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.
Twist is a critical epithelial-mesenchymal transition (EMT)-inducing transcription factor that increases expression of vimentin. How Twist1 regulates this expression remains unclear. Here, we report ...that Twist1 regulates Cullin2 (Cul2) circular RNA to increase expression of vimentin in EMT. Twist1 bound the Cul2 promoter to activate its transcription and to selectively promote expression of Cul2 circular RNA (circ-10720), but not mRNA. circ-10720 positively correlated with Twist1, tumor malignance, and poor prognosis in hepatocellular carcinoma (HCC). Twist1 promoted vimentin expression by increasing levels of circ-10720, which can absorb miRNAs that target vimentin. circ-10720 knockdown counteracted the tumor-promoting activity of Twist1
and in patient-derived xenograft and diethylnitrosamine-induced TetOn-Twist1 transgenic mouse HCC models. These data unveil a mechanism by which Twist1 regulates vimentin during EMT. They also provide potential therapeutic targets for HCC treatment and provide new insight for circular RNA (circRNA)-based diagnostic and therapeutic strategies.
A circRNA-based mechanism drives Twist1-mediated regulation of vimentin during EMT and provides potential therapeutic targets for treatment of HCC.
http://cancerres.aacrjournals.org/content/canres/78/15/4150/F1.large.jpg
.
This study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation ...(MSDT) or who received unmanipulated haploidentical allografts.
A retrospective study (n = 339) and a prospective study (n = 340) were performed. MRD was determined using multiparameter flow cytometry.
Either after retrospective or prospective analysis, patients with negative pre-MRD (pre-MRDneg) had a lower incidence of relapse than those with positive pre-MRD (pre-MRDpos) in MSDT settings (P < 0.001 for all), but relapse was comparable in Haplo-SCT settings for patients with pre-MRDneg versus pre-MRDpos (P = 0.866 and 0.161, respectively). In either the retrospective (n = 65) or the prospective study (n = 76), pre-MRDpos subjects receiving Haplo-SCT experienced a lower incidence of relapse than those who underwent MSDT (P < 0.001 and p = 0.017, respectively). Of the patients with pre-MRDpos in either the total (n = 141) or the subgroup excluding cases which received donor lymphocyte infusion (DLI; n = 105), those who underwent MSDT had a higher incidence of relapse than those receiving haplo-SCT (P < 0.01 for all). Multivariate analysis showed that, for pre-MRDpos cases, haplo-SCT was associated with a low incidence of relapse and with better LFS and OS in either retrospective group, prospective group, combination groups, or subgroup not including cases which received DLI.
The results indicated that, for pre-MRD-positive AML patients, haplo-SCT was associated with lower incidence of relapse and better survival, suggesting a stronger anti-leukemia effect.
Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal ...candidates warrants further investigation.
We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT (n = 169) or MSDT (n = 39).
The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19-33%) and 44% (95% CI, 28-60%) for HIDT and MSDT, respectively (P = 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31-63% vs. 23%, 95% CI, 17-29%; P = 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27-59% vs. 65%, 95% CI, 58-72%; P = 0.023) and overall survival (OS; 46%, 95% CI, 30-62% vs. 68%, 95% CI, 61-75%; P = 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1-19% vs. 11%, 95% CI, 6-16%; P = 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202-0.655; P = 0.001) and better LFS (HR = 0.414; 95% CI, 0.246-0.695; P = 0.001) and OS (HR = 0.380; 95% CI, 0.220-0.656; P = 0.001).
HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population.
ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014. https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&draw=2&rank=1.
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.
We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk ...acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio OR = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.
Heavy metal pollution in soil is a global problem with serious impacts on human health and ecological security. Phytoextraction in phytoremediation, in which plants uptake and transport heavy metals ...(HMs) to the tissues of aerial parts, is the most environmentally friendly method to reduce the total amount of HMs in soil and has wide application prospects. However, the molecular mechanism of phytoextraction is still under investigation. The uptake, translocation, and retention of HMs in plants are mainly mediated by a variety of transporter proteins. A better understanding of the accumulation strategy of HMs via transporters in plants is a prerequisite for the improvement of phytoextraction. In this review, the biochemical structure and functions of HM transporter families in plants are systematically summarized, with emphasis on their roles in phytoremediation. The accumulation mechanism and regulatory pathways related to hormones, regulators, and reactive oxygen species (ROS) of HMs concerning these transporters are described in detail. Scientific efforts and practices for phytoremediation carried out in recent years suggest that creation of hyperaccumulators by transgenic or gene editing techniques targeted to these transporters and their regulators is the ultimate powerful path for the phytoremediation of HM contaminated soils.
Display omitted
•The phylogenies and domain composition of 13 heavy metal transporter families•The accumulation and non-accumulation mechanisms of heavy metal transporters•Heavy metal transporters are regulated by Ca2+, ROS, NO, and phytohormones.•Four optimal phytoremediation strategies related to transporter were proposed.
Abstract
In this paper, we investigate the astrophysical processes of stellar-mass black holes (sMBHs) embedded in advection-dominated accretion flows (ADAFs) of supermassive black holes (SMBHs) in ...low-luminosity active galactic nuclei. The sMBH is undergoing Bondi accretion at a rate lower than the SMBH. Outflows from the sMBH-ADAF dynamically interact with their surroundings and form a cavity inside the SMBH-ADAF, thereby quenching the accretion onto the sMBH. Rejuvenation of the Bondi accretion is rapidly done by turbulence. These processes give rise to quasi-periodic episodes of sMBH activities and create flickerings from relativistic jets developed by the Blandford–Znajek mechanism if the sMBH is maximally rotating. Accumulating successive sMBH-outflows trigger a viscous instability of the SMBH-ADAF, leading to a flare following a series of flickerings. Recently, the similarity of near-infrared flare’s orbits has been found by GRAVITY/VLTI astrometric observations of Sgr A
∗
: their loci during the last 4 yr consist of a ring in agreement with the well-determined SMBH mass. We apply the present model to Sgr A*, which shows quasi-periodic flickerings. An sMBH of ∼40
M
⊙
is preferred orbiting around the central SMBH of Sgr A* from fitting radio to X-ray continuum. Such an extreme mass ratio inspiraling provides an excellent laboratory for LISA/Taiji/Tianqin detection of mHz gravitational waves with strains of ∼10
−17
, as well as their polarization.
Keratin is a kind of natural polymer that is abundant in feathers, wool, and hair. Being one of the natural biomolecules, keratin has excellent biological activity, biocompatibility, ...biodegradability, favorable material mechanical properties, and natural abundance, which exhibit significant biological and biomedical application potentials. At present, the strategies commonly used for preparing keratin from hair, feathers, wool, etc. include physical, chemical, and enzymatic methods. The present article mainly reviews the structure, classification, preparation methods, and the main biological applications of keratin, and these applications cover wound healing, hemostasis, targeted release of tissue engineering drugs, and so on. It is expected to lay the foundations for its future in-depth investigations and wide applications of keratin biomaterials.
Key points
•
There are several pathways to prepare biologically active keratin from wool, feathers, and human hair, etc
•
Promoting blood coagulation by keratin is related to the adhesion and activation of platelets and the aggregation of fibrin
•
The biological applications of keratin, including wound healing and tissue engineering, are summarized
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