Neddylation, a post-translational modification that conjugates an ubiquitin-like protein NEDD8 to substrate proteins, is an important biochemical process that regulates protein function. The ...best-characterized substrates of neddylation are the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family of E3 ubiquitin ligases, control many important biological processes, including tumorigenesis, through promoting ubiquitylation and subsequent degradation of a variety of key regulatory proteins. Recently, increasing pieces of experimental evidence strongly indicate that the process of protein neddylation modification is elevated in multiple human cancers, providing sound rationale for its targeting as an attractive anticancer therapeutic strategy. Indeed, neddylation inactivation by MLN4924 (also known as pevonedistat), a small molecule inhibitor of E1 NEDD8-activating enzyme currently in phase I/II clinical trials, exerts significant anticancer effects by inducing cell cycle arrest, apoptosis, senescence and autophagy in a cell-type and context dependent manner. Here, we summarize the latest progresses in the field with a major focus on preclinical studies in validation of neddylation modification as a promising anticancer target.
•Neddylation is one type of post-translational modifications that alters protein function.•Several components that catalyze neddylation modification are over-expressed in multiple human cancers.•Small molecular inhibitor of neddylation modification suppresses cancer cell growth via multiple mechanisms.•Neddylation modification has been validated as a promising anti-cancer target.
A combined process was presented to recover valuable metals from lithium nickel cobalt manganese (NCM) cathodes of spent lithium-ion batteries. In this process, the cathode scrap was first roasted ...with carbonaceous reductant, and then carbonation water leaching was employed to selectively extract Li from the roasted cathodes. Finally, the obtained residue was leached in sulfuric acid solution to recover Co, Ni and Mn. A systematic investigation combining thermodynamic analysis, leaching experiments and characterization was conducted to explore the effect of operating conditions and leaching mechanism. The results indicate that the leaching of Li is significantly improved by injecting of CO2 into the leaching system, and more than 80% of Li can be leached within 10 min at a low liquid-solid ratio. High-quality Li2CO3 can be prepared from the leachate by direct evaporation. More than 96% of Ni, Co and Mn are extracted without adding reductant under the conditions of a H2SO4 dosage of 1.15 times the theoretical value, a time of 2.5 h, a temperature of 55 °C and a liquid-solid ratio of 3.5 mL g−1. The acid leaching process is more efficient and economical, which is ascribed to the transformation of the low-valence states of metals with high activity after reduction roasting.
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•An efficient and economical process was proposed for recovering spent LIBs.•Over 85% of Li was selectively extracted at a low L/S ratio by carbonation leaching.•High-quality Li2CO3 was prepared via direct evaporation of carbonation leachate.•More than 98% of Ni, Mn and 96% of Co were leached without adding reductant.•Leaching mechanism of Co, Ni and Mn was explained by thermodynamic calculation.
Introduction:
Although soil microbial populations are a good predictor of soil texture, little is known about how they react to alpine meadow deterioration.
Methods:
This study utilized Illumina ...HiSeq sequencing to investigate the effects of alpine meadow degradation on soil microbial communities in the Yangtze River source basin at five different degradation levels i.e., non–degraded (ND), slightly degraded (LD), moderately degraded (MD), severely degraded (SD), and very severely degraded (VD).
Results:
The results indicated that bacterial and fungal α-diversity were not substantially different (
p
> 0.05) across the damaged alpine meadows, while β-diversity significantly differed (
p
< 0.01), indicating a higher variation in the microbial community due to alpine meadow degradation. Proteobacteria reduced considerably (
p
< 0.05) by 8.75%, 22.99%, and 24.65%, while Acidobacteria increased significantly (
p
< 0.05) by 41.67%, 85.20%, and 108.67%, in MD, SD, and VD compared with ND, respectively. Ascomycota declined significantly (
p
< 0.05) in the MD, whereas unclassified phyla rose significantly (
p
> 0.05) in the VD compared to the ND. The heatmaps of bacterial and fungal communities revealed two clusters: a ND, LD, and MD group and a SD and VD group, suggesting significant changes in soil microorganisms of alpine meadow in the SD and VD. Redundancy analysis (RDA) revealed that soil moisture, soil bulk density, soil organic carbon, total nitrogen, and plant biomass could explain 73.8% and 39.4% of the variance in bacterial and fungal community structure, respectively.
Discussion:
These findings imply that degradation of the alpine meadow impacts both plant and soil qualities, ultimately leading to changes in soil microbial populations in the Yangtze River’s source region.
