Summary
The Wnt1‐Cre transgenic mouse line is widely used to express the CRE recombinase in neural crest lineages, but it overexpresses WNT1 itself, which can cause undesired phenotypes. To address ...this, we and others previously developed a Wnt1‐Cre2 line based on the same regulatory elements as Wnt1‐Cre but without ectopic Wnt1 expression. However, while Wnt1‐Cre2 exhibits normal activity when transmitted from female mice, it exhibits unexpected activity in the male germline. The Wnt1‐Cre2 transgene was previously mapped to the E2f1 locus. Several genes in this genomic region exhibit significant expression in spermatogonia or spermatocytes, suggesting that local regulatory elements may be driving ectopic transgene expression. The Wnt1‐Cre2 line can therefore be used both as a neural crest specific and a general deleter, and care should be taken when setting up genetic crosses.
Although substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a ...potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.
A rapidly spinning magnetar in a young supernova (SN) can produce a superluminous transient by converting a fraction of its rotational energy into radiation. Here, we present the first ...three-dimensional hydrodynamical simulations ever performed of a magnetar-powered SN in the circumstellar medium formed by the ejection of the outer layers of the star prior to the blast. We find that hydrodynamical instabilities form on two scales in the ejecta, not just one as in ordinary core-collapse SNe: in the hot bubble energized by the magnetar and in the forward shock of the SN as it plows up ambient gas. Pressure from the bubble also makes the instabilities behind the forward shock more violent and causes more mixing in the explosion than in normal SNe, with important consequences for the light curves and spectra of the event that cannot be captured by one-dimensional models. We also find that the magnetar can accelerate Ca and Si to velocities of ∼12,000 and account for their broadened emission lines in observations. Our simulations also reveal that energy from even weak magnetars can accelerate iron-group elements deep in the ejecta to 5000-7000 and explain the high-velocity Fe observed at early times in some core-collapse SNe such as SN 1987A.
Abstract
Understanding the formation of the supermassive black holes (SMBHs) present in the centers of galaxies is a crucial topic in modern astrophysics. Observations have detected SMBHs with masses ...of 10
9
M
⊙
in the high-redshift galaxies with
z
∼ 7. However, how SMBHs grew to such huge masses within the first billion years after the Big Bang remains elusive. One possible explanation is that SMBHs grow quickly through the frequent mergers of galaxies, which provides sustainable gas to maintain rapid growth. This study presents the hydrodynamics simulations of the SMBHs’ growth with their host galaxies using the
GIZMO
code. In contrast to previous simulations, we have developed a giant molecular cloud (GMC) model by separating molecular gas particles from atomic gas particles and then evolving them independently. During major mergers, we show that the more massive molecular gas particles’ cloud bears stronger dynamical friction. Consequently, GMCs are substantially accreted onto the galactic centers that grow SMBHs from ∼10
7
to ∼10
9
M
⊙
within 300 Myr, which explains the rapid growth of SMBHs, and this accretion also triggers a violent starburst at the galactic center. Furthermore, we examine the impact of minor mergers on the bulge of a Milky Way–like galaxy and find that the size and mass of the bulge can increase from 0.92 to 1.9 kpc and from 4.7 × 10
10
to 7 × 10
10
M
⊙
.
Physics of superluminous supernovae Chen, Ke-Jung
International journal of modern physics D,
03/2021, Letnik:
30, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Understanding how massive stars die as supernovae (SNe) is a crucial question in modern astrophysics. SNe are powerful stellar explosions and key drivers in the cosmic baryonic cycles by injecting ...their explosion energy and heavy elements to the interstellar medium that forms new stars. After decades of effort, astrophysicists have built up a stand model for the explosion mechanism of massive stars. However, this model is challenged by new kinds of stellar explosions discovered in the recent transit surveys. In particular, the new population called superluminous SNe, which are a hundred times brighter than typical SNe, is revolutionizing our understanding of SNe. New studies suggest the superluminous SNe are associated with the unusual demise of very massive stars and their extreme SNe powered by the radioactive isotopes or compact objects formed after the explosion. Studying these SNe fills a gap of knowledge between the death of massive stars and their explosions; furthermore, we may apply their intense luminosity to light up the distant universe. This paper aims to provide a timely review of superluminous SNe physics, focusing on the latest development of their theoretical models.
