Oxygen-Bridged Cu Binuclear Sites for Efficient Electrocatalytic CO2 Reduction to Ethanol at Ultralow Overpotential.

Electrocatalytic CO2 reduction (CO2RR) to alcohols offers a promising strategy for converting waste CO2 into valuable fuels/chemicals but usually requires large overpotentials. Herein, we report a catalyst comprising unique oxygen-bridged Cu binuclear sites (CuOCu-N4) with a Cu···Cu distance of 3.0-3.1 Å and concomitant conventional Cu-N4 mononuclear sites on hierarchical nitrogen-doped carbon nanocages (hNCNCs). The catalyst exhibits a state-of-the-art low overpotential of 0.19 V (versus reversible hydrogen electrode) for ethanol and an outstanding ethanol Faradaic efficiency of 56.3% at an ultralow potential of -0.30 V, with high-stable Cu active-site structures during the CO2RR as confirmed by operando X-ray adsorption fine structure characterization. Theoretical simulations reveal that CuOCu-N4 binuclear sites greatly enhance the C-C coupling at low potentials, while Cu-N4 mononuclear sites and the hNCNC support increase the local CO concentration and ethanol production on CuOCu-N4. This study provides a convenient approach to advanced Cu binuclear site catalysts for CO2RR to ethanol with a deep understanding of the mechanism.

Recent Progress in Modular Electrochemical Synthesis of Hydrogen and High-Value-added Chemicals based on Solid Redox Mediator.

Electrochemical synthesis of H2 and high-value-added chemicals is an efficient and cost-effective approach that can be powered using renewable electricity. Compared to a conventional electrochemical production system, the modular electrochemical production system (MEPS) based on a solid redox mediator (SRM) can separate the anodic and cathodic reactions in time and space. The MEPS can avoid the use of membranes and formation of useless products, as well as eliminate the mutual dependence of production rates at anode and cathode. The SRM can temporarily store or release electrons and ions to pair with cathodic and anodic reactions, respectively, in MEPS. Designing of SRMs with large charge capacity and good cyclability is of great significance for constructing a high-performance MEPS. This work summarizes the design principles, recent advances in MEPS based on SRM, and application in redox flow cells. Moreover, structure design strategies as well as in situ characterization techniques and theoretical calculations for SRM is also proposed. It is expected to promote the vigorous development of MEPS based on SRM. Finally, the challenges and perspectives of MEPS based on SRM are discussed.

Controlling nonlinear collapse of ellipticity and orientation of a co-variant vector optical field.

A vector optical field with inhomogeneous spatial polarization distribution offers what we believe to be a new paradigm to form controllable filaments. However, it is challenging to steer multiple performances (e.g. number, orientation, and interval) of filaments in transparent nonlinear media at one time. Herein, we theoretically self-design and generate a kind of believed to be novel ellipticity and orientation co-variant vector optical field to interact with Kerr medium to solve this issue. The collapsing behaviors of such a new hybrid vector optical field reveal that, by judiciously adjusting the inherent topological charge and initial phase of incident optical field, we are able to give access to stable collapsing filamentation with tunable numbers, orientations and interval. Additionally, the collapsing patterns presented are immune nearly to the extra random noise. The relevant mechanism behind the collapse of the vector optical field is elucidated as well. The findings in this work may have huge potential in optical signal processing, laser machining, and other related applications.

Mslar: Microbial synthetic lethal and rescue database.

Synthetic lethality (SL) occurs when mutations in two genes together lead to cell or organism death, while a single mutation in either gene does not have a significant impact. This concept can also be extended to three or more genes for SL. Computational and experimental methods have been developed to predict and verify SL gene pairs, especially for yeast and Escherichia coli. However, there is currently a lack of a specialized platform to collect microbial SL gene pairs. Therefore, we designed a synthetic interaction database for microbial genetics that collects 13,313 SL and 2,994 Synthetic Rescue (SR) gene pairs that are reported in the literature, as well as 86,981 putative SL pairs got through homologous transfer method in 281 bacterial genomes. Our database website provides multiple functions such as search, browse, visualization, and Blast. Based on the SL interaction data in the S. cerevisiae, we review the issue of duplications' essentiality and observed that the duplicated genes and singletons have a similar ratio of being essential when we consider both individual and SL. The Microbial Synthetic Lethal and Rescue Database (Mslar) is expected to be a useful reference resource for researchers interested in the SL and SR genes of microorganisms. Mslar is open freely to everyone and available on the web at http://guolab.whu.edu.cn/Mslar/.

