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Rapid advances in single-cell transcriptome analysis provide deeper insights into the study of tissue heterogeneity at the cellular level. Unsupervised clustering can identify potential cell populations in single-cell RNA-sequencing (scRNA-seq) data, but fail to further determine the identity of each cell. Existing automatic annotation methods using scRNA-seq data based on machine learning mainly use single feature set and single classifier. In view of this, we propose a Weighted Ensemble classification framework for Cell Type Annotation, named scWECTA, which improves the accuracy of cell type identification. scWECTA uses five informative gene sets and integrates five classifiers based on soft weighted ensemble framework. And the ensemble weights are inferred through the constrained non-negative least squares. Validated on multiple pairs of scRNA-seq datasets, scWECTA is able to accurately annotate scRNA-seq data across platforms and across tissues, especially for imbalanced data containing rare cell types. Moreover, scWECTA outperforms other comparable methods in balancing the prediction accuracy of common cell types and the unassigned rate of non-common cell types at the same time. The source code of scWECTA is freely available at https://github.com/ttren-sc/scWECTA.

Graphene nanomaterials have rapidly developed in recent years. However, its antimicrobial activity does not achieve satisfactory effect. During the past years, it has been found that antimicrobial peptides (AMP) have a good inhibitory effect on pathogenic microbes. In this study, we synthesized AMP-grafted graphene oxide (GO) nanosheets, i.e., D28@GO, against the pathogens such as Candida albicans and Escherichia coli. Growth inhibition assays showed that D28@GO had strong inhibitory effect against the pathogens and this toxicity contributes to cell membrane damage caused by interaction between D28@GO and macrobiomolecules. In vivo experiments further showed that D28@GO severely suppressed systemic infections of pathogens. This study provides novel light on development of GO-based antimicrobial materials.

Utilization of F-T synthetic to produce value-added C8 linear α-olefin is a promising alternative approach, however, the purification of α-olefin from F-T synthetic products is a great challenge, especially for removing 2-methyl-1-heptene (MH). This article addresses the novel method of etherification reaction to remove MH from F-T synthetic products, and develop by far the most efficiency reactive distillation (RD) method to intensified the etherification process. The scarcity of thermodynamic data was measured and regressed by the activity coefficient models, furthermore, kinetics of the etherification reaction of MH with methanol was explored using an ion exchange resin as catalyst, and then fitted by a pseudo-homogeneous model. The pilot-scale RD experimental results show that the conversion of MH reaches 91.83 % and the purity of α-olefin increases by 14.9 wt% (percentage points). Process analysis method was used to realize the optimization of design and operating parameters of etherification RD column based on the developed rigorous model. The optimization results show that the conversion of MH achieves 99.74 % and the purity of α-olefin achieves 96.87 wt%, which is also illustrated that the novel method for removing MH is proposed paving the way for purification of α-olefin from F-T synthetic products.

Co3O4 nanoparticles (NPs) are one kind of the important nanomaterials that have the application potential in catalyst, electrochromic devices, sensors, etc. However, their biological effect remains to be detailed. In this study, we investigated the effect of the as-synthesized Co3O4 NPs (15–30 nm) on the growth of mammalian cells, and found that the NPs severely inhibited cell growth at the sublethal concentrations from 12.5 to 200 mg/L. Interestingly, the NPs did not cause obvious cell death and ROS accumulation, indicating that their inhibitory effect was not attributed to both apoptosis- or necrosis-related cell death and ROS accumulation. Transcription profiling analysis revealed that the NPs caused remarkable down regulation of the genes involved in mitochondrial functions. Transmission electron microscopy (TEM) and biochemical analysis further showed that the NPs might interact with the mitochondria, impairing the mitochondrial membrane potential (MMP) and ATP production. This study uncovers a mitochondrial respiratory chain-related and ROS-independent toxicity mechanism of Co3O4 NPs in eukaryotic cells.

Cavitation is important for good design and performance on engineering machinery, especially for devices such as injector nozzles. In this study, an enhanced cavitation model is proposed with the consideration of vapor transport, bubble dynamics, nucleation, turbulence and the dissolved gas. Based on the classical nucleation theory (CNT), the analysis of nucleation formation process has been carried out in this model. The bubble size distribution obtained from experimental data is also taken into account in this model. Besides, the turbulence effect on the pressure fluctuations is discussed based on the Boussinesq approximation. According to Henry's law, the dissolved gas effect is incorporated into this model by dividing dissolved gas into several different amount and types of gases. All the coefficients used in this model can be either set at recommended values or obtained from previous experiments. The validation of this model is conducted on the experiments of sharp-edged orifice and the NASA CR-2156 hydrofoil. The results show that the proposed model is in good agreement with experiments. This model is also extended into a vortex form in order to simulate the string cavitation phenomenon observed in the visualized multi-orifice diesel nozzle experiment. The proposed model has captured the string cavitation phenomenon and made a preliminary investigation on vortex cavitation inside diesel nozzle.

