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•A novel CNTs@HEA hybrid reinforcement was prepared.•CNTs with good structural integrity were evenly dispersed into the Al matrix owing to the carrying effect of HA particles.•The ...precipitation of Al4C3 and Cr7C3 enhanced the interface bonding of CNT/Al and results in bimodal grain distribution.•The high strength of composite can attribute to the multi-phase coupling synergistic strengthening effect.•The good ductility of the composite is attributed to the bimodal grain distribution and the existence of stacking faults.
Here we present a novel design strategy for the manufacturing carbon nanotube (CNT)-high entropy alloy (HEA) particles co-reinforced aluminum matrix composites (AMCs) with heterogeneous structures. This strategy involves in situ synthesis of CNTs@HEA hybrid reinforcement. The results demonstrate that the fabricated CNTs@HEA/Al composites have bimodal grain structure and nano-reinforced particle spatial distribution. The dispersion of CNTs within the Al matrix was achieved via the transport of micron-sized HEA particles. Simultaneously, the formation of Al4C3 and Cr7C3 occurred at the HEA/CNTs/Al interface, thereby augmenting the load-bearing capacity of CNTs. The enhanced strength of CNTs@HEA/Al composites is mainly attributed to the synergistic effect of load transfer, back stress strengthening, Orowan strengthening, grain refinements and stacking faults (SFs) strengthening. Moreover, the bimodal grains and SFs of the composite contribute sustained strain hardening, resulting in satisfactory tensile ductility.
Current practical methods for finding the equilibrium dissociation constant, Kd, of protein–small molecule complexes have inherent sources of inaccuracy. Introduced here is “accurate constant via ...transient incomplete separation” (ACTIS), which appears to be free of inherent sources of inaccuracy. Conceptually, a short plug of the pre‐equilibrated protein–small molecule mixture is pressure‐propagated in a capillary, causing fast transient incomplete separation of the complex from the unbound small molecule. A superposition of signals from these two components is measured near the capillary exit and used to calculate a fraction of unbound small molecule, which, in turn, is used to calculate Kd. Herein the validity of ACTIS is proven theoretically, its accuracy is verified by computer simulation, and its practical use is demonstrated. ACTIS has the potential to become a reference‐standard method for determining Kd values of protein–small molecule complexes.
Constant focus: Introduced here is a method called accurate constant via transient incomplete separation (ACTIS). This approach serves to measure accurate equilibrium dissociation constants (Kd) of protein–small molecule complexes (PL).
Hydrogen peroxide (H(2)O(2)) is emerging as a ubiquitous small-molecule messenger in biology, particularly in the brain, but underlying mechanisms of peroxide signaling remain an open frontier for ...study. For example, dynamic dopamine transmission in dorsolateral striatum is regulated on a subsecond timescale by glutamate via H(2)O(2) signaling, which activates ATP-sensitive potassium (K(ATP)) channels to inhibit dopamine release. However, the origin of this modulatory H(2)O(2) has been elusive. Here we addressed three possible sources of H(2)O(2) produced for rapid neuronal signaling in striatum: mitochondrial respiration, monoamine oxidase (MAO), and NADPH oxidase (Nox). Evoked dopamine release in guinea-pig striatal slices was monitored with carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Using direct fluorescence imaging of H(2)O(2) and tissue analysis of ATP, we found that coapplication of rotenone (50 nM), a mitochondrial complex I inhibitor, and succinate (5 mM), a complex II substrate, limited H(2)O(2) production, but maintained tissue ATP content. Strikingly, coapplication of rotenone and succinate also prevented glutamate-dependent regulation of dopamine release, implicating mitochondrial H(2)O(2) in release modulation. In contrast, inhibitors of MAO or Nox had no effect on dopamine release, suggesting a limited role for these metabolic enzymes in rapid H(2)O(2) production in the striatum. These data provide the first demonstration that respiring mitochondria are the primary source of H(2)O(2) generation for dynamic neuronal signaling.
The back-streaming neutrons (back-n) is a white neutron experimental facility at the China spallation neutron source (CSNS). The time structure of the primary proton beam makes it fully applicable to ...use the time-of-flight (TOF) method for neutron energy measuring. We implemented the electronics of TOF measurement on the general-purpose readout electronics designed for all the seven detectors in back-n. The electronics are based on the peripheral component interconnect express eXtensions for instrumentation (PXIe) platform, which is composed of field digitizer modules (FDM), trigger and clock modules (TCM), and signal conditioning modules. The T0 signal synchronous to the CSNS accelerator represents the neutron emission from the target. It is the start of the time stamp. The TCM receives, synchronizes, and distributes the T0 signal to each FDM based on the PXIe backplane bus. Meanwhile, the detector signals, after being conditioned, are fed into FDMs for waveform digitizing. The first sample point of the signal waveform is the stop of the time stamp. According to the time stamp and the time of the signal over the threshold, the total TOF can be obtained. The time-to-digital converter (TDC) based on field-programmable gate array (FPGA) is implemented on the TCM to accurately acquire the time interval between the asynchronous T0 signal and the global synchronous clock phase. There is also an FPGA-based TDC on the FDM to accurately acquire the time interval between the T0 signal arriving at the FDM and the first sample point of the signal waveform. The over-threshold time of signal is obtained offline. This method for TOF measurement is efficient and not needed for additional modules. Test results showed that the accuracy of TOF is subnanosecond and can meet the requirement for back-n at the CSNS.
