•Baicalein alleviates HP.•Baicalein inhibits pyroptosis and inflammation by upregulating miR-192-5p.•miR-192-5p targets TXNIP.•Silencing miR-192-5p or TXNIP overexpression abolishes baicalein’s ...effect.•Baicalein mitigates pyroptosis and inflammation in HP via the NLRP3/Caspase-1.
Hyperlipidemia is a main reason of pancreatitis. Baicalein can ameliorate the pathological manifestations of pancreatitis. This study evaluated underlying molecular mechanism of baicalein in hyperlipidemic pancreatitis (HP).
HP rat model was successfully established and treated with baicalein. Amylase (AMY) activity and concentrations of triglyceride (TG) and total cholesterol (TC) were detected. Levels of pyroptosis-related proteins (GSDMD, IL-1β, IL-18) were detected by Western blot. Expressions of inflammatory factors (IL-6, TNF-α, IL-4) were detected by ELISA. Toxicity of baicalein on pancreatic acinar cells (PACs) was detected by MTT assay. HP cell model was established by 0.1 mM palmitic acid and CCK-8 stimulation. Target relation of miR-192-5p and TXNIP was predicted and verified by RNA22 v2 database and dual-luciferase reporter assay. Expressions of miR-192-5p and TXNIP were detected by RT-qPCR. Pyroptosis and inflammation in PACs were detected after baicalein treatment combined with silencing miR-192-5p or TXNIP overexpression. Protein levels of NLRP3/Caspase-1 pathway in vivo and vitro were detected.
Baicalein reduced concentrations of TG and TC, AMY activity, and pathological scores in HP rat model, reduced LDH activity, pyroptosis and alleviated inflammation in vivo and in vitro. Mechanically, miR-192-5p targeted TXNIP, and baicalein inhibited pyroptosis and inflammation by up-regulating miR-192-5p and down-regulating TXNIP. Silencing miR-192-5p or TXNIP overexpression partially abolished the anti-pyroptosis and anti-inflammatory effect of baicalein on PACs. Baicalein attenuated HP by inhibiting the NLRP3/Caspase-1 pathway.
Baicalein alleviated pyroptosis and inflammation in HP by inhibiting the NLRP3/Caspase-1 pathway through miR-192-5p upregulation and TXNIP inhibition.
Damaged deoxyribonucleic acid (DNA) is a primary pathologic factor for osteoarthritis (OA); however, the mechanism by which DNA damage drives OA is unclear. Previous research demonstrated that the ...cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) participates in DNA damage response. As a result, the current study aimed at exploring the role STING, which is the major effector in the cGAS-STING signaling casacde, in OA progress in vitro, as well as in vivo. In this study, the expression of STING was evaluated in the human and mouse OA tissues, and in chondrocytes exposed to interleukin-1 beta (IL-1β). The influences of STING on the metabolism of the extracellular matrix (ECM), apoptosis, and senescence, were assessed in STING overexpressing and knocking-down chondrocytes. Moreover, the NF-κB-signaling casacde and its role in the regulatory effects of STING on ECM metabolism, apoptosis, and senescence were explored. The STING knockdown lentivirus was intra-articularly injected to evaluate its therapeutic impact on OA in mice in vivo. The results showed that the expression of STING was remarkably elevated in the human and mouse OA tissues and in chondrocytes exposed to IL-1β. Overexpression of STING promoted the expression of MMP13, as well as ADAMTS5, but suppressed the expression of Aggrecan, as well as Collagen II; it also enhanced apoptosis and senescence in chondrocytes exposed to and those untreated with IL-1β. The mechanistic study showed that STING activated NF-κB signaling cascade, whereas the blockage of NF-κB signaling attenuated STING-induced apoptosis and senescence, and ameliorated STING-induced ECM metabolism imbalance. In in vivo study, it was demonstrated that STING knockdown alleviated destabilization of the medial meniscus-induced OA development in mice. In conclusion, STING promotes OA by activating the NF-κB signaling cascade, whereas suppression of STING may provide a novel approach for OA therapy.
Based on a symmetrical cable-stayed bridge, the wind resistance performance of a proposed π-type composite beam is analyzed, and the influence of changing the bridge deck cross slope ratio on the ...static and dynamic wind characteristics is emphatically studied. The purpose is to provide a design reference for the preliminary wind resistance study of the cable-stayed bridge. The CFD (Computational Fluid Dynamics) numerical calculation method is used to solve the vibration problem of wind-bridge coupling with the help of the software Fluent. It is found that variation of four deck cross slope rates 0%, 1.5%, 2%, and 2.5% has large effects on the static wind coefficient and flutter critical wind speed of a π-type combination beam. In the range of a −3–3° wind attack angle, the static wind drag coefficient will be decreased as the beam deck cross slope rate increases, and in which the drag coefficient at 0% slope rate is the largest. Within the discounted wind speed 13, changing the bridge deck cross slope has little effect on the aerodynamic derivatives of a π-type composite beam. However, the beam deck slope increases the critical wind speed of the bridge, and the critical wind speed at 2.5% is the largest of the four deck slope rates. In addition, it is found that the beam leeward surface keeps generating up and down vortices when the incoming flow wind speed is in the range of 2.5–4.0 m/s, which led the beam to be under vertical vortex vibration, and further research is needed on vibration suppression measures.