The traditional English examination and the current examination system have been unable to meet the needs of the education industry for English examinations. In view of this, based on the neural ...network algorithm, this study proposes a hierarchical network management model from the user’s perspective. Based on the in-depth study of the neural network, this study combined with the network performance characteristics of large data volume, complex data to propose a new BP neural network algorithm. By dynamically changing the momentum factor and learning rate, the algorithm has greatly improved the accuracy and stability of the error. In addition, this study proposes a user perception prediction model, and the model is continuously trained on the model based on the improved BP neural network algorithm and the monitored network performance. In order to study the performance of the research model, a control experiment is designed to analyze the performance of the model. The research results show that the intelligent model and algorithm proposed in this paper are completely feasible and effective.
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•Highly active and tunable iron- and cobalt-based pincer complexes for ethylene oligo-/polymerization.•Modifications of ligand sets enhancing thermal stabilities and activities of ...complex precatalysts.•Correlations between the ligand structures and catalytic behaviors.•Synergic effects of precatalysts and co-catalysts.•Unique microstructures of obtained polyethylenes: highly linear or/and vinyl-group.
Recent progress in the application of homogeneous iron and cobalt catalysts in ethylene oligo-/polymerization is reviewed with particular emphasis placed on the tuning of catalyst performance through the introduction of controlled amounts of ring strain to the ligand frame. While new examples of catalysts bearing the prototypical bis(arylimino)pyridine continue to emerge in the literature, the last decade has witnessed a number of key advances concerned with the fusion of carbocyclic units to the N,N,N-pincer manifold with a view to enhancing both the catalytic activities and thermal stablility of their resultant catalysts. Some notable examples include iron complexes containing aryl-fused imino-phenanthroline ligands, which have proved highly active catalysts for ethylene oligomerization and indeed have shown considerable industrial promise on the pilot plant scale. Elsewhere, bis(arylimino)pyridines incorporating singly or doubly fused cycloalkyl units with the ring sizes anywhere between five- and eight-membered have been systematically developed and have proved versatile supports for both metal centers. More significantly, clear correlations between structure and activity as well as oligo-/polymer properties are a feature of these strain-adjustable catalysts. In many cases, linear vinyl-polyethylenes are accessible which are in demand for the production of long-chain branched copolymers, functional polymers as well as coating materials.
C-reactive protein (CRP) is a widely accepted biomarker of cardiovascular disease and inflammation. In this study, a RNA aptamer-based electrochemical sandwich type aptasensor for CRP detection was ...described using the functionalized silica microspheres as immunoprobes. Silica microspheres (Si MSs), which have good monodispersity and uniform shape, were firstly synthesized. The silica microspheres functionlized with gold nanoparticles (Au NPs) provided large surface area for immobilizing signal molecules (Zinc ions, Zn2+) and antibodies (Ab). RNA aptamers, which were specific recognized to CRP, were assembled on the surface of Au NPs modified electrode via gold-sulfur affinity. In the presence of CRP, a sandwich structure of aptamer-CRP-immunoprobe was formed. Square wave voltammetry (SWV) was employed to record the sensing signal, and a clearly reductive peak corresponding to Zn2+ at about −1.16V (vs. SCE) was obtained. Under optimal conditions, the aptasensor showed wide linear range (0.005ngmL−1 to 125ngmL−1) and low detection limit (0.0017ngmL−1 at a signal-to-noise ratio of 3). Some possible interfering substance was also investigated, and the results obtained showed that the aptasensor possessed good selectivity. When the aptasensor was applied to real serum samples analysis, the satisfied results were obtained, indicating that the aptasensor possessed potential real application ability.
•An aptamer-based electrochemical aptasensor for detection of CRP was fabricated.•A sandwich structure of aptamer-CRP-immunoprobe was formed.•The gold nanoparticles-coated silica microspheres composites were synthesized for signal amplification.•The aptasensor possessed wide linear range and high sensitivity.
Currently there is no unified data classification and coding standard for the existing human disease animal model resource data worldwide. Different data classification and coding systems produce ...different retrieval methods. Some of these methods are inefficient and difficult to use. This research investigated the rules for the classification and coding of such data based on the Replication Methodology of Animal Models for Human Disease, the Classification and Coding Rules for Health Information Data Set (WS/T 306-2009), the Science and Technology Resource Identification (GB/T 32843-2016), the Scientific Data Management Measures (000014349/2018-00052), and The Generic Description Specification for Natural Science and Technology Resources. This research aimed to develop a classification and coding system for data obtained from human disease animal model resource based on the Internet environment to provide a standardized and unified foundation for the collection, saving, retrieval, and sharing of data from this resource.
A complete data classification and coding table compiled in the form of letters and numbers was produced, with a classification infrastructure that expanded layer by layer according to the three dimensions (namely, system diseases, animal species, and modeling methods) and essential attributes. When necessary, it adopted the hierarchy of major, intermediate, and minor categories for certain layer and also one-to-one matched the code and classification result.