Prediction of protein-coding small ORFs in multi-species using integrated sequence-derived features and the random forest model.

Proteins encoded by small open reading frames (sORFs) can serve as functional elements playing important roles in vivo. Such sORFs also constitute the potential pool for facilitating the de novo gene birth, driving evolutionary innovation and species diversity. Therefore, their theoretical and experimental identification has become a critical issue. Herein, we proposed a protein-coding sORFs prediction method merely based on integrative sequence-derived features. Our prediction performance is better or comparable compared with other nine prevalent methods, which shows that our method can provide a relatively reliable research tool for the prediction of protein-coding sORFs. Our method allows users to estimate the potential expression of a queried sORF, which has been demonstrated by the correlation analysis between our possibility estimation and codon adaption index (CAI). Based on the features that we used, we demonstrated that the sequence features of the protein-coding sORFs in the two domains have significant differences implying that it might be a relatively hard task in terms of cross-domain prediction, hence domain-specific models were developed, which allowed users to predict protein-coding sORFs both in eukaryotes and prokaryotes. Finally, a web-server was developed and provided to boost and facilitate the study of the related field, which is freely available at http://guolab.whu.edu.cn/codingCapacity/index.html.

GMMAD: a comprehensive database of human gut microbial metabolite associations with diseases.

BACKGROUND: The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs. RESULTS: We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD . CONCLUSIONS: As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.

Study on Room-Temperature Wet Oxidation of Silicon Catalyzed by Copper.

The anomalously fast growth of the silicon oxide layer at room temperature has been reported for the Cu/Si system. However, the systematical exploration of such a reaction under humidity conditions has not yet been carried out. Through one combination of the experiments and first-principle density functional theory (DFT) simulations, here, we investigate the influence of the imparted Cu atoms in Cu/Si on the oxidation of Si with the presence of H2O. The Cu addition causes the geometric distortion of the Si lattice, which alters the charge transfer to absorbed H2O and decreases its dissociation energy. This results in the experimental formation of much defective SiOx for the Cu/Si system than bare Si under humidity conditions. Furthermore, the presence of such an oxide structure and the catalytic effect of Cu provide the suitable diffusion channels and adsorption sites for the H2O transport and its dissociation. This enhances the oxidation rate of Si consequently and results in the fast growth of the oxide layer on Cu/Si at room temperature.

PLOD3 regulates the expression of YAP1 to affect the progression of non-small cell lung cancer via the PKCδ/CDK1/LIMD1 signaling pathway.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3) is a crucial oncogene in human lung cancer, whereas protein kinase C δ (PKCδ) acts as a tumor suppressor. In this study, we aimed to explore the regulation by PLOD3 on the expression of YAP1 to affect the progression of non-small cell lung cancer (NSCLC) via the PKCδ/CDK1/LIMD1 signaling pathway. We found that PLOD3, CDK1, and YAP1 were highly expressed, while LIMD1 was poorly expressed in NSCLC tissues. Mechanistic investigation demonstrated that silencing PLOD3 promoted the cleavage of PKCδ in a caspase-dependent manner to generate a catalytically active fragment cleaved PKCδ, enhanced phosphorylation levels of CDK1, and LIMD1 but suppressed nuclear translocation of YAP1. Furthermore, functional experimental results suggested that loss of PLOD3 led to increased phosphorylation levels of CDK1 and LIMD1 and downregulated YAP1, thereby suppressing the proliferation, colony formation, cell cycle entry, and resistance to apoptosis of NSCLC cells in vitro and inhibiting tumor growth in vivo. Taken together, these results show that PLOD3 silencing activates the PKCδ/CDK1/LIMD1 signaling pathway to prevent the progression of NSCLC, thus providing novel insight into molecular targets for treating NSCLC.

Comprehensive review of the identification of essential genes using computational methods: focusing on feature implementation and assessment.

