In situ construction of covalent-organic framework on hydrogen-bond organic framework: Fluorescence detection and removal of 4-nitrophenol and metamitron in aqueous media.

A multifunctional COF@HOF (ETTA-DFP@TCBP-HOF) composite is prepared by adding red-fluorescent ETTA-DFP COF to the blue-fluorescent TCBP-HOF preparation system through molecular hydrogen bonding or π - π stacking interactions in situ one-pot synthesis. ETTA-DFP@TCBP-HOF is a multifunctional material for the quantitative detection and simultaneous adsorption of 4-nitrophenol (4-NP) and metamitron (MET) in aqueous solution. As a dual-emission fluorescent sensor, the ETTA-DFP@TCBP-HOF has both fluorescence of TCBP-HOF at 474 nm and ETTA-DFP COF at 592 nm, which shows a ratiometric response to 4-NP and MET with high selectivity, good sensitivity, good anti-interference performance and fast response. As a adsorbent, ETTA-DFP@TCBP-HOF displays rapid adsorption kinetics, and acceptable adsorption capacity for 4-NP and MET. In conclusion, this work constructs a novel multifunctional hybrid material with dual-emission center of HOF and COF, which can not only be used as a ratiometric fluorescent probe for detection, but also for removal of hazardous pollutants, suggesting a new strategy for environmental remediation and human health.

In Situ Generated Dye@MOF/COF Heterostructure for Fluorescence Detection of Chloroquine Phosphate and Folic Acid via Different Luminescent Channels.

Metal-organic framework (MOF) and covalent-organic framework (COF) hybrid materials can combine the unique properties of MOF and COF components, and their applications in fluorescence sensing have attracted more and more attention. Herein, ZIF-90 is grown on 3D-COF by a simple in situ growing method in which the 7-amino-4-methylcoumarin (AMC) is encapsulated in ZIF-90 to construct a fluorescent sensor. Chloroquine phosphate (CQP) can coordinate with Zn2+ to decompose the ZIF-90 and release AMC. At 365 nm excitation, the ratiometric fluorescence signal AMC/3D-COF (I430/I598) increases linearly with CQP in a linear range of 4 × 10-5 to 4 × 10-4 M in urine. Under 340 nm excitation, quantitative analysis of CQP in the serum (3 × 10-6 to 4 × 10-5 M) is based on the fluorescence intensity of Zn-CQP/3D-COF (I384/I598). In addition, AMC@ZIF-90/3D-COF (1) exhibits high anti-interference and selectivity in sensing of FA with a "turn off" mode, with a correlation range of 1 × 10-5 to 1 × 10-3 M. The fluorescence color changes triggered by CQP under different excitation conditions, and the different fluorescence responses caused by CQP make it a highly secure anticounterfeiting platform. The synthesized dye@MOF/COF hybrids not only provide a new way to integrate multiple emission to design fluorescent probes for differentiation detection but also offer ideas for the design of anticounterfeiting platforms.

AIMedGraph: a comprehensive multi-relational knowledge graph for precision medicine.

The development of high-throughput molecular testing techniques has enabled the large-scale exploration of the underlying molecular causes of diseases and the development of targeted treatment for specific genetic alterations. However, knowledge to interpret the impact of genetic variants on disease or treatment is distributed in different databases, scientific literature studies and clinical guidelines. AIMedGraph was designed to comprehensively collect and interrogate standardized information about genes, genetic alterations and their therapeutic and diagnostic relevance and build a multi-relational, evidence-based knowledge graph. Graph database Neo4j was used to represent precision medicine knowledge as nodes and edges in AIMedGraph. Entities in the current release include 30 340 diseases/phenotypes, 26 140 genes, 187 541 genetic variants, 2821 drugs, 15 125 clinical trials and 797 911 supporting literature studies. Edges in this release cover 621 731 drug interactions, 9279 drug susceptibility impacts, 6330 pharmacogenomics effects, 30 339 variant pathogenicity and 1485 drug adverse reactions. The knowledge graph technique enables hidden knowledge inference and provides insight into potential disease or drug molecular mechanisms. Database URL: http://aimedgraph.tongshugene.net:8201.

