Background and purpose
MicroRNAs (miRNAs) have been demonstrated to play crucial roles in the early stage of acute ischaemic stroke (AIS). The purpose of this study was to investigate the expression ...patterns of miRNAs in peripheral blood mononuclear cells (PBMCs) from AIS patients and further explore related molecular mechanisms in stroke‐induced immunodeficiency syndrome (SIDS).
Methods
The miRNA expression patterns of PBMCs were detected by miRNA microarray and validated by quantitative real‐time polymerase chain reaction (qRT‐PCR) in AIS patients and healthy controls. Bioinformatics methods and luciferase reporter assays were used to detect the downstream target genes. Following stimulation with lipopolysaccharide and interleukin‐4, the expression of miR‐4443, tumor necrosis factor receptor associated factor 4 (TRAF4) and the nuclear factor kappa B (NF‐κB) pathway were evaluated. Furthermore, transfection with miR‐4443 mimic or inhibitor in the monocytes was carried out to gain insight into the mechanisms in SIDS.
Results
Interleukin‐10 in AIS patients was significantly higher than that of healthy controls. The miRNA microarray analysis and qRTPCR validation showed that only miR‐4443 was upregulated expressed in PBMCs from AIS patients, especially in monocytes. miR‐4443 was shown to directly interact with the 3′ untranslated regions of TRAF4, resulting in suppression of TRAF4 protein expression. Furthermore, the expression of miR‐4443 and TRAF4 was regulated by stimulation with lipopolysaccharide or interleukin‐4. Additionally, overexpression of miR‐4443 suppressed the TRAF4/Iκα/NF‐κB signaling pathway to activate the expression of anti‐inflammatory cytokines in monocytes.
Conclusions
The increased expression of miR‐4443 induced monocyte dysfunction by targeting TRAF4, which may function as a crucial mediator in SIDS.
The cosmogenic isotope 41Ca with a half-life of 99,000 years can, in principle, serve as a tracer for environmental processes at an age scale beyond the reach of 14C. With accelerator mass ...spectrometry, the ratio of 41Ca/Ca has been measured down to the 10−15 level in natural samples. A wide range of potential applications, such as the burial dating of bones and exposure dating of rocks, require measuring even smaller 41Ca/Ca ratios in the range of 10−16 to 10−15. Here we achieved this by employing the atom-trap trace analysis method in which individual 41Ca atoms are selectively captured in a magneto-optical trap and counted by detecting their fluorescence. We realized a precision of 12% on the 41Ca/Ca ratio at the level of 10−16 and achieved a detection limit at the level of 10−17, which is below the distribution of natural abundances. We verified the accuracy of the 41Ca/Ca results through a series of measurements of reference samples, and performed demonstration analyses on bone, rock and seawater samples. Our table-top method has the potential to explore the suitability of 41Ca as a tracer.The calcium isotope 41Ca is a promising candidate to complement dating methods relying on radiocarbon. Small levels of 41Ca can be measured with atom-trap trace analysis, which brings the use of 41Ca a step closer to applications.
Aims
Few studies have analysed the effect of sleep duration and snoring on hypertension and glycaemic control in patients with diabetes. This study aims to investigate the relationship of sleep ...duration and snoring on prevalent hypertension and glycaemic control in people with diabetes.
Methods
In the baseline survey of the REACTION study, 56 032 patients with diabetes were categorized into four groups according to self‐reported sleep duration: < 6, 6–7.9, 8–8.9 and ≥ 9 h. Snoring frequency was evaluated as ‘usually’, ‘occasionally’ or ‘never’. Hypertension was assessed by systolic blood pressure, diastolic blood pressure, self‐reported previous diagnosis and antihypertensive medications. ‘Good’ glycaemic control was defined as HbA1c < 53 mmol/mol (7.0%) and ‘poor’ glycaemic control as HbA1c ≥ 53 mmol/mol (7.0%).
Results
Controlling for potential confounders and intermediates, sleep ≥ 9 h relative to intermediate sleep (6–7.9 h) was significantly associated with prevalent hypertension (OR: 1.25, 95% CI: 1.18–1.32) and poor glycaemic control (OR: 1.11, 95% CI: 1.05–1.18), and a U‐shaped association was found between sleep duration and prevalent hypertension (P for quadratic trend = 0.019). Usually snoring was positively associated with prevalent hypertension (OR: 1.30, 95% CI: 1.23–1.37), whereas the association between snoring and poor glycaemic control was only on the borderline of statistical significance.
Conclusions
Compared with a sleep duration of 6–7.9 h, longer sleep duration was associated with a higher prevalence of hypertension and poor glycaemic control in people with diabetes. Moreover, the relationship between sleep duration and prevalent hypertension was U‐shaped. These findings may propose important public health implications for diabetes management.
What's new?
Longer sleep duration (≥ 8 h) was positively associated with prevalent hypertension and poor glycaemic control in patients with diabetes, and the association between sleep duration and prevalent hypertension was U‐shaped. The findings may have implications for diabetes management.
