, Ri Le Ge, Hongmei Cao, Wei Dong, Guohui Yang, Lan Wu, Jiao Guo, Jing Cheng

    The global prevalence of diabetes is steadily increasing, with a high percentage of patients unaware of their disease status. Screening for diabetes is of great significance in preventive medicine and may benefit from deep learning technology. In traditional Chinese medicine, specific features on the ocular surface have been explored as diagnostic indicators for systemic diseases. Here we explore the feasibility of using features from the entire ocular surface to construct deep learning models for risk assessment and detection of type 2 diabetes (T2DM). We performed an observational, multicenter study using ophthalmic images of the ocular surface to develop a deep convolutional network, OcularSurfaceNet. The deep learning system was trained and validated with a multicenter dataset of 416580 images from 67151 participants and tested independently using an additional 91422 images from 12544 participants, and can be used to identify individuals at high risk of T2DM with areas under the receiver operating characteristic curve (AUROC) of 0.89-0.92 and T2DM with AUROC of 0.70-0.82. Our study demonstrated a qualitative relationship between ocular surface images and T2DM risk level, which provided new insights for the potential utility of ocular surface images in T2DM screening. Overall, our findings suggest that the deep learning framework using ocular surface images can serve as an opportunistic screening toolkit for noninvasive and low-cost large-scale screening of the general population in risk assessment and early identification of T2DM patients.

  • Review
    Kangfan Ji, Yuejun Yao, Xinwei Wei, Wei Liu, Juan Zhang, Yun Liu, Yang Zhang, Jinqiang Wang, Zhen Gu

    Frequent insulin injections remain the primary method for controlling the blood glucose level of individuals with diabetes mellitus but are associated with low compliance. Accordingly, oral administration has been identified as a highly desirable alternative due to its non-invasive nature. However, the harsh gastrointestinal environment and physical intestinal barriers pose significant challenges to achieving optimal pharmacological bioavailability of insulin. As a result, researchers have developed a range of materials to improve the efficiency of oral insulin delivery over the past few decades. In this review, we summarize the latest advances in material design that aim to enhance insulin protection, permeability, and glucoseresponsive release. We also explore the opportunities and challenges of using these materials for oral insulin delivery.

  • Correction
    Hector E. Muñoz, Jonathan Lin, Bonnie G. Yeh, Tridib Biswas, Dino Di Carlo
    Med-X. 2023, 1(1): 12-12. https://doi.org/10.1007/s44258-023-00012-0
  • Review
    Junyi Yin, Shaolei Wang, Aiden Di Carlo, Austin Chang, Xiao Wan, Jing Xu, Xiao Xiao, Jun Chen

    Merging electronics with textiles has become an emerging trend since textiles hold magnificent wearing comfort and userfriendliness compared with conventional wearable bioelectronics. Smart textiles can be effectively integrated into our daily wearing to convert on-body biomechanical, biochemical, and body heat energy into electrical signals for long-term, real-time monitoring of physiological states, showing compelling medical and economic benefits. This review summarizes the current progress in self-powered biomonitoring textiles along three pathways: biomechanical, body heat, and biochemical energy conversion. Finally, it also presents promising directions and challenges in the field, as well as insights into future development. This review aims to highlight the frontiers of smart textiles for self-powered biomonitoring, which could contribute to revolutionizing our traditional healthcare into a personalized model.

  • Research article
    Lingna Wang, Huicong Liu, Jiaqing Liu, Haitao Yuan, Chen Wu, Xiyang Li, Kaikai Xu, Jiang Hong, Guoyan Wu, Fangfang Zhu

    The Severe Acute Respiratory Syndrome (SARS)-CoV-2-induced Coronavirus Disease 2019 (COVID-19) pandemic has caused an overwhelming influence on public health because of its high morbidity and mortality. Critical-illness cases often manifest as acute respiratory distress syndrome (ARDS). Previous evidence has suggested platelets and thrombotic events as key mediators of SARS-CoV-2-associated ARDS. However, how the balance of platelet regeneration from the hematopoietic system is changed in ARDS remains elusive. Here, we reported a more severe inflammation condition and hyperactivity of platelets in COVID-19 ARDS patients compared with those infected but without ARDS. Analysis of peripheral blood revealed an increased proportion of hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), megakaryocyteerythrocyte progenitors (MEPs), and megakaryocyte progenitors (MkPs) in ARDS patients, suggesting a megakaryocytic-differentiation tendency. Finally, we found altered gene expression pattern in HSCs in COVID-19 ARDS patients. Surprisingly, genes representing platelet-primed HSCs were downregulated, indicating these cells are being stimulated to differentiate. Taken together, our findings shed light on the response of the hematopoietic system to replenish platelets that were excessively consumed in COVID-19 ARDS, providing a mechanism for disease progression and further therapeutic development.

