Necroptosis, a novel type of programmed cell death, is involved in stroke-induced ischemic brain injury. Although studies have sought to explore the mechanisms of necroptosis, its signaling pathway ...has not yet to be completely elucidated. Thus, we used oxygen-glucose deprivation (OGD) and middle cerebral artery occlusion (MCAO) models mimicking ischemic stroke (IS) conditions to investigate mechanisms of necroptosis. We found that OGD and MCAO induced cell death, local brain ischemia and neurological deficit, while zVAD-fmk (zVAD, an apoptotic inhibitor), GSK'872 (a receptor interacting protein kinase-3 (RIP3) inhibitor), and combined treatment alleviated cell death and ischemic brain injury. Moreover, OGD and MCAO upregulated protein expression of the triggers of necroptosis: receptor interacting protein kinase-1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL). The upregulation of these proteins was inhibited by GSK'872, combination treatments and RIP3 siRNA but not zVAD treatment. Intriguingly, hypoxia-inducible factor-1 alpha (HIF-1α), an important transcriptional factor under hypoxic conditions, was upregulated by OGD and MCAO. Similar to their inhibitory effects on aforementioned proteins upregulation, GSK'872, combination treatments and RIP3 siRNA decreased HIF-1α protein level. These findings indicate that necroptosis contributes to ischemic brain injury induced by OGD and MCAO and implicate HIF-1α, RIP1, RIP3, and MLKL in necroptosis.
The catalytic bis‐allylation of alkynes is an important but challenging protocol to construct all‐carbon tetra‐substituted alkenes. Particularly, the catalytic unsymmetrical bis‐allylation of alkynes ...remains as an underexplored task to date. We herein report an unprecedented unsymmetrical bis‐allylation by simultaneously utilizing electrophilic trifluoromethyl alkene and nucleophilic allylboronate as the allylic reagents. With the aid of robust Ni0/NHC catalysis, valuable skipped trienes can be obtained in high regio‐ and stereo‐selectivities under mild conditions. Mechanistic studies indicate that the reaction may proceed through a β‐fluorine elimination of a nickelacycle followed by a transmetalation step with allylboronate. The present method exhibits a good tolerance of various functional groups. Besides, the skipped triene products can undergo an array of elaborate transformations, which highlights the potential applications of this strategy.
An efficient unsymmetrical bis‐allylation of alkynes has been developed by simultaneously utilizing electrophilic trifluoromethyl alkenes and nucleophilic allylboronates as the allylic reagents. With the aid of a robust Ni0/NHC catalysis, valuable skipped trienes can be obtained in high regio‐ and stereo‐selectivities under mild conditions.
Online shopping is becoming one of the most popular applications on the Internet. Websites are the important interfaces in HCI (Human–Computer Interaction). Website design significantly affects ...online shopping behavior. This research used eye-tracker to track the eye-movement process for 42 college students when they were surfing websites with different levels of complexity and completing simple and complex tasks respectively. The study examines how website complexity and task complexity jointly affect users' visual attention and behavior due to different cognitive loads. The study fills a research gap by examining this phenomenon from the cognitive load perspective and taking the moderate effect of task complexity into consideration. The results show that task complexity can moderate the effect of website complexity on users' visual attention and behavior. Specifically, when users conducted a simple task, fixation count and task completion time were at the highest level on the website with high complexity, while fixation duration was not significantly different on the websites with different complexity. However, when users conducted a complex task on a website with medium complexity, task completion time, fixation count, and fixation duration were all at their highest level. The load theory of attention was used to provide the explanation for the results. The findings provide guidelines for website managers and designers to maximize users' visual attention.
•Investigate the interaction effect of website complexity and task complexity•Employ eye-tracking method•Task complexity can moderate the effect of website complexity on users' attention.•Provide the explanation for the findings from the perspective of cognitive load•Provide guidelines for website managers and designers
Optical biosensor, which perceptively captures the variety of refractive index (RI) of the surrounding environment, has great potential applications in detecting property changes and types of ...analytes. However, the disequilibrium of light-matter interaction in different polarizations lead to the polarization-dependence and low sensitivity. Here, we propose a polarization-independent and ultrasensitive biosensor by introducing a one-dimensional topological photonic crystal (1D TPhC), where two N-period 1D photonic crystals (PhC1 and PhC2) with different topological invariants are designed for compressing the interaction region of the optical fields, and enhancing the interaction between the light and analyte. Since the strong light-matter interaction caused by the band-inversion is polarization-independent, the biosensor can obtain superior sensing performance both for TE and TM polarization modes. The sensitivity and Figure of Merit (FOM) of the designed biosensor are 1.5677×10
6
RIU
−1
(1.3497 × 10
6
RIU
−1
) and 7.8387×10
10
RIU
−1
deg
−1
(4.4990×10
10
RIU
−1
deg
−1
) for TM (TE) polarization mode, which performs two orders of magnitude enhancement compared with the reported biosensors. With the protection of the topological edge state, this biosensor has high tolerance to the thickness deviations and refractive index (RI) variations of the component materials, which can reduce the requirements on fabrication and working environment. It is anticipated that the proposed biosensor possesses excellent sensing performances, may have great potentials in environmental monitoring, medical detection, etc.
