Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene.

There has been considerable debate as to whether obesity can act as an accelerator of type 1 diabetes (T1D). We assessed this possibility using transgenic mice (MIP-TF mice) whose ß-cells express enhanced green fluorescent protein (EGFP). Infecting these mice with EGFP-expressing murine herpes virus-68 (MHV68-EGFP) caused occasional transient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not spread to other ß-cell antigens. We hypothesized that obesity-related systemic inflammation and ß-cell stress could exacerbate the MHV68-EGFP-induced ß-cell autoreactivity. We crossed MIP-TF mice with Avy mice which develop obesity and provide models of metabolic disease alongside early stage T2D. Unlike their MIP-TF littermates, MHV68-EGFP-infected Avy/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia. MHV68-EGFP infection induced a more pronounced intra-insulitis in older, more obese, Avy/MIP-TF mice. Moreover, in MHV68-EGFP-infected Avy/MIP-TF mice, Th1 reactivity spread from EGFP to other ß-cell antigens. Thus, the spreading of autoreactivity among ß-cell antigens corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese Avy/MIP-TF mice but not lean MIP-TF mice. These observations are consistent with the notion that obesity-associated systemic inflammation and ß-cell stress lowers the threshold necessary for T cell autoreactivity to spread from EGFP to other ß-cell autoantigens

A note on eigenvalues of random block Toeplitz matrices with slowly growing bandwidth

This paper can be thought of as a remark of \cite{llw}, where the authors studied the eigenvalue distribution $\mu_{X_N}$ of random block Toeplitz band matrices with given block order $m$. In this note we will give explicit density functions of $\lim\limits_{N\to\infty}\mu_{X_N}$ when the bandwidth grows slowly. In fact, these densities are exactly the normalized one-point correlation functions of $m\times m$ Gaussian unitary ensemble (GUE for short). The series $\{\lim\limits_{N\to\infty}\mu_{X_N}|m\in\mathbb{N}\}$ can be seen as a transition from the standard normal distribution to semicircle distribution. We also show a similar relationship between GOE and block Toeplitz band matrices with symmetric blocks.Comment: 6 page

Human-centred artificial intelligence for mobile health sensing:challenges and opportunities

Advances in wearable sensing and mobile computing have enabled the collection of health and well-being data outside of traditional laboratory and hospital settings, paving the way for a new era of mobile health. Meanwhile, artificial intelligence (AI) has made significant strides in various domains, demonstrating its potential to revolutionize healthcare. Devices can now diagnose diseases, predict heart irregularities and unlock the full potential of human cognition. However, the application of machine learning (ML) to mobile health sensing poses unique challenges due to noisy sensor measurements, high-dimensional data, sparse and irregular time series, heterogeneity in data, privacy concerns and resource constraints. Despite the recognition of the value of mobile sensing, leveraging these datasets has lagged behind other areas of ML. Furthermore, obtaining quality annotations and ground truth for such data is often expensive or impractical. While recent large-scale longitudinal studies have shown promise in leveraging wearable sensor data for health monitoring and prediction, they also introduce new challenges for data modelling. This paper explores the challenges and opportunities of human-centred AI for mobile health, focusing on key sensing modalities such as audio, location and activity tracking. We discuss the limitations of current approaches and propose potential solutions

