ABSTRACT
MYC amplification is frequently observed in approximately 50% of human cancers, rendering it a highly desired anticancer target. Given the challenge of direct pharmacological inhibiting of MYC, impairing the interaction of MYC and its key cofactor WDR5 has been proposed as a promising strategy for MYC-driven cancer treatment. Herein, we report the discovery of 5-thiocyanatothiazol-2-amines that disrupt the WDR5-MYC interaction. Hit fragments were initially identified in a fluorescence polarization (FP)-based screening of an in-house library, and structural-activity relationship exploration resulted in the lead compounds 4m and 4o with potent inhibitory activities on WDR5-MYC interaction (K i = 2.4 µM for 4m; K i = 1.0 µM for 4o). These compounds were further validated via differential scanning fluorimetry (DSF) and coimmunoprecipitation (Co-IP). Moreover, 4m and 4o exhibited good cellular activities with the IC50 values at the micromolar level (IC50 = 0.71-7.40 µM) against multiple MYC-driven cancer cell lines. Our findings afforded a potential small molecule blocking the WDR5-MYC interaction.
ABSTRACT
BACKGROUND: WRKY proteins are important transcription factors (TFs) in plants, involved in growth and development and responses to environmental changes. Although WRKY TFs have been studied at the genome level in Arachis genus, including oil crop and turfgrass, their regulatory networks in controlling flowering time remain unclear. The aim of this study was to predict the molecular mechanisms of WRKY TFs regulation flowering time in Arachis genus at the genome level using bioinformatics approaches. RESULTS: The flowering-time genes of Arachis genus were retrieved from the flowering-time gene database. The regulatory networks between WRKY TFs and downstream genes in Arachis genus were predicted using bioinformatics tools. The results showed that WRKY TFs were involved in aging, autonomous, circadian clock, hormone, photoperiod, sugar, temperature, and vernalization pathways to modulate flowering time in Arachis duranensis, Arachis ipaensis, Arachis monticola, and Arachis hypogaea cv. Tifrunner. The WRKY TF binding sites in homologous flowering-time genes exhibited asymmetric evolutionary pattern, indicating that the WRKY TFs interact with other transcription factors to modulate flowering time in the four Arachis species. Protein interaction network analysis showed that WRKY TFs interacted with FRUITFULL and APETALA2 to modulate flowering time in the four Arachis species. WRKY TFs implicated in regulating flowering time had low expression levels, whereas their interaction proteins had varying expression patterns in 22 tissues of A. hypogaea cv. Tifrunner. These results indicate that WRKY TFs exhibit antagonistic or synergistic interactions with the associated proteins. CONCLUSIONS: This study reveals complex regulatory networks through which WRKY TFs modulate flowering time in the four Arachis species using bioinformatics approaches.
Subject(s)
Arachis , Computational Biology , Flowers , Plant Proteins , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Flowers/genetics , Flowers/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Arachis/genetics , Arachis/physiology , Arachis/metabolism , Gene Expression Regulation, Plant , Gene Regulatory NetworksABSTRACT
Hierarchical-porous-structured materials have been widely used in the field of electromagnetic wave (EMW) absorption, playing a critical role in minimizing EMW interference and pollution. High-quality EMW absorbers, characterized by a lower thickness, lighter weight, wider absorption band, and stronger absorption capacity, have been instrumental in reducing damage and preventing malfunctions in the automotive and aviation industries. The utilization of discarded nut shells through recycling can not only alleviate environmental problems but relieve resource constraints. Herein, a facile method for the preparation of hierarchical porous biomass carbon derived from abandoned Xanthoceras Sorbifolium Bunge Shell (XSS) biomass was developed for high-performance EMW absorption. The porous structures of XSS biochar were studied by using different levels of the K2CO3 activator and simple carbonization. The effect of K2CO3 on the EMW parameters, including the complex permittivity, complex permeability, polarization relaxation, and impedance matching, was analyzed. The best EMW absorption performance of the XSS biochar was observed at a mass ratio of activator-to-biomass of 2:1. A minimum reflection loss (RLmin) of -38.9 dB was achieved at 9.12 GHz, and a maximum effective absorption bandwidth (EABmax) of up to 3.28 GHz (14.72~18.0 GHz) could be obtained at a 1.8 mm thickness. These results demonstrated that hierarchical porous XSS carbon was prepared successfully. Simultaneously, the prepared XSS biochar was confirmed as a potential and powerfully attractive EMW-absorbing material. The proposal also provided a simple strategy for the development of a green, low-cost, and sustainable biochar as a lightweight high-performance absorbing material.
