Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan ...domestic mammals compared to reciprocal lowlanders. Furthermore, m
A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
Abstract
The first discovered extrasolar worlds—giant, “hot Jupiter” planets on short-period orbits—came as a surprise to solar system–centric models of planet formation, prompting the development of ...new theories for planetary system evolution. The near absence of observed nearby planetary companions to hot Jupiters has been widely quoted as evidence in support of high-eccentricity tidal migration, a framework in which hot Jupiters form further out in their natal protoplanetary disks before being thrown inward with extremely high eccentricities, stripping systems of any close-in planetary companions. In this work, we present new results from a search for transit timing variations across the full 4 yr Kepler data set, demonstrating that at least 12% ± 6% of hot Jupiters have a nearby planetary companion. This subset of hot Jupiters is expected to have a quiescent dynamical history such that the systems could retain their nearby companions. We also demonstrate a ubiquity of nearby planetary companions to warm Jupiters (≥70% ± 16%), indicating that warm Jupiters typically form quiescently. We conclude by combining our results with existing observational constraints to propose an “eccentric migration” framework for the formation of short-period giant planets through postdisk dynamical sculpting in compact multiplanet systems. Our framework suggests that hot Jupiters constitute the natural end stage for giant planets spanning a wide range of eccentricities, with orbits that reach small enough periapses—either from their final orbital configurations in the disk phase or from eccentricity excitation in the postdisk phase—to trigger efficient tidal circularization.
Hydrogen Sulfide Biology and Its Role in Cancer Khattak, Saadullah; Rauf, Mohd Ahmar; Khan, Nazeer Hussain ...
Molecules (Basel, Switzerland),
05/2022, Volume:
27, Issue:
11
Journal Article
Peer reviewed
Open access
Hydrogen sulfide (H
S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously ...produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H
S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H
S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H
S in different malignancies has been reported. The study summarizes the synthesis of H
S, its roles, signaling routes, expressions, and H
S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H
S in the scientific community.
The earthworm is particularly fascinating to biologists because of its strong regenerative capacity. However, many aspects of its regeneration in nature remain elusive. Here we report ...chromosome-level genome, large-scale transcriptome and single-cell RNA-sequencing data during earthworm (Eisenia andrei) regeneration. We observe expansion of LINE2 transposable elements and gene families functionally related to regeneration (for example, EGFR, epidermal growth factor receptor) particularly for genes exhibiting differential expression during earthworm regeneration. Temporal gene expression trajectories identify transcriptional regulatory factors that are potentially crucial for initiating cell proliferation and differentiation during regeneration. Furthermore, early growth response genes related to regeneration are transcriptionally activated in both the earthworm and planarian. Meanwhile, single-cell RNA-sequencing provides insight into the regenerative process at a cellular level and finds that the largest proportion of cells present during regeneration are stem cells.
Abstract
The formation of hot Jupiters has been a subject of interest in the field of exoplanet science. According to conventional scenarios, these gas giants are believed to form beyond the snow ...line and subsequently migrate inward. Although the early formation history of hot Jupiters is not well understood, they may emerge in resonant chains as a result of disk migration. Here we study the formation of hot Jupiters via the disruption of resonant chains after the gas disk disappears. We perform
N
-body simulations on planetary systems consisting of one gas giant and several super-Earths. The initial configuration involves all neighboring planet pairs being in a 3:2 mean motion resonance. We track the evolution of these resonant chains after the gas disk has vanished. Our results reveal that the resonant chains are prone to instability following the dispersal of the gas disk, with more than 80% of instabilities occurring within 3 million years. Only approximately 4% of resonant chains can survive the dynamical evolution. Notably, we find that resonant chains hosting hot Jupiters are more likely to be unstable compared to those hosting warm Jupiters. Our simulations indicate that 33% ± 4% hot Jupiters and 70% ± 4% warm Jupiters could possess nearby companions. Furthermore, incorporating the effects of general relativity and tidal dissipation increases the isolation of hot Jupiters, resulting in nearby companion occurrence rates of 20% ± 4% for hot Jupiters and 69% ± 6% for warm Jupiters.
Although many studies have been done to reveal artificial selection signatures in commercial and indigenous chickens, a limited number of genes have been linked to specific traits. To identify more ...trait-related artificial selection signatures and genes, we re-sequenced a total of 85 individuals of five indigenous chicken breeds with distinct traits from Yunnan Province, China.
We found 30 million non-redundant single nucleotide variants and small indels (< 50 bp) in the indigenous chickens, of which 10 million were not seen in 60 broilers, 56 layers and 35 red jungle fowls (RJFs) that we compared with. The variants in each breed are enriched in non-coding regions, while those in coding regions are largely tolerant, suggesting that most variants might affect cis-regulatory sequences. Based on 27 million bi-allelic single nucleotide polymorphisms identified in the chickens, we found numerous selective sweeps and affected genes in each indigenous chicken breed and substantially larger numbers of selective sweeps and affected genes in the broilers and layers than previously reported using a rigorous statistical model. Consistent with the locations of the variants, the vast majority (~ 98.3%) of the identified selective sweeps overlap known quantitative trait loci (QTLs). Meanwhile, 74.2% known QTLs overlap our identified selective sweeps. We confirmed most of previously identified trait-related genes and identified many novel ones, some of which might be related to body size and high egg production traits. Using RT-qPCR, we validated differential expression of eight genes (GHR, GHRHR, IGF2BP1, OVALX, ELF2, MGARP, NOCT, SLC25A15) that might be related to body size and high egg production traits in relevant tissues of relevant breeds.