Essential genes have attracted increasing attention in recent years due to the important functions of these genes in organisms. Among the methods used to identify the essential genes, accurate and efficient computational methods can make up for the deficiencies of expensive and time-consuming experimental technologies. In this review, we have collected researches on essential gene predictions in prokaryotes and eukaryotes and summarized the five predominant types of features used in these studies. The five types of features include evolutionary conservation, domain information, network topology, sequence component and expression level. We have described how to implement the useful forms of these features and evaluated their performance based on the data of Escherichia coli MG1655, Bacillus subtilis 168 and human. The prerequisite and applicable range of these features is described. In addition, we have investigated the techniques used to weight features in various models. To facilitate researchers in the field, two available online tools, which are accessible for free and can be directly used to predict gene essentiality in prokaryotes and humans, were referred. This article provides a simple guide for the identification of essential genes in prokaryotes and eukaryotes.

Anti-CRISPRdb: a comprehensive online resource for anti-CRISPR proteins.

CRISPR-Cas is a tool that is widely used for gene editing. However, unexpected off-target effects may occur as a result of long-term nuclease activity. Anti-CRISPR proteins, which are powerful molecules that inhibit the CRISPR-Cas system, may have the potential to promote better utilization of the CRISPR-Cas system in gene editing, especially for gene therapy. Additionally, more in-depth research on these proteins would help researchers to better understand the co-evolution of bacteria and phages. Therefore, it is necessary to collect and integrate data on various types of anti-CRISPRs. Herein, data on these proteins were manually gathered through data screening of the literatures. Then, the first online resource, anti-CRISPRdb, was constructed for effectively organizing these proteins. It contains the available protein sequences, DNA sequences, coding regions, source organisms, taxonomy, virulence, protein interactors and their corresponding three-dimensional structures. Users can access our database at http://cefg.uestc.edu.cn/anti-CRISPRdb/ without registration. We believe that the anti-CRISPRdb can be used as a resource to facilitate research on anti-CRISPR proteins and in related fields.

Characterization of a New Intracellular Alginate Lyase with Metal Ions-Tolerant and pH-Stable Properties.

Alginate lyases play an important role in alginate oligosaccharides (AOS) preparation and brown seaweed processing. Many extracellular alginate lyases have been characterized to develop efficient degradation tools needed for industrial applications. However, few studies focusing on intracellular alginate lyases have been conducted. In this work, a novel intracellular alkaline alginate lyase Alyw202 from Vibrio sp. W2 was cloned, expressed and characterized. Secretory expression was performed in a food-grade host, Yarrowia lipolytica. Recombinant Alyw202 with a molecular weight of approximately 38.3 kDa exhibited the highest activity at 45 °C and more than 60% of the activity in a broad pH range of 3.0 to 10.0. Furthermore, Alyw202 showed remarkable metal ion-tolerance, NaCl independence and the capacity of degrading alginate into oligosaccharides of DP2-DP4. Due to the unique pH-stable and high salt-tolerant properties, Alyw202 has potential applications in the food and pharmaceutical industries.

lncRNA H19 prevents endothelial-mesenchymal transition in diabetic retinopathy.

AIMS/HYPOTHESIS: The pathophysiology of diabetic retinopathy is linked to hyperglycaemia and its effect on retinal microvascular tissues. The resulting endothelial injury changes the endothelial cell phenotype to acquire mesenchymal properties (i.e. endothelial-mesenchymal transition [EndMT]). Such changes can be regulated by epigenetic mechanisms, including long non-coding RNAs (lncRNAs). lncRNA H19 may influence EndMT through TGF-ß. We investigated the role of H19 in regulating EndMT during diabetic retinopathy. METHODS: H19 was overexpressed or silenced in human retinal endothelial cells exposed to various glucose levels. The cells were examined for H19, endothelial and mesenchymal markers. We then expanded the study to retinal tissues in a mouse model of diabetic retinopathy and also examined vitreous humour samples from individuals with proliferative diabetic retinopathy. RESULTS: Expression of H19 was downregulated in high glucose conditions (25 mmol/l). H19 overexpression prevented glucose-induced EndMT. Such changes appear to involve TGF-ß through a Smad-independent mechanism. Diabetes caused downregulation of retinal H19. Using H19 knockout mice, we demonstrated similar EndMT in the retina. Examination of vitreous humour from individuals with proliferative diabetic retinopathy also reinforced the downregulation of H19 in diabetes. CONCLUSIONS/INTERPRETATION: We therefore concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms. DATA AVAILABILITY: The results from our previous microarray can be found online using the GEO accession number GSE122189.

Zisland Explorer: detect genomic islands by combining homogeneity and heterogeneity properties.

