135 research outputs found
Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma
Synergies and Prospects for Early Resolution of the Neutrino Mass Ordering
The measurement of neutrino Mass Ordering (MO) is a fundamental element for
the understanding of leptonic flavour sector of the Standard Model of Particle
Physics. Its determination relies on the precise measurement of and using either neutrino vacuum oscillations, such
as the ones studied by medium baseline reactor experiments, or matter effect
modified oscillations such as those manifesting in long-baseline neutrino beams
(LBB) or atmospheric neutrino experiments. Despite existing MO indication
today, a fully resolved MO measurement (5) is most likely to
await for the next generation of neutrino experiments: JUNO, whose stand-alone
sensitivity is 3, or LBB experiments (DUNE and
Hyper-Kamiokande). Upcoming atmospheric neutrino experiments are also expected
to provide precious information. In this work, we study the possible context
for the earliest full MO resolution. A firm resolution is possible even before
2028, exploiting mainly vacuum oscillation, upon the combination of JUNO and
the current generation of LBB experiments (NOvA and T2K). This opportunity
is possible thanks to a powerful synergy boosting the overall sensitivity where
the sub-percent precision of by LBB experiments is found
to be the leading order term for the MO earliest discovery. We also found that
the comparison between matter and vacuum driven oscillation results enables
unique discovery potential for physics beyond the Standard Model.Comment: Entitled in arXiv:2008.11280v1 as "Earliest Resolution to the
Neutrino Mass Ordering?
High-Level Expression of Notch1 Increased the Risk of Metastasis in T1 Stage Clear Cell Renal Cell Carcinoma
Background: Although metastasis of clear cell renal cell carcinoma (ccRCC) is basically observed in late stage tumors, T1 stage metastasis of ccRCC can also be found with no definite molecular cause resulting inappropriate selection of surgery method and poor prognosis. Notch signaling is a conserved, widely expressed signal pathway that mediates various cellular processes in normal development and tumorigenesis. This study aims to explore the potential role and mechanism of Notch signaling in the metastasis of T1 stage ccRCC. Methodology/Principal Findings: The expression of Notch1 and Jagged1 were analyzed in tumor tissues and matched normal adjacent tissues obtained from 51 ccRCC patients. Compared to non-tumor tissues, Notch1 and Jagged1 expression was significantly elevated both in mRNA and protein levels in tumors. Tissue samples of localized and metastatic tumors were divided into three groups based on their tumor stages and the relative mRNA expression of Notch1 and Jagged1 were analyzed. Compared to localized tumors, Notch1 expression was significantly elevated in metastatic tumors in T1 stage while Jagged1 expression was not statistically different between localized and metastatic tumors of all stages. The average size of metastatic tumors was significantly larger than localized tumors in T1 stage ccRCC and the elevated expression of Notch1 was significantly positive correlated with the tumor diameter. The functional significance of Notch signaling was studied by transfection of 786-O, Caki-1 and HKC cell lines with full-length expression plasmids of Notch1 and Jagged1
Real-time Monitoring for the Next Core-Collapse Supernova in JUNO
Core-collapse supernova (CCSN) is one of the most energetic astrophysical
events in the Universe. The early and prompt detection of neutrinos before
(pre-SN) and during the SN burst is a unique opportunity to realize the
multi-messenger observation of the CCSN events. In this work, we describe the
monitoring concept and present the sensitivity of the system to the pre-SN and
SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is
a 20 kton liquid scintillator detector under construction in South China. The
real-time monitoring system is designed with both the prompt monitors on the
electronic board and online monitors at the data acquisition stage, in order to
ensure both the alert speed and alert coverage of progenitor stars. By assuming
a false alert rate of 1 per year, this monitoring system can be sensitive to
the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos
up to about 370 (360) kpc for a progenitor mass of 30 for the case
of normal (inverted) mass ordering. The pointing ability of the CCSN is
evaluated by using the accumulated event anisotropy of the inverse beta decay
interactions from pre-SN or SN neutrinos, which, along with the early alert,
can play important roles for the followup multi-messenger observations of the
next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure
Detection of the Diffuse Supernova Neutrino Background with JUNO
As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO
Potential of Core-Collapse Supernova Neutrino Detection at JUNO
JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve
Effects of Resveratrol on Mouse B16 Melanoma Cell Proliferation through the SHCBP1-ERK1/2 Signaling Pathway
Melanoma originates from the malignant mutational transformation of melanocytes in the basal layer of the epidermal layer of the skin. It can easily spread and metastasize in the early stage, resulting in a poor prognosis. Therefore, it is particularly important to find effective antitumor adjuvant drugs to inhibit the occurrence and development of melanoma. In this study, we found that resveratrol, a polyphenolic compound from grape plants, can significantly inhibit the proliferation, colony formation and migration of mouse melanoma B16 cells. Notably, resveratrol was also found to inhibit the expression of SHCBP1 in B16 cells. Transcriptional analysis and cellular studies showed that SHCBP1 can activate the MAPK/ERK signaling pathway to regulate cyclin expression and promote the G1/S phase transition of the cell cycle by upregulating ERK1/2 phosphorylation levels. Resveratrol further downregulates the phosphorylation level of ERK1/2 by inhibiting SHCBP1 expression, thus inhibiting tumor cell proliferation. In conclusion, resveratrol inhibits the proliferation of B16 cells by regulating the ERK1/2 signaling pathway through SHCBP1. As an upstream protein of the ERK1/2 signaling pathway, SHCBP1 may be involved in the process of resveratrol-mediated inhibition of tumor cell proliferation
Constructing biomimetic liver models through biomaterials and vasculature engineering.
The occurrence of various liver diseases can lead to organ failure of the liver, which is one of the leading causes of mortality worldwide. Liver tissue engineering see the potential for replacing liver transplantation and drug toxicity studies facing donor shortages. The basic elements in liver tissue engineering are cells and biomaterials. Both mature hepatocytes and differentiated stem cells can be used as the main source of cells to construct spheroids and organoids, achieving improved cell function. To mimic the extracellular matrix (ECM) environment, biomaterials need to be biocompatible and bioactive, which also help support cell proliferation and differentiation and allow ECM deposition and vascularized structures formation. In addition, advanced manufacturing approaches are required to construct the extracellular microenvironment, and it has been proved that the structured three-dimensional culture system can help to improve the activity of hepatocytes and the characterization of specific proteins. In summary, we review biomaterials for liver tissue engineering, including natural hydrogels and synthetic polymers, and advanced processing techniques for building vascularized microenvironments, including bioassembly, bioprinting and microfluidic methods. We then summarize the application fields including transplant and regeneration, disease models and drug cytotoxicity analysis. In the end, we put the challenges and prospects of vascularized liver tissue engineering
Clinical Characteristics of Aldosterone- and Cortisol-Coproducing Adrenal Adenoma in Primary Aldosteronism
Aldosterone- and cortisol-coproducing adrenal adenoma (A/CPA) cases have been observed in patients with primary aldosteronism (PA). This study investigated the incidence, clinical characteristics, and molecular biological features of patients with A/CPAs. We retrospectively identified 22 A/CPA patients from 555 PA patients who visited the Chinese People’s Liberation Army General Hospital between 2004 and 2015. Analysis of clinical parameters revealed that patients with A/CPAs had larger tumors than those with pure APAs (P<0.05). Moreover, they had higher proportions of cardiovascular complications, glucose intolerance/diabetes, and osteopenia/osteoporosis compared to the pure APA patients (P<0.001). In the molecular biological findings, quantitative real-time PCR analysis revealed similar CYP11B1 and CYP17A1 mRNA expressions in resected A/CPA specimens and in pure APA specimens. Western blot and immunochemical analyses showed CYP11B1, CYP11B2, and CYP17A1 expressions in both A/CPAs and pure APAs. Seventeen cases with KCNJ5 mutations were detected among the 22 A/CPA DNA samples, but no PRKACA or other causative mutations were observed. Each patient improved following adrenalectomy. In conclusion, A/CPAs were not rare among PA patients. These patients associated with high incidences of cardiovascular events and metabolic disorders. Screening for excess cortisol secretion is necessary for PA patients
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