Molecular genetic characteristics of thymic epithelial tumors with distinct histological subtypes.

BACKGROUND: Due to the low incidence and histological heterogeneity, the molecular features and underlying carcinogenic mechanisms of thymic epithelial tumors (TETs) are yet to be fully elucidated, especially for different subtypes of TETs. METHODS: Tumor tissue samples of 43 TETs with distinct histological subtypes were collected. We analyzed the molecular characteristics in different subtypes based on whole exome sequencing data. RESULTS: The mutational profiles of the different subtypes of TETs varied. Compared with thymomas, thymic carcinomas (TCs) had a higher mutation frequency of MYO16 (33% vs. 3%, p = 0.024) and a lower frequency of ZNF729 mutations (0% vs. 35%, p = 0.044). No significant difference was observed in the median tumor mutation burden across different subtypes. The value of copy number variation burden, weighted genome instability index, and the number of amplified segments were all higher in TCs than thymomas, and they also tended to be higher in B3 thymoma than in non-B3 thymomas, while they had no significant differences between B3 thymoma and TCs. Clustering analyses revealed that Wnt, MAPK, Hedgehog, AMPK, and cell junction assembly signaling pathways were exclusively enriched in non-B3 thymomas, lysine degradation pathway in B3 thymoma, and extracellular matrix-receptor (ECM-receptor) interaction, positive regulation of cell cycle process, and activation of innate immune response pathways in TCs. CONCLUSIONS: This study revealed distinct molecular landscapes of different subtypes of TETs, suggesting diverse pathogenesis of non-B3 thymomas, B3 thymomas, and TCs. Our findings warrant further validation in future large-scale studies and may provide a theoretical basis for potential personalized therapeutic strategies.

Predicting colorectal cancer microsatellite instability with a self-attention-enabled convolutional neural network.

This study develops a method combining a convolutional neural network model, INSIGHT, with a self-attention model, WiseMSI, to predict microsatellite instability (MSI) based on the tiles in colorectal cancer patients from a multicenter Chinese cohort. After INSIGHT differentiates tumor tiles from normal tissue tiles in a whole slide image, features of tumor tiles are extracted with a ResNet model pre-trained on ImageNet. Attention-based pooling is adopted to aggregate tile-level features into slide-level representation. INSIGHT has an area under the curve (AUC) of 0.985 for tumor patch classification. The Spearman correlation coefficient of tumor cell fraction given by expert pathologist and INSIGHT is 0.7909. WiseMSI achieves a specificity of 94.7% (95% confidence interval [CI] 93.7%-95.7%), a sensitivity of 84.7% (95% CI 82.6%-86.9%), and an AUC of 0.954 (95% CI 0.948-0.960). Comparative analysis shows that this method has better performance than the other five classic deep learning methods.

Eu(III) Functionalized Crystalline Polyimide Hydrogel Film as a Multifunctional Platform for Consecutive Sensing of Spermine and Copper Ions.

In this study, a novel Eu(III) functionalized crystalline polyimide hydrogel film (Eu-1) is fabricated by incorporating highly stable polyimide (PI) into a sodium alginate (SA) matrix, followed by cross-linking reaction with Eu3+ ions. Based on different fluorescence responses, Eu-1 is used for the consecutive detection of spermine (Spm) and copper ions (Cu2+). Eu-1 can be employed as a sensor for polyamine, especially for Spm with significant fluorescence enhancement based on the "turn on" mode. The fluorescent sensor Eu-1@Spm constructed by the Eu-1 and Spm can be further used as a "turn off" sensor to quantitatively monitor Cu2+. The good selectivity combined with the low detection limit of the sensor meets the requirements for monitoring Cu2+. The possible luminescence response mechanisms to Spm and Cu2+ have been studied through experimental data and theoretical calculations. In addition, a back-propagation neural network (BPNN) model based on an Eu-1@Spm sensor is constructed, which can accurately distinguish Cu2+ concentrations by deep machine learning (ML). This work not only puts forward a facile method to prepare a novel Eu-functionalized PI-based hybrid film but also demonstrates the potential of PI-based film materials for fluorescence detection.