ABSTRACT
Nitrite is one of the most common nitrogenous compounds, which is not only an important indicator of aquaculture water but also widely used as a food additive. Its potential toxicity poses a huge threat to aquatic products and human health. Therefore, it is important to develop a convenient and rapid sensor for the high-efficient onsite detection of nitrite. In this work, a novel electrochemical sensor was developed for the qualitative and quantitative analysis of nitrite. The developed nitrite electrochemical detection system is easily applied in onsite detection. The electrochemical working electrode was constructed based on the combination of Ag-CeO2 and conductive carbon paste (CPE) with excellent electrocatalysis activity and rapid electron transfer ability. By the application of the developed system and under the optimal conditions, the linear range was from 40.0 µM to 500.0 µM, and the detection limit was reduced to 4.3 µM. The recovery was between 92.1% and 108.1%, and the relative standard deviations (RSDs) were 0.49%~9.31%. The sensor exhibited superior reproducibility, high stability sensitivity, and anti-interference ability, confirming its effectiveness for nitrite analysis. Finally, the developed electrochemical sensor was successfully applied to detect nitrite in beverages and aquaculture water samples, indicating that this approach has great potential in onsite food testing and environmental monitoring.
Subject(s)
Aquaculture , Beverages , Cerium , Electrochemical Techniques , Nitrites , Nitrites/analysis , Electrochemical Techniques/methods , Cerium/chemistry , Beverages/analysis , Silver/chemistry , Limit of Detection , Water Pollutants, Chemical/analysis , Electrodes , Reproducibility of Results , Water/chemistry , Water/analysisABSTRACT
To assess the effectiveness and underlying mechanism of pulse-alternating current coagulation (PACC) for treating manganese-laden wastewater, we examined the influence of various parameters. Specifically, we investigated the impact of current density, initial pH, initial Mn2+ concentration, electrolyte concentration, and alternating current frequency on the removal efficacy. The removal mechanism was meticulously examined using an adsorption kinetics analysis, Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared Spectrum (FTIR), and X-ray Photoelectron Spectroscopy (XPS). The findings indicated that the concentration of Re(Mn2+) was 99.09% under the specified conditions: j = 2.5 A·m-2, pH0 = 7, c0(Mn2+) = 50â mg·dm-3, f = 500 Hz, c0(NaCl) = 500â mg·dm-3 and t = 40 min. When Re(Mn2+) = 98%, the energy consumption (EEC) was significantly lower for PACC at 1.23 kWh·m-3, compared to 1.52 kWh·m-3 for direct current condensation (DCC). This indicated a reduction in EEC by 19.1% when using PACC over DCC. The adsorption process of Mn2+ by the iron sol adheres to the principles of pseudo-second order kinetics. The primary component of flocs generated in the PACC process is α-FeOOH. The mechanism of Mn2+ removal in the PACC process involved the synthesis of Mn oxides, the formation of metal hydroxide precipitates and adsorption by nano-iron sol. This study provides a theoretical basis and technical support for the application of PACC technology in the field of manganese-containing wastewater treatment.
ABSTRACT
BACKGROUND: Expression quantitative trait locus (eQTL) analysis aims to detect the genetic variants that influence the expression of one or more genes. Gene-level eQTL testing forms a natural grouped-hypothesis testing strategy with clear biological importance. Methods to control family-wise error rate or false discovery rate for group testing have been proposed earlier, but may not be powerful or easily apply to eQTL data, for which certain structured alternatives may be defensible and may enable the researcher to avoid overly conservative approaches. RESULTS: In an empirical Bayesian setting, we propose a new method to control the false discovery rate (FDR) for grouped hypotheses. Here, each gene forms a group, with SNPs annotated to the gene corresponding to individual hypotheses. The heterogeneity of effect sizes in different groups is considered by the introduction of a random effects component. Our method, entitled Random Effects model and testing procedure for Group-level FDR control (REG-FDR), assumes a model for alternative hypotheses for the eQTL data and controls the FDR by adaptive thresholding. As a convenient alternate approach, we also propose Z-REG-FDR, an approximate version of REG-FDR, that uses only Z-statistics of association between genotype and expression for each gene-SNP pair. The performance of Z-REG-FDR is evaluated using both simulated and real data. Simulations demonstrate that Z-REG-FDR performs similarly to REG-FDR, but with much improved computational speed. CONCLUSION: Our results demonstrate that the Z-REG-FDR method performs favorably compared to other methods in terms of statistical power and control of FDR. It can be of great practical use for grouped hypothesis testing for eQTL analysis or similar problems in statistical genomics due to its fast computation and ability to be fit using only summary data.
