•CD21 has a dose-dependent neuroprotective effect on ischemic brain injury.•CD21 can inhibit TLR4/NF-κB signaling pathway activation in 2VO mice.•CD21 can inhibit NLRP3/ASC/Caspase-1 signaling ...pathway activation in 2VO mice.
The activation of NLRP3 inflammasome is closely related to ischemic brain injury and inhibition of NLRP3 inflammasome activation may be a new therapeutic strategy for ischemic stroke. Our previous studies showed that ligustilide (LIG) had a dose-dependent neuroprotective effect on various models of cerebral ischemia and dementia in vivo and in vitro. CD21, a kind of phthalide derivative, was modified from LIG. In this study, we established a global cerebral ischemia–reperfusion model in mice by bilateral common carotid artery ligation (2VO), and explored the neuroprotective effect of CD21 and its anti-inflammatory mechanism on cerebral ischemia mice. CD21 significantly improved weight loss, neurobehavioral deficits and neurons loss in hippocampal CA1 and caudate putamen (CPu) subregions, which were induced by 2VO in mice. CD21 significantly inhibited the overactivation of astrocyte and microglia, and decreased the mRNA level of IL-6, TNF-α and IL-1β. Moreover, CD21 significantly inhibited the activation of TLR4/NF-κB signaling pathway mediated by HMGB1 and NLRP3/ASC/Caspase-1 signaling pathway mediated by Cathepsin B, thus inhibiting the activation of NLRP3 inflammasome. Our results demonstrated that CD21 may exert a neuroprotection by inhibiting NLRP3 inflammasome activation after cerebral ischemia. These findings provide a new strategy for the treatment of ischemic stroke.
By designing novel chemical compositions and controlling precursor powders, perfect transparent ceramics (TCs) of Gd3Al4GaO12:2%Ce3+ garnets (GAGG:2%Ce3+) were achieved for the first time. Ce3+ ...distributions in ceramics were revealed by micromorphology and micro-cathodoluminescence. Benefiting from the components that are rich in red emission, warm light with a correlated color temperature of about 2800 K was generated when TC was used in high-power (hp) blue light emitting diodes (LEDs) (∼450 nm, ∼34 W driven at 1 A). The hp LED device shows high brightness with a luminous flux nearly 2100 lm. The luminous efficacy even reaches 388 lm/W, which is the highest value reported till now, indicating that the use of GAGG:2%Ce3+ TCs promises energy saving. We believe that this work will open a new perspective to develop TCs for next-generation hp LED lighting to substitute traditional hp xenon lamps and high-pressure sodium lamps.
The proinflammatory properties of extracellular peroxiredoxins (Prxs) via induction of Toll-like receptor 4 (TLR4) activation have been gradually revealed under diverse stress conditions, including ...cerebral ischemia but not hemorrhage. Prx1 is proposed to be a major hemorrhagic stress-inducible isoform of Prxs during acute and subacute phases of intracerebral hemorrhage (ICH). However, the potential of Prx1 in the neuroinflammatory injury after ICH remains unclear. This study investigated the proinflammatory effect and underlying mechanism of extracellular Prx1 in cultured murine macrophages and a collagenase-induced mouse ICH model. The current results show that incubation of exogenous Prx1 (0–50nM) with murine RAW264.7 macrophages resulted in increased expression of TLR4, nuclear translocation of nuclear factor κB (NF-κB) p65 and production of proinflammatory mediators (NO, TNF-a and IL-6) in a concentration-dependent manner. In addition, ICH induced murine neurological deficits, cerebral edema and neuropathological alterations, such as neuron injury, astrocyte and microglia/macrophage activation, and neutrophil and T lymphocyte invasion up to 72h after ICH. Moreover, ICH stimulated Prx1 expression and extracellular release, TLR4/NF-κB signaling activation, reflected by increases in TLR4 expression, extracellular signal-regulated kinase (ERK) 1/2 and NF-κB activation, and production of cytokines (TNF-α, IL-6 and IL-17). Taken together, these findings suggest that extracellular Prx1-mediated TLR4/NF-κB pathway activation probably contributes to neuroinflammatory injury after ICH, and thus blocking Prx1-TLR4 signaling might provide a novel anti-neuroinflammatory strategy with extended therapeutic window for hemorrhagic stroke.
