Molecular mechanisms of LTBP4-related cutis laxa

Structural proteins of the extracellular matrix (ECM) and associated proteins build up a complex network that is abundant in the human body. In addition to serving key biomechanical roles, ECM proteins play an important role in storage, presentation and contextualization of growth factors, including transforming growth factor-β (TGFβ). This work focused on investigating the biomechanical consequences of and molecular disease mechanisms leading to cutis laxa (CL), a rare inherited disorder characterized by loose skin and frequently associated with systemic involvement, including aortic aneurysms, pulmonary artery disease, and emphysema. A DermaLab suction cup device was used to evaluate the mechanical properties of the skin in CL patients. The results showed significant reduction of elastic and viscoelastic moduli (VE). VE appeared to be a reliable measurement of biomechanical aging of the skin and also offered a predictive value in distinguishing cases from controls. To study molecular disease mechanisms in CL, control and LTBP4-mutant human dermal fibroblasts were used to investigate TGFβ activity and signaling. In LTBP4-mutant cells, despite elevated extracellular TGFß activity, downstream signaling molecules of the TGFß pathway were markedly suppressed. TGFß receptors (TGFBR1 and TGFBR2) were reduced at the protein, but not at the RNA level. Treatment with exogenous TGFβ1 led to a further decrease in downstream signaling and receptor abundance. Upon treatment with TGFBR1 kinase inhibitor, endocytosis inhibitors or a lysosomal inhibitor, the levels of TGFBR1 and TGFBR2 were normalized. Antisense mophorlino oligonucleotide-mediated knockdown of LTBP4 reduced TGFβ receptor abundance and signaling in normal cells and supplementation of recombinant LTBP4 enhanced these measures in mutant cells. I conclude that, in the absence of LTBP4, TGFBR1 and TGFBR2 are internalized and degraded by lysosomes in a ligand-dependent and receptor kinase activity-dependent manner. Thus, LTBP4 is a key molecule required for the stabilization of the TGFβ receptor complex. Increased TGFβ levels have been found in patients with cardiomyopathy, diabetic nephropathy, cancer, and lung fibrosis, in all cases correlating with disease severity. The discovery of a new mechanism for TGFβ receptor regulation will be helpful in developing novel therapeutic reagents for systemic diseases of major public health impact

A Deep Learning Approach to Radar-based QPE

In this study, we propose a volume-to-point framework for quantitative precipitation estimation (QPE) based on the Quantitative Precipitation Estimation and Segregation Using Multiple Sensor (QPESUMS) Mosaic Radar data set. With a data volume consisting of the time series of gridded radar reflectivities over the Taiwan area, we used machine learning algorithms to establish a statistical model for QPE in weather stations. The model extracts spatial and temporal features from the input data volume and then associates these features with the location-specific precipitations. In contrast to QPE methods based on the Z-R relation, we leverage the machine learning algorithms to automatically detect the evolution and movement of weather systems and associate these patterns to a location with specific topographic attributes. Specifically, we evaluated this framework with the hourly precipitation data of 45 weather stations in Taipei during 2013-2016. In comparison to the operational QPE scheme used by the Central Weather Bureau, the volume-to-point framework performed comparably well in general cases and excelled in detecting heavy-rainfall events. By using the current results as the reference benchmark, the proposed method can integrate the heterogeneous data sources and potentially improve the forecast in extreme precipitation scenarios.Comment: 22 pages, 11 figures. Published in Earth and Space Scienc

Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria) and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM) in chicken embryo and human vascular endothelial cells (HUVECs). The matrix metalloproteinase-2 (MMP-2) activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS), exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs

Detection of genetic and epigenetic DNA markers in urine for the early detection of primary and recurrent hepatocellular carcinoma

Poster presented at American Association of the Study of Liver Diseases (AASLD) meeting in San Francisco California. Objective: Develop a urine test using a panel of select genetic and epigenetic markers for the early detection of primary and recurrent HCC. Introduction: Hepatocellular carcinoma (HCC) or liver cancer is an aggressive disease and one of the fastest growing cancers by incidence in the United States. Early detection is the key for effective treatment of HCC as the 5-year survival rate is 26% in early stage HCC as compared to only 2% when found after spreading to distant organs. The current marker, alpha-feto protein (AFP) and its fucosylated glycoform, L3, are of limited value with only 40-60% sensitivity.https://jdc.jefferson.edu/gastrohepposters/1000/thumbnail.jp

Spatiotemporal Trends in Oral Cancer Mortality and Potential Risks Associated with Heavy Metal Content in Taiwan Soil

Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972–2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran’s I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology

Multi-Segment Foam Flow Field in Ambient Pressure Polymer Exchange Membrane Fuel Cell

In order to produce low-cost flow field plates for polymer electrolyte membrane fuel cells, we used nickel foam in this study rather than conventional flow field. Nickel foam has high electron conductivity, thermal conductivity, and mechanical strength. Electrochemical impedance spectrum analysis is carried out to evidence the use on flow field plates of nickel foam. From the impedance fitting results, the nickel foam cases showed the lower contact resistance than the serpentine. However, such plates have poor performance at low temperatures and ambient pressure. In order to overcome this, a multi-segment foam flow field is designed in this study. This increased the performance of the polarization curve by 70% from 162 to 275.5 mw cm-2 than the original nickel foam design. Also, the mass transfer resistance was reduced, and the Warburg impedance value of the operation voltage decreased by 0.4 V. The numerical analysis results demonstrate that increased segment numbers can increase the performance of the multi-segment foam flow field

Porphyrin-based metal–organic frameworks for neuromorphic electronics

Porphyrin-based metal–organic frameworks (PP-MOFs) have some special features beyond ordinary MOFs, including superior optoelectronic characteristics, the ability to form 2D layered structure, and customizability, which prompt the increasing attention of PP-MOFs in the field of neuromorphic electronics. The related application research is in the initial stage, and a timely summary and guidance are necessary. The PP-MOFs fabrication should be shifted from powder synthesis in a chemistry laboratory to high-quality film preparation under a clean environment to ensure device performance. This article highlights the PP-MOFs film preparation methods and the application advances in neuromorphic electronics, performs comparative analysis in detail, and puts forward the challenges and future research directions, with the aim to attract the attention of experts in various areas (e.g., chemists, materials scientists, and engineers) and promote the application of PP-MOFs in neuromorphic electronics

The role of echocardiographic study in patients with chronic kidney disease

Despite the recent enormous advances in medicine, high mortality and morbidity rates among the chronic kidney disease (CKD) patients remain an important but unresolved issue. Cardiovascular disease is a major cause of mortality and morbidity in patients with CKD. Abnormal left ventricular geometry and functions are common in this patient group and have been proven to be correlated with a high cardiovascular mortality/morbidity and all-cause mortality. For this reason, echocardiographic study plays an important role in evaluating cardiac structure and functions as well as in stratifying prognostic risk. We here summarize the reported findings on the usefulness of echocardiographic methodologies and identify their roles in diagnostic and prognostic clinical approaches