Abstract
Compact objects are expected to exist in the accretion disks of supermassive black holes (SMBHs) in active galactic nuclei (AGNs), and in the presence of such a dense environment (∼10
14
cm
...−3
), they will form a new kind of stellar population denoted as accretion-modified stars (AMSs). This hypothesis is supported by recent LIGO/Virgo detection of the mergers of very high-mass stellar binary black holes (BHs). We show that the AMSs will be trapped by the SMBH disk within a typical AGN lifetime. In the context of SMBH disks, the rates of Bondi accretion onto BHs are ∼10
9
L
Edd
/
c
2
, where
L
Edd
is the Eddington luminosity and
c
is the speed of light. Outflows developed from the hyper-Eddington accretion strongly impact the Bondi sphere and induce episodic accretion. We show that the hyper-Eddington accretion will be halted after an accretion interval of
t
a
∼ 10
5
m
1
s, where
m
1
=
m
•
/10
M
⊙
is the BH mass. The kinetic energy of the outflows accumulated during
t
a
is equivalent to 10 supernovae driving an explosion of the Bondi sphere and developing blast waves. We demonstrate that a synchrotron flare from relativistic electrons accelerated by the blast waves peaks in the soft X-ray band (∼0.1 keV), significantly contributing to the radio, optical, UV, and soft X-ray emission of typical radio-quiet quasars. External inverse Compton scattering of the electrons peaks around 40 GeV and is detectable through Fermi-LAT. The flare, decaying with
t
−6/5
with a few months, will appear as a slowly varying transient. The flares, occurring at a rate of a few per year in radio-quiet quasars, provide a new mechanism for explaining AGN variability.
Abstract
The recent advanced LIGO/Virgo detections of gravitational waves (GWs) from stellar binary black hole (BBH) mergers, in particular GW190521, which is potentially associated with a quasar, ...have stimulated renewed interest in active galactic nuclei as factories of merging BBHs. Compact objects evolving from massive stars are unavoidably enshrouded by a massive envelope to form accretion-modified stars (AMSs) in the dense gaseous environment of a supermassive black hole (SMBH) accretion disk. We show that most AMSs form binaries due to gravitational interaction with each other during radial migration in the SMBH disk, forming BBHs inside the AMS. When a BBH is born, its orbit is initially governed by the tidal torque of the SMBH. Bondi accretion onto a BBH at a hyper-Eddington rate naturally develops and then controls the evolution of its orbits. We find that Bondi accretion leads to efficient removal of the orbital angular momentum of the binary, whose final merger produces a GW burst. Meanwhile, the Blandford–Znajek mechanism pumps the spin energy of the merged BH to produce an electromagnetic counterpart (EMC). Moreover, hyper-Eddington accretion onto the BBH develops powerful outflows and triggers a Bondi explosion, which manifests itself as an EMC of the GW burst, depending on the viscosity of the accretion flow. Thermal emission from the Bondi sphere appears as one of the EMCs. The BBHs radiate GWs with frequencies of ∼10
2
Hz, which are accessible to LIGO.
Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by the presence of amyloid‐β (Aβ) plaques. We previously reported that Klotho lowered Aβ levels in the brain and ...protected against cognitive deficits in amyloid precursor protein/presenilin 1(APP/PS1) mice. However, the underlying mechanism remains unclear. In this study, we induced intracerebral Klotho overexpression in 13‐month‐old APP/PS1 mice by injecting lentivirus that carried full‐length mouse Klotho cDNA in the lateral ventricle of the brain. We examined the effects of Klotho overexpression on cognition, Aβ burden, Aβ‐related neuropathology, microglia transformation, and Aβ transport systems in vivo. Additionally, we investigated the effects of Klotho on Aβ transport at the blood–cerebrospinal fluid barrier by knocking down Klotho in primary human choroid plexus epithelial cells (HCPEpiCs). The upregulation of Klotho levels in the brain and serum significantly ameliorated Aβ burden, neuronal and synaptic loss and cognitive deficits in aged APP/PS1 mice. Klotho treatment significantly inhibited NACHT, LRR, and PYD domain‐containing protein 3 (NLRP3) and the subsequent transformation of microglia to the M2 type that may enhance microglia‐mediated Aβ clearance. Meanwhile, Klotho overexpression also regulated Aβ transporter expression, which may promote Aβ transporter‐mediated Aβ clearance. Moreover, the ability of HCPEpiCs to transport Aβ in vitro was also significantly impaired by Klotho knockdown. Given the neuroprotective effect of Klotho overexpression, the present findings suggest that Klotho should be further investigated as a potential therapeutic target for AD.
