Matter evolved under the influence of gravity from minuscule density fluctuations. Nonperturbative structure formed hierarchically over all scales and developed non-Gaussian features in the Universe, ...known as the cosmic web. To fully understand the structure formation of the Universe is one of the holy grails of modern astrophysics. Astrophysicists survey large volumes of the Universe and use a large ensemble of computer simulations to compare with the observed data to extract the full information of our own Universe. However, to evolve billions of particles over billions of years, even with the simplest physics, is a daunting task. We build a deep neural network, the Deep Density Displacement Model (D³M), which learns from a set of prerun numerical simulations, to predict the nonlinear large-scale structure of the Universe with the Zel’dovich Approximation (ZA), an analytical approximation based on perturbation theory, as the input. Our extensive analysis demonstrates that D³M outperforms the second-order perturbation theory (2LPT), the commonly used fast-approximate simulation method, in predicting cosmic structure in the nonlinear regime. We also show that D³M is able to accurately extrapolate far beyond its training data and predict structure formation for significantly different cosmological parameters. Our study proves that deep learning is a practical and accurate alternative to approximate 3D simulations of the gravitational structure formation of the Universe.
As the world enters a new round of large-scale urbanization, the coordination of a balance between social, economic, and environmental systems to promote sustainable urban development has become a ...global focus. Scholars have explored sustainable urbanization, collected relevant literature, and analyzed the influence of research in different countries, finding that China’s influence is second only to that of the US. Accordingly, this study uses the literature in China National Knowledge Infrastructure (CNKI), the world’s largest Chinese database. It selects 3640 studies on sustainable urbanization from Web of Science and Scopus (W&S), and CNKI. Using the bibliometric method in Citespace, it systematically analyzes the research status, development course, and potential trends of research on sustainable urbanization. The results show that: (1) The number of studies on sustainable urbanization in CNKI is decreasing by year, while it has increased gradually in W&S. China currently has the most literature in the field of sustainable urbanization. The US, China, and Germany have the most influential studies. (2) W&S and CNKI each have their separate and complementary emphases. (3) The two datasets are more similar in terms of the nature of their research institutions, but cooperation between the institutions is closer in W&S than in CNKI. There are no aggregation or scaling effects in the Chinese research institutions. The Chinese Academy of Sciences and Hong Kong Polytechnic University are leaders in this field. (4) The top five topics in the studies from W&S are urban development models and public administration, urban planning issues, protection of urban ecosystems, urban land-use changes, and pollution and resource consumption during urbanization. The top five topics in the CNKI studies are strategy of sustainable development, urban development, urbanization and population urbanization, land financing and urban economics, and urban development planning. The construction of urban ecosystems with reasonable structure, efficient processes, and complete functions is an important breakthrough in the application of sustainable urbanization. Reasonably controlling the pace of urban expansion, efficiently coordinating urban and rural development, formulating evidence-based urban development strategies, and ensuring the living standard of urban settlements are the key problems in sustainable urbanization, and will become important directions for related future research.
•We assess research on sustainable urbanization via a bibliometric analysis.•CiteSpace is used to generate visual maps and interpret existing literature.•We make a comparative analysis of the studies on sustainable urbanization.•We explore the development and frontiers of the research on sustainable urbanization.•We provide useful reference for follow-up research on sustainable urbanization.
We demonstrate a new method to constrain gravity on the largest cosmological scales by combining measurements of cosmic microwave background (CMB) lensing and the galaxy velocity field. EG
is a ...statistic, constructed from a gravitational lensing tracer and a measure of velocities such as redshift-space distortions (RSD), that can discriminate between gravity models while being independent of clustering bias and σ8. While traditionally, the lensing field for EG
has been probed through galaxy lensing, CMB lensing has been proposed as a more robust tracer of the lensing field for EG
at higher redshifts while avoiding intrinsic alignments. We perform the largest-scale measurement of EG
ever, up to 150 Mpc h
−1, by cross-correlating the Planck CMB lensing map with the Sloan Digital Sky Survey III (SDSS-III) CMASS galaxy sample and combining this with our measurement of the CMASS auto-power spectrum and the RSD parameter β. We report EG
(z = 0.57) = 0.243 ± 0.060 (stat) ± 0.013 (sys), a measurement in tension with the general relativity (GR) prediction at a level of 2.6σ. Note that our EG
measurement deviates from GR only at scales greater than 80 Mpc h
−1, scales which have not been probed by previous EG
tests. Upcoming surveys, which will provide an order-of-magnitude reduction in statistical errors, can significantly constrain alternative gravity models when combined with better control of systematics.
