The design, especially the numerical calibration, of a circular touch mode capacitive pressure sensor is highly dependent on the accuracy of the analytical solution of the contact problem between the ...circular conductive membrane and the rigid plate of the sensor. In this paper, the plate/membrane contact problem is reformulated using a more accurate in-plane equilibrium equation, and a new and more accurate analytical solution is presented. On this basis, the design and numerical calibration theory for circular touch mode capacitive pressure sensors has been greatly improved and perfected. The analytical relationships of pressure and capacitance are numerically calculated using the new and previous analytical solutions, and the gradually increasing difference between the two numerical calculation results with the gradual increase in the applied pressure is graphically shown. How to use analytical solutions and analytical relationships to design and numerically calibrate a circular touch mode capacitive pressure sensor with a specified pressure detecting range is illustrated in detail. The effect of changing design parameters on capacitance-pressure analytical relationships is comprehensively investigated; thus, the direction of changing design parameters to meet the required or desired range of pressure or capacitance is clarified.
Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo‐ and enantioselective ...synthetic methods for constructing C3 quaternary oxindoles have been well‐developed. However, the efficient synthesis of chiral 3‐substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N‐aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5‐tricyclic lactone core structure of Speradine A.
Ternary catalysis enabled the three‐component reaction of N‐aryl diazoamides, aldehydes, and enamines/indoles, providing access to polyfunctionalized oxindoles in good yields with excellent diastereoselectivities and enantioselectivities (>90 examples, up to 94 % yield, 99 % ee, and >20 : 1 dr). The reaction involves the assembly of two highly reactive intermediates generated in situ by orthogonal catalytic processes under mild and operationally simple reaction conditions.
Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β‐catenin pathway. Despite extensive research efforts, effective therapies are still not available. ...Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt‐mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor‐β (TGF‐β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α‐SMA and collagen I) and the TGF‐β signalling pathway that include smad2/3 and its phosphorylated form p‐smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β‐catenin revealed epithelial–mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β‐catenin in regulation of the signalling network, which acts to counteract autocrine TGF‐β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1‐smad2/3 signalling through Wnt/β‐catenin contribute to lung fibrosis.
Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain.
We performed ...two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used.
Forward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10
). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10
). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR.
We identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels.
Idiopathic pulmonary fibrosis is a persistent disease of the lung interstitium for which there is no efficacious pharmacological therapy. Protodioscin, a steroidal saponin, possesses diverse ...pharmacological properties; however, its function in pulmonary fibrosis is yet to be established. Hence, in this investigation, it was attempted to figure out the anti-pulmonary fibrosis influences of protodioscin and its pharmacological properties related to oxidative stress.
A mouse lung fibrosis model was generated using tracheal injections of bleomycin, followed by intraperitoneal injection of different concentrations of protodioscin, and the levels of oxidative stress and fibrosis were detected in the lungs. Multiple fibroblasts were treated with TGF-β to induce their transition to myofibroblasts. It was attempted to quantify myofibroblast markers' expression levels and reactive oxygen species levels as well as Nrf2 activation after co-incubation of TGF-β with fibroblasts and different concentrations of protodioscin. The influence of protodioscin on the expression and phosphorylation of p62, which is associated with Nrf2 activation, were detected, and p62 related genes were predicted by STRING database. The effects of Nrf2 inhibitor or silencing of the Nrf2, p62 and NBR1 genes, respectively, on the activation of Nrf2 by protodioscin were examined. The associations between p62, NBR1, and Keap1 in the activation of Nrf2 by protodioscin was demonstrated using a co-IP assay. Nrf2 inhibitor were used when protodioscin was treated in mice with pulmonary fibrosis and lung tissue fibrosis and oxidative stress levels were detected.
In vivo, protodioscin decreased the levels of fibrosis markers and oxidative stress markers and activated Nrf2 in mice with pulmonary fibrosis, and these effects were inhibited by Nrf2 inhibitor. In vitro, protodioscin decreased the levels of myofibroblast markers and oxidative stress markers during myofibroblast transition and promoted Nrf2 downstream gene expression, with reversal of these effects after Nrf2, p62 and NBR1 genes were silenced or Nrf2 inhibitors were used, respectively. Protodioscin promoted the binding of NBR1 to p62 and Keap1, thereby reducing Keap1-Nrf2 binding.
The NBR1-p62-Nrf2 axis is targeted by protodioscin to reduce oxidative stress and inhibit pulmonary fibrosis.
•Co-exposure of nano Fe2O3 and Cd2+ significantly promotes transfer of RP4 plasmid.•Antioxidant enzyme activities were enhanced by Cd2+-nano Fe2O3 treatment.•Bacterial cell permeability and ...conjugation genes expression were accelerated.•The majority of transconjugants were identified to be human pathogens.
Conjunctive transfer of antibiotic resistance genes (ARGs) among bacteria driven by plasmids facilitated the evolution and spread of antibiotic resistance. Heavy metal exposure accelerated the plasmid-mediated conjunctive transfer of ARGs. Nanomaterials are well-known adsorbents for heavy metals removal, with the capability of combatting resistant bacteria/facilitating conjunctive transfer of ARGs. However, co-effect of heavy metals and nanomaterials on plasmid-mediated conjunctive transfer of ARGs was still unknown. In this study, we investigated the effect of the simultaneous exposure of Cd2+ and nano Fe2O3 on conjugative transfer of plasmid RP4 from Pseudomonas putida KT2442 to water microbial community. The permeability of bacterial cell membranes, antioxidant enzyme activities and conjugation gene expression were also investigated. The results suggested that the combination of Cd2+ and high concentration nano Fe2O3 (10 mg/L and 100 mg/L) significantly increased conjugative transfer frequencies of RP4 plasmid (p < 0.05). The most transconjugants were detected in the treatment of co-exposure to Cd2+ and nano Fe2O3, the majority of which were identified to be human pathogens. The mechanisms of the exacerbated conjugative transfer of ARGs were involved in the enhancement of cell membrane permeability, antioxidant enzyme activities, and mRNA expression levels of the conjugation genes by the co-effect of Cd2+ and nano Fe2O3. This study confirmed that the simultaneous exposure to Cd2+and nano Fe2O3 exerted a synergetic co-effect on plasmid-mediated conjunctive transfer of ARGs, emphasizing that the co-effect of nanomaterials and heavy metals should be prudently evaluated when combating antibiotic resistance.
As an essential and universal hydrolase, alkaline phosphatase (ALP) has been identified as a crucial indicator of various diseases. Herein, we, for the first time, expanded the application of ...fluorescent polydopamine (F-PDA) nanoparticles to nanoquencher-based biosensing system, as well as discovered the reversible quenching effect of manganese dioxide (MnO2) nanosheets on the fluorescence of F-PDA nanoparticles and intensively confirmed the quenching mechanism of Förster resonance energy transfer by using transmission electron microscopy, UV–vis, Fourier transform infrared spectroscopy, and fluorescence lifetime experiments. By means of the ALP-triggered generation of ascorbic acid (AA) from the substrate ascorbic acid 2-phosphate, the AA-triggered reduction of MnO2 nanosheets to Mn2+, as well as the clear quenching mechanism of F-PDA nanoparticles by MnO2 nanosheets, we have developed a label-free, low-cost, visual, and facile synthetic fluorescent biosensor for convenient assay of ALP activity. The fluorescent bioassay shows a good linear relationship from 1 to 80 mU/mL (R 2 = 0.999), with a low detection limit of 0.34 mU/mL, and the excellent applicability in human serum samples demonstrates potential applications in clinical diagnosis and biomedical research.
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