The study of RUNX3 in tumor pathogenesis is a rapidly expanding area of cancer research. Functional inactivation of RUNX3-through mutation, epigenetic silencing, or cytoplasmic mislocalization-is ...frequently observed in solid tumors of diverse origins. This alone indicates that RUNX3 inactivation is a major risk factor in tumorigenesis and that it occurs early during progression to malignancy. Conversely, RUNX3 has also been described to have an oncogenic function in a subset of tumors. Although the mechanism of how RUNX3 switches from tumor suppressive to oncogenic activity is unclear, this is of clinical relevance with implications for cancer detection and prognosis. Recent developments have significantly contributed to our understanding of the pleiotropic tumor suppressive properties of RUNX3 that regulate major signaling pathways. This review summarizes the important findings that link RUNX3 to tumor suppression.
This study aims at investigating the effects of MSW incinerator fly ash (FA) and bottom ash (BA) on the anaerobic co-digestion of OFMSW with FA or BA. It also simulates the biogas production from ...various dosed and control bioreactors. Results showed that suitable ashes addition (FA/MSW 10 and 20
g
L
−1 and BA/MSW 100
g
L
−1) could improve the MSW anaerobic digestion and enhance the biogas production rates. FA/MSW 20
g
L
−1 bioreactor had the higher biogas production and rate implying the potential option for MSW anaerobic co-digestion. Modeling studies showed that exponential plot simulated better for FA/MSW 10
g
L
−1 and control bioreactors while Gaussian plot was applicable for FA/MSW 20
g
L
−1 one. Linear and exponential plot of descending limb both simulated better for BA/MSW 100
g
L
−1 bioreactor. Modified Gompertz plot showed higher correlation of biogas accumulation than exponential rise to maximum plot for all bioreactors.
Runt-related transcription factor 3 (RUNX3) is a well-documented tumour suppressor that is frequently inactivated in gastric cancer. Here, we define a novel mechanism by which RUNX3 exerts its tumour ...suppressor activity involving the TEAD-YAP complex, a potent positive regulator of proliferative genes. We report that the TEAD-YAP complex is not only frequently hyperactivated in liver and breast cancer, but also confers a strong oncogenic activity in gastric epithelial cells. The increased expression of TEAD-YAP in tumour tissues significantly correlates with poorer overall survival of gastric cancer patients. Strikingly, RUNX3 physically interacts with the N-terminal region of TEAD through its Runt domain. This interaction markedly reduces the DNA-binding ability of TEAD that attenuates the downstream signalling of TEAD-YAP complex. Mutation of RUNX3 at Arginine 122 to Cysteine, which was previously identified in gastric cancer, impairs the interaction between RUNX3 and TEAD. Our data reveal that RUNX3 acts as a tumour suppressor by negatively regulating the TEAD-YAP oncogenic complex in gastric carcinogenesis.
Summary Background Itch is the cardinal symptom of atopic dermatitis (AD). β‐Endorphin, a neuropeptide, is increased in both AD skin and sera. Interleukin (IL)‐31, an itch‐relevant cytokine, ...activates IL‐31 receptors in keratinocytes. However, how IL‐31 and β‐endorphin interact in AD skin remains elusive.
Objectives To investigate the mechanistic interaction of IL‐31 and β‐endorphin in AD.
Methods This was a prospective cross‐sectional study. We recruited adult patients with AD and controls according to Hanifin’s AD criteria. Serum levels of IL‐31 and β‐endorphin were measured by enzyme‐linked immunosorbent assay. Expressions of IL‐31 receptor A (IL‐31RA) and β‐endorphin in the skin were assessed by immunohistochemistry. Their expression in the skin and blood was compared and correlated in patients with AD and in controls. We also treated primary keratinocytes with IL‐31 and measured calcium influx, β‐endorphin production and signalling pathways to define their mechanistic interactions.