A good modeling of the stress–strain behavior of FRP-confined concrete prism is necessary for the design of rectangular columns retrofitted with FRP composites. Existing stress–strain models for ...FRP-confined concrete prisms are mostly presented based on the concept of steel-confined concrete columns. Based on the results of more than one hundred specimens, the mechanical behavior of FRP-confined concrete prisms are studied in this paper. It is found that the stress–strain relationship of FRP-confined prism has either a strain-hardening or a strain-softening response, which mainly depends on the confinement strength of FRP, corner radius of cross-section, etc. Equations to predict the transitional stress and strain of FRP-confined concrete prisms are presented. By reducing the corresponding ultimate strength and strain of equivalent concrete cylinders confined with equivalent FRP, the ultimate strength and strain of FRP-confined concrete prisms can be predicted rationally. Three design-oriented models, which can be applied to various conditions, are suggested. The feature of those models is simple, and they agree well with extensive experimental results.
Pyrite-structured PdSb2 with the nonsymmorphic crystalline symmetry, has long been predicted to host sixfold-degenerate exotic fermions beyond Dirac and Weyl. Although magnetotransport measurements ...on PdSb2 have suggested its topologically nontrivial character, the direct spectroscopic evidence still remains absent. By utilizing high-resolution angle-resolved photoemission spectroscopy, we present a systematic study on the low-energy bulk and surface electronic structure of pyrite-structured PdSb2. Through careful comparison with first-principles calculations, we verify the existence of sixfold fermions in this compound, which are formed by three doubly degenerate bands centered at the R point in the Brillouin zone. These bands exhibit parabolic dispersion close to sixfold fermion nodes, in sharp contrast to previously reported sixfold double spin-1 chiral fermions. Furthermore, our findings reveal no protected Fermi arcs in PdSb2, which is compatible with its achiral structure. Our findings suggest that pyrite-structured PdSb2 provides an ideal platform for the investigation of fermions and their potential applications.
Abstract
The atmospheric abundance of
81
Kr is a global integrator of cosmic rays. It is insensitive to climate shifts, geographical variations, and short‐term solar cycle activity, making it an ...ideal standard to test models of cosmic‐ray flux on the time scale of 10
5
years. Here we present the first calculation of absolute
81
Kr production rates in the atmosphere, and a measurement of the atmospheric
81
Kr/Kr abundance via the Atom Trap Trace Analysis method. The measurement result significantly deviates from previously reported values. The agreement between measurement and model prediction supports the current understanding of the production mechanisms. Additionally, the calculated
81
Kr atmospheric inventory over the past 1.5 Myr provides a more accurate input function for radiokrypton dating.
Plain Language Summary
Krypton‐81 is a long‐lived radioactive isotope produced in the Earth's atmosphere by cosmic rays. It stays in the atmosphere as a noble gas for hundreds of thousands of years until its eventual nuclear decay. As a result, its abundance uniquely reflects the long‐term accumulation record of cosmic rays across the entire globe. We performed the first precise measurement of the atmospheric abundance of krypton‐81. The result agrees with the prediction of a realistic isotope production model, thus confirming the current understanding of the cosmic‐ray flux, isotope production mechanisms, and the past terrestrial and space magnetic field environment.
Key Points
Conducted new precision measurement of
81
Kr isotopic abundance in the atmosphere; new result differs significantly from previous values
First ever cosmic‐ray flux models of
81
Kr production in the atmosphere are presented; models successfully predict new measured value
Measurement and models provide more accurate input function for radiokrypton dating over the past 1.5 Myr
We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell ...death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT.
We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model.
We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein–Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008 and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51).
Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.
•Patients with dmNPC receiving chemotherapy plus anti-PD-1 mAbs had an ORR of 92.0% and a median PFS of 20 months.•Chemotherapy plus anti-PD-1 monoclonal antibodies followed by LRRT improves survival outcomes.•Early clearance of EBV DNA is a biomarker for identifying suitable LRRT candidates in the era of immunotherapy.
A reconnaissance investigation of noble gas radionuclides (39Ar, 81Kr, and 85Kr) in gas emissions from several geothermal features at Yellowstone National Park was performed to explore tracer ...applications of these nuclides in an active hydrothermal system. Prior studies of the Yellowstone system using stable noble gas isotopes show that the thermal fluids contain a mixture of atmospheric, mantle, and crustal components. Noble gas radionuclide measurements provide complementary chronometric information regarding subsurface residence times of thermal fluids, from decay of 81Kr and 85Kr as well as in situ production and release of nucleogenic 39Ar and radiogenic 40Ar* in the reservoir rock. Argon-39 isotopic abundances in air-corrected samples exceed those of atmospheric Ar by 705 to 1217%, indicating substantial Ar contribution to thermal fluids by fluid–rock interaction. Upper limits on deep thermal fluid mean residence times, estimated from 39Ar/40Ar* ratios, are about 100kyr for features in the Gibbon and Norris Geyser Basin areas, and is about 30kyr in Lower Geyser Basin, with the key assumption that the fluid acquires its crustal component of Ar in Quaternary volcanic rock of the Yellowstone caldera. Input of crustal Ar from older aquifer rocks would reduce these apparent mean residence times. 81Kr isotopic abundances in the gas samples yield upper limits on residence time that are consistent with those obtained from 39Ar/40Ar* ratios.
► We report abundances of 39Ar, 81Kr, and 85Kr in gas emissions at Yellowstone National Park ► Krypton-81 isotopic abundances yield residence time of <100 kyr ► Argon-39 isotopic abundances indicate contribution of nucleogenic Ar from rock. ► Thermal fluids' mean residence times are estimated from 39Ar/40Ar* ratios
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