Metal-organic frameworks (MOFs), comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous, crystalline materials. Their tunable porosity, chemical ...composition, size and shape, and easy surface functionalization make this large family more and more popular for drug delivery. There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. This article presents an overall review and perspectives of MOFs-based drug delivery systems (DDSs), starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands. Then, the synthesis and characterization of MOFs for DDSs are developed, followed by the drug loading strategies, applications, biopharmaceutics and quality control. Importantly, a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics, diseases therapy and advanced DDSs. In particular, the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed. Finally, challenges in MOFs development for DDSs are discussed, such as biostability, biosafety, biopharmaceutics and nomenclature.
This review focuses on metal–organic frameworks (MOFs)-based drug delivery systems (DDSs), including classification, synthesis, characterization, applications and biopharmaceutics of MOFs for DDSs. Display omitted
Trimethylamine (TMA) is a gut microbiota-derived metabolite which comes from diets rich of choline, betaine or
l
-carnitine and could be further converted to Trimethylamine-N-oxide (TMAO) in the ...liver. As the function of gut microbiota and its metabolites being explored so far, studies suggest that TMAO may be a potential risk factor of cardiovascular diseases independent of other traditional risk factors. However, the precise role of TMAO is controversial as some converse results were discovered. In recent studies, it is hypothesized that TMA may also participate in the progression of cardiovascular diseases and some cytotoxic effect of TMA has been discovered. Thus, exploring the relationship between TMA, TMAO and CVD may bring a novel insight into the diagnosis and therapy of cardiovascular diseases. In this review, we discussed the factors which influence the TMA/TMAO’s process of metabolism in the human body. We have also summarized the pathogenic effect of TMA/TMAO in cardiovascular diseases, as well as the limitation of some controversial discoveries.
The significant role of VEGF (vascular endothelial growth factor) as an angiogenesis inducer is well recognized. Besides VEGF, EphrinB2/EphB4 also plays essential roles in vascular development and ...postnatal angiogenesis. Compared with classical proangiogenic factors, not only does EphrinB2/EphB4 promote sprouting of new vessels, it is also involved in the vessel maturation. Given their involvement in many physiologic and pathological conditions, EphB4 and EphrinB2 are increasingly recognized as attractive therapeutic targets for angiogenesis-related diseases through modulating their expression and function. Previous works mainly focused on the individual role of VEGF and EphrinB2/EphB4 in angiogenesis, respectively, but the correlation between EphrinB2/EphB4 and VEGF in angiogenesis has not been fully disclosed. Here, we summarize the structure and bidirectional signaling of EphrinB2/EphB4, provide an overview on the relationship between EphrinB2/EphB4 signaling and VEGF pathway in angiogenesis and highlight the associated potential usefulness in anti-angiogenetic therapy.
Abstract
Previous studies have shown the filamentary structures in the cosmic web influence the alignments of nearby galaxies. We study this effect in the LOWZ sample of the Sloan Digital Sky Survey ...using the ‘Cosmic Web Reconstruction' filament catalogue. We find that LOWZ galaxies exhibit a small but statistically significant alignment in the direction parallel to the orientation of nearby filaments. This effect is detectable even in the absence of nearby galaxy clusters, which suggests it is an effect from the matter distribution in the filament. A non-parametric regression model suggests that the alignment effect with filaments extends over separations of 30–40 Mpc. We find that galaxies that are bright and early-forming align more strongly with the directions of nearby filaments than those that are faint and late-forming; however, trends with stellar mass are less statistically significant, within the narrow range of stellar mass of this sample.