The conjugation of biomolecules by chemoselective oxime ligation is of great interest for the site-specific modification of proteins, peptides, nucleic acids, and carbohydrates. These conjugations ...proceed optimally at a reaction pH of 4–5, but some biomolecules are not soluble or stable under these conditions. Aniline can be used as a nucleophilic catalyst to enhance the rate of oxime formation, but even in its presence, the reaction rate at neutral pH can be slower than desired, particularly at low reagent concentrations and/or temperature. Recently, alternative catalysts with improved properties were reported, including anthranilic acid derivatives for small molecule ligations, as well as m-phenylenediamine at high concentrations for protein conjugations. Here, we report that p-substituted anilines containing an electron-donating ring substituent are superior catalysts of oxime-based conjugations at pH 7. One such catalyst, p-phenylenediamine, was studied in greater detail. This catalyst was highly effective at neutral pH, even at the low concentration of 2 mM. In a model oxime ligation using aminooxy-functionalized PEG, catalysis at pH 7 resulted in a 120-fold faster rate of protein PEGylation as compared to an uncatalyzed reaction, and 19-fold faster than the equivalent aniline-catalyzed reaction. p-Phenylenediamine (10 mM) was also an effective catalyst under acidic conditions and was more efficient than aniline throughout the pH range 4–7. This catalyst allows efficient oxime bioconjugations to proceed under mild conditions and low micromolar concentrations, as demonstrated by the PEGylation of a small protein.
Infrastructure-based vehicular networks (consisting of a group of Base Stations (BSs) along the road) will be widely deployed to support Wireless Access in Vehicular Environment (WAVE) and a series ...of safety and non-safety related applications and services for vehicles on the road. As an important measure of user satisfaction level, uplink connectivity probability is defined as the probability that messages from vehicles can be received by the infrastructure (i.e., BSs) through multi-hop paths. While on the system side, downlink connectivity probability is defined as the probability that messages can be broadcasted from BSs to all vehicles through multi-hop paths, which indicates service coverage performance of a vehicular network. This paper proposes an analytical model to predict both uplink and downlink connectivity probabilities. Our analytical results, validated by simulations and experiments, reveal the trade-off between these two key performance metrics and the important system parameters, such as BS and vehicle densities, radio coverage (or transmission power), and maximum number of hops. This insightful knowledge enables vehicular network engineers and operators to effectively achieve high user satisfaction and good service coverage, with necessary deployment of BSs along the road according to traffic density, user requirements and service types.
Despite high‐surface area carbons, e.g., graphene‐based materials, being investigated as anodes for lithium (Li)‐ion batteries, the fundamental mechanism of Li‐ion storage on such carbons is ...insufficiently understood. In this work, the evolution of the electrode/electrolyte interface is probed on a single‐layer graphene (SLG) film by performing Raman spectroscopy and Fourier transform infrared spectroscopy when the SLG film is electrochemically cycled as the anode in a half cell. The utilization of SLG eliminates the inevitable intercalation of Li ions in graphite or few‐layer graphene, which may have complicated the discussion in previous work. Combining the in situ studies with ex situ observations and ab initio simulations, the formation of solid electrolyte interphase and the structural evolution of SLG are discussed when the SLG is biased in an electrolyte. This study provides new insights into the understanding of Li‐ion storage on SLG and suggests how high‐surface‐area carbons could play proper roles in anodes for Li‐ion batteries.
A single‐layer graphene film is electrochemically cycled as an anode in a half cell to probe the evolution of the electrode/electrolyte interface and lithium‐storage mechanism, which are followed by in operando Raman spectroscopy and Fourier transform infrared spectroscopy. The understanding may provide new insight on the Li deposition on carbon and the role of high‐specific‐surface‐area carbons as anodes for Li‐ion batteries.
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•K+ cations can tailor the eight-membered ring window size of RHO zeolite to selectively adsorb N2 from CH4 based on their difference in kinetic diameters.•Ion-exchanged degree of K+ ...cations in RHO zeolite can be controlled to obtain greater N2/ CH4 separation performance.•In the PSA simulation, K-RHO zeolite exhibits higher CH4 throughput than ETS-4 owing to higher N2 working capacity of K-RHO zeolite.