Multi-omics analysis of intra-tumoural and inter-tumoural heterogeneity in pancreatic ductal adenocarcinoma.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is associated with the tumour heterogeneity. To explore intra- and inter-tumoural heterogeneity in PDAC, we analysed the multi-omics profiles of 61 PDAC lesion samples, along with the matched pancreatic normal tissue samples, from 19 PDAC patients. Haematoxylin and Eosin (H&E) staining revealed that diversely differentiated lesions coexisted both within and across individual tumours. Whole exome sequencing (WES) of samples from multi-region revealed diverse types of mutations in diverse genes between cancer cells within a tumour and between tumours from different individuals. The copy number variation (CNV) analysis also showed that PDAC exhibited intra- and inter-tumoural heterogeneity in CNV and that high average CNV burden was associated poor prognosis of the patients. Phylogenetic tree analysis and clonality/timing analysis of mutations displayed diverse evolutionary pathways and spatiotemporal characteristics of genomic alterations between different lesions from the same or different tumours. Hierarchical clustering analysis illustrated higher inter-tumoural heterogeneity than intra-tumoural heterogeneity of PDAC at the transcriptional levels as lesions from the same patients are grouped into a single cluster. Immune marker genes are differentially expressed in different regions and tumour samples as shown by tumour microenvironment (TME) analysis. TME appeared to be more heterogeneous than tumour cells in the same patient. Lesion-specific differentially methylated regions (DMRs) were identified by methylated DNA immunoprecipitation sequencing (MeDIP-seq). Furthermore, the integration analysis of multi-omics data showed that the mRNA levels of some genes, such as PLCB4, were significantly correlated with the gene copy numbers. The mRNA expressions of potential PDAC biomarkers ZNF521 and KDM6A were correlated with copy number alteration and methylation, respectively. Taken together, our results provide a comprehensive view of molecular heterogeneity and evolutionary trajectories of PDAC and may guide personalised treatment strategies in PDAC therapy.

Facile fabrication of Tb3+-functionalized COF mixed-matrix membrane as a highly sensitive platform for the sequential detection of oxolinic acid and nitrobenzene.

A novel Tb3+-functionalized covalent organic framework-based polymer mixed-matrix membrane (Tb3+@COF MMM) has been successfully fabricated by incorporating the highly stable Tb3+@PI-COF as filler into polyvinylidene fluoride (PVDF) solution. Compared with pure COF membrane, MMM exhibits its good flexibility, processability and high detection sensitivity. The obtained Tb3+@COF-MMM (M) can be employed as a highly sensitive sensing platform for the sequential detection of oxolinic acid (OA) and nitrobenzene (NB) based on a "off-on-off" process. M has performed its great selectivity, high sensitivity, and low detection limit for detecting OA with "turn-on" mechanism. Moreover, owing to the good chemical stability and anti-interference of M sensor, it is prospective to efficiently detect residues of OA in serum or river water. After the detection of M-15 toward OA, the obtained fluorescent M-15/OA exhibits the rapid quenching, facile manipulation, cycling utility and low detection limits for sensing NB solution and vapor. This work has proposed a typical case of developing flexible Ln3+-functionalized COF-based polymer mixed-matrix membrane as a highly sensitive sensing platform for detecting OA and NB, simultaneously revealed the applied potentiality of M for monitoring animal health and environmental pollution.

Unravelling the role of active-site isolation in reactivity and reaction pathway control for acetylene hydrogenation.

Supported bimetallic PdxCuy catalysts with precisely controlled Pd/Cu ratios were prepared and characterized by combining sample averaged and microscopic techniques. The active-site isolation effect on reactivity and reaction pathway control with different extent of Pd ensembles in acetylene hydrogenation is unravelled systematically.

Quantitative Analysis Method for Nitrogen Electron Energy-Loss Near-Edge Structures in Nanocarbons Based on Density Functional Theory Calculations and Linear Regression.