Motion-resilient Heart Rate Monitoring with In-ear Microphones

With the soaring adoption of in-ear wearables, the research community has started investigating suitable in-ear heart rate (HR) detection systems. HR is a key physiological marker of cardiovascular health and physical fitness. Continuous and reliable HR monitoring with wearable devices has therefore gained increasing attention in recent years. Existing HR detection systems in wearables mainly rely on photoplethysmography (PPG) sensors, however, these are notorious for poor performance in the presence of human motion. In this work, leveraging the occlusion effect that can enhance low-frequency bone-conducted sounds in the ear canal, we investigate for the first time \textit{in-ear audio-based motion-resilient} HR monitoring. We first collected the HR-induced sound in the ear canal leveraging an in-ear microphone under stationary and three different activities (i.e., walking, running, and speaking). Then, we devise a novel deep learning based motion artefact (MA) mitigation framework to denoise the in-ear audio signals, followed by an HR estimation algorithm to extract HR. With data collected from 20 subjects over four activities, we demonstrate that hEARt, our end-to-end approach, achieves a mean absolute error (MAE) of 5.46$\pm$6.50BPM, 12.34$\pm$9.24BPM, 14.22$\pm$10.69BPM and 15.44$\pm$11.43BPM for stationary, walking, running and speaking, respectively, opening the door to a new non-invasive and affordable HR monitoring with usable performance for daily activities. Not only does the performance hEARt outperform that of previous in-ear HR monitoring work, but is comparable (and even better whenever full-body motion is concerned) to that reported by in-ear PPG works

IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3-Dependent Mechanisms

Psoriasis, an immunological skin disease, is characterized by epidermal hyperproliferation, chronic inflammation, and an accumulation of infiltrating T cells. IL-17A is a key cytokine that has a critical role in the pathogenesis of psoriasis. Keratin 17 (K17) is strongly expressed in psoriatic lesions but not in normal skin. Thus, K17 expression is regarded as a hallmark of psoriasis. We previously reported that the K17/T cells/cytokine autoimmune loop was involved in psoriasis. However, the relationship between IL-17A and K17 has yet to be determined. In the present study, IL-17A-induced K17 expression was confirmed in cultured keratinocytes in both mRNA and protein levels. In addition, increased K17 expression was found in the epidermis of IL-17A-injected mouse skin. The regulatory mechanism of K17 expression was further investigated. We found that both the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways were involved in the upregulation of K17 expression induced by IL-17A, and that such regulation could be partially suppressed by STAT1 or STAT3 small interfering RNA and inhibitor. Our data suggest that IL-17A can upregulate K17 expression in keratinocytes in a dose-dependent manner through STAT1- and STAT3-dependent mechanisms. The results indicate that IL-17A might be an important cytokine in the K17/T cells/cytokine autoimmune loop associated with psoriasis

Drug Abuse, Relapse, and Prevention Education in Malaysia: Perspective of University Students Through a Mixed Methods Approach

In recent years, there have been increasing accounts of illegal substance abuse among university students and professional groups in Malaysia. This study looks at university students’ perceptions about this phenomenon. Students from Malaysian universities were asked for their impressions about drug availability and abuse, as well as factors contributing to drug abuse and relapse. The questionnaire also inquired into their knowledge and views regarding government versus private rehabilitation centres, as well as their exposure to, and views about, school-based drug-prevention education. Participants were 460 university students from five Malaysian states: Penang, Selangor, Kuala Lumpur, Sabah, and Sarawak. Results showed gender differences in perceptions of relapse prevention strategies, as well as factors leading to drug abuse and relapse. Students also believed that drug education would be more effective if initiated between the ages of 11 to 12 years, which is slightly older than the common age of first exposure, and provided suggestions for improving existing programs. Implications of student perceptions for the improvement of current interventions and educational programs are discussed

Studies on the protective effect of total flavonoids from Cichorium glandulosum roots against carbon tetrachloride-induced liver fibrosis in rats

