Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and ...clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
The prevalence of diabetes in China is among the highest in the world. For this reason, findings from the 2016 Global Burden of Disease (GBD) study were used to calculate the burden of hyperglycaemia ...and diabetes in China.
Following the general analytical strategy used in GBD 2016, diabetes prevalence and mortality were analyzed by age and gender. Trends in disability-adjusted life years (DALYs) due to diabetes were assessed in 33 province-level administrative units from 1990 to 2016, and similar data were provided for chronic kidney disease (CKD) related to diabetes and, as an overall summarizing measure, for hyperglycaemia expressed as high fasting plasma glucose (HFPG).
From 1990 to 2016, all-age prevalence of diabetes rose from 3.7% to 6.6%, and all-age diabetes and diabetes-related CKD mortality rates increased by 63.5% and 33.3%, respectively, with both rates increasing more rapidly in diabetes patients aged 15–49 years than in any other age groups. In 2016, HFPG became China's sixth leading cause of DALYs, and the attributable DALYs burden was 1802.3/100,000 population. Although the number of diabetes DALYs increased by 95% from 1990 to 2016, age-standardized diabetes DALYs rates increased by only 2.3%. Also, from 1990 to 2016, rates of age-standardized DALYs due to diabetes decreased in 14 provinces, but increased in 19 provinces. High BMI Scores and diets low in whole grains, nuts and seeds were the most important risk factors for diabetes in 2016.
Diabetes and hyperglycaemia constitute a huge health burden in China. The substantial increase in diabetes-related burden represents an ongoing challenge, given the rapidly ageing Chinese population. Thus, a targeted control and preventative strategy needs to be developed at risk factor level to reduce this burden.
MicroRNA in ovarian function Maalouf, S. W; Liu, W. S; Pate, J. L
Cell and Tissue Research,
01/2016, Volume:
363, Issue:
1
Journal Article, Book Review
Peer reviewed
The mammalian ovary is a dynamic organ. The coordination of follicle recruitment, selection, and ovulation and the timely development and regression of the corpus luteum are essential for a ...functional ovary and fertility. Deregulation of any of these processes results in ovarian dysfunction and potential infertility. MicroRNA (miRNA) are short noncoding RNA that regulate developmental processes and time-sensitive functions. The expression of miRNA in the ovary varies with cell type, function, and stage of the estrous cycle. miRNA are involved in the formation of primordial follicles, follicular recruitment and selection, follicular atresia, oocyte-cumulus cell interaction, granulosal cell function, and luteinization. miRNA are differentially expressed in luteal cells at the various stages of the estrous cycle and during maternal recognition of pregnancy, suggesting a role in luteal development, maintenance, and regression. An understanding of the patterns of expression and functions of miRNA in the ovary will lead to novel therapeutics to treat ovarian dysfunction and improve fertility and, potentially, to the development of better contraceptives.
Antibiotics and hormones in swine wastewater have become a critical concern worldwide due to the severe threats to human health and the eco-environment. Removal of most detectable antibiotics and ...hormones, such as sulfonamides (SAs), SMs, tetracyclines (TCs), macrolides, and estrogenic hormones from swine wastewater utilizing various biological processes were summarized and compared. In biological processes, biosorption and biodegradation are the two major removal mechanisms for antibiotics and hormones. The residuals in treated effluents and sludge of conventional activated sludge and anaerobic digestion processes can still pose risks to the surrounding environment, and the anaerobic processes' removal efficiencies were inferior to those of aerobic processes. In contrast, membrane bioreactors (MBRs), constructed wetlands (CWs) and modified processes performed better because of their higher biodegradation of toxicants. Process modification on activated sludge, anaerobic digestion and conventional MBRs could also enhance the performance (e.g. removing up to 98% SMs, 88.9% TCs, and 99.6% hormones from wastewater). The hybrid process combining MBRs with biological or physical technology also led to better removal efficiency. As such, modified conventional biological processes, advanced biological technologies and MBR hybrid systems are considered as a promising technology for removing toxicants from swine wastewater.