Subject(s)
Genomics , Quantitative Trait Loci , Computer Simulation , Bayes Theorem , GenotypeABSTRACT
BACKGROUND AND AIMS: It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF. We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms. APPROACH AND RESULTS: Whole-genome sequencing was available in 4082 people with CF with pancreatic insufficiency (n = 516 with severe CFLD; n = 3566 without CFLD). We tested ~15.9 million single nucleotide polymorphisms (SNPs) for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including (1) genetic variant ( SERPINA1 ; Z allele) previously associated with severe CFLD; (2) candidate SNPs (n = 205) associated with non-CF liver diseases; (3) genome-wide association study of common/rare SNPs; (4) transcriptome-wide association; and (5) gene-level and pathway analyses. The Z allele was significantly associated with severe CFLD ( p = 1.1 × 10 -4 ). No significant candidate SNPs were identified. A genome-wide association study identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 ( p = 8.05 × 10 -10 ) and FNBP1 ( p = 4.74 × 10 -9 ); suggestive, DUSP6 ( p = 1.51 × 10 -7 ) and ANKUB1 ( p = 4.69 × 10 -7 )] relevant to severe CFLD pathophysiology. The transcriptome-wide association identified 3 genes [ CXCR1 ( p = 1.01 × 10 -6 ) , AAMP ( p = 1.07 × 10 -6 ), and TRBV24 ( p = 1.23 × 10 -5 )] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies. CONCLUSION: These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation, innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD.
ABSTRACT
Per- and poly-fluoroalkyl substances (PFAS) are extensively used in commerce leading to their prevalence in the environment. Due to their chemical stability, PFAS are considered to be persistent and bioaccumulative; they are frequently detected in both the environment and humans. Because of this, PFAS as a class (composed of hundreds to thousands of chemicals) are contaminants of very high concern. Little information is available for the vast majority of PFAS, and regulatory agencies lack safety data to determine whether exposure limits or restrictions are needed. Cell-based assays are a pragmatic approach to inform decision-makers on potential health hazards; therefore, we hypothesized that a targeted battery of human in vitro assays can be used to determine whether there are structure-bioactivity relationships for PFAS, and to characterize potential risks by comparing bioactivity (points of departure) to exposure estimates. We tested 56 PFAS from 8 structure-based subclasses in concentration response (0.1-100⯵M) using six human cell types selected from target organs with suggested adverse effects of PFAS - human induced pluripotent stem cell (iPSC)-derived hepatocytes, neurons, and cardiomyocytes, primary human hepatocytes, endothelial and HepG2 cells. While many compounds were without effect; certain PFAS demonstrated cell-specific activity highlighting the necessity of using a compendium of in vitro models to identify potential hazards. No class-specific groupings were evident except for some chain length- and structure-related trends. In addition, margins of exposure (MOE) were derived using empirical and predicted exposure data. Conservative MOE calculations showed that most tested PFAS had a MOE in the 1-100 range; â¼20% of PFAS had MOE<1, providing tiered priorities for further studies. Overall, we show that a compendium of human cell-based models can be used to derive bioactivity estimates for a range of PFAS, enabling comparisons with human biomonitoring data. Furthermore, we emphasize that establishing structure-bioactivity relationships may be challenging for the tested PFAS.
Subject(s)
Fluorocarbons , Induced Pluripotent Stem Cells , Humans , Biological Monitoring , Fluorocarbons/chemistryABSTRACT
In the present study, we conducted optimization of pyramoxadone and synthesized a series of novel oxazolidinediones. Antifungal assays showed that these compounds exhibited moderate to excellent antifungal activity against various pathogens. Further SAR analysis revealed that the introduction of substituents to the benzene ring of the phenoxy group or the inclusion of bulky groups, such as tert-butyl, on the aniline moiety, had a detrimental effect on the activity. However, the inclusion of fluorine atoms in the aniline moiety significantly enhanced the antifungal efficacy. Notably, compound 2-4 displayed significantly higher activity compared to both pyramoxadone and famoxadone against R. solani, B. cinerea, S. sclerotiorum, and P. oryzae, where it demonstrated EC50 values of 1.78, 2.47, 2.33, and 2.23 µg/mL, respectively. Furthermore, compound 2-4 exhibited potent protective and curative effects against the tomato gray mold in vivo. A mechanistic investigation revealed that compound 2-4 significantly impacted the mycelial morphology, inhibited spore germination, and impeded mycelial respiration, ultimately leading to the inhibition of pathogenic fungus growth. These findings indicate that compound 2-4 has the potential to serve as a cyt bc1 inhibitor and should be further investigated for development.