Zeolite RHO, a microporous zeolite, has the great possibility for N2/CH4 separation by regulating the size of the eight-membered ring window on the RHO framework. In this work, the ability of ion-exchanged RHO zeolites for N2/CH4 separation is investigated, and a highly nitrogen selectivity adsorbents are developed. RHO samples were prepared by hydrothermal synthesis. Alkali metal cations (Na+, K+, Cs+) was used for ion exchange. Adsorption equilibrium isotherms of N2 and CH4 were measured at normal temperature and fitted by the Langmuir equation. The adsorbent selection parameters (S parameters) were calculated based on the working capacity and equilibrium selectivity of N2/CH4, which are used to comprehensively evaluate the selectivity of N2/CH4. The results indicate that the cations have effects on the regulation of the eight-membered ring window. In particularly, K-RHO no.2 sample which is obtained by ion exchange of K+ cations exhibit the best N2/CH4 separation performance, which is a potential nitrogen selective adsorbent. In addition, the product throughputs of RHO and the commercial adsorbent ETS-4 were compared by common PSA simulation process with essentially the same product purity and recovery. The results show that K-RHO no.2 has 36 % higher product throughput than ETS-4, which can compensate for the problem of low N2 working capacity of ETS-4 in industrial application.
Wound healing is delayed in diabetic patients. Increased apoptosis and endothelial progenitor cell (EPC) dysfunction are implicated in delayed diabetic wound healing. Melatonin, a major secretory ...product of the pineal gland, promotes diabetic wound healing; however, its mechanism of action remains unclear. Here, EPCs were isolated from the bone marrow of mice. Treatment of EPCs with melatonin alleviated advanced glycation end product (AGE)-induced apoptosis and cellular dysfunction. We further examined autophagy flux after melatonin treatment and found increased light chain 3 (LC3) and p62 protein levels in AGE-treated EPCs. However, lysosome-associated membrane protein 2 expression was decreased, indicating that autophagy flux was impaired in EPCs treated with AGEs. We then evaluated autophagy flux after melatonin treatment and found that melatonin increased the LC3 levels, but attenuated the accumulation of p62, suggesting a stimulatory effect of melatonin on autophagy flux. Blockage of autophagy flux by chloroquine partially abolished the protective effects of melatonin, indicating that autophagy flux is involved in the protective effects of melatonin. Furthermore, we found that the AMPK/mTOR signaling pathway is involved in autophagy flux stimulation by melatonin. An in vivo study also illustrated that melatonin treatment ameliorated impaired wound healing in a streptozotocin-induced diabetic wound healing model. Thus, our study shows that melatonin protects EPCs against apoptosis and dysfunction via autophagy flux stimulation and ameliorates impaired wound healing in vivo, providing insight into its mechanism of action in diabetic wound healing.
miR-511-3p is upregulated in HSOS in vivo and in vitro models. miR-511-3p activates the Hedgehog pathway by directly targeting Ptch1. Knockdown of miR-511-3p shows a protective effect against LSEC ...injury and apoptosis via Hedgehog signaling pathway. Inhibition of Ptch1 reserves the effect of miR-511-3p knockdown on LSEC damage and apoptosis.
As a major complication of hematopoietic stem cell transplantation, the incidence of hepatic sinusoidal obstruction syndrome (HSOS) is as high as 70%. Previous evidence has demonstrated that miR-511-3p was involved in HSOS, but the mechanism remains unclear. This study aims to examine the mechanism underlying miR-511-3p regulating HSOS. Monocrotaline (MCT) was used to create an HSOS rat model and to treat liver sinusoidal endothelial cells (LSECs). Hematoxylin & eosin (H&E) and Masson staining were used to detect pathological changes in liver tissue. The expression of miR-511-3p and Hedgehog pathway-related proteins was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of miR-511-3p in regulating HSOS was investigated by 3-(4,5)-dimethylthiahiazo-2)-3,5-diphenytetrazoliumromide (MTT), enzyme-linked immunosorbent assay (ELISA) assay, and flow cytometry. Finally, the interaction between miR-511-3p and patched1 (Ptch1) was determined by luciferase reporter assay. The rats showed a typical HSOS phenotype, including LSEC damage, liver injury, and fibrosis after MCT administration. miR-511-3p was upregulated in hepatic tissue of rat HSOS model and MCT-induced LSECs. miR-511-3p directly targeted Ptch1 and suppressed Ptch1 expression to activate the Hedgehog signaling pathway. Depletion of miR-511-3p showed a protective effect against MCT-induced HSOS, as evidenced by decreased HSOS pathogenesis factors, matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), tumor necrosis factor-α (TNF-α), and interleukin 1 β (IL-1β), and decreased LSEC apoptosis rates. Nevertheless, knockdown of Ptch1 reversed the protective effect of miR-511-3p depletion against MCT-induced LSEC injury and apoptosis. miR-511-3p aggravates HSOS by activating the Hedgehog signaling pathway through targeting Ptch1, and miR-511-3p may develop as the potential therapy for the treatment of HSOS.
NEW & NOTEWORTHY miR-511-3p is upregulated in HSOS in vivo and in vitro models. miR-511-3p activates the Hedgehog pathway by directly targeting Ptch1. Knockdown of miR-511-3p shows a protective effect against LSEC injury and apoptosis via Hedgehog signaling pathway. Inhibition of Ptch1 reserves the effect of miR-511-3p knockdown on LSEC damage and apoptosis.
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