Nonmetallic heteroatoms found in carbon nanomaterials act as active sites and exhibit excellent catalytic performance. Owing to structural complexity and the limitations of characterization technology, the identification of active sites in nanocarbon is challenging and controversial. Electron energy-loss spectroscopy is an electron microscope technique with high spatial resolution and a powerful tool for identifying the arrangement of heteroatoms. However, structural information regarding the configuration and distribution of heteroatoms is difficult to obtain using existing analytical methods. Herein, we have developed a method for the quantitative analysis of electron energy-loss near-edge structures to identify accurately nitrogen species in nanocarbon. Based on this approach, the relative amounts of nitrogen species were obtained from linear regression with calculated spectra. The concentration distribution of nanocarbon obtained by this method was consistent with the result of X-ray photoelectron spectroscopy analysis at different depths. Therefore, this fitting method can be used for the quantitative analysis of nitrogen K-edge structures. This provides a new strategy for studying the structure-activity relationships of carbon-based materials and the further design of custom nanocarbon catalysts with high active site densities.

Construction of an Aminated MIL-53(Al)-Functionalized Carbon Nanotube for the Efficient Removal of Bisphenol AF and Metribuzin.

A versatile organic-inorganic hybrid structure makes a metal-organic framework (MOF) an outstanding host for different kinds of guests; in addition, its easy pyrolysis nature has been proven to be useful as precursors in the construction of carbon-based materials with a special porous structure. Herein, a novel porous composite nanostructure of an aminated MIL-53(Al)@carbon nanotube (CNT) has been successfully constructed for the first time based on in situ synthesis combining the pyrolysis of ZIF-67. The resulting composite nanostructure was performed by the means of scanning electron microscopy, Brunauer-Emmett-Teller analysis, typical and high-resolution transmission electronic microscopy, X-ray photoelectron spectroscopy, etc. The results showed that a compact heterostructure has been formed between an aminated MIL-53(Al) and a CNT. The resulting composites, named N-MIL@CNT, represent distinct promoted activities in the removal of Bisphenol AF (BPAF) and Metribuzin from wastewater, and the maximum adsorption values were 274 mg/g (BPAF) and 213 mg/g (Metribuzin), which are larger than the results obtained by other MOF-based nanomaterials. The adsorption isotherm, kinetics, and thermodynamics were studied in detail, and the selective adsorption mechanism was also suggested. The excellent selectivity, reusability, and structure stability suggest the potential application of this composite nanostructure in the selective removal of BPAF or Metribuzin from the practical wastewater.

Ecological speciation in sympatric palms: 3. Genetic map reveals genomic islands underlying species divergence in Howea.

Although it is now widely accepted that speciation can occur in the face of continuous gene flow, with little or no spatial separation, the mechanisms and genomic architectures that permit such divergence are still debated. Here, we examined speciation in the face of gene flow in the Howea palms of Lord Howe Island, Australia. We built a genetic map using a novel method applicable to long-lived tree species, combining it with double digest restriction site-associated DNA sequencing of multiple individuals. Based upon various metrics, we detected 46 highly differentiated regions throughout the genome, four of which contained genes with functions that are particularly relevant to the speciation scenario for Howea, specifically salt and drought tolerance.

Surface functionalization of MIL-101(Cr) by aminated mesoporous silica and improved adsorption selectivity toward special metal ions.

Developing novel solid adsorbents with high efficiency and excellent selectivity is always an important target in the removal of toxic metal ions from waste water. In this study, a composite nano-adsorbent NH2-mSiO2@MIL-101(Cr) has been fabricated and applied in the efficient removal of Pb(ii) and Cr(vi) for the first time. The nanocomposites were characterized by using field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), fourier-transform infrared (FT-IR) spectroscopy and thermal gravimetry analysis (TG). The results indicate that a typical core@shell structure has been fabricated by fully coating a mesoporous SiO2 shell over the micro/mesoporous MIL-101(Cr). As a result, the surface charge and the zeta potentials change significantly. Two toxic metal ions, namely, Pb(ii) and Cr(vi) were chosen as the main adsorption targets to evaluate the surface adsorption activities. The adsorption conditions were optimized, the influences of other coexisting ions were explored, and the adsorption selectivity was investigated. Interestingly, the NH2-mSiO2@MIL-101(Cr) nanocomposites display a prominent adsorption activity compared with the original MIL-101(Cr) and non-aminated mSiO2@MIL-101(Cr) and excellent selectivity toward Pb(ii) in the presence of other divalent metal ions. The adsorption kinetics and adsorption thermodynamics were simulated accordingly, and the enhanced adsorption mechanism was also suggested. The good reusability and adsorption selectivity of the NH2-mSiO2@MIL-101(Cr) suggest their potential applications in the selective removal of special metal ions such as Pb(ii) from the waste water.