Klotho, as an anti‐aging gene, has been studied in the field of AD in recent years. Our data showed that Klotho overexpression inhibited NLRP3 inflammasome activation and promoted Aβ clearance through an increase in M2 type microglia and the regulation of Aβ transporters in APP/PS1 mice, which effectively relieved neuroinflammation and Aβ burden and ameliorated AD‐like phenotypes.
Abstract
Strong iron lines are a common feature of the optical spectra of active galactic nuclei (AGNs) and quasars from
z
∼ 6−7 to the local universe, and Fe/Mg ratios do not show cosmic evolution. ...During active episodes, accretion disks surrounding supermassive black holes (SMBHs) inevitably form stars in the self-gravitating part, and these stars accrete with high accretion rates. In this paper, we investigate the population evolution of accretion-modified stars (AMSs) to produce iron and magnesium in AGNs. The AMSs, as a new type of star, are allowed to have any metallicity but without significant loss from stellar winds, since the winds are choked by the dense medium of the disks and return to the core stars. Mass functions of the AMS population show a pile-up or cutoff pile-up shape in top-heavy or top-dominant forms if the stellar winds are strong, consistent with the narrow range of supernovae (SNe) explosions driven by the known pair-instability. This provides an efficient way to produce metals. Meanwhile, SN explosions support an inflated disk as a dusty torus. Furthermore, the evolving top-heavy initial mass functions lead to bright luminosity in infrared bands in dusty regions. This contributes a new component in infrared bands, which is independent of the emissions from the central part of accretion disks, appearing as a long-term trending of the NIR continuum compared to optical variations. Moreover, the model can be further tested through reverberation mapping of emission lines, including LIGO/LISA detections of gravitational waves and signatures from spatially resolved observations of GRAVITY+/VLTI.
Epidemiological studies suggest that chronic periodontitis (CP) is closely associated with the incidence and progression of cognitive impairment. The present study investigated the causal ...relationship between CP and cognitive decline and the underlying mechanism in mice. Long-term ligature around the left second maxillary molar tooth was used to induce CP in mice. Severe alveolar bone loss and inflammatory changes were observed in gingival tissues, accompanied by progressive cognitive deficits during a 12-month period. We also observed cerebral neuronal and synaptic injury and glial activation in this mouse model of CP. Furthermore, CP mice exhibited significant dysbiosis of the oral and gut microbiota, disruption of the intestinal barrier and blood-brain barrier, increases in the serum contents of proinflammatory cytokines and lipopolysaccharide (LPS), and increases in brain LPS levels, Toll-like receptor 4 (TLR4) expression, nuclear factor-κB (NF-κB) nuclear translocation and proinflammatory cytokine mRNA levels. These results indicate that CP may directly induce progressive cognitive decline and its mechanism is probably related to microbiota-gut-brain axis disorders, LPS/TLR4/NF-κB signaling activation and neuroinflammatory responses in mice. Therefore, the microbiota-gut-brain axis may provide the potential strategy for the prevention and treatment of CP-associated cognitive impairment.
•Chronic periodontitis (CP) mice displayed progressive cognitive deficits.•Murine CP aggravated neuronal injury and neuroinflammation.•Murine CP caused the oral and gut microbiota dysbiosis.•Murine CP induced intestinal barrier damage and inflammation.•Murine CP injured blood-brain barrier and activated TLR4 pathway in the brain.
Time–temperature indicator (TTI) technologies allow for nondestructive and real‐time quality management of perishable products during the entire transport–storage process, which provides an important ...guarantee for the product safety of end users. However, the existing TTI technologies still have shortcomings in recyclability, sensitivity, and environmental tolerance, limiting their widespread applications. Herein, a new TTI route based on the light storage effect in persistent luminescent (PersL) materials is proposed. Such TTI is designed on account of the principle that the release rate of light‐induced trapped carriers in PersL materials is closely dependent on the storage time and temperature, enabling to establish a correlation between the number of residual carriers and the freshness of perishable products. Taking KZnF3:Mn2+ as a model material, the light‐storage‐based TTI technology shows excellent recyclability, reliability, and environmental stability. This work reveals great potentials of PersL phosphors as information recording materials in advanced TTI application and next‐generation biological detection technology.
