Voriconazole is frequently utilized for the prevention and treatment of invasive fungal infections (IFIs), and is extensively metabolized by the cytochrome P450 (CYP) system. The impact of activity ...of the genes encoding CYP3A4, CYP3A5, and CYP2C9 on the pharmacokinetics of voriconazole cannot be ignored because, second to CYP2C19, they are the most important enzymes involved in voriconazole metabolism. The influence of genetic polymorphisms in
CYP3A4
,
CYP3A5
, and
CYP2C9
on the plasma concentrations of voriconazole was evaluated in the present study. The study cohort comprised 158 patients with IFIs in whom 22 single-nucleotide polymorphisms (SNPs) in
CYP3A4
,
CYP3A5
, and
CYP2C9
were genotyped using the Sequenom MassARRAY RS1000 system, and voriconazole plasma concentrations were measured by high-performance liquid chromatography (HPLC). 40, 91, and 27 patients presented with low (<1 mg/L), normal (1–4 mg/L), and high (>4 mg/L) plasma voriconazole concentrations, respectively. Correlation analysis between polymorphisms and the plasma voriconazole concentration revealed an association between the presence of the rs4646437 T allele and a higher plasma voriconazole concentration
p
= 0.033, odds ratio (OR) = 2.832, 95 % confidence interval (CI) = 1.086–7.384. This study has identified a new SNP related to the metabolism of voriconazole, potentially providing novel insight into the influence of CYP3A4 on the pharmacokinetics of this antifungal agent.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
With the rapidly growing attention to human-robot interfaces, soft robotics has attracted a great deal of interest. Soft robots have diverse advantages, including compliancy and safety, which ...contribute to seamless interactions with humans. To boost progress in the field, there is a need for compliant materials. Hydrogels are promising as compliant materials for soft robots because of their outstanding features, including high stretchability, transparency, ion conductivity, and biocompatibility. Furthermore, hydrogels provide innovative capabilities for soft robotics based on their unique responsiveness to stimuli. In this review, we discuss the unique features of hydrogel-based soft robots, from their fundamental working mechanisms to notable applications. Finally, we suggest perspectives on future directions that addressing potential challenges in the field of hydrogel soft robotics.
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•Unique features of hydrogel-based soft robots are reviewed from their fundamental working mechanisms to notable applications.•Covering all components of hydrogel-based soft robots including actuators, sensors, communicators, power sources, and computation circuits.•Suggesting perspectives on future directions for addressing potential challenges in the field of hydrogel soft robotics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
From 2006 to 2007, the daily concentrations of major inorganic water-soluble constituents, mineral aerosol, organic carbon (OC) and elemental carbon (EC) in ambient PM10 samples were investigated ...from 16 urban, rural and remote sites in various regions of China, and were compared with global aerosol measurements. A large difference between urban and rural chemical species was found, normally with 1.5 to 2.5 factors higher in urban than in rural sites. Optically-scattering aerosols, such as sulfate (~16%), OC (~15%), nitrate (~7%), ammonium (~5%) and mineral aerosol (~35%) in most circumstance, are majorities of the total aerosols, indicating a dominant scattering feature of aerosols in China. Of the total OC, ~55%–60% can be attributed to the formation of the secondary organic carbon (SOC). The absorbing aerosol EC only accounts for ~3.5% of the total PM10. Seasonally, maximum concentrations of most aerosol species were found in winter while mineral aerosol peaks in spring. In addition to the regular seasonal maximum, secondary peaks were found for sulfate and ammonium in summer and for OC and EC in May and June. This can be considered as a typical seasonal pattern in various aerosol components in China. Aerosol acidity was normally neutral in most of urban areas, but becomes some acidic in rural areas. Based on the surface visibility observations from 681 meteorological stations in China between 1957 and 2005, four major haze areas are identified with similar visibility changes, namely, (1) Hua Bei Plain in N. China, and the Guanzhong Plain; (2) E. China with the main body in the Yangtze River Delta area; (3) S. China with most areas of Guangdong and the Pearl River Delta area; (4) The Si Chuan Basin in S.W. China. The degradation of visibility in these areas is linked with the emission changes and high PM concentrations. Such quantitative chemical characterization of aerosols is essential in assessing their role in atmospheric chemistry and weather-climate effects, and in validating atmospheric models.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Mergers of neutron stars are known to be associated with short γ-ray bursts
. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density ...increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field
(that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts
. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst
. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown
. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf
. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref.
). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do
. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, ...propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°<l<125°, |b|<5°) and outer (125°<l<235°, |b|<5°) Galactic plane are detected with 29.1σ and 12.7σ significance, respectively. The outer Galactic plane diffuse emission is detected for the first time in the very- to ultra-high-energy domain (E>10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Since there have been individual reports of persistent haze–fog events in January 2013 in central-eastern China, questions on factors causing the drastic differences in changes in 2013 from changes ...in adjacent years have been raised. Changes in major chemical components of aerosol particles over the years also remain unclear. The extent of meteorological factors contributing to such changes is yet to be determined. The study intends to present the changes in daily based major water-soluble constituents, carbonaceous species, and mineral aerosol in PM10 at 13 stations within different haze regions in China from 2006 to 2013, which are associated with specific meteorological conditions that are highly related to aerosol pollution (parameterized as an index called Parameter Linking Aerosol Pollution and Meteorological Elements – PLAM). No obvious changes were found in annual mean concentrations of these various chemical components and PM10 in 2013, relative to 2012. By contrast, wintertime mass of these components was quite different. In Hua Bei Plain (HBP), sulfate, organic carbon (OC), nitrate, ammonium, element carbon (EC), and mineral dust concentrations in winter were approximately 43, 55, 28, 23, 21, and 130 μg m−3, respectively; these masses were approximately 2 to 4 times higher than those in background mass, which also exhibited a decline during 2006 to 2010 and then a rise till 2013. The mass of these concentrations and PM10, except minerals, respectively, increased by approximately 28 to 117 % and 25 % in January 2013 compared with that in January 2012. Thus, persistent haze–fog events occurred in January 2013, and approximately 60 % of this increase in component concentrations from 2012 to 2013 can be attributed to severe meteorological conditions in the winter of 2013. In the Yangtze River Delta (YRD) area, winter masses of these components, unlike HBP, have not significantly increase since 2010; PLAM were also maintained at a similar level without significant changes. In the Pearl River Delta (PRD) area, the regional background concentrations of the major chemical components were similar to those in the YRD, accounting for approximately 60–80 % of those in HBP. Since 2010, a decline has been found for winter concentrations, which can be partially attributable to persistently improving meteorological conditions and emission cutting with an emphasis on coal combustion in this area. In addition to the scattered and centralized coal combustion for heating, burning biomass fuels contributed to the large increase in concentrations of carbonaceous aerosol in major haze regions in winter, except in the PRD. No obvious changes were found for the proportions of each chemical components of PM10 from 2006 to 2013. Among all of the emissions recorded in chemical compositions in 2013, coal combustion was still the largest anthropogenic source of aerosol pollution in various areas in China, with a higher sulfate proportion of PM10 in most areas of China, and OC was normally ranked third. PM10 concentrations increased by approximately 25 % in January of 2013 relative to 2012, which caused persistent haze–fog events in HBP; emissions also reduced by approximately 35 % in Beijing and its vicinity (BIV) in late autumn of 2014, thereby producing the Asia Pacific Economic Cooperation (APEC) blue (extremely good air quality); thus, one can expect that the persistent haze–fog events would be reduced significantly in the BIV, if approx. one-third of the 2013 winter emissions were reduced, which can also be viewed as the upper limit of atmospheric aerosol pollution capacity in this area.
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