Candida albicans is a common pathogenic fungus with high mortality in immunocompromised patients. However, the mechanism by which C. albicans invades host epithelial cells and causes serious tissue damage remains to be further investigated. In this study, we established the C. albicans–293T renal epithelial cell interaction model to investigate the mechanism of epithelial infection by this pathogen. It was found that C. albicans infection causes severe cell death and reactive oxygen species (ROS) accumulation in epithelial cells. Further investigations revealed that C. albicans infection might up-regulate expression of nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX), inhibit the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and suppress the p38–Nrf2–heme oxygenase-1 (HO-1) pathway which plays an important role in the elimination of intracellular ROS. Furthermore, epithelial cell death caused by the fungal infection could be strikingly alleviated by addition of the antioxidant agent glutathione, indicating the critical role of ROS accumulation in cell death caused by the fungus. This study revealed that disturbance of the redox homeostasis system and ROS accumulation in epithelial cells is involved in cell death caused by C. albicans infection, which sheds light on the application of antioxidants in the suppression of tissue damage caused by fungal infection.

Candida albicans is an important opportunistic fungal pathogen, and hyphal polarized growth is critical for its invasive infection to the host. Both the vacuolar transient receptor potential (TRP) Ca

Heavy metal contamination is becoming a global problem threatening human health. Heavy metal removal by engineered microbes by cellular adsorption and uptake is a promising strategy for treatment of heavy metal contamination. However, this strategy is confronted with limited heavy metal-capturing elements. In this study, we performed a transcription profiling-guided strategy for construction of heavy metal-capturing synthetic bacteria. Transcription profiling of a heavy metal-tolerating Cupriavidus taiwanensis strain revealed up-regulation of sulfur metabolism-related operons (e.g., iscSAU and moaEDAB) by Pb2+ and Cd2+. A synthetic Escherichia coli strain, EcSSMO, was constructed by design of a synthetic sulfur metabolism operon (SSMO) based on iscSAU/moaEDAB. Biochemical analysis and X-ray photoelectron spectroscopy (XPS) revealed that the synthetic bacteria had remodeled sulfur metabolism and enhanced heavy metal-tolerating capacity, with higher surviving EcSSMO cells than the surviving control cells Ec0 (not containing SSMO) at 50 mg/L of Pb2+ and Cd2+ (>92 % versus 90 % of Pb2+ and Cd2+ at 5 mg/L of Pb2+ and Cd2+, and >40 % of both heavy metals even at 50 mg/L of Pb2+ and Cd2+. This study reveals emphasizes feasibility of transcription profiling-guided construction of synthetic organisms by large-scale remodeling metabolic network.

Accetohydroxyacid synthase (AHAS) is the first enzyme involved in the biosynthetic pathway of branched-chain amino acids. Earlier gene mutation of Candida albicans in a mouse model suggested that this enzyme is a promising target of antifungals. Recent studies have demonstrated that some commercial AHAS-inhibiting sulfonylurea herbicides exerted desirable antifungal activity. In this study, we have designed and synthesized 68 novel ethoxysulfulron (ES) derivatives and evaluated their inhibition constants (Ki) against C. albicans AHAS and cell based minimum inhibitory concentration (MIC) values. The target compounds 5-1, 5-10, 5-22, 5-31 and 5-37 displayed stronger AHAS inhibitions than ES did. Compound 5-1 had the best Ki of 6.7 nM against fungal AHAS and MIC values of 2.5 mg/L against Candida albicans and Candica parapsilosis after 72 h. A suitable nematode model was established here and the antifungal activity of 5-1 was further evaluated in vivo. A possible binding mode was simulated via molecular docking and a comparative field analysis (CoMFA) model was constructed to understand the structure-activity relationship. The current study has indicated that some ES derivatives should be considered as promising hits to develop antifungal drugs with novel biological target.

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Candida albicans is an important opportunistic fungal pathogen, and hyphal polarized growth is critical for its invasive infection to the host. Both the vacuolar transient receptor potential (TRP) Ca2+ channel Yvc1 and the NADPH oxidase Fre8-governed reactive oxygen species (ROS) gradient are involved in hyphal development, but the relationship between Yvc1 and Fre8 during hyphal polarized growth remains to be investigated. Herein, we found that deletion of YVC1 led to dispersed distribution of ROS along the germ tube, while it was concentrated at the hyphal tip in WT cells. Moreover, Fre8 localization was altered as YVC1 was disrupted. Besides, similar to deletion of YVC1, addition of the Ca2+ chelating agent EGTA caused depolarization of Fre8-GFP in the wild-type cells, indicating the critical role of Yvc1-maintained Ca2+ gradient in polarized distribution of Fre8-GFP and consequent disruption of tip ROS gradient. By constructing a series of GFP-tagged polarized growth-related proteins, including Bud6, Exo70 and Lifeact, we found that these proteins, similar to Fre8 and ROS, had depolarized localization in yvc1Δ/Δ. Thus, our work provides a mechanic explanation of Yvc1-governed and ROS-related hyphal polarized growth, and shed a novel light on the role of Ca2+ signaling in maintenance of redox homeostasis and morphogenesis in the fungal pathogens.

By employing dual of one direction S-rough sets (dual of one direction singular rough sets) and its dynamic characteristic, this paper presents the concepts of F-ladder knowledge and F-ladder degree. Using these concepts, the discernibility theorem of F-ladder knowledge, the hiding-discovery theorem of maximum F-ladder knowledge, the hiding-discovery theorem of maximum F-ladder knowledge and the dependence-filter theorem of knowledge discovery are proposed, and the interior hiding principle of F-ladder knowledge, the hiding-discovery criterion of F-ladder knowledge and its applications are given. The results given in this paper show the new characteristics of dual of one direction S-rough sets and the new applications of the dynamic characteristic of dual of one direction S-rough sets.