Genomic islands are genomic fragments of alien origin in bacterial and archaeal genomes, usually involved in symbiosis or pathogenesis. In this work, we described Zisland Explorer, a novel tool to predict genomic islands based on the segmental cumulative GC profile. Zisland Explorer was designed with a novel strategy, as well as a combination of the homogeneity and heterogeneity of genomic sequences. While the sequence homogeneity reflects the composition consistence within each island, the heterogeneity measures the composition bias between an island and the core genome. The performance of Zisland Explorer was evaluated on the data sets of 11 different organisms. Our results suggested that the true-positive rate (TPR) of Zisland Explorer was at least 10.3% higher than that of four other widely used tools. On the other hand, the new tool did not lose overall accuracy with the improvement in the TPR and showed better equilibrium among various evaluation indexes. Also, Zisland Explorer showed better accuracy in the prediction of experimental island data. Overall, the tool provides an alternative solution over other tools, which expands the field of island prediction and offers a supplement to increase the performance of the distinct predicting strategy. We have provided a web service as well as a graphical user interface and open-source code across multiple platforms for Zisland Explorer, which is available at http://cefg.uestc.edu.cn/Zisland_Explorer/ or http://tubic.tju.edu.cn/Zisland_Explorer/.

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art.

Molecular dynamics (MD) simulation is a useful technique to study the interaction between molecules and how they are affected by various processes and processing conditions. This review summarizes the application of MD simulations in food processing and safety, with an emphasis on the effects that emerging nonthermal technologies (for example, high hydrostatic pressure, pulsed electric field) have on the molecular and structural characteristics of foods and biomaterials. The advances and potential projection of MD simulations in the science and engineering aspects of food materials are discussed and focused on research work conducted to study the effects of emerging technologies on food components. It is expected by showing key case studies that it will stir novel developments as a valuable tool to study the effects of emerging food technologies on biomaterials. This review is useful to food researchers and the food industry, as well as researchers and practitioners working on flavor and nutraceutical encapsulations, dietary carbohydrate product developments, modified starches, protein engineering, and other novel food applications.

Effect of sodium chloride concentration on off-flavor removal correlated to glucosinolate degradation and red radish anthocyanin stability.

Anthocyanin-rich concentrates from different red radish can be used as natural food colorants. However, the development of off-flavor during extraction has been major challenge in processing industries. This work aimed to evaluate the effect of sodium chloride (NaCl) concentration in phosphoric acidified medium pH 2.5 on removal of off-flavor from red radish anthocyanin. The effect of NaCl concentration on anthocyanin properties was also evaluated. Results showed that the total glucosinolate was highly degraded at high NaCl concentration (< 500 mM) compared with control, leading to higher off-flavor development. Additionally, the glucosinolate degradation was positively and significantly correlated to isothiocyanate, while was negatively and significantly correlated with dimethyl di-, trisulfide, cedrol, triacetin, 6-methyl-5-hepten-2-one. Moreover, total monomeric and color properties of extracted anthocyanins were degraded at high NaCl concentration (< 500 mM) compared with control. The tentative anthocyanin identification by UPLC-TQ-MS showed 12 glycosylated anthocyanins substituted at C3 and C5 in tested anthocyanin extracts. In conclusion, higher NaCl concentration (< 500 mM) could not be useful for red radish off-flavor removal and anthocyanin properties.

ANRIL regulates production of extracellular matrix proteins and vasoactive factors in diabetic complications.

noncoding RNAs (lncRNAs) have gained widespread interest due to their prevailing presence in various diseases. lncRNA ANRIL (a. k. a. CDKN2B-AS1) is located on human chromosome 9 (p21.3) and transcribed in opposite direction to the INK4b-ARF-INK4a gene cluster. It has been identified as a highly susceptible region for diseases such as coronary artery diseases and type 2 diabetes. Here, we explored its regulatory role in diabetic nephropathy (DN) and diabetic cardiomyopathy (DCM) in association with epigenetic modifiers p300 and polycomb repressive complex 2 (PRC2) complex. We used an ANRIL-knockout (ANRILKO) mouse model for this study. The wild-type and ANRILKO animals with or without streptozotocin-induced diabetes were monitored for 2 min. At the end of the time point, urine and tissues were collected. The tissues were measured for fibronectin (FN), type IV collagen (Col1α4), and VEGF mRNA and protein expressions. Renal function was determined by the measurement of 24-h urine volume and albumin/creatinine ratio at euthanasia. Renal and cardiac structures were investigated using periodic acid-Schiff stain and/or immunohistochemical analysis. Elevated expressions of extracellular matrix (ECM) proteins were prevented in ANRILKO diabetic animals. Furthermore, ANRILKO had a protective effect on diabetic mouse kidneys, as evidenced by lowering of urine volume and urine albumin levels in comparison with the wild-type diabetic animals. These alterations regulated by ANRIL may be mediated by p300 and enhancer of zeste 2 (EZH2) of the PRC2 complex. Our study concludes that ANRIL regulates functional and structural alterations in the kidneys and hearts in diabetes through controlling the expressions of ECM proteins and VEGF.