•Peroxiredoxin1 (Prx1) induced TLR4/NF-κB activation and inflammation in macrophages.•Hemorrhagic stress stimulated expression and spillage of Prx1in brain.•Prx1-mediated TLR4/NF-κB activation was involved in post-hemorrhage brain injury.
Abstract
We present the first results from the ongoing, intensive, multiwavelength monitoring program of the luminous Seyfert 1 galaxy Mrk 817. While this active galactic nucleus was, in part, ...selected for its historically unobscured nature, we discovered that the X-ray spectrum is highly absorbed, and there are new blueshifted, broad, and narrow UV absorption lines, which suggest that a dust-free, ionized obscurer located at the inner broad-line region partially covers the central source. Despite the obscuration, we measure UV and optical continuum reverberation lags consistent with a centrally illuminated Shakura–Sunyaev thin accretion disk, and measure reverberation lags associated with the optical broad-line region, as expected. However, in the first 55 days of the campaign, when the obscuration was becoming most extreme, we observe a de-coupling of the UV continuum and the UV broad emission-line variability. The correlation recovered in the next 42 days of the campaign, as Mrk 817 entered a less obscured state. The short C
iv
and Ly
α
lags suggest that the accretion disk extends beyond the UV broad-line region.
Alzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. However, the role of Klotho in the ...progression of AD remains elusive. The present study explored the effects and underlying mechanism of Klotho in a mouse model of AD. The upregulation of cerebral Klotho expression was mediated by an intracerebroventricular injection of a lentiviral vector that encoded Klotho (LV-KL) in 7-month-old amyloid precursor protein/presenilin 1 transgenic mice. Three months later, LV-KL significantly induced Klotho overexpression in the brain and effectively ameliorated cognitive deficit and AD-like pathology in amyloid precursor protein/presenilin 1 mice. LV-KL induced autophagy activation and protein kinase B/mammalian target of rapamycin inhibition both in AD mice and BV2 murine microglia. These results suggest that the upregulation of Klotho expression in the brain may promote the autophagic clearance of amyloid beta and protect against cognitive deficits in AD mice. These findings highlight the preventive and therapeutic potential of Klotho for the treatment of AD.
•Lentivirus-mediated Klotho upregulation improved the decrease of Klotho in Alzheimer's disease (AD) mice.•Klotho upregulation improved AD-like cognitive impairment and pathological changes.•Klotho improved the cerebral vascular function in AD mice.•Klotho inhibited protein kinase B/mammalian target of rapamycin pathways to activate the autophagy in vitro and in vivo.
Abstract We report first-time reverberation-mapping results for 14 active galactic nuclei (AGNs) from the ongoing Monitoring AGNs with H β Asymmetry campaign (MAHA). These results utilize optical ...spectra obtained with the Long Slit Spectrograph on the Wyoming Infrared 2.3 m Telescope between 2017 November and 2023 May. MAHA combines long-duration monitoring with high cadence. We report results from multiple observing seasons for nine of the 14 objects. These results include H β time lags, supermassive black hole masses, and velocity-resolved time lags. The velocity-resolved lags allow us to investigate the kinematics of the broad-line region.
Background and Aims
The predominant distribution of the antiaging Klotho protein in both the kidneys and brain may point to its essential role in protecting against dysfunction of the kidney-brain ...axis during the aging process. Our previous study showed that the downregulation of Klotho was involved in aging-related cognitive impairment in aged senescence-accelerated mouse prone-8 (SAMP8) mice. The present study investigated the potential role of Klotho in aging-associated inflammation and renal injury.
Methods
Age- and gender-matched groups of SAMP8 mice and their corresponding normal control senescence-accelerated mouse resistant-1 (SAMR1) were used to investigate the potential role of Klotho in aging-associated inflammation and renal injury.
Results
Compared with aged SAMR1 controls, early-stage chronic kidney disease (CKD), which is associated with an increase in the urinary albumin-to-creatinine ratio, inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis, was observed in aged SAMP8 mice. Furthermore, the aging-related loss of Klotho-induced activation of the retinoic acid-inducible gene 1/nuclear factor-κB (RIG-I/NF-κB) signaling pathway and subsequent production of the proinflammatory mediators tumor necrosis factor α, interleukin-6, and inducible nitric oxide synthase in the kidneys of aged SAMP8 mice compared with SAMR1 controls.