ABSTRACT
Antibiotic-containing wastewater is a typical biochemical refractory organic wastewater and general treatment methods cannot effectively and quickly degrade the antibiotic molecules. In this study, a novel boron-doped diamond (BDD) pulse electrochemical oxidation (PEO) technology was proposed for the efficient removal of levofloxacin (LFXN) from wastewater. The effects of current density (j), initial pH (pH0), frequency (f), electrolyte types and initial concentration (c0(LFXN)) on the degradation of LFXN were systematically investigated. The degradation kinetics under four different processes have also been studied. The possible degradation mechanism of LFXN was proposed by Density functional theory calculation and analysis of degradation intermediates. The results showed that under the optimal parameters, the COD removal efficiency (η(COD)) was 94.4% and the energy consumption (EEC) was 81.43 kWh·m-3 at t = 120 min. The degradation of LFXN at pH = 2.8/c(H2O2) followed pseudo-first-order kinetics. The apparent rate constant was 1.33 × 10-2 min-1, which was much higher than other processes. The degradation rate of LFXN was as follows: pH = 2.8/c(H2O2) > pH = 2.8 > pH = 7/c(H2O2) > pH = 7. Ten aromatic intermediates were formed during the degradation of LFXN, which were further degraded to F-, NH4+, NO3-, CO2 and H2O. This study provides a promising approach for efficiently treating LFXN antibiotic wastewater by pulsed electrochemical oxidation with a BDD electrode without adding H2O2.
Subject(s)
Wastewater , Water Pollutants, Chemical , Anti-Bacterial Agents , Levofloxacin/analysis , Hydrogen Peroxide , Water Pollutants, Chemical/chemistry , Boron/chemistry , Diamond/chemistry , Oxidation-Reduction , ElectrodesABSTRACT
Human cell-based test methods can be used to evaluate potential hazards of mixtures and products of petroleum refining ("unknown or variable composition, complex reaction products, or biological materials" substances, UVCBs). Analyses of bioactivity and detailed chemical characterization of petroleum UVCBs were used separately for grouping these substances; a combination of the approaches has not been undertaken. Therefore, we used a case example of representative high production volume categories of petroleum UVCBs, 25 lower olefin substances from low benzene naphtha and resin oils categories, to determine whether existing manufacturing-based category grouping can be supported. We collected two types of data: nontarget ion mobility spectrometry-mass spectrometry of both neat substances and their organic extracts and in vitro bioactivity of the organic extracts in five human cell types: umbilical vein endothelial cells and induced pluripotent stem cell-derived hepatocytes, endothelial cells, neurons, and cardiomyocytes. We found that while similarity in composition and bioactivity can be observed for some substances, existing categories are largely heterogeneous. Strong relationships between composition and bioactivity were observed, and individual constituents that determine these associations were identified. Overall, this study showed a promising approach that combines chemical composition and bioactivity data to better characterize the variability within manufacturing categories of petroleum UVCBs.
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Although many studies have examined polybrominated diphenyl ethers (PBDEs) and novel brominated flame retardants (NBFRs) in biota, information on the bioaccumulation characteristics of NBFRs from field works is limited. This study investigated the tissue-specific exposure to PBDEs and NBFRs in two reptilian (short-tailed mamushi and red-backed rat snake) and one amphibian species (black-spotted frog) prevalent in the Yangtze River Delta, China. The levels of ΣPBDEs and ΣNBFRs ranged from 4.4-250 and 2.9-22 ng/g lipid weight for snakes respectively and 2.9-120 and 7.1-97 ng/g lipid weight for frogs respectively. BDE-209, BDE-154, and BDE-47 were three major PBDE congeners while decabromodiphenylethane (DBDPE) dominated in NBFRs. Tissue burdens indicated that snake adipose was the major storage site of PBDEs and NBFRs. The biomagnification factors (BMFs) estimated from black-spotted frog to red-backed rat snake indicated the biomagnification of penta- to nona-BDE congeners (BMFs 1.1-4.0) but the lack of biomagnification of other BDE and all NBFR congeners (BMFs 0.16-0.78). Mother to egg transfer of PBDEs and NBFRs evaluated in frogs showed that maternal transfer efficiency was positively related to chemical lipophilicity. This is the first field study on the tissue distribution of NBFRs in reptiles and amphibians and the maternal transfer behavior of 5 major NBFRs. The results underline the bioaccumulation potential of alternative NBFRs.