Comprehensive exploration of the enzymes catalysing oxygen-involved reactions and COGs relevant to bacterial oxygen utilization.

To better understand the mechanisms of bacterial adaptation in oxygen environments, we explored the aerobic living-associated genes in bacteria by comparing Clusters of Orthologous Groups of proteins' (COGs) frequencies and gene expression analyses and 38 COGs were detected at significantly higher frequencies (p-value less than 1e-6) in aerobes than in anaerobes. Differential expression analyses between two conditions further narrowed the prediction to 27 aerobe-specific COGs. Then, we annotated the enzymes associated with these COGs. Literature review revealed that 14 COGs contained enzymes catalysing oxygen-involved reactions or products involved in aerobic pathways, suggesting their important roles for survival in aerobic environments. Additionally, protein-protein interaction analyses and step length comparisons of metabolic networks suggested that the other 13 COGs may function relevantly with the 14 enzymes-corresponding COGs, indicating that these genes may be highly associated with oxygen utilization. Phylogenetic and evolutionary analyses showed that the 27 COGs did not have similar trees, and all suffered purifying selection pressures. The divergent times of species containing or lacking aerobic COGs validated that the appearing time of oxygen-utilizing gene was approximately 2.80 Gyr ago. In addition to help better understand oxygen adaption, our method may be extended to identify genes relevant to other living environments.

Accurate prediction of human essential genes using only nucleotide composition and association information.

MOTIVATION: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. RESULTS: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. AVAILABILITY AND IMPLEMENTATION: http://cefg.uestc.edu.cn/Pheg. CONTACT: fbguo@uestc.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

ACFIS: a web server for fragment-based drug discovery.

In order to foster innovation and improve the effectiveness of drug discovery, there is a considerable interest in exploring unknown 'chemical space' to identify new bioactive compounds with novel and diverse scaffolds. Hence, fragment-based drug discovery (FBDD) was developed rapidly due to its advanced expansive search for 'chemical space', which can lead to a higher hit rate and ligand efficiency (LE). However, computational screening of fragments is always hampered by the promiscuous binding model. In this study, we developed a new web server Auto Core Fragment in silico Screening (ACFIS). It includes three computational modules, PARA_GEN, CORE_GEN and CAND_GEN. ACFIS can generate core fragment structure from the active molecule using fragment deconstruction analysis and perform in silico screening by growing fragments to the junction of core fragment structure. An integrated energy calculation rapidly identifies which fragments fit the binding site of a protein. We constructed a simple interface to enable users to view top-ranking molecules in 2D and the binding mode in 3D for further experimental exploration. This makes the ACFIS a highly valuable tool for drug discovery. The ACFIS web server is free and open to all users at http://chemyang.ccnu.edu.cn/ccb/server/ACFIS/.

BDB: biopanning data bank.

The BDB database (http://immunet.cn/bdb) is an update of the MimoDB database, which was previously described in the 2012 Nucleic Acids Research Database issue. The rebranded name BDB is short for Biopanning Data Bank, which aims to be a portal for biopanning results of the combinatorial peptide library. Last updated in July 2015, BDB contains 2904 sets of biopanning data collected from 1322 peer-reviewed papers. It contains 25,786 peptide sequences, 1704 targets, 492 known templates, 447 peptide libraries and 310 crystal structures of target-template or target-peptide complexes. All data stored in BDB were revisited, and information on peptide affinity, measurement method and procedures was added for 2298 peptides from 411 sets of biopanning data from 246 published papers. In addition, a more professional and user-friendly web interface was implemented, a more detailed help system was designed, and a new on-the-fly data visualization tool and a series of tools for data analysis were integrated. With these new data and tools made available, we expect that the BDB database would become a major resource for scholars using phage display, with improved utility for biopanning and related scientific communities.