Targeting VEGFR-1 and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy

Increasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.published_or_final_versio

Local Implicit Normalizing Flow for Arbitrary-Scale Image Super-Resolution

Flow-based methods have demonstrated promising results in addressing the ill-posed nature of super-resolution (SR) by learning the distribution of high-resolution (HR) images with the normalizing flow. However, these methods can only perform a predefined fixed-scale SR, limiting their potential in real-world applications. Meanwhile, arbitrary-scale SR has gained more attention and achieved great progress. Nonetheless, previous arbitrary-scale SR methods ignore the ill-posed problem and train the model with per-pixel L1 loss, leading to blurry SR outputs. In this work, we propose "Local Implicit Normalizing Flow" (LINF) as a unified solution to the above problems. LINF models the distribution of texture details under different scaling factors with normalizing flow. Thus, LINF can generate photo-realistic HR images with rich texture details in arbitrary scale factors. We evaluate LINF with extensive experiments and show that LINF achieves the state-of-the-art perceptual quality compared with prior arbitrary-scale SR methods.Comment: CVPR 2023 camera-ready versio

ECG Signal Super-resolution by Considering Reconstruction and Cardiac Arrhythmias Classification Loss

With recent advances in deep learning algorithms, computer-assisted healthcare services have rapidly grown, especially for those that combine with mobile devices. Such a combination enables wearable and portable services for continuous measurements and facilitates real-time disease alarm based on physiological signals, e.g., cardiac arrhythmias (CAs) from electrocardiography (ECG). However, long-term and continuous monitoring confronts challenges arising from limitations of batteries, and the transmission bandwidth of devices. Therefore, identifying an effective way to improve ECG data transmission and storage efficiency has become an emerging topic. In this study, we proposed a deep-learning-based ECG signal super-resolution framework (termed ESRNet) to recover compressed ECG signals by considering the joint effect of signal reconstruction and CA classification accuracies. In our experiments, we downsampled the ECG signals from the CPSC 2018 dataset and subsequently evaluated the super-resolution performance by both reconstruction errors and classification accuracies. Experimental results showed that the proposed ESRNet framework can well reconstruct ECG signals from the 10-times compressed ones. Moreover, approximately half of the CA recognition accuracies were maintained within the ECG signals recovered by the ESRNet. The promising results confirm that the proposed ESRNet framework can be suitably used as a front-end process to reconstruct compressed ECG signals in real-world CA recognition scenarios

Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP) in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel) of the tumor and muscle (at the symmetric site) was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV) for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis

Gender- and Age-Specific Associations between Visceral Obesity and Renal Function Impairment

Objective: Although obesity is associated with an increased risk of chronic kidney disease, this trend becomes nonsignificant following adjustment for cardiovascular risk factors. The present study aims to investigate whether visceral obesity is independently associated with renal function impairment. Method: The medical records of 14,529 male and 10,561 female Chinese adults undergoing health check-ups during 2013–2015 were retrospectively collected. The baseline characteristics, including the degree of visceral fat and the percentage of body fat, were compared. The association between study groups and renal function impairment was investigated using regression models adjusted for confounding factors. Results: All variables differed significantly among non-obese, peripheral, and central type obese subjects, both younger and older, and of both genders, except for hsCRP in older male subjects (p = 0.053) and eGFR in older female subjects (p = 0.098). Unadjusted univariate analysis showed that central obesity contributed significantly to renal function impairment in all age groups and in both genders. After adjusting for possible confounding factors, only central obesity was found to be an independent factor of renal function impairment in all groups, except for men under 45 years of age. Conclusion: Visceral obesity is independently associated with renal function impairment in all ages and both genders, except for males younger than 45 years

Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression

Background: One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibit or delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities. Methods: In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR. Results: The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G2/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1. Conclusion: Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality. © 2012 Elsevier Ltd

Flexible Temperature Sensor Array Based on a Graphite-Polydimethylsiloxane Composite

This paper presents a novel method to fabricate temperature sensor arrays by dispensing a graphite-polydimethylsiloxane composite on flexible polyimide films. The fabricated temperature sensor array has 64 sensing cells in a 4 × 4 cm2 area. The sensor array can be used as humanoid artificial skin for sensation system of robots. Interdigitated copper electrodes were patterned on the flexible polyimide substrate for determining the resistivity change of the composites subjected to ambient temperature variations. Polydimethylsiloxane was used as the matrix. Composites of different graphite volume fractions for large dynamic range from 30 °C to 110 °C have been investigated. Our experiments showed that graphite powder provided the composite high temperature sensitivity. The fabricated temperature sensor array has been tested. The detected temperature contours are in good agreement with the shapes and magnitudes of different heat sources

AV-SUPERB: A Multi-Task Evaluation Benchmark for Audio-Visual Representation Models

Audio-visual representation learning aims to develop systems with human-like perception by utilizing correlation between auditory and visual information. However, current models often focus on a limited set of tasks, and generalization abilities of learned representations are unclear. To this end, we propose the AV-SUPERB benchmark that enables general-purpose evaluation of unimodal audio/visual and bimodal fusion representations on 7 datasets covering 5 audio-visual tasks in speech and audio processing. We evaluate 5 recent self-supervised models and show that none of these models generalize to all tasks, emphasizing the need for future study on improving universal model performance. In addition, we show that representations may be improved with intermediate-task fine-tuning and audio event classification with AudioSet serves as a strong intermediate task. We release our benchmark with evaluation code and a model submission platform to encourage further research in audio-visual learning.Comment: Submitted to ICASSP 2024; Evaluation Code: https://github.com/roger-tseng/av-superb Submission Platform: https://av.superbbenchmark.or

Systematic microcarrier screening and agitated culture conditions improves human mesenchymal stem cell yield in bioreactors

Production of human mesenchymal stem cells for allogeneic cell therapies requires scalable, cost-effective manufacturing processes. Microcarriers enable the culture of anchorage-dependent cells in stirred-tank bioreactors. However, no robust, transferable methodology for microcarrier selection exists, with studies providing little or no reason explaining why a microcarrier was employed. We systematically evaluated 13 microcarriers for human bone marrow-derived MSC (hBM-MSCs) expansion from three donors to establish a reproducible and transferable methodology for microcarrier selection. Monolayer studies demonstrated input cell line variability with respect to growth kinetics and metabolite flux. HBM-MSC1 underwent more cumulative population doublings over three passages in comparison to hBM-MSC2 and hBM-MSC3. In 100 mL spinner flasks, agitated conditions were significantly better than static conditions, irrespective of donor, and relative microcarrier performance was identical where the same microcarriers outperformed others with respect to growth kinetics and metabolite flux. Relative growth kinetics between donor cells on the microcarriers were the same as the monolayer study. Plastic microcarriers were selected as the optimal microcarrier for hBM-MSC expansion. HBM-MSCs were successfully harvested and characterised, demonstrating hBM-MSC immunophenotype and differentiation capacity. This approach provides a systematic method for microcarrier selection, and the findings identify potentially significant bioprocessing implications for microcarrier-based allogeneic cell therapy manufacture. Large-scale production of human bone-marrow derived mesenchymal stem cells (hBM-MSCs) requires expansion on microcarriers in agitated systems. This study demonstrates the importance of microcarrier selection and presents a systematic methodology for selection of an optimal microcarrier. The study also highlights the impact of an agitated culture environment in comparison to a static system, resulting in a significantly higher hBM-MSC yield under agitated conditions