A hardware-friendly bisection neural network (BNN) topology is proposed in this work for approximately implementing massive pieces of complex functions in arbitrary on-chip configurations. Instead of ...the conventional reconfigurable fully connected neural network (FC-NN) circuit topology, the proposed hardware-friendly topology performs NN behaviors in a bisection structure, in which each neuron includes two constant synapse connections for both inputs and outputs. Compared with the FC-NN one, the reconfiguration of the BNN circuit topology eliminates the remarkable amount of dummy synapse connections in hardware. As the main target application, this work aims at building a general-purpose BNN circuit topology that offers a great amount of NN regressions. To achieve this target, we prove that the NN behaviors of the FC-NN circuit topologies can be migrated to the BNN circuit topologies equivalently. We introduce two approaches including the refining training algorithm and the inverted-pyramidal strategy to further reduce the number of neurons and synapses. Finally, we conduct the inaccuracy tolerance analysis to suggest the guideline for ultra-efficient hardware implementations. Compared with the state-of-the-art FC-NN circuit topology-based TrueNorth baseline, the proposed design can achieve 17.8-22.2<inline-formula> <tex-math notation="LaTeX">\times</tex-math> </inline-formula> hardware reduction and less than 1% inaccuracy.
The confined surface plasmon of fundamental wave and second harmonic wave (SHW) are investigated in graphene grating structure. The linear-optical absorption spectra with various fermi energy and ...carrier mobility are investigated with the finite difference time domain (FDTD) simulations and coupled mode theory (CMT). Based on the CMT, a theoretical model for the graphene grating is established to study the spectrum features of fundamental wave. The lifetimes of linear-optical resonant modes in theoretical model are investigated through the theoretical fitting of exact values in simulation, which are tunable with both the fermi energy and carrier mobility. We also have investigated the second-order nonlinearity of graphene grating by introducing the second-order nonlinear source. The proposed configuration and method are useful for research of the absorption, local field enhancement factor, lifetime of light, and nonlinear optical processes in highly integrated graphene photoelectric devices.
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the ...main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the
in vivo
therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)–fed mice and oleic acid (OA)–treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis
via
GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased
Lactobacillus
and
Romboutsia
, while BBR increased beneficial bacteria, such as
Akkermansia
and
Bacteroides
, and BRB increased beneficial bacteria, such as
Ileibacterium
and
Mucispirillum
. Altogether, both BRB and BBR were active in alleviating NAFLD
in vivo
and BRB might be used as a functional material to treat NAFLD clinically.
Glycyrrhhizic acid (GA), including 18α-glycyrrhizic acid (18α-GA) and 18β-glycyrrhizic acid (18β-GA), is the main active ingredient of licorice. GA is generally considered an effective ...pharmacological strategy protecting against hepatic disease; however, the optimal compatibility proportion of 18α-GA and 18β-GA against alcoholic liver disease (ALD) and the underlying mechanism are not well established. Hence, this study was designed to explore the optimal compatibility proportion of 18α-GA and 18β-GA against ALD, followed by investigating the underlying mechanisms. SD rats were administered 40% ethanol once a day, accompanied by treatment with different proportions of 18α-GA and 18β-GA for four weeks. Then all rats were anesthetized with chloral hydrate and blood samples were taken from the abdominal aorta for biochemical assay. Livers were also collected and the liver function, lipid profile, ROS production, and mRNA and protein levels of related genes involved in lipid metabolism were assessed. The results showed that 18α-GA and 18β-GA, particularly at a proportion of 4:6, significantly reduced liver damage, lipid accumulation, and oxidative stress in ethanol-induced rats, as indicated by the decreased levels of alanine aminotransferase (ALT) and aminotransferase (AST) in serum, improvement of liver histopathological changes, regulation of total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), and modulation of superoxide dismutase (SOD), glutathione (GSH), and malonaldehyde (MDA). Moreover, the combination treatment with 18α-GA and 18β-GA substantially reduced the mRNA and protein levels of sterol regulatory element-binding protein-1c (SREBP-1c) and acetyl-coal carboxylase (ACC); meanwhile, increased levels of peroxisome proliferators activated receptor-α (PPAR-α) and carnitine palmitoy transferase-1 (CTP-1) in the liver tissues of ethanol-induced rats. In conclusion, our results indicated that the optimal compatibility proportion of 18α-GA and 18β-GA protecting against ALD was 4:6, and the mechanism was associated with the regulation of oxidative stress and lipid metabolism.
Although it had been reported that Israeli acute paralysis virus (IAPV) can cause systemic infection in honey bees, little is known about how it establishes this infection and results in the typical ...symptoms, paralysis and trembling. Here, we used our previously constructed IAPV infectious clone to investigate viral loads in different tissues of honey bees and further identify the relation between tissue tropism and paralytic symptoms. Our results showed that tracheae showed a greater concentration of viral abundance than other tissues. The abundance of viral protein in the tracheae was positively associated with viral titers, and was further confirmed by immunological and ultrastructural evidence. Furthermore, higher viral loads in tracheae induced remarkable down-regulation of succinate dehydrogenase and cytochrome c oxidase genes, and progressed to causing respiratory failure of honey bees, resulting in the appearance of typical symptoms, paralysis and body trembling. Our results showed that paralysis symptoms or trembling was actually to mitigate tachypnea induced by IAPV infection due to the impairment of honey bee tracheae, and revealed a direct causal link between paralysis symptoms and tissue tropism. These findings provide new insights into the understanding of the underlying mechanism of paralysis symptoms of honey bees after viral infection and have implications for viral disease prevention and specific therapeutics in practice.
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