We identify 30 million single nucleotide variants and small indels in the five indigenous chicken breeds, 10 million of which are novel. We predict substantially more selective sweeps and affected genes than previously reported in both indigenous and commercial breeds. These variants and affected genes are good candidates for further experimental investigations of genotype-phenotype relationships and practical applications in chicken breeding programs.
Biomimetic assembly of high-quality nanosheets into nacre-like structures can produce macroscopic films with favorable mechanical and optical performances due to the intrinsic properties and high ...level of ordering of the nanoscale building blocks. Natural ground mica is abundant and exhibits great application potential. However, large size and low aspect ratio greatly limit its biomimetic assembly. Moreover, exfoliation of ground mica into high-quality nanosheets remains a significant challenge. Here, we report that large-scale exfoliation of ground mica into mono- or few-layered mica nanosheets with a production rate of ~1.0 g h
can be successfully achieved. The mica nanosheets are then assembled into strong biomimetic polymeric mica film that inherits the high electric insulation, excellent visible transmittance, and unique ultraviolet-shielding properties of natural mica. Its overall performance is superior to that of natural sheet mica and other biomimetic films, making the polymeric mica film a suitable substrate for flexible and transparent devices.
Immiscible fluid‐fluid displacement in permeable media is important in many subsurface processes, including enhanced oil recovery and geological CO2 sequestration. Controlled by capillary and viscous ...forces, displacement patterns of one fluid displacing another more viscous one exhibit capillary and viscous fingering, and crossover between the two. Although extensive studies investigated viscous and capillary fingering in porous media, a few studies focused on the crossover in rough fractures, and how viscous and capillary forces affect the crossover remains unclear. Using a transparent fracture‐visualization system, we studied how the two forces impact the crossover in a horizontal rough fracture. Drainage experiments of water displacing oil were conducted at seven flow rates (capillary number log10Ca ranging from −7.07 to −3.07) and four viscosity ratios (M=1/1000,1/500,1/100 and 1/50). We consistently observed lower invading fluid saturations in the crossover zone. We also proposed a phase diagram for the displacement patterns in a rough fracture that is consistent with similar studies in porous media. Based on real‐time imaging and statistical analysis of the invasion morphology, we showed that the competition between capillary and viscous forces is responsible for the saturation reduction in the crossover zone. In this zone, finger propagation toward the outlet (characteristic of viscous fingering) as well as void‐filling in the transverse/backward directions (characteristic of capillary fingering), are both suppressed. Therefore, the invading fluid tends to occupy larger apertures with higher characteristic front velocity, promoting void‐filling toward the outlet with thinner finger growth and resulting in a larger volume of defending fluid left behind.
Key Points
Lower invading fluid saturations were observed in the crossover zone and a phase diagram was obtained for rough fracture
The saturation reduction in the crossover zone is induced by the significant suppression of both viscous and capillary fingerings
In the crossover, invading fluid occupies larger aperture spaces with higher front velocity, stimulating void‐filling toward the outlet
Asymmetric one‐carbon homologation or ring expansion of ketones with formal insertion of carbene intermediate, is a challenging but useful strategy to construct a complex skeleton. Sc(III) and chiral ...ligands have been employed in this regard. However, due to flexible conformations and a variety of stereo models, the origin of stereochemistry remains ambiguous. Density functional theory (DFT) calculations were carried out to explore the interactions that control the stereoselectivity of a Sc(III)‐catalyzed asymmetric homologation. The trans influence of counterions was found to affect the coordination mode of ketone to Sc(III), and consequently affect the stereoselectivity.
DFT study of Sc(III)‐catalyzed asymmetric homologation of ketones with diazo compounds revealed a new coordination mode of substrates which was rationalized by the trans influence. The origin of stereo‐selectivity was explored based on the coordination mode. A promising new strategy to adjust stereo‐selectivity by trans influence was proposed.
The utility of electronically conductive metal–organic frameworks (EC‐MOFs) in high‐performance devices has been limited to date by a lack of high‐quality thin film. The controllable thin‐film ...fabrication of an EC‐MOF, Cu3(HHTP)2, (HHTP=2,3,6,7,10,11‐hexahydroxytriphenylene), by a spray layer‐by‐layer liquid‐phase epitaxial method is reported. The Cu3(HHTP)2 thin film can not only be precisely prepared with thickness increment of about 2 nm per growing cycle, but also shows a smooth surface, good crystallinity, and high orientation. The chemiresistor gas sensor based on this high‐quality thin film is one of the best room‐temperature sensors for NH3 among all reported sensors based on various materials.
A wafer‐thin sensor: The preparation of a crystalline, highly‐oriented, and thickness‐controlled thin film with an electronically conductive MOF is reported. Chemiresistive sensors based on these thin films show a high response, excellent selectivity, fast response speed, and good long‐term stability towards NH3 gas at room temperature.
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