491 research outputs found
Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy
Hepatitis C virus (HCV) infection commonly causes progressive liver diseases that deteriorate from chronic inflammation to fibrosis, cirrhosis and even to hepatocellular carcinoma. A long-term, persistent and uncontrolled inflammatory response is a hallmark of these diseases and further leads to hepatic injury and more severe disease progression. The levels of inflammatory cytokines and chemokines change with the states of infection and treatment, and therefore, they may serve as candidate biomarkers for disease progression and therapeutic effects. The mechanisms of HCV-induced inflammation involve classic pathogen pattern recognition, inflammasome activation, intrahepatic inflammatory cascade response, and oxidative and endoplasmic reticulum stress. Direct-acting antivirals (DAAs) are the first-choice therapy for effectively eliminating HCV, but DAAs alone are not sufficient to block the uncontrolled inflammation and severe liver injury in HCV-infected individuals. Some patients who achieve a sustained virologic response after DAA therapy are still at a long-term risk for progression to liver cirrhosis and hepatocellular carcinoma. Therefore, coupling with anti-inflammatory/hepatoprotective agents with anti-HCV effects is a promising therapeutic regimen for these patients during or after treatment with DAAs. In this review, we discuss the relationship between inflammatory mediators and HCV infection, summarize the mechanisms of HCV-induced inflammation, and describe the potential roles of anti-inflammatory/hepatoprotective drugs with anti-HCV activity in the treatment of advanced HCV infection
β-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-β/Smad Signaling Pathway
Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two β-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (–)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-β1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-β/Smad signaling pathway. As a newly identified β-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents
Laser Direct Writing of Visible Spin Defects in Hexagonal Boron Nitride for Applications in Spin-Based Technologies
Optically addressable spins in two-dimensional hexagonal boron nitride (hBN)
attract widespread attention for their potential advantage in on-chip quantum
devices, such as quantum sensors and quantum network. A variety of spin defects
have been found in hBN, but no convenient and deterministic generation methods
have been reported for other defects except negatively charged boron vacancy
(). Here we report that by using femtosecond laser direct writing
technology, we can deterministically create spin defect ensembles with spectra
range from 550 nm to 800 nm on nanoscale hBN flakes. Positive single-peak
optically detected magnetic resonance (ODMR) signals are detected in the
presence of magnetic field perpendicular to the substrate, and the contrast can
reach 0.8%. With the appropriate thickness of hBN flakes, substrate and
femtosecond laser pulse energy, we can deterministically and efficiently
generate bright spin defect array. Our results provide a convenient
deterministic method to create spin defects in hBN, which will motivate more
endeavors for future researches and applications of spin-based technologies
such as quantum magnetometer array
Пути развития дополнительного образования взрослых
ОБРАЗОВАНИЕ МЕДИЦИНСКОЕДОПОЛНИТЕЛЬНОЕ ОБРАЗОВАНИЕДОПОЛНИТЕЛЬНОЕ ОБРАЗОВАНИЕ ВЗРОСЛЫХОБРАЗОВАНИЕ МЕДИЦИНСКОЕ ПОСЛЕДИПЛОМНОЕ НЕПРЕРЫВНО
An Updated Search of Steady TeV Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array
Using the data taken from Tibet II High Density (HD) Array (1997
February-1999 September) and Tibet-III array (1999 November-2005 November), our
previous northern sky survey for TeV ray point sources has now been
updated by a factor of 2.8 improved statistics. From to
in declination (Dec) range, no new TeV ray point
sources with sufficiently high significance were identified while the
well-known Crab Nebula and Mrk421 remain to be the brightest TeV ray
sources within the field of view of the Tibet air shower array. Based on the
currently available data and at the 90% confidence level (C.L.), the flux upper
limits for different power law index assumption are re-derived, which are
approximately improved by 1.7 times as compared with our previous reported
limits.Comment: This paper has been accepted by hepn
JUNO Conceptual Design Report
The Jiangmen Underground Neutrino Observatory (JUNO) is proposed to determine
the neutrino mass hierarchy using an underground liquid scintillator detector.
It is located 53 km away from both Yangjiang and Taishan Nuclear Power Plants
in Guangdong, China. The experimental hall, spanning more than 50 meters, is
under a granite mountain of over 700 m overburden. Within six years of running,
the detection of reactor antineutrinos can resolve the neutrino mass hierarchy
at a confidence level of 3-4, and determine neutrino oscillation
parameters , , and to
an accuracy of better than 1%. The JUNO detector can be also used to study
terrestrial and extra-terrestrial neutrinos and new physics beyond the Standard
Model. The central detector contains 20,000 tons liquid scintillator with an
acrylic sphere of 35 m in diameter. 17,000 508-mm diameter PMTs with high
quantum efficiency provide 75% optical coverage. The current choice of
the liquid scintillator is: linear alkyl benzene (LAB) as the solvent, plus PPO
as the scintillation fluor and a wavelength-shifter (Bis-MSB). The number of
detected photoelectrons per MeV is larger than 1,100 and the energy resolution
is expected to be 3% at 1 MeV. The calibration system is designed to deploy
multiple sources to cover the entire energy range of reactor antineutrinos, and
to achieve a full-volume position coverage inside the detector. The veto system
is used for muon detection, muon induced background study and reduction. It
consists of a Water Cherenkov detector and a Top Tracker system. The readout
system, the detector control system and the offline system insure efficient and
stable data acquisition and processing.Comment: 328 pages, 211 figure
Synthesis and applications of porous non-silica metal oxide submicrospheres
© 2016 Royal Society of Chemistry. Nowadays the development of submicroscale products of specific size and morphology that feature a high surface area to volume ratio, well-developed and accessible porosity for adsorbates and reactants, and are non-toxic, biocompatible, thermally stable and suitable as synergetic supports for precious metal catalysts is of great importance for many advanced applications. Complex porous non-silica metal oxide submicrospheres constitute an important class of materials that fulfill all these qualities and in addition, they are relatively easy to synthesize. This review presents a comprehensive appraisal of the methods used for the synthesis of a wide range of porous non-silica metal oxide particles of spherical morphology such as porous solid spheres, core-shell and yolk-shell particles as well as single-shell and multi-shell particles. In particular, hydrothermal and low temperature solution precipitation methods, which both include various structure developing strategies such as hard templating, soft templating, hydrolysis, or those taking advantage of Ostwald ripening and the Kirkendall effect, are reviewed. In addition, a critical assessment of the effects of different experimental parameters such as reaction time, reaction temperature, calcination, pH and the type of reactants and solvents on the structure of the final products is presented. Finally, the practical usefulness of complex porous non-silica metal oxide submicrospheres in sensing, catalysis, biomedical, environmental and energy-related applications is presented
Aggregation-Induced Emission (AIE), Life and Health
Light has profoundly impacted modern medicine and healthcare, with numerous luminescent agents and imaging techniques currently being used to assess health and treat diseases. As an emerging concept in luminescence, aggregation-induced emission (AIE) has shown great potential in biological applications due to its advantages in terms of brightness, biocompatibility, photostability, and positive correlation with concentration. This review provides a comprehensive summary of AIE luminogens applied in imaging of biological structure and dynamic physiological processes, disease diagnosis and treatment, and detection and monitoring of specific analytes, followed by representative works. Discussions on critical issues and perspectives on future directions are also included. This review aims to stimulate the interest of researchers from different fields, including chemistry, biology, materials science, medicine, etc., thus promoting the development of AIE in the fields of life and health
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
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