A great deal of concern has recently arisen regarding the safety of anaesthesia in infants and children. There is mounting and convincing preclinical evidence in rodents and non-human primates that ...anaesthetics in common clinical use are neurotoxic to the developing brain in vitro and cause long-term neurobehavioural abnormalities in vivo. An estimated 6 million children (including 1.5 million infants) undergo surgery and anaesthesia each year in the USA alone, so the clinical relevance of anaesthetic neurotoxicity is an urgent matter of public health. Clinical studies that have been conducted on the long-term neurodevelopmental effects of anaesthetic agents in infants and children are retrospective analyses of existing data. Two large-scale clinical studies are currently underway to further address this issue. The PANDA study is a large-scale, multisite, ambi-directional sibling-matched cohort study in the USA. The aim of this study is to examine the neurodevelopmental effects of exposure to general anaesthesia during inguinal hernia surgery before 36 months of age. Another large-scale study is the GAS study, which will compare the neurodevelopmental outcome between two anaesthetic techniques, general sevoflurane anaesthesia and regional anaesthesia, in infants undergoing inguinal hernia repair. These study results should contribute significant information related to anaesthetic neurotoxicity in children.
Abstract
Two-dimensional (2D) topological insulators (TIs) are promising platforms for low-dissipation spintronic devices based on the quantum-spin-Hall (QSH) effect, but experimental realization of ...such systems with a large band gap suitable for room-temperature applications has proven difficult. Here, we report the successful growth on bilayer graphene of a quasi-freestanding WSe
2
single layer with the 1
T
′ structure that does not exist in the bulk form of WSe
2
. Using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy/spectroscopy (STM/STS), we observe a gap of 129 meV in the 1
T
′ layer and an in-gap edge state located near the layer boundary. The system′s 2D TI characters are confirmed by first-principles calculations. The observed gap diminishes with doping by Rb adsorption, ultimately leading to an insulator–semimetal transition. The discovery of this large-gap 2D TI with a tunable band gap opens up opportunities for developing advanced nanoscale systems and quantum devices.
Prostate cancer cells escape growth inhibition from transforming growth factor β (TGFβ) by downregulating TGFβ receptors. However, the mechanism by which cancer cells downregulate TGFβ receptors in ...prostate is not clear. Here, we showed that coordinated action of miR-21 and androgen receptor (AR) signaling had a critical role in inhibiting TGFβ receptor II (TGFBR2) expression in prostate cancer cells. Our results revealed that miR-21 suppresses TGFBR2 levels by binding to its 3'-UTR and AR signaling further potentiates this effect in both untransformed and transformed human prostate epithelial cells as well as in human prostate cancers. Analysis of primary prostate cancers showed that increased miR-21/AR expression parallel a significantly reduced expression of TGFBR2. Manipulation of androgen signaling or the expression levels of AR or miR-21 negatively altered TGFBR2 expression in untransformed and transformed human prostate epithelial cells, human prostate cancer xenografts and mouse prostate glands. Importantly, we demonstrated that miR-21 and AR regulated each other's expression resulting in a positive feedback loop. Our results indicated that miR-21/AR mediate its tumor-promoting function by attenuating TGFβ-mediated Smad2/3 activation, cell growth inhibition, cell migration and apoptosis. Together, these results suggest that the AR and miR-21 axis exerts its oncogenic effects in prostate tumors by downregulating TGFBR2, hence inhibiting the tumor-suppressive activity of TGFβ pathway. Targeting miR-21 alone or in combination with AR may restore the tumor inhibitory activity of TGFβ in prostate cancer.
Two-mode interferometers lay the foundations for quantum metrology. Instead of exploring quantum entanglement in the two-mode interferometers, a single bosonic mode also promises a measurement ...precision beyond the shot-noise limit (SNL) by taking advantage of the infinite-dimensional Hilbert space of Fock states. Here, we demonstrate a single-mode phase estimation that approaches the Heisenberg limit (HL) unconditionally. Due to the strong dispersive nonlinearity and long coherence time of a microwave cavity, quantum states of the form Formula: see text can be generated, manipulated and detected with high fidelities, leading to an experimental phase estimation precision scaling as ∼N
. A 9.1 dB enhancement of the precision over the SNL at N = 12 is achieved, which is only 1.7 dB away from the HL. Our experimental architecture is hardware efficient and can be combined with quantum error correction techniques to fight against decoherence, and thus promises quantum-enhanced sensing in practical applications.
•An alternating test of chloride immersion diffusion and freeze-thaw was carried out.•The test process is more in line with the actual situation of high latitudes.•Total amount of chloride transport ...is larger than diffusion amount.•Boundary concentration of chloride increases with the freeze-thaw cycles.•Phase transition of pore solution can also drive the migration of chloride ions.
For the reinforced concrete structure in high latitude marine environment, the influence of freeze-thaw on chloride ion transport has been paid more and more attention. This paper intends to explore whether there is any other unknown coupling mode, by an alternating experiment of rapid freeze-thaw and chloride diffusion. For the purpose of data comparison, the tests of pure immersion diffusion are also carried out. It is found that the transport rate of chloride ions in the alternating test is significantly higher than that in the control groups; and the boundary concentration increases with the number of freeze-thaw cycles. The result indicates that there exists another influence mechanism of freeze-thaw on the transport of chloride ions, in addition to increasing the diffusion coefficient. Then, a new hypothesis mode is proposed and its mechanism is explained from the micro scale, i.e. the phase transition of pore solution during the freeze-thaw process can drive the migration of chloride ions dissolved in it.
AIM: The goal of this study was to investigate the synergic effects between magnolol and azoles, and the potential antifungal mechanisms. METHODS AND RESULTS: Microdilution checkerboard, time‐kill ...and agar diffusion assay were employed to evaluate the synergic effects between magnolol and fluconazole (FLC). Magnolol significantly decreased the efflux of rhodamine 123 (Rh123), leading to greater intracellular accumulation of Rh123 in Candida albicans cells. Compared to the Candida drug resistance (cdr) 2 or multidrug resistance (mdr) 1 deletion mutant, the growth of cdr1 strain was most sensitive to magnolol exposure. In the presence of magnolol, MDR1 overexpressing cells were sensitive to FLC, whereas CDR1 and CDR2 overexpressing cells displayed tolerance to FLC. Magnolol treatment correlated with up‐regulation of transporter and ergosterol biosynthesis pathway genes, analyzed by real‐time reverse transcription‐polymerase chain reaction. The ergosterol content of C. albicansSC5314 was significantly decreased after magnolol exposure. CONCLUSIONS: Magnolol synergizes with azoles for targeting of C. albicans by inducing a higher intracellular content of antifungals, by tapping into the competitive effect of ABC transporter Cdr1p substrates, and enhancing the effect by targeting of the ergosterol biosynthesis pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide the first evidence that magnolol may function as a Cdr1p substrate and as an inhibitor of ergosterol biosynthesis. This function can thus be exploited in combination with azoles to reverse multidrug resistance of C. albicans strains.
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