  • Research article
    Li Lin, Haoqi He, Ruiyang Xue, Yumin Zhang, Ziwen Wang, Shuming Nie, Jian Ye

    Optical imaging and spectroscopic modalities are of broad interest for in-vivo molecular imaging, fluorescence guided cancer surgery, minimally invasive diagnostic procedures, and wearable devices. However, considerable debate still exists as to how deeply visible and near-infrared (NIR) light could penetrate normal and diseased tissues under clinically relevant conditions. Here we report the use of surface-enhanced Raman scattering (SERS) nanotags embedded in ex-vivo animal tissues for direct and quantitative measurements of light attenuation and spectroscopic detection depth at both the NIR-I and NIR-II spectral windows. SERS nanotags are well suited for this purpose because of their sharp spectral features that can be accurately differentiated from fluorescence and background emission. For the first time, the spectroscopic detection depth is quantitatively defined and measured as the maximal thickness of tissues through which the embedded SERS nanotags are still detected at a signal-to-noise ratio (SNR) of three (99.7% confidence level). Based on data from six types of fresh ex-vivo tissues (brain, kidney, liver, muscle, fat, and skin), we find that the maximum detection depth values range from 1—3 mm in the NIR-I window, to 3—6 mm in the NIR-II window. The depth values are largely determined by two factors - the intrinsic optical properties of the tissue, and the overall SNRs of the system without the tissue (system SNR, a result of nanotag brightness, instrument efficiency, and data acquisition parameters). In particular, there is an approximately linearlogarithmic relationship between the system SNR and maximum detection depth. Thus, the detection of hidden or occult lesions can be improved by three strategies - reducing tissue attenuation, minimizing background noise, and maximizing the system’s performance as judged by SNR.

  • Review
    Kimberly Seaman, Yu Sun, Lidan You
    Med-X. 2023, 1(1): 11-11. https://doi.org/10.1007/s44258-023-00011-1

    Three-dimensional cancer-on-a-chip tissue models aim to replicate the key hallmarks of the tumour microenvironment and allow for the study of dynamic interactions that occur during tumour progression. Recently, complex cancer-on-a-chip models incorporating multiple cell types and biomimetic extracellular matrices have been developed. These models have generated new research directions in engineering and medicine by allowing for the real-time observation of cancer-host cell interactions in a physiologically relevant microenvironment. However, these cancer-on-a-chip models have yet to overcome limitations including the complexity of device manufacturing, the selection of optimal materials for preclinical drug screening studies, long-term microfluidic cell culture as well as associated challenges, and the technical robustness or difficulty in the use of these microfluidic platforms. In this review, an overview of the tumour microenvironment, its unique characteristics, and the recent advances of cancer-on-a-chip models that recapitulate native features of the tumour microenvironment are presented. The current challenges that cancer-on-a-chip models face and the future directions of research that are expected to be seen are also discussed.

  • Review
    Jia-peng Wu, Jie Yu, J. Brian Fowlkes, Ping Liang, Christian Pállson Nolsøe

    Ablation under ultrasound (US) guidance for the treatment of various tumors in liver, thyroid, prostate, kidney, uterine and many other organs evolved extensively in the past decades. Major ablative techniques, including radiofrequency ablation, microwave ablation, high intensity focused ultrasound, cryoablation, percutaneous ethanol injection, laser ablation and irreversible electroporation, have all been widely applied and ablation is recommended by several guidelines as first-line or alternative therapy e.g. hepatocellular carcinoma in early stage, T1a stage renal cell carcinoma and thyroid nodules. In the current article, we reviewed 2508 articles on tumor ablation under US guidance and present the status of US-guided tumor ablation globally.

  • Review
    Ruosen Xie, Yuyuan Wang, Jacobus C. Burger, Dongdong Li, Min Zhu, Shaoqin Gong

    The success of brain-targeted gene therapy and therapeutic genome editing hinges on the efficient delivery of biologics bypassing the blood-brain barrier (BBB), which presents a significant challenge in the development of treatments for central nervous system disorders. This is particularly the case for nucleic acids and genome editors that are naturally excluded by the BBB and have poor chemical stability in the bloodstream and poor cellular uptake capability, thereby requiring judiciously designed nanovectors administered systemically for intracellular delivery to brain cells such as neurons. To overcome this obstacle, various strategies for bypassing the BBB have been developed in recent years to deliver biologics to the brain via intravenous administration using non-viral vectors. This review summarizes various brain targeting strategies and recent representative reports on brain-targeted non-viral delivery systems that allow gene therapy and therapeutic genome editing via intravenous administration, and highlights ongoing challenges and future perspectives for systemic delivery of biologics to the brain via non-viral vectors.

  • Review
    Shaoping Huang, Chuqian Lou, Ying Zhou, Zhao He, Xuejun Jin, Yuan Feng, Anzhu Gao, Guang-Zhong Yang

    Magnetic Resonance Imaging (MRI) is now a widely used modality for providing multimodal, high-quality soft tissue contrast images with good spatiotemporal resolution but without subjecting patients to ionizing radiation. In addition to its diagnostic potential, its future theranostic value lies in its ability to provide MRI-guided robot intervention with combined structural and functional mapping, as well as integrated instrument localization, target recognition, and in situ, in vivo monitoring of the therapeutic efficacy. Areas of current applications include neurosurgery, breast biopsy, cardiovascular intervention, prostate biopsy and radiotherapy. Emerging applications in targeted drug delivery and MRI-guided chemoembolization are also being pursued. Whilst promising progress has been made in recent years, there are still significant basic science research and engineering challenges. This paper provides a comprehensive review of the current state-of-the-art in MRI-guided robot intervention and allied technologies in actuation, sensing, new materials, interventional instruments, and interactive/real-time MRI. Potential future research directions and new clinical developments are also discussed.