Methanobactins (Mbns) are a family of copper-binding peptides involved in copper uptake by methanotrophs, and are potential therapeutic agents for treating diseases characterized by disordered copper ...accumulation. Mbns are produced via modification of MbnA precursor peptides at cysteine residues catalyzed by the core biosynthetic machinery containing MbnB, an iron-dependent enzyme, and MbnC. However, mechanistic details underlying the catalysis of the MbnBC holoenzyme remain unclear. Here, we present crystal structures of MbnABC complexes from two distinct species, revealing that the leader peptide of the substrate MbnA binds MbnC for recruitment of the MbnBC holoenzyme, while the core peptide of MbnA resides in the catalytic cavity created by the MbnB-MbnC interaction which harbors a unique tri-iron cluster. Ligation of the substrate sulfhydryl group to the tri-iron center achieves a dioxygen-dependent reaction for oxazolone-thioamide installation. Structural analysis of the MbnABC complexes together with functional investigation of MbnB variants identified a conserved catalytic aspartate residue as a general base required for MbnBC-mediated MbnA modification. Together, our study reveals the similar architecture and function of MbnBC complexes from different species, demonstrating an evolutionarily conserved catalytic mechanism of the MbnBC holoenzymes.
Abstract
Measuring the sum of the three active neutrino masses,
M
ν
, is one of the most important challenges in modern cosmology. Massive neutrinos imprint characteristic signatures on several ...cosmological observables, in particular, on the large-scale structure of the universe. In order to maximize the information that can be retrieved from galaxy surveys, accurate theoretical predictions in the nonlinear regime are needed. Currently, one way to achieve those predictions is by running cosmological numerical simulations. Unfortunately, producing those simulations requires high computational resources—several hundred to thousand core hours for each neutrino mass case. In this work, we propose a new method, based on a deep-learning network (D
3
M), to quickly generate simulations with massive neutrinos from standard ΛCDM simulations without neutrinos. We computed multiple relevant statistical measures of deep-learning generated simulations and conclude that our approach is an accurate alternative to the traditional
N
-body techniques. In particular the power spectrum is within ≃6% down to nonlinear scales
k
= 0.7 h Mpc
−1
. Finally, our method allows us to generate massive neutrino simulations 10,000 times faster than the traditional methods.
Abstract
Background
Pyroptosis is a form of programmed cell death involved in the pathophysiological progression of hypoxic pulmonary hypertension (HPH). Emerging evidence suggests that ...N6-methyladenosine (m6A)-modified transcripts of long noncoding RNAs (lncRNAs) are important regulators that participate in many diseases. However, whether m6A modified transcripts of lncRNAs can regulate pyroptosis in HPH progression remains unexplored.
Methods
The expression levels of FENDRR in hypoxic pulmonary artery endothelial cells (HPAECs) were detected by using quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). Western blot, Lactate dehydrogenase (LDH) release assay, Annexin V-FITC/PI double staining, Hoechst 33342/PI fluorescence staining and Caspase-1 activity assay were used to detect the role of FENDRR in HPAEC pyroptosis. The relationship between FENDRR and dynamin-related protein 1 (DRP1) was explored using bioinformatics analysis, Chromatin Isolation by RNA Purification (CHIRP), Electrophoretic mobility shift assay (EMSA) and Methylation-Specific PCR (MSP) assays. RNA immunoprecipitation (RIP) and m6A dot blot were used to detect the m6A modification levels of FENDRR. A hypoxia-induced mouse model of pulmonary hypertension (PH) was used to test preventive effect of conserved fragment TFO2 of FENDRR.
Results
We found that FENDRR was significantly downregulated in the nucleus of hypoxic HPAECs. FENDRR overexpression inhibited hypoxia-induced HPAEC pyroptosis. Additionally, DRP1 is a downstream target gene of FENDRR, and FENDRR formed an RNA–DNA triplex with the promoter of DRP1, which led to an increase in DRP1 promoter methylation that decreased the transcriptional level of DRP1. Notably, we illustrated that the m6A reader YTHDC1 plays an important role in m6A-modified FENDRR degradation. Additionally, conserved fragment TFO2 of FENDEE overexpression prevented HPH in vivo.
Conclusion
In summary, our results demonstrated that m6A-induced decay of FENDRR promotes HPAEC pyroptosis by regulating DRP1 promoter methylation and thereby provides a novel potential target for HPH therapy.
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