Biodegradable, flexible silicon nanomembrane-based NO x gas sensor system with record-high performance for transient environmental monitors and medical implants

Abstract: A novel transient electronics technology that is capable of completely dissolving or decomposing in certain conditions after a period of operation offers unprecedented opportunities for medical implants, environmental sensors, and other applications. Here, we describe a biodegradable, flexible silicon-based electronic system that detects NO species with a record-breaking sensitivity of 136 Rs (5 ppm, NO2) and 100-fold selectivity for NO species over other substances with a fast response (~30 s) and recovery (~60 s). The exceptional features primarily depend on not only materials, dimensions, and design layouts but also temperatures and electrical operations. Large-scale sensor arrays in a mechanically pliable configuration exhibit negligible deterioration in performance under various modes of applied loads, consistent with mechanics modeling. In vitro evaluations demonstrate the capability and stability of integrated NOx devices in severe wet environments for biomedical applications

Breast Cancer with Increased Drug Resistance, Invasion Ability, and Cancer Stem Cell Properties through Metabolism Reprogramming

Breast cancer is a heterogeneous disease, and the survival rate of patients with breast cancer strongly depends on their stage and clinicopathological features. Chemoradiation therapy is commonly employed to improve the survivability of patients with advanced breast cancer. However, the treatment process is often accompanied by the development of drug resistance, which eventually leads to treatment failure. Metabolism reprogramming has been recognized as a mechanism of breast cancer resistance. In this study, we established a doxorubicin-resistant MCF-7 (MCF-7-D500) cell line through a series of long-term doxorubicin in vitro treatments. Our data revealed that MCF-7-D500 cells exhibited increased multiple-drug resistance, cancer stemness, and invasiveness compared with parental cells. We analyzed the metabolic profiles of MCF-7 and MCF-7-D500 cells through liquid chromatography–mass spectrometry. We observed significant changes in 25 metabolites, of which, 21 exhibited increased levels (>1.5-fold change and p p < 0.05) in MCF-7 cells with doxorubicin resistance. These results suggest the involvement of metabolism reprogramming in the development of drug resistance in breast cancer, especially the activation of glycolysis, the tricarboxylic acid (TCA) cycle, and the hexamine biosynthesis pathway (HBP). Furthermore, most of the enzymes involved in glycolysis, the HBP, and the TCA cycle were upregulated in MCF-7-D500 cells and contributed to the poor prognosis of patients with breast cancer. Our findings provide new insights into the regulation of drug resistance in breast cancer, and these drug resistance-related metabolic pathways can serve as targets for the treatment of chemoresistance in breast cancer

Automated image based prominent nucleoli detection

Nucleolar changes in cancer cells are one of the cytologic features important to the tumor pathologist in cancer assessments of tissue biopsies. However, inter-observer variability and the manual approach to this work hamper the accuracy of the assessment by pathologists. In this paper, we propose a computational method for prominent nucleoli pattern detection.Thirty-five hematoxylin and eosin stained images were acquired from prostate cancer, breast cancer, renal clear cell cancer and renal papillary cell cancer tissues. Prostate cancer images were used for the development of a computer-based automated prominent nucleoli pattern detector built on a cascade farm. An ensemble of approximately 1000 cascades was constructed by permuting different combinations of classifiers such as support vector machines, eXclusive component analysis, boosting, and logistic regression. The output of cascades was then combined using the RankBoost algorithm. The output of our prominent nucleoli pattern detector is a ranked set of detected image patches of patterns of prominent nucleoli.The mean number of detected prominent nucleoli patterns in the top 100 ranked detected objects was 58 in the prostate cancer dataset, 68 in the breast cancer dataset, 86 in the renal clear cell cancer dataset, and 76 in the renal papillary cell cancer dataset. The proposed cascade farm performs twice as good as the use of a single cascade proposed in the seminal paper by Viola and Jones. For comparison, a naive algorithm that randomly chooses a pixel as a nucleoli pattern would detect five correct patterns in the first 100 ranked objects.Detection of sparse nucleoli patterns in a large background of highly variable tissue patterns is a difficult challenge our method has overcome. This study developed an accurate prominent nucleoli pattern detector with the potential to be used in the clinical settings

Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface

Zyxin regulates mouse embryonic stem cell differentiation by integrating mechanical cues through actin stress fibres and focal adhesions and biochemical cues through YAP signalling

Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution

10.1016/j.ebiom.2021.103262EBioMedicine6510326

Zyxin Is involved in fibroblast rigidity sensing and durotaxis

Focal adhesions (FAs) are specialized structures that enable cells to sense their extracellular matrix rigidity and transmit these signals to the interior of the cells, bringing about actin cytoskeleton reorganization, FA maturation, and cell migration. It is known that cells migrate towards regions of higher substrate rigidity, a phenomenon known as durotaxis. However, the underlying molecular mechanism of durotaxis and how different proteins in the FA are involved remain unclear. Zyxin is a component of the FA that has been implicated in connecting the actin cytoskeleton to the FA. We have found that knocking down zyxin impaired NIH3T3 fibroblast’s ability to sense and respond to changes in extracellular matrix in terms of their FA sizes, cell traction stress magnitudes and F-actin organization. Cell migration speed of zyxin knockdown fibroblasts was also independent of the underlying substrate rigidity, unlike wild type fibroblasts which migrated fastest at an intermediate substrate rigidity of 14 kPa. Wild type fibroblasts exhibited durotaxis by migrating toward regions of increasing substrate rigidity on polyacrylamide gels with substrate rigidity gradient, while zyxin knockdown fibroblasts did not exhibit durotaxis. Therefore, we propose zyxin as an essential protein that is required for rigidity sensing and durotaxis through modulating FA sizes, cell traction stress and F-actin organization

Does HLA-B*27 subtypes and ethnicity matter in Ankylosing Spondylitis?

Ankylosing Spondylitis (AS) is a chronic, progressive inflammatory disorder that results in ankylosis of the vertebral column and sacroiliac joints. More than 30% of patients with AS carry a heavy burden of disease and have a decreased quality of life. The HLA-B*27 is a well known genetic risk variant for ankylosing spondylitis (AS). However, the degree of association varies for different subtypes and depends on ethnicity. Malaysia is a multi-ethnic country comprises Malays as the largest ethnic group, followed by Chinese, Indians and mixed-ethnicities

Preliminary report: April 2009 - August 2010 National Inflammatory Arthritis Registry (NIAR)

Rheumatoid Arthritis (RA) is the most common form of infl ammatory arthritis. It is estimated to affect about 1% of the population. Of unknown aetiology, it typically affects many joints, causing acute inflammation, in most cases leading to joint erosions and joint damage (1). The NIAR, initiated in 2008, was set up with the aim of obtaining information about patients with Rheumatoid Arthritis. Information about patients with the other inflammatory arthritides will be collected in the future