Alternative splicing is a tightly regulated biological process by which the number of gene products for any given gene can be greatly expanded. Genomic variants in splicing regulatory sequences can ...disrupt splicing and cause disease. Recent developments in sequencing technologies and computational biology have allowed researchers to investigate alternative splicing at an unprecedented scale and resolution. Population-scale transcriptome studies have revealed many naturally occurring genetic variants that modulate alternative splicing and consequently influence phenotypic variability and disease susceptibility in human populations. Innovations in experimental and computational tools such as massively parallel reporter assays and deep learning have enabled the rapid screening of genomic variants for their causal impacts on splicing. In this review, we describe technological advances that have greatly increased the speed and scale at which discoveries are made about the genetic variation of alternative splicing. We summarize major findings from population transcriptomic studies of alternative splicing and discuss the implications of these findings for human genetics and medicine.
Offshore oil and gas production is increasingly growing popular globally. Produced water (PW), which is the largest byproduct of oil and gas production, is a complex mixture of dissolved and ...undissolved organic and inorganic substances. PW contributes considerably to oil pollution in the offshore petroleum and gas industry owing to the organic substances, which mainly include hydrocarbons; this is a major concern to researchers because of the long-term adverse effects on the ecosystem. Since the development of offshore petroleum and gas industry, the PW treatment process has been classified into pretreatment, standard-reaching treatment, and advanced purification treatment based on the characteristics of PW and has been coupled with the environmental, economic, and regulatory considerations. The mechanism, design principle, application, and development of conventional technologies for PW treatment, such as gravity and enhanced gravity sedimentation, hydrocyclone, gas flotation, and medium filtration, are summarized in this study. Novel methods for further application, such as tubular separation, combined fibers coalescence, and membrane separation, are also discussed. Enhancement of treatment with multiple physical fields and environmentally friendly chemical agents, coupled with information control technology, would be the preferred PW treatment approach in the future. Moreover, the PW treatment system should be green, efficient, secure, and intelligent to satisfy the large-scale, unmanned, and abyssal exploration of offshore oil and gas production in the future.
Classical offshore gas field platforms with connecting bridges in the South China Sea and the standby ship beside the platforms. Functions of three platforms in the figure are well drilling and workover, gas production, and accommodation of personnel Display omitted
•Produced water (PW) has danger or potential danger to the ocean environment.•Oil and suspend solid removal were two important steps for PW treatment.•PW management is based on fundamental characteristics, regulations and standards.•Intellectualization and automation will be the development trend for this industry.•Physical devices coupled with chemical agents are the realistic treatment process.
The objective of this work is to synthesize mullite from associated rare‐earth kaolin. The effects of 300 mesh (48 μm) and 400 mesh (38 μm) associated rare earth kaolin and sintering temperature on ...the phase composition, microstructure, sintering behavior, and mechanical properties of mullite were studied. The study showed that the relative mullite content, average aspect ratio, relative density, micro Vickers hardness, and flexural strength of mullite synthesized by using 400‐mesh calcined associated rare earth kaolin as raw material and sintered at 1500°C for 4 h were 76.6%, 5.55 μm, 90.19%, 12.05 GPa, and 166.35 MPa, respectively. Compared with mullite synthesized from 300‐mesh calcined associated rare earth kaolin, the use of 400‐mesh associated rare earth kaolin can reduce the mullitization temperature by about 100°C, increase the average aspect ratio and relative density of mullite by 5.23% and 9.47%, and increase the microscopic Vickers hardness and flexural strength by 6.09% and 17.04%, respectively. This provides new ideas for the comprehensive utilization of associated rare earth kaolin mineral resources and new ways for the high value‐added utilization of associated rare earth kaolin, which has great economic value.
A major limitation of RNA sequencing (RNA-seq) analysis of alternative splicing is its reliance on high sequencing coverage. We report DARTS (https://github.com/Xinglab/DARTS), a computational ...framework that integrates deep-learning-based predictions with empirical RNA-seq evidence to infer differential alternative splicing between biological samples. DARTS leverages public RNA-seq big data to provide a knowledge base of splicing regulation via deep learning, thereby helping researchers better characterize alternative splicing using RNA-seq datasets even with modest coverage.
This study confirmed the enhancement on the reducibility of ZVI from both the additional H+ and generated ROS after the addition of oxidizers. The contribution of generated ROS for reductive reaction ...was quantified.
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It is well known that zero-valent iron (ZVI) could catalyze the oxidation of various oxidants to realize the rapid oxidation removal of pollutants. However, in this study, we found that the addition of different oxidants could regulate the redox function of ZVI system. In three different co-treatment systems, the effects of different oxidizers (peroxymonosulfate (PMS), persulfate (PDS), hydrogen peroxide (H2O2)) dosages on the ratios of oxidative degradation rate and reductive degradation rate of p-nitrophenol (PNP) were studied. The effect of the H+ released from oxidizers and the generated reactive oxygen species (ROS) in ZVI/PMS, ZVI/PDS, ZVI/H2O2 systems were detailed discussed. Especially, the contribution of generated ROS for reductive degradation of PNP was quantified in the ZVI/H2O2 system. Based on the results of TOC removal, UV–vis absorption spectra, and intermediates concentration curves, it was found that the degradation of PNP changed from reduction to oxidation with the increase of oxidant proportion. When the molar ratio of ZVI to oxidizer equal to 100, PNP was mainly degraded by reduction accompanied by slight oxidation. Combined with the results of SEM-EDS and XPS, it was confirmed that the enhanced degradation of PNP under the addition of oxidant was mainly related to the generated ROS, the additional H+, and the corrosion products of ZVI.