The differentiation deficiencies of osteoclast precursors (pre-OCs) may contribute to osteoporosis. Research on osteoporosis has recently focused on microRNAs (miRNAs) that play crucial roles in ...pre-OC differentiation. In the current study, we aimed to analyze the expression and function of the glucocorticoid (GC)-associated miRNA-338-3p (miR-338-3p) in osteoclast formation. We found that dexamethasone induced osteoclast differentiation and inhibited miR-338-3p expression. Overexpression of an miR-338-3p mimic in osteoclast precursor cells attenuated GC-induced osteoclast formation and bone resorption, whereas inhibition of miR-338-3p reversed these effects. The expression of the nuclear factor κB ligand RANKL, a potential target gene of miR-338-3p, was inversely correlated with miR-338-3p expression in pre-OCs. Furthermore, we demonstrated that RANKL was directly regulated by miR-338-3p and re-introduction of RANKL reversed the inhibitory effects of miR-338-3p on osteoclast formation and bone resorption. Taken together, these findings demonstrate that miR-338-3p may play a significant role in GC-induced osteoclast differentiation and function by targeting RANKL in osteoclasts.
The chemokine receptor CXCR3 promotes the trafficking of activated T and NK cells in response to three ligands, CXCL9, CXCL10, and CXCL11. Although these chemokines are produced in the CNS in ...multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), their role in the pathogenesis of CNS autoimmunity is unresolved. We examined the function of CXCR3 signaling in EAE using mice that were deficient for CXCR3 (CXCR3(-/-)). The time to onset and peak disease severity were similar for CXCR3(-/-) and wild-type (WT) animals; however, CXCR3(-/-) mice had more severe chronic disease with increased demyelination and axonal damage. The inflammatory lesions in WT mice consisted of well-demarcated perivascular mononuclear cell infiltrates, mainly in the spinal cord and cerebellum. In CXCR3(-/-) mice, these lesions were more widespread throughout the CNS and were diffused and poorly organized, with T cells and highly activated microglia/macrophages scattered throughout the white matter. Although the number of CD4(+) and CD8(+) T cells infiltrating the CNS were similar in CXCR3(-/-) and WT mice, Foxp3(+) regulatory T cells were significantly reduced in number and dispersed in CXCR3(-/-) mice. The expression of various chemokine and cytokine genes in the CNS was similar in CXCR3(-/-) and WT mice. The genes for the CXCR3 ligands were expressed predominantly in and/or immediately surrounding the mononuclear cell infiltrates. We conclude that in EAE, CXCR3 signaling constrains T cells to the perivascular space in the CNS and augments regulatory T cell recruitment and effector T cell interaction, thus limiting autoimmune-mediated tissue damage.
Puberty is a so-called critical period for overweight development and is characterized by physiological insulin resistance during mid-puberty. This study addressed the hypothesis that habitual ...consumption of a diet inducing higher levels of postprandial glycemia or insulinemia during puberty may have an unfavorable effect on the body composition in young adulthood.
Multivariate regression analysis was performed on 262 participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study with at least two 3-day weighed dietary records during puberty (baseline: girls 9-14 years; boys 10-15 years) and anthropometric measurements in young adulthood (18-25 years). A published dietary glycemic index was assigned to each carbohydrate-containing food. Similarly, each food was assigned a food insulin index (insulinemic response to a 1 MJ portion of food relative to 1 MJ of glucose) using 121 values measured at Sydney University.
Dietary glycemic index or glycemic load during puberty was not related to body composition in young adulthood. In contrast, a higher dietary insulin index and a higher dietary insulin load during puberty were associated with higher levels of percentage of body fat (%BF) in young adulthood, even after adjustment for early life, socioeconomic and nutritional factors; %BF in energy-adjusted tertiles of dietary insulin index were 22.9 (95% confidence intervals (CI): 21.6, 24.1), 24.5 (23.2, 25.7), 24.7 (23.5, 25.9) %, P (for trend)=0.01; %BF in energy-adjusted tertiles of dietary insulin load were 22.8 (95% CI: 21.5, 24.0), 24.5 (23.2, 25.7), 24.8 (23.6, 26.0) %, P (for trend)=0.01. Adjustment for baseline %BF attenuated these relationships (P (for trend)=0.1 and=0.08, respectively). Dietary insulin demand was not related to body mass index.