A time–temperature indicator method based on the light‐storage effect in persistent luminescence materials is proposed for the first time. Such time–temperature indicators show excellent recyclability, reliability, and environmental stability, and exhibit great prospects in next‐generation intelligent packaging technology and biological detection technology.
•Age-related cognitive deficits and neuronal injury occurred in aged mice.•The gut microbiota in aged mice appeared to represent a proinflammatory phenotype.•Intestinal barrier and blood-brain ...barrier injuries were induced in aged mice.•LPS-activated TLR4 pathway contributed to age-related peripheral inflammation.•LPS/TLR4 pathway activation was involved in age-related neuroinflammation.
Age-related cognitive decline is associated with chronic low grade neuroinflammation that may result from a complex interplay among many factors, such as bidirectional communication between the central nervous system (CNS) and gut microbiota. The present study used 2-month-old (young group) and 15-month-old (aged group) male C57BL/6 mice to explore the potential association between age-related cognitive decline and the microbiota-gut-brain axis disorder. We observed that aged mice exhibited significant deficits in learning and memory, neuronal and synaptic function compared with young mice. Aged mice also exhibited significant dysbiosis of the gut microbiota. Disruptions of the intestinal barrier and blood-brain barrier were also observed, including increases in intestinal, low-grade systemic and cerebral inflammation. Furthermore, plasma and brain levels of lipopolysaccharide (LPS) were significantly higher in aged mice compared with young mice, with increasing expression of Toll-like receptor 4 (TLR4) and myeloid differential protein-88 (MyD88) and the nuclear translocation of nuclear factor κB (NF-κB) in intestinal and brain tissues. These findings showed that microbiota-gut-brain axis dysfunction that occurs through LPS-induced activation of the TLR4/NF-κB signaling pathway is implicated in age-related neuroinflammation and cognitive decline.
Blocking TLR4/peroxiredoxin (Prx6) signaling is proposed to be a novel therapeutic strategy for ischemic stroke because extracellular Prx6 released from ischemic cells may act as an endogenous ligand ...for TLR4 and initiate destructive immune responses in ischemic brain. Our previous studies showed that ligustilide (LIG) exerted antineuroinflammatory and neuroprotective effects against ischemic insult, but the underlying mechanisms remain unclear. This study investigated whether the TLR4/Prx6 pathway is involved in the protective effect of LIG against postischemic neuroinflammation and brain injury induced by transient middle cerebral artery occlusion (MCAO) in rats. Intraperitoneal LIG administration (20 and 40mg/kg/day) at reperfusion onset after MCAO resulted in a reduction of brain infarct size and improved neurological outcome over 72h. LIG-induced neuroprotection was accompanied by improvement of neuropathological alterations, including neuron loss, astrocyte and microglia/macrophage activation, neutrophil and T-lymphocyte invasion, and regulation of inflammatory mediators expression. Moreover, LIG significantly inhibited the expression and extracellular release of Prx6 and activation of TLR4 signaling, reflected by decreased TLR4 expression, extracellular signal-regulated kinase 1/2 phosphorylation, and transcriptional activity of NF-κB and signal transducer and activator of transcription 3 in the ischemic brain. Our results demonstrate that LIG may provide an early and direct neuroprotection by inhibiting TLR4/Prx6 signaling and subsequent immunity and neuroinflammation after cerebral ischemia. These findings support the translational potential of blocking TLR4/Prx6 signaling for the treatment of ischemic stroke.
•Brain ischemia induced release of peroxiredoxin 6 into cerebrospinal fluid.•Toll-like receptor 4 and peroxiredoxin 6 levels were increased in ischemic brain.•Ligustilide attenuated postischemic neuroinflammation and brain injury.•Ligustilide reduced Toll-like receptor 4/peroxiredoxin 6 in ischemic brain.•Toll-like receptor 4 signaling was inhibited by ligustilide.
Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and ...signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model.
Rats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase.
Our findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke.
•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.
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