Epidermal growth factor receptor somatic mutation analysis in 354 Chinese patients with non-small cell lung cancer.

Lung cancer is one of the most common types of cancer worldwide, with the highest mortality rate of all types of cancer. In the present study, epidermal growth factor receptor (EGFR) mutations of 354 primary patients with non-small cell lung cancer (NSCLC) of Chinese ethnicity were detected following formalin-fixed and paraffin-embedded specimen DNA extraction, polymerase chain reaction amplification, and sanger sequencing. The total rate of occurrence of EGFR somatic mutation in these 354 patients was 48.02%. Of these detected EGFR mutations, 27.40% were located in exon 19 and 25.99% in exon 21. The most frequent mutation in exon 19 was E746-A750del (8.47%), and in exon 21, L858R (10.17%). EGFR mutation rates were significantly associated with sex [female vs. male: 60.13 vs. 38.81%; adjusted odds ratio (OR), 1.93, 95% confidence interval (CI), 1.07-3.51, P=0.029], age (<60 vs. ≥60; 58.62 vs. 40.67%; adjusted OR, 1.87; 95% CI, 1.20-2.92; P=0.006) and histology [adenocarcinoma (ADC) vs. non-ADC; 52.76 vs. 26.56%; adjusted OR, 2.35; 95% CI, 1.28-4.50; P=0.007]. The frequency of E746_A750del, Q787Q and L858R mutations were significantly different in ADC patients compared with squamous cell carcinoma patients (P<0.001). Furthermore, a novel EGFR mutation, M793K, was detected in 7 NSCLC patients with possible gefitinib resistance. The present study analyzed the EGFR exon 18-21 mutation occurrence profile for Chinese patients with NSCLC and identified significant associations between different EGFR mutations with demographic and histological factors. These results may offer clinical benefits and potential novel treatments.

The Genome of the "Great Speciator" Provides Insights into Bird Diversification.

Among birds, white-eyes (genus Zosterops) have diversified so extensively that Jared Diamond and Ernst Mayr referred to them as the "great speciator." The Zosterops lineage exhibits some of the fastest rates of species diversification among vertebrates, and its members are the most prolific passerine island colonizers. We present a high-quality genome assembly for the silvereye (Zosterops lateralis), a white-eye species consisting of several subspecies distributed across multiple islands. We investigate the genetic basis of rapid diversification in white-eyes by conducting genomic analyses at varying taxonomic levels. First, we compare the silvereye genome with those of birds from different families and searched for genomic features that may be unique to Zosterops. Second, we compare the genomes of different species of white-eyes from Lifou island (South Pacific), using whole genome resequencing and restriction site associated DNA. Third, we contrast the genomes of two subspecies of silvereye that differ in plumage color. In accordance with theory, we show that white-eyes have high rates of substitutions, gene duplication, and positive selection relative to other birds. Below genus level, we find that genomic differentiation accumulates rapidly and reveals contrasting demographic histories between sympatric species on Lifou, indicative of past interspecific interactions. Finally, we highlight genes possibly involved in color polymorphism between the subspecies of silvereye. By providing the first whole-genome sequence resources for white-eyes and by conducting analyses at different taxonomic levels, we provide genomic evidence underpinning this extraordinary bird radiation.

Large-scale modelling of the divergent spectrin repeats in nesprins: giant modular proteins.