Subject(s)
Colubridae , Flame Retardants , Animals , Halogenated Diphenyl Ethers/analysis , Environmental Monitoring/methods , Flame Retardants/analysis , Bioaccumulation , Tissue Distribution , China , Anura , LipidsABSTRACT
Multivariate heterogeneous responses and heteroskedasticity have attracted increasing attention in recent years. In genome-wide association studies, effective simultaneous modeling of multiple phenotypes would improve statistical power and interpretability. However, a flexible common modeling system for heterogeneous data types can pose computational difficulties. Here we build upon a previous method for multivariate probit estimation using a two-stage composite likelihood that exhibits favorable computational time while retaining attractive parameter estimation properties. We extend this approach to incorporate multivariate responses of heterogeneous data types (binary and continuous), and possible heteroskedasticity. Although the approach has wide applications, it would be particularly useful for genomics, precision medicine, or individual biomedical prediction. Using a genomics example, we explore statistical power and confirm that the approach performs well for hypothesis testing and coverage percentages under a wide variety of settings. The approach has the potential to better leverage genomics data and provide interpretable inference for pleiotropy, in which a locus is associated with multiple traits.
Subject(s)
Genome-Wide Association Study , Genomics , Genome-Wide Association Study/methods , Phenotype , Genomics/methods , ProbabilityABSTRACT
BACKGROUND: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV1 decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection. METHODS: Participants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV1 adjusted for relevant covariates. Models contained interaction terms between age and Pa stage. RESULTS: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39-58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV1 decline and chronic Pa infection with the greatest FEV1 decline. The most rapid FEV1 decline and strongest association with Pa infection stage was seen in early adolescence (ages 12-15). CONCLUSIONS: Annual FEV1 decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV1 decline and improve survival.
Subject(s)
Cystic Fibrosis , Pseudomonas Infections , Adolescent , Humans , Child , Child, Preschool , Cystic Fibrosis/complications , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/epidemiology , Pseudomonas Infections/complications , Prospective Studies , Respiratory Function Tests , Pseudomonas aeruginosa , LungABSTRACT
Spatiotemporal dynamics of small-molecule metabolites have gained increasing attention for their essential roles in deciphering the fundamental machinery of life. However, subcellular-level regulatory mechanisms remain less studied, particularly due to a lack of tools to track small-molecule metabolites. To address this challenge, we developed high-resolution stimulated Raman scattering (SRS) imaging of a genetically engineered model (GEM) to map metabolites in subcellular resolution. As a result, an unexpected regulatory mechanism of a critical metabolite, sterol, was discovered in yeast by amplifying the strength of vibrational imaging by genetic modulation. Specifically, isozymes of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were evident to promote ergosterol distribution to distinct subcellular locations, where ergosterol was enriched by a local HMGR-directed synthesis. The heterogeneity of this expression pattern thus provides new insights into sterol metabolism and related disease treatment strategies. These findings demonstrate SRS-GEM as a promising platform for new possibilities in investigating metabolic regulation, disease mechanisms, and biopharmaceutical research.
ABSTRACT
Antibiotics are considered a new type of organic pollutant. Antibiotic residues have become a global issue due to their harm to human health. As the use of antibiotics is increasing in human life, such as in medicine, crops, livestock, and even drinking water, the accurate analysis of antibiotics is very vital. In order to develop rapid and on-site approaches for the detection of antibiotics and the analysis of trace-level residual antibiotics, a high-sensitivity, simple, and portable solution is required. Meanwhile, the rapid nanotechnology development of a variety of nanomaterials has been achieved. In this review, nanomaterial-based techniques for antibiotic detection are discussed, and some reports that have employed combined nanomaterials with optical techniques or electrochemical techniques are highlighted.