Conclusions
The present results suggest that aging-related inflammation and the development of early-stage CKD are likely associated with the downregulation of Klotho and induction of the RIG-I/NF-κB signaling pathway in 12-month-old SAMP8 mice. Moreover, aged SAMP8 mice with cognitive deficits and renal damage may be a potential mouse model for investigating the kidney-brain axis in the aging process.
ABSTRACT
We conduct a systematic search for quasars with periodic variations from the archival photometric data of the Zwicky Transient Facility by cross-matching with the quasar catalogues of the ...Sloan Digital Sky Survey and Véron-Cetty and Véron. We first select out 184 primitive periodic candidates using the generalized Lomb–Scargle periodogram and autocorrelation function and then estimate their statistical significance of periodicity based on two red-noise models, i.e. damped random walk (DRW) and single power-law (SPL) models. As such, we finally identify 106 (DRW) and 86 (SPL) candidates with the most significant periodic variations out of 143 700 quasars. We further compare DRW and SPL models using Bayes factors, which indicate a relative preference of the SPL model for our primitive sample. We thus adopt the candidates identified with SPL as the final sample and summarize its basic properties. We extend the light curves of the selected candidates by supplying other archival survey data to verify their periodicity. However, only three candidates (with 6–8 cycles of periods) meet the selection criteria. This result clearly implies that, instead of being strictly periodic, the variability must be quasi-periodic or caused by stochastic red-noise. This exerts a challenge to the existing search approaches and calls for developing new effective methods.
Xiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as ...the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications.
We used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP. The 16S rRNA sequencing method was used to explore the effect of XP on the gut microbiota of HFD rats, and the effects of XP on ileum pathology, intestinal barrier and circulatory inflammation in HFD rats were also investigated. We further explored the molecular mechanism of XP treating liver inflammation in rats with HFD by regulating toll-like receptor 4 (TLR4) signaling.
We found that XP could regulate the imbalance of gut microbiota in HFD rats, and up-regulate the expression of tight junction protein in intestinal epithelium of HFD rats, thereby improving the intestinal barrier damage and intestinal inflammatory response. In addition, XP could significantly reduce the levels of inflammatory cytokines in HFD rats, and inhibit TLR4 signaling pathway, thereby reducing liver inflammation in HFD rats.
XP can effectively improve the imbalance of gut-liver axis in hyperlipidemic rats and alleviate the inflammatory damage of liver. Its mechanism may be related to regulating the disorder of gut microbiota and inhibiting TLR4 signal pathway, so as to achieve the therapeutic effect on hyperlipidemic fatty liver in rats.
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•XP can regulate the imbalance of gut microbiota in high fat diet rats.•XP improves intestinal barrier damage and intestinal inflammatory reaction.•XP reduces the levels of inflammatory cytokines in high fat diet rats.•XP inhibits the TLR4/LPS signaling pathway to alleviate liver inflammatory response.
When plates with edge cracks in the rolling process is straightened by cyclic tensile and compressive stress, the tip of edge crack always accompanied by stress concentration, which leads to crack ...propagation. In this paper, damage parameters are imported into the plate straightening model based on determining the GTN damage parameters of magnesium alloy materials by inverse finite element calibration method, the influence of different straightening process schemes and prefabricated V-shaped crack geometry on crack growth is analyzed through the way of the combination of simulation and straightening experiment. The results show that the peak values of equivalent stress and equivalent strain under each straightening roll appear at the crack tip. The value of longitudinal stress and equivalent stain decrease with the distance to crack tip becomes larger. The peak value of longitudinal stress appears when the crack circumferential angle is about 100°, and the crack tip is easy to form crack propagation; when the plate passes roll 2 and roll 4, the equivalent stress and strain concentration at the crack tip are most obvious; when the reduction reaches a certain degree, the void volume fraction (VVF) reaches the VVF of the material breaking; with the increase of the entrance reduction, the number of VVF at the crack tip which reaches the material fracture increases, and the length of crack propagation increases; the stress concentration at the tip of V-shaped crack with large length-width ratio is obvious, and the VVF is more likely to reach the VVF at the time of material fracture, crack initiates and propagates easily.
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