Results β‐Endorphin was increased in the supernatant from IL‐31‐treated keratinocytes. IL‐31 receptor activation resulted in calcium influx and STAT3 activation; pretreatment with STAT3 inhibitor stopped the increase of β‐endorphin. Notably, either replacement of extracellular calcium or treatment with 2‐aminoethoxydiphenyl borate, an inhibitor for the store‐operated channel, blocked STAT3 activation. We found higher levels of blood β‐endorphin and IL‐31, which were significantly correlated, in patients with AD. Moreover, IL‐31RA and β‐endorphin were increased and colocalized both in AD human skin and TPA‐painted mouse skin.
Conclusions IL‐31 receptor activation in keratinocytes induces calcium influx and STAT3‐dependent production of β‐endorphin. These results might contribute to an understanding of the regulatory mechanisms underlying peripheral itch.
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
Context. Complex organic molecules (COMs) have been detected ubiquitously in protostellar systems. However, at shorter wavelengths (~0.8 mm), it is generally more difficult to detect larger molecules ...than at longer wavelengths (~3 mm) because of the increase in millimeter dust opacity, line confusion, and unfavorable partition function. Aims. We aim to search for large molecules (more than eight atoms) in the Atacama Large Millimeter/submillimeter Array (ALMA) Band 3 spectrum of IRAS 16293-2422 B. In particular, the goal is to quantify the usability of ALMA Band 3 for molecular line surveys in comparison to similar studies at shorter wavelengths. Methods. We used deep ALMA Band 3 observations of IRAS 16293-2422 B to search for more than 70 molecules and identified as many lines as possible in the spectrum. The spectral settings were set to specifically target three-carbon species such as i- and n-propanol and glycerol, the next step after glycolaldehyde and ethylene glycol in the hydrogenation of CO. We then derived the column densities and excitation temperatures of the detected species and compared the ratios with respect to methanol between Band 3 (~3 mm) and Band 7 (~1 mm, Protostellar Interferometric Line Survey) observations of this source to examine the effect of the dust optical depth. Results. We identified lines of 31 molecules including many oxygen-bearing COMs such as CH 3 OH, CH 2 OHCHO, CH 3 CH 2 OH, and c-C 2 H 4 O and a few nitrogen- and sulfur-bearing ones such as HOCH 2 CN and CH 3 SH. The largest detected molecules are gGg-(CH 2 OH) 2 and CH 3 COCH 3 . We did not detect glycerol or i- and n-propanol, but we do provide upper limits for them which are in line with previous laboratory and observational studies. The line density in Band 3 is only ~2.5 times lower in frequency space than in Band 7. From the detected lines in Band 3 at a ≳ 6σ level, ~25–30% of them could not be identified indicating the need for more laboratory data of rotational spectra. We find similar column densities and column density ratios of COMs (within a factor ~2) between Band 3 and Band 7. Conclusions. The effect of the dust optical depth for IRAS 16293-2422 B at an off-source location on column densities and column density ratios is minimal. Moreover, for warm protostars, long wavelength spectra (~3 mm) are not only crowded and complex, but they also take significantly longer integration times than shorter wavelength observations (~0.8 mm) to reach the same sensitivity limit. The 3 mm search has not yet resulted in the detection of larger and more complex molecules in warm sources. A full deep ALMA Band 2–3 (i.e., ~3–4 mm wavelengths) survey is needed to assess whether low frequency data have the potential to reveal more complex molecules in warm sources.
A low voltage and wide locking range injection-locked frequency divider using a standard 0.18-μm complementary metal oxide semiconductor (CMOS) process is presented. The wide locking range and the ...low-voltage operation are performed by adding an injection nMOS between the differential outputs of the divider that contains on-chip transformers which result in positive feedback loops to swing the output signals above the supply and below the ground potential. This dual-swing capability maximizes the carrier power and achieves low-voltage performance. The measurement results show that at the supply voltage of 0.75-V, the divider free-running frequency is 2.02 GHz, and at the incident power of 0 dBm the locking range is about 1.49 GHz (36.88%), from the incident frequency 3.27 to 4.64GHz.
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•Multilayer assembly of electrospun/electrosprayed PVDF-based nanofibers and beads was designed and fabricated.•The flexible PPy/PVDF electrodes were fabricated by chemical vapour ...phase polymerization.•The CsPbBr3@PVDF beads were introduced into NFMs to effectively deliver external force.•The 3D multilayer NFMs exhibited enhanced piezoelectricity and high sensitivity.