Local lung microbiota is closely associated with lung tumorigenesis and therapeutic response. It is found that lung commensal microbes induce chemoresistance in lung cancer by directly inactivating ...therapeutic drugs via biotransformation. Accordingly, an inhalable microbial capsular polysaccharide (CP)-camouflaged gallium-polyphenol metal-organic network (MON) is designed to eliminate lung microbiota and thereby abrogate microbe-induced chemoresistance. As a substitute for iron uptake, Ga
released from MON acts as a "Trojan horse" to disrupt bacterial iron respiration, effectively inactivating multiple microbes. Moreover, CP cloaks endow MON with reduced immune clearance by masquerading as normal host-tissue molecules, significantly increasing residence time in lung tissue for enhanced antimicrobial efficacy. In multiple lung cancer mice models, microbe-induced drug degradation is remarkably inhibited when drugs are delivered by antimicrobial MON. Tumor growth is sufficiently suppressed and mouse survival is prolonged. The work develops a novel microbiota-depleted nanostrategy to overcome chemoresistance in lung cancer by inhibiting local microbial inactivation of therapeutic drugs.
Accumulating evidences have demonstrated that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of diabetic nephropathy (DN). lncRNA SOX2OT plays an essential role in many diseases, ...including diabetes. Herein, we aim to investigate the underlying mechanism of lncRNA SOX2OT in DN pathogenesis.
Streptozotocin-induced DN mouse models and high glucose-induced mouse mesangial cells were constructed to examine the expression pattern of lncRNA SOX2OT. The activation of autophagy was evaluated using immunohistochemistry, immunofluorescence and western blot analysis, respectively. SOX2OT overexpressing plasmid was applied to further verify the functional role of SOX2OT in DN pathogenesis. CCK-8 and EDU assays were performed to the proliferation of mesangial cells. Additionally, rapamycin, the inhibitor of mTOR signaling, was used to further clarify whether SOX2OT controls DN development through Akt/mTOR pathway.
lncRNA SOX2OT was markedly down-regulated both in streptozotocin-induced DN mice and high glucose-induced mouse mesangial cells. Moreover, overexpression of lncRNA SOX2OT was able to diminish the suppression of autophagy and alleviate DN-induced renal injury. Functionally, CCK-8 and EDU assays indicated that lncRNA SOX2OT overexpression significantly suppressed the proliferation and fibrosis of mesangial cells. Additionally, an obvious inhibition of Akt/mTOR was also observed with lncRNA SOX2OT overexpression, which was then further verified in vivo.
In summary, we demonstrated that lncRNA SOX2OT alleviates the pathogenesis of DN via regulating Akt/mTOR-mediated autophagy, which may provide a novel target for DN therapy.
The bidding strategies in electricity markets are non-conventional sources of flexibility. The market bids are usually in the form of a price and quantity quotation, and they state how much the ...seller or buyers are willing to buy or sell and for what price. These new developments in renewable energy systems are thoroughly discussed in this paper. This paper defines renewable energy systems and shows how they are applied in a smart grid. This fact has led the resources to a distributed load. The growing load resources have raised bidding and settlement in the power spot market. This paper presents a Distributed Adjustable Load Resources and settlement (DALRS) model to enhance the power of the payment spot market bidding systems. Flexible resources in smart grids and this report provide a comprehensive evaluation and analysis of the current market trading arrangements for these renewable energy systems.
Furthermore, strategic market bidding analysis and resource bidding allocation technique has been introduced in distributed resources in the spot market to maximize overall benefits; each supplier chooses the coefficients for linear energy supply functions and decides on unit commitment. Thus the adjustable price bids can facilitate market access to structural providers. The resource bidding allocation technique has been integrated with DALRS to enrich the bidding schemes and develop an overall bidding strategy.
Revealing the origin of self-trapped excitons is a prerequisite for further improving the photoluminescence efficiency of low-dimensional organic perovskites. Here, the microscopic formation ...mechanism of intrinsic self-trapped excitons in one-dimensional (1D) C
4
N
2
H
14
PbX
4
(X = Cl, Br and I) systems is investigated, and the polarization-luminescence relationship is established. Our results show that 1D-C
4
N
2
H
14
PbX
4
has a low electronic dimension (flat band characteristics), which facilitates the formation of intrinsic self-trapped excitons. The potential well formed by local distortion of the PbX
6
octahedron is the origin of exciton self-trapping. Combined with the electronic density of states and partial charge density, we further confirmed the existence of intrinsic self-trapping excitons in 1D-C
4
N
2
H
14
PbX
4
. In addition, we found that the breaking of the central inversion symmetry will induce electric polarization, which greatly improves the transition probability of electrons. These results could potentially offer a new direction for improving the luminescence properties of 1D organic lead halide perovskites.
Our work reveals the formation mechanism of self-trapped excitons in low-dimensional perovskite systems, and provides some unique opinions on the structure distortion-polarization-luminescence relationship.
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