Nesprin-1 and nesprin-2 are nuclear envelope (NE) proteins characterized by a common structure of an SR (spectrin repeat) rod domain and a C-terminal transmembrane KASH [Klarsicht-ANC-Syne-homology] domain and display N-terminal actin-binding CH (calponin homology) domains. Mutations in these proteins have been described in Emery-Dreifuss muscular dystrophy and attributed to disruptions of interactions at the NE with nesprins binding partners, lamin A/C and emerin. Evolutionary analysis of the rod domains of the nesprins has shown that they are almost entirely composed of unbroken SR-like structures. We present a bioinformatical approach to accurate definition of the boundaries of each SR by comparison with canonical SR structures, allowing for a large-scale homology modelling of the 74 nesprin-1 and 56 nesprin-2 SRs. The exposed and evolutionary conserved residues identify important pbs for protein-protein interactions that can guide tailored binding experiments. Most importantly, the bioinformatics analyses and the 3D models have been central to the design of selected constructs for protein expression. 1D NMR and CD spectra have been performed of the expressed SRs, showing a folded, stable, high content α-helical structure, typical of SRs. Molecular Dynamics simulations have been performed to study the structural and elastic properties of consecutive SRs, revealing insights in the mechanical properties adopted by these modules in the cell.

OpenKnowledge for peer-to-peer experimentation in protein identification by MS/MS.

BACKGROUND: Traditional scientific workflow platforms usually run individual experiments with little evaluation and analysis of performance as required by automated experimentation in which scientists are being allowed to access numerous applicable workflows rather than being committed to a single one. Experimental protocols and data under a peer-to-peer environment could potentially be shared freely without any single point of authority to dictate how experiments should be run. In such environment it is necessary to have mechanisms by which each individual scientist (peer) can assess, locally, how he or she wants to be involved with others in experiments. This study aims to implement and demonstrate simple peer ranking under the OpenKnowledge peer-to-peer infrastructure by both simulated and real-world bioinformatics experiments involving multi-agent interactions. METHODS: A simulated experiment environment with a peer ranking capability was specified by the Lightweight Coordination Calculus (LCC) and automatically executed under the OpenKnowledge infrastructure. The peers such as MS/MS protein identification services (including web-enabled and independent programs) were made accessible as OpenKnowledge Components (OKCs) for automated execution as peers in the experiments. The performance of the peers in these automated experiments was monitored and evaluated by simple peer ranking algorithms. RESULTS: Peer ranking experiments with simulated peers exhibited characteristic behaviours, e.g., power law effect (a few dominant peers dominate), similar to that observed in the traditional Web. Real-world experiments were run using an interaction model in LCC involving two different types of MS/MS protein identification peers, viz., peptide fragment fingerprinting (PFF) and de novo sequencing with another peer ranking algorithm simply based on counting the successful and failed runs. This study demonstrated a novel integration and useful evaluation of specific proteomic peers and found MASCOT to be a dominant peer as judged by peer ranking. CONCLUSION: The simulated and real-world experiments in the present study demonstrated that the OpenKnowledge infrastructure with peer ranking capability can serve as an evaluative environment for automated experimentation.

When a module is not a domain: the case of the REJ module and the redefinition of the architecture of polycystin-1.

The extracellular region of a group of cell-surface receptors known as the polycystic kidney disease 1 family, containing, among others, polycystin-1, has been controversially described as containing four FNIII (fibronectin type III) domains or one REJ (receptor of egg jelly protein) module in the same portion of polypeptide. Stimulated by recent atomic force microscopy work, we re-examined the similarity of these four domains with a FNIII sequence profile showing the evolutionary relationship. Two of the predicted domains could be expressed in bacteria and refolded to give a protein suitable for biophysical study, and one of these expressed solubly. CD spectroscopy showed that both domains contain a significant amount of ß-sheet, in good agreement with theoretical predictions. Confirmation of independent folding as a domain is obtained from highly co-operative thermal and urea unfolding curves. Excellent dispersion of peaks in the high-field region of one-dimensional NMR spectra confirms the presence of a hydrophobic core. Analytical ultracentrifugation and analytical gel filtration agree very well with the narrow linewidths in the NMR spectra that at least one of the domains is monomeric. On the basis of this combined theoretical and experimental analysis, we show that the extracellular portion of polycystin-1 does indeed contain ß-sheet domains, probably FNIII, and that, consequently, the REJ module is not a single domain.