Purpose: To study the protective influence of total flavonoids from Cichorium glandulosum roots (TFCG) against carbon tetrachloride-mediated hepatic fibrosis in rats, and the probable mechanism of action involved.Methods: Rats with liver fibrosis were orally administered TFCG (50, 100 or 200 mg/kg) once a day for 13 weeks. Liver index and liver injury indices in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), γ-glutamyl transpeptidase (γ-GT), hydroxyproline (HYP), albumin (ALB) and malondialdehyde (MDA) were determined using electronic balance or corresponding assay kits, as appropriate. Following staining with hematoxylin and eosin and Van Gieson, histopathological changes in liver tissues were examined by light microscopy. TGF-β/Smad pathway-related protein expressions in liver tissues, viz, transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3), Smad7, toll-like receptor 4 (TLR4) and α-smooth muscle actin (α-SMA) were determined using immunohistochemical techniques.Results: Exposure to TFCG significantly reversed abnormal serum levels of ALT, AST, AKP, LDH, γ- GT, HYP, ALB and MDA rats with liver fibrosis to normal levels, and also decreased their liver index values (p < 0.01). Moreover, TFCG improved histopathological changes in the liver tissues of fibrotic rats, and significantly reversed abnormal TGF-β1, Smad3, Smad7, TLR4 and α-SMA protein expressions in the liver tissues of fibrotic rats to normal levels (p < 0.05 or 0.01).Conclusion: These results indicate that TFCG exerts protective effect against liver fibrosis via a mechanism related to inactivation of TGF-β/Smad pathway. Thus, TFCG may find application in liver fibrosis therapy.Keywords: Cichorium glandulosum, Flavonoids, Liver, Fibrosis, TGF-β/Smad pathwa

Assessment of mitochondrial dysfunction and implications in cardiovascular disorders

Mitochondria play a pivotal role in cellular function, not only acting as the powerhouse of the cell, but also regulating ATP synthesis, reactive oxygen species (ROS) production, intracellular Ca2+ cycling, and apoptosis. During the past decade, extensive progress has been made in the technology to assess mitochondrial functions and accumulating evidences have shown that mitochondrial dysfunction is a key pathophysiological mechanism for many diseases including cardiovascular disorders, such as ischemic heart disease, cardiomyopathy, hypertension, atherosclerosis, and hemorrhagic shock. The advances in methodology have been accelerating our understanding of mitochondrial molecular structure and function, biogenesis and ROS and energy production, which facilitates new drug target identification and therapeutic strategy development for mitochondrial dysfunction-related disorders. This review will focus on the assessment of methodologies currently used for mitochondrial research and discuss their advantages, limitations and the implications of mitochondrial dysfunction in cardiovascular disorders

Contact-dependent carcinoma aggregate dispersion by M2a macrophages via ICAM-1 and β2 integrin interactions

Tumor-associated macrophages (TAMs) can constitute up to 50% of the tumor mass and have strong implications in tumor progression and metastasis. Macrophages are plastic and can polarize to various subtypes that differ in terms of surface receptor expression as well as cytokine and chemokine production and effector function. Conventionally, macrophages are grouped into two major subtypes: the classically activated M1 macrophages and the alternatively activated M2 macrophages. M1 macrophages are pro-inflammatory, promote T helper (Th) 1 responses, and show tumoricidal activity, whereas M2 macrophages contribute to tissue repair and promote Th2 responses. Herein, we present a microfluidic system integrating tumor cell aggregates and subtypes of human monocyte-derived macrophages in a three-dimensional hydrogel scaffold, in close co-culture with an endothelial monolayer to create an in vitro tumor microenvironment. This platform was utilized to study the role of individual subtypes of macrophages (M0, M1, M2a, M2b and M2c) in human lung adenocarcinoma (A549) aggregate dispersion, as a representation of epithelial-mesenchymal transition (EMT). A significant difference was observed when M2a macrophages were in direct contact with or separated from A549 aggregates, suggesting a possible mechanism for proximity-induced, contact-dependent dissemination via ICAM-1 and integrin β2 interactions. Indeed, M2a macrophages tended to infiltrate and release cells from carcinoma cell aggregates. These findings may help in the development of immunotherapies based on enhancing the tumor-suppressive properties of TAMs.Singapore-MIT Alliance for Research and Technology (SMART - BioSym IRG)National University of Singapore. Biochemistry departmentSingapore. Biomedical Research CouncilSingapore. Agency for Science, Technology and Researc