Through this study, a sharing and joint construction mechanism for data from this resource can be developed by all research institutes in this field. As a case study, this research also offered technical support for constructing the database for the National Human Disease Animal Model Resource Center. The technological innovation of this paper is to derive a research oriented retrieval method, which provides technical support for the research on the current COVID-19 epidemic and on possible future epidemics.
The key of reactive power planning (RPP), or Var planning, is the optimal allocation of reactive power sources considering location and size. Traditionally, the locations for placing new Var sources ...were either simply estimated or directly assumed. Recent research works have presented some rigorous optimization-based methods in RPP. This paper will first review various objectives of RPP. The objectives may consider many cost functions such as variable Var cost, fixed Var cost, real power losses, and fuel cost. Also considered may be the deviation of a given voltage schedule, voltage stability margin, or even a combination of different objectives as a multi-objective model. Secondly, different constraints in RPP are discussed. These different constraints are the key of various optimization models, identified as optimal power flow (OPF) model, security-constrained OPF (SCOPF) model, and SCOPF with voltage-stability consideration. Thirdly, the optimization-based models will be categorized as conventional algorithms, intelligent searches, and fuzzy set applications. The conventional algorithms include linear programming, nonlinear programming, mixed-integer nonlinear programming, etc. The intelligent searches include simulated annealing, evolutionary algorithms, and tabu search. The fuzzy set applications in RPP address the uncertainties in objectives and constraints. Finally, this paper will conclude the discussion with a summary matrix for different objectives, models, and algorithms.
Foreign atom doping is known to not only modify the electronic structure but also improve the intrinsic activity of catalysts. Herein, we fabricate three-dimensional (3D) self-supporting nanoporous ...cobalt–aluminum intermetallic (np-Co(Al)) through dealloying of Al90Co10 master alloy to in situ introduce Al element into the precursor. The intrinsic Al dopant is determined to be insensitive to S vapor but beneficial to generate numerous Al-doped CoS2 nanowires (Al-CoS2 NWs) when they were subjected to solid–vapor sulfurization treatment. The density functional theory (DFT) calculations evidence that spontaneous Al-doping in CoS2 crystal could enhance the hybridization between Co d-orbital and S p-orbital near the Fermi level. On the one hand, the Co-sites are more active than that of the S-sites, and the intermediate hydrogen (H*) adsorption free energy (ΔG H*) of Al-CoS2 is only −0.16 eV when adsorbed on the bridge site of Co. On the other hand, the embedded Al can not only facilitate the activity improvement of Co-sites but also greatly activate the inert S-sites in CoS2. An overpotential as small as 86 and 191 mV to reach 10 and 100 mA cm–2 H2-evolving current, a small Tafel slope of 62.47 mV dec–1, and long-term operational stability are achieved on the Al-doped CoS2 catalyst. This finding opens up an easily accessible in situ doping route via alloying-dealloying followed by inheritance to nanoporous earth-abundant chalcogenide electrocatalyst for regulating their physicochemical and electrochemical properties, accelerating the development of high performance H2-evolving electrode for electrochemical hydrogen production.
The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases
. Tau assemblies seem to spread through specific neural networks in each ...disease
, with short filaments having the greatest seeding activity
. The abundance of tau inclusions strongly correlates with disease symptoms
. Six tau isoforms are expressed in the normal adult human brain-three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms that lack the second repeat (3R tau)
. In various diseases, tau filaments can be composed of either 3R or 4R tau, or of both. Tau filaments have distinct cellular and neuroanatomical distributions
, with morphological and biochemical differences suggesting that they may be able to adopt disease-specific molecular conformations
. Such conformers may give rise to different neuropathological phenotypes
, reminiscent of prion strains
. However, the underlying structures are not known. Using electron cryo-microscopy, we recently reported the structures of tau filaments from patients with Alzheimer's disease, which contain both 3R and 4R tau
. Here we determine the structures of tau filaments from patients with Pick's disease, a neurodegenerative disorder characterized by frontotemporal dementia. The filaments consist of residues Lys254-Phe378 of 3R tau, which are folded differently from the tau filaments in Alzheimer's disease, establishing the existence of conformers of assembled tau. The observed tau fold in the filaments of patients with Pick's disease explains the selective incorporation of 3R tau in Pick bodies, and the differences in phosphorylation relative to the tau filaments of Alzheimer's disease. Our findings show how tau can adopt distinct folds in the human brain in different diseases, an essential step for understanding the formation and propagation of molecular conformers.
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