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•Biological antibiotics and hormones treatment process for swine wastewater was reviewed.•Mechanisms of antibiotics/hormones removal can be biosorption and biodegradation.•Conventional AS and AD are ineffective for antibiotics & hormones removal.•MBRs/hybrid MBRs and constructed wetlands can improve toxicants removal.•Modified conventional bioreactors are also efficient in antibiotics and hormones removal.
Abstract
We report on analysis of observations of the bright transient X-ray pulsar Swift J0243.6+6124 obtained during its 2017-2018 giant outburst with Insight-HXMT, NuSTAR, and Swift observatories. ...We focus on the discovery of a sharp state transition of the timing and spectral properties of the source at super-Eddington accretion rates, which we associate with the transition of the accretion disk to a radiation pressure dominated (RPD) state, the first ever directly observed for magnetized neutron star. This transition occurs at slightly higher luminosity compared to already reported transition of the source from sub- to super-critical accretion regime associate with onset of an accretion column. We argue that this scenario can only be realized for comparatively weakly magnetized neutron star, not dissimilar to other ultra-luminous X-ray pulsars (ULPs), which accrete at similar rates. Further evidence for this conclusion is provided by the non-detection of the transition to the propeller state in quiescence which strongly implies compact magnetosphere and thus rules out magnetar-like fields.
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
We present X-ray timing results of the new black hole candidate MAXI J1535−571 during its 2017 outburst from Hard X-ray Modulation Telescope (Insight-HXMT) observations taken from 2017 September 6 to ...23. Following the definitions given by Belloni, we find that the source exhibits transitions from the low/hard state to the hard intermediate state, and eventually to the soft intermediate state. Quasi-periodic oscillations (QPOs) are found in the intermediate states, which suggest different types of QPOs. With the large effective area of Insight-HXMT at high energies, we are able to present the energy dependence of the QPO amplitude and centroid frequency up to 100 keV, which has rarely been explored by previous satellites. We also find that the phase lag at the type-C QPOs centroid frequency is negative (soft lag) and strongly correlated with the centroid frequency. Assuming a geometrical origin of type-C QPOs, the source is consistent with being a high-inclination system.
The RAS-RAF-MEK-extracellular signal-regulated kinase (ERK) pathway plays a pivotal role in various cellular responses, including cellular growth, differentiation, survival and motility. Constitutive ...activation of the ERK pathway has been linked to the development and progression of human cancers. Here, we reported that mitogen-activated protein kinase phosphatase (MKP)-3, a negative regulator of ERK1/2, lost its expression particularly in the protein level, was significantly correlated with high ERK1/2 activity in primary human ovarian cancer cells using quantitative reverse transcription–polymerase chain reaction and western blot analyses. Intriguingly, the loss of MKP3 protein was associated with ubiquitination/proteosome degradation mediated by high intracellular reactive oxygen species (ROS) accumulation such as hydrogen peroxide in ovarian cancer cells. Functionally, short hairpin RNA knock down of endogenous MKP3 resulted in increased ERK1/2 activity, cell proliferation rate, anchorage-independent growth ability and resistance to cisplatin in ovarian cancer cells. Conversely, enforced expression of MKP3 in MKP3-deficient ovarian cancer cells significantly reduced ERK1/2 activity and inhibited cell proliferation, anchorage-independent growth ability and tumor development in nude mice. Furthermore, the enforced expression of MKP3 succeeded to sensitize ovarian cancer cells to cisplatin-induced apoptosis in vitro and in vivo. These results suggest a molecular mechanism by which the accumulation of ROS during ovarian cancer progression may cause the degradation of MKP3, which in turn leads to aberrant ERK1/2 activation and contributes to tumorigenicity and chemoresistance of human ovarian cancer cells.
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
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