Subject(s)
Biosensing Techniques , Nanostructures , Humans , Anti-Bacterial Agents/analysis , Biosensing Techniques/methods , Nanostructures/chemistry , Nanotechnology/methods , Electrochemical Techniques/methodsABSTRACT
Rationale: Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance. Objectives: Identify genetic modifier loci and genes/pathways associated with pulmonary disease severity. Methods: Whole-genome sequencing data on 4,248 unique pwCF with pancreatic insufficiency and lung function measures were combined with imputed genotypes from an additional 3,592 patients with pancreatic insufficiency from the United States, Canada, and France. This report describes association of approximately 15.9 million SNPs using the quantitative Kulich normal residual mortality-adjusted (KNoRMA) lung disease phenotype in 7,840 pwCF using premodulator lung function data. Measurements and Main Results: Testing included common and rare SNPs, transcriptome-wide association, gene-level, and pathway analyses. Pathway analyses identified novel associations with genes that have key roles in organ development, and we hypothesize that these genes may relate to dysanapsis and/or variability in lung repair. Results confirmed and extended previous genome-wide association study findings. These whole-genome sequencing data provide finely mapped genetic information to support mechanistic studies. No novel primary associations with common single variants or rare variants were found. Multilocus effects at chr5p13 (SLC9A3/CEP72) and chr11p13 (EHF/APIP) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects. Conclusions: This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.
Subject(s)
Cystic Fibrosis , Humans , Cystic Fibrosis/genetics , Genome-Wide Association Study/methods , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Patient Acuity , Lung , Microtubule-Associated Proteins/geneticsABSTRACT
Anion-exchange reactions are recognized as a vital and facile post-synthesis method to precisely manipulate the emission spectra of perovskite quantum dots (QDs). However, the anion-exchange process often induces adverse structural evolution and trap-mediated mechanisms, so mixed-halide perovskite QDs suffer inefficient anion exchange and poor spectra-stability issues, which limits access to high-quality primary color perovskite QDs for display applications. Here we report an Al3+ bonding-doping synergistic strategy for manufacturing stable mixed Br/Cl deep-blue perovskite QDs. By doping Al3+ into perovskite QDs, highly-efficient Cl- anion exchange and a large-range blue shift of the PL spectrum (â¼62 nm with only 0.1 mmol of Cl feed) can be easily achieved. Notably, the Al3+-mediated deep-blue emission sample exhibits superior stability against moisture and electric fields. It also shows an elevated valence band maximum level. Based on the anion-exchanged QDs, a spectrum-stable deep-blue QLED with an EQE of 1.38% at 463 nm is achieved. Our findings demonstrate a feasible and promising strategy for developing high-performance deep-blue perovskite materials and optoelectronic devices.
ABSTRACT
The microbiota has proved to be one of the critical factors for many diseases, and researchers have been using microbiome data for disease prediction. However, models trained on one independent microbiome study may not be easily applicable to other independent studies due to the high level of variability in microbiome data. In this study, we developed a method for improving the generalizability and interpretability of machine learning models for predicting three different diseases (colorectal cancer, Crohn's disease, and immunotherapy response) using nine independent microbiome datasets. Our method involves combining a smaller dataset with a larger dataset, and we found that using at least 25% of the target samples in the source data resulted in improved model performance. We determined random forest as our top model and employed feature selection to identify common and important taxa for disease prediction across the different studies. Our results suggest that this leveraging scheme is a promising approach for improving the accuracy and interpretability of machine learning models for predicting diseases based on microbiome data.
ABSTRACT
In order to treat domestic wastewater containing phosphorus and chemical oxygen demand (COD), the new technology of Sinusoidal Alternating Current (AC) Fenton Oxidation-Coagulation (SACFOC) was used to improve the removal efficiency (Re) and reduce energy consumption (EEC). The morphology, elemental composition, crystal structure and functional groups of the sludge were characterised by Scanning Electron Microscope (SEM), Energy-dispersive X-ray Spectroscopy (EDS), X-ray diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The results show that total phosphorus removal efficiency {Re(TP)} and removal efficiency of organic matter {Re(COD)} can reach 97.56% and 87.77%, respectively, but EEC is only 0.09â kWh·m-3 under the optimum conditions of pH0 = 3, current density (j) = 0.5â A·m-2, c0(TP) = 18â mg·dm-3, c0(COD) = 300â mg·dm-3, c0(H2O2) = 0.06â mol·dm-3, t = 45â min. As compared with direct current (DC) Fenton Oxidation-Coagulation (DCFOC), the COD removal efficiency of SACFOC treatment was improved by 37%, but the energy consumption was reduced by 45%. The degradation process of total phosphorus and COD by SACFOC abides by the quasi-first-order kinetic model. The process of SACFOC includes double effects of electrocoagulation of iron sol by electrolysis and degrade COD by oxidation of formed hydroxyl radicals (·OH) in wastewater, which improves removal efficiency of total phosphorus and COD in wastewater. Our research findings will provide technical guidance and a theoretical basis for the simultaneous treatment of wastewater containing phosphorus and COD applying SACFOC process.