Flexible high-performance piezoelectric nanogenerators (PNG) that can convert mechanical energy into electricity are crucial for the development of self-powered wearable electronic devices. In this work, a 3D multilayer assembly of flexible organic polypyrrole (PPy) electrodes, electrospun poly(vinylidene fluoride) (PVDF) nanofibers and electrosprayed CsPbBr3@PVDF beads was proposed for a high-performance PNG, wherein two layers of CsPbBr3@PVDF beads were inserted between the top/bottom PPy electrodes and PVDF nanofibers layer, respectively. The PPy electrodes were fabricated via vapour phase polymerization of pyrrole monomers on the surface of the electrospun PVDF nanofibers with FeCl3 acted as an oxidant. As for the active piezoelectric layers, both the PVDF nanofibers and CsPbBr3@PVDF beads possessed high fractions of β crystalline phase, i.e., 83.5% and 94%, respectively, which helps to provide favorable polarization response. Besides, the introduction of the globular CsPbBr3@PVDF particles also facilitated the stress excitation to the piezoelectric layers, thus leading to enhanced output performance and high sensitivity. Piezoelectric results showed that the 3D multilayer NFMs based PNG exhibited a high open-circuit voltage of 10.3 V and a short-circuit current density of 1.29 μA/cm2, and could detect a weak pressure as low as 7.4 Pa. Furthermore, the PNG based fabrics also demonstrated excellent ability to harvest energy from the temperature fluctuations through pyroelectric effect. The structuration method of embedding globular particles into electrospun PVDF NFMs may open up the feasibility of fabricating high-output PNG.
Widely distributed bottom simulating reflectors (BSRs) imply the potential existence of gas hydrates offshore southwestern Taiwan. To compare the distribution of methane concentrations along passive ...and active margins in the region, bottom waters and cored sediments were collected during four cruises from 2005 to 2006. The results reveal that sites with high methane concentrations are predominantly distributed in the active margin and site GS5 is the only site that contains very high methane concentrations in the passive margin of studied area. Anomalously high methane fluxes still can be obtained from the calculation of diffusive methane flux, although there might be some gas leakage during or after sampling procedures. The profiles of methane and sulfate concentration reveal very shallow depths of the sulfate-methane interface (SMI) at some sites. There is evidence that sulfate reduction is mainly driven by the process of anaerobic methane oxidation. Thus, sulfate fluxes can be used as a proxy for methane fluxes through the use of diffusion equations; and the results show that the fluxes are very high in offshore southwestern Taiwan. The depths of the SMI are different at sites GH6 and C; however, both methane profiles reveal parallel methane gradients below the SMI. This might be because of methane migration to surface sediments from the same reservoir with the same diffusion rates. Although BSRs are widely distributed both in the active margin and in the passive margin, most sites with high methane concentrations have been found in the active margin. Therefore, the specific tectonic settings in offshore SW Taiwan might strongly control the stability of gas hydrates, and thus affect the methane concentrations and fluxes of the sediments and sea waters. Furthermore, the carbon isotopic composition of methane shows that a biogenic gas source is dominant at shallower depth; however, some thermogenic gases might be introduced through the fracture/fault zones from deeper source in the active region of studied area.
Summary
Background
In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG‐IFN) for 48‐weeks results in higher rates of hepatitis B surface antigen ...(HBsAg) loss than either monotherapy.
Aim
To identify baseline and on‐treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks.
Methods
A secondary analysis of data from an open‐label study where patients were randomised to TDF (300 mg/day, oral) plus PEG‐IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI‐48w); TDF plus PEG‐IFN for 16 weeks, TDF for 32 weeks (TDF/PI‐16w+TDF‐32w); TDF for 120 weeks (TDF‐120w) or PEG‐IFN for 48 weeks (PI‐48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72.
Results
Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI‐48w group (6.5%) than in the TDF/PI‐16w+TDF‐32w (0.5%), TDF‐120w (0%) and PI‐48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI‐48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72.
Conclusions
HBsAg decline at Week 24 of TDF plus PEG‐IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.
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