We reported an integrated database of Compendium of Protein Lysine Modifications (CPLM; http://cplm.biocuckoo.org) for protein lysine modifications (PLMs), which occur at active ε-amino groups of ...specific lysine residues in proteins and are critical for orchestrating various biological processes. The CPLM database was updated from our previously developed database of Compendium of Protein Lysine Acetylation (CPLA), which contained 7151 lysine acetylation sites in 3311 proteins. Here, we manually collected experimentally identified substrates and sites for 12 types of PLMs, including acetylation, ubiquitination, sumoylation, methylation, butyrylation, crotonylation, glycation, malonylation, phosphoglycerylation, propionylation, succinylation and pupylation. In total, the CPLM database contained 203,972 modification events on 189,919 modified lysines in 45,748 proteins for 122 species. With the dataset, we totally identified 76 types of co-occurrences of various PLMs on the same lysine residues, and the most abundant PLM crosstalk is between acetylation and ubiquitination. Up to 53.5% of acetylation and 33.1% of ubiquitination events co-occur at 10 746 lysine sites. Thus, the various PLM crosstalks suggested that a considerable proportion of lysines were competitively and dynamically regulated in a complicated manner. Taken together, the CPLM database can serve as a useful resource for further research of PLMs.
New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a ...novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.
This study is based on the practice of cleaner production (CP) audits in more than 300 enterprises. After reviewing 1484 CP options, it is found that 82.5% of the options are directly and indirectly ...related to management. Moreover, there are common problems such as the poor sustainability of CP audit results. This shows that enterprise management plays a significant role in implementing CP options. Based on these, this study proposes a new concept of cleaner production management (CPM) system, and draws lessons from the modern environmental management theory and method to establish the framework of CPM system. This system combines the theory and method of CP with the management system of enterprises and presents the CPM requirements in the current enterprise management system, which mainly includes CPM responsibilities, CP objectives, CPM indexes, CP energy resources management, CP process control, CP product management, CPM inspections, and CP performance evaluation. The characteristic of the proposed system is to construct a modern information-based CPM system. With highly systematic, concise structure, and easy operability, this system not only simplifies and improves the CP work in enterprises and reduces several tedious tasks such as document preparation, but also enhance the enterprise management efficiency and motivate the willingness of employees to participate in CP. Innovated and developed for CP implementation, the system has been implemented and applied in Chinese enterprises, and the implementation and application have obvious effects on improving production level as well as environmental and economic benefits.
Single-atom catalysts (SACs) have attracted extensive attention due to their unique catalytic properties and wide range of applications. Advanced characterization techniques, such as ...energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, scanning electron microscopy, and X-ray absorption fine-structure spectroscopy, have been used to investigate the elemental compositions, structural morphologies, and chemical bonding states of SACs in detail, aiming at unraveling the catalytic mechanism. Meanwhile, theoretical calculations, such as quantum chemical calculations and kinetic simulations, were used to predict the catalytic reaction pathways, active sites, and reaction kinetic behaviors of SACs, providing theoretical guidance for the design and optimization of SACs. This review overviews advanced characterization techniques and theoretical calculations for SACs in Fenton-like chemistry. Moreover, this work highlights the importance of advanced characterization techniques and theoretical calculations in the study of SACs and provides perspectives on the potential applications of SACs in the field of environmental remediation and the challenges of practical engineering.
Steps of mRNA maturation are important gene regulatory events that occur in distinct cellular locations. However, transcriptomic analyses often lose information on the subcellular distribution of ...processed and unprocessed transcripts. We generated extensive RNA-seq data sets to track mRNA maturation across subcellular locations in mouse embryonic stem cells, neuronal progenitor cells, and postmitotic neurons. We find disparate patterns of RNA enrichment between the cytoplasmic, nucleoplasmic, and chromatin fractions, with some genes maintaining more polyadenylated RNA in chromatin than in the cytoplasm. We bioinformatically defined four regulatory groups for intron retention, including complete cotranscriptional splicing, complete intron retention in the cytoplasmic RNA, and two intron groups present in nuclear and chromatin transcripts but fully excised in cytoplasm. We found that introns switch their regulatory group between cell types, including neuronally excised introns repressed by polypyrimidine track binding protein 1 (PTBP1). Transcripts for the neuronal gamma-aminobutyric acid (GABA) B receptor, 1 (
) are highly expressed in mESCs but are absent from the cytoplasm. Instead, incompletely spliced
RNA remains sequestered on chromatin, where it is bound by PTBP1, similar to certain long noncoding RNAs. Upon neuronal differentiation,
RNA becomes fully processed and exported for translation. Thus, splicing repression and chromatin anchoring of RNA combine to allow posttranscriptional regulation of
over development. For this and other genes, polyadenylated RNA abundance does not indicate functional gene expression. Our data sets provide a rich resource for analyzing many other aspects of mRNA maturation in subcellular locations and across development.
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