This study suggests a prospective adverse influence of dietary insulin demand during puberty on %BF in young adulthood. Postprandial increases in insulinemia rather than increases in glycemia appear to be implicated in an unfavorable development of body composition.
Pulmonary arterial hypertension (PAH) is characterized by sustained elevation of pulmonary vascular resistance resulting from endothelial and smooth muscle cell dysfunction and collagen deposition in ...pulmonary vascular walls. In this study, we investigated the role of the adenosine A(2A) receptor (A(2A)R) in the development of PAH by determining the effect of genetic inactivation of A(2A)Rs on pulmonary vascular remodeling in mice.
We characterized hemodynamic, histological and ultrastructural changes in pulmonary vascular remodeling in A(2A)R knockout (KO) mice compared with their wild-type (WT) littermates after exposure to normoxia and hypoxic conditions. After exposure to normoxia, compared to WT mice, A(2A)R KO mice displayed: (1) increased right ventricular systolic pressures and an elevated ratio of the right ventricle over left ventricle plus septum (Fulton index), (2) increased wall area and thickness as well as enhanced smooth muscle actin immunoreactivity in pulmonary resistance vessels, (3) increased proliferating cell nuclear antigen-positive cells in pulmonary resistance vessels and (4) increased smooth muscle cells hypertrophy and collagen deposition in the adventitia of pulmonary arteriole walls as revealed by electron microscope. By contrast, histological analysis revealed no features of hypertensive nephropathy in A(2A)R KO mice and there was no significant difference in systemic blood pressure, and left ventricular masses among the 3 genotypes. Furthermore, following chronic exposure to hypoxia, A(2A)R KO mice exhibited exacerbated elevation in right ventricular systolic pressure, hypertrophy of pulmonary resistance vessels and increased cell proliferation in pulmonary resistance vessels, compared to WT littermates. Thus, genetic inactivation of A(2A)Rs selectively produced PAH and associated increased smooth muscle proliferation and collagen deposition.
Extracellular adenosine acting at A(2A)Rs represents an important regulatory mechanism to control the development of PAH and pulmonary vascular remodeling.
The p-type Bi0.4Sb1.6Te3 system compounds with fine microstructure were prepared by mechanical alloying (MA) and equal channel angular extrusion (ECAE) in the present work. A preferentially ...orientated microstructure that the (1 1 0) plane preferentially orientated along the perpendicular direction to extrusion and the basal planes (0 0 l) preferentially orientated along the extrusion direction was formed in the ECAE process, and the orientation factors F of the basal planes (0 0 l) of the extruded alloys was about 0.36. The electrical and thermal transmission performances were strongly affected by the preferential orientation and the thermoelectric properties in the extrusion direction were obviously improved by the ECAE process. The maximum dimensionless figure of merit of the 4 wt.% Te-doped Bi0.4Sb1.6Te3 alloys was obtained in the extrusion direction at testing temperature 343 K, ZT = 0.979.
Rabies is one of the major public health problems in China, and the mortality rate of rabies remains the highest among all notifiable infectious diseases. A meta-analysis was conducted to investigate ...the post-exposure prophylaxis (PEP) vaccination rate and risk factors for human rabies in mainland China. The PubMed, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical and Wanfang databases were searched for articles on rabies vaccination status (published between 2007 and 2017). In total, 10 174 human rabies cases from 136 studies were included in this meta-analysis. Approximately 97.2% (95% confidence interval (CI) 95.1-98.7%) of rabies cases occurred in rural areas and 72.6% (95% CI 70.0-75.1%) occurred in farmers. Overall, the vaccination rate in the reported human rabies cases was 15.4% (95% CI 13.7-17.4%). However, among vaccinated individuals, 85.5% (95% CI 79.8%-83.4%) did not complete the vaccination regimen. In a subgroup analysis, the PEP vaccination rate in the eastern region (18.8%, 95% CI 15.9-22.1%) was higher than that in the western region (13.3%, 95% CI 11.1-15.8%) and this rate decreased after 2007. Approximately 68.9% (95% CI 63.6-73.8%) of rabies cases experienced category-III exposures, but their PEP vaccination rate was 27.0% (95% CI 14.4-44.9%) and only 6.1% (95% CI 4.4-8.4%) received rabies immunoglobulin. Together, these results suggested that the PEP vaccination rate among human rabies cases was low in mainland China. Therefore, standardised treatment and vaccination programs of dog bites need to be further strengthened, particularly in rural areas.
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