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GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

Fluidic system and sample preparation

The breakpoints of MIC values for Enterobacteriaceae bacteria in this study. (PDF 102 kb)

Heatmap of KEGG pathway annotation results of age groups based on PICRUSt (level 1). (PDF 792 kb)

Heatmap of the detailed annotation information for metabolic pathway among four age groups (level 3). (PDF 1096 kb)

The PCR primers for different resistant genes in this study. (PDF 359 kb)

The workflow for Enterobacteriaceae isolation and identification in this study. (PDF 1115 kb)

We demonstrated an image-guided cell sorter using the techniques of spatial-temporal coding for high throughput cell imaging, real-time image processing and machine learning for cell classification, and microfluidic device in a disposable cartridge for cell sorting.

Heatmap of the detailed annotation information for metabolic pathway among gender groups (level 3). (PDF 1016 kb)

Heatmap of the metabolic pathways results of gender groups (level 2). (PDF 1021 kb)

New treatments that are noninferior or equivalent to-but not necessarily superior to-the reference treatment may still be beneficial to patients because they have fewer side effects, are more convenient, take less time, or cost less. The noninferiority test is widely used in medical research to provide guidance in such situation. In addition, categorical variables are frequently encountered in medical research, such as in studies involving patient-reported outcomes. In this paper, we develop a noninferiority testing procedure for correlated ordinal categorical variables based on a paired design with a latent normal distribution approach. Misclassification is frequently encountered in the collection of ordinal categorical data; therefore, we further extend the procedure to account for misclassification using information in the partially validated data. Simulation studies are conducted to investigate the accuracy of the estimates, the type I error rates, and the power of the proposed procedure. Finally, we analyze one substantive example to demonstrate the utility of the proposed approach.

The phase behaviors of the giant surfactant constructed from a nanoparticle (NP) monotethered by a single AB diblock copolymer chain were investigated by combining self-consistent field theory and density functional theory. Three types of giant surfactants with different chain architectures were constructed via changing the location of NP on the diblock copolymer chain. The simulation results show that the introduction of the NP can induce phase separation of the originally disordered AB diblock copolymers, and phase diagrams as a function of the chain length ratio of A block and the attraction between A block and NP were constructed for the three giant surfactant systems. Via changing the location of NP from the end of B block to the AB-junction point and to the end of A block, the conformational entropies of the systems gradually decrease, leading to a significant difference in phase behaviors. When the NP is tethered to the end of B block, the giant surfactant system has the smallest phase-separation region in the phase diagram, and the resulting ordered structures have the smallest feature sizes. However, when the NP is tethered to the end of A block, the giant surfactant system has the largest phase-separation region, as well as the largest feature sizes of ordered structures. Moreover, the distributions of the NPs within microphase-separated domain can be well tailored by changing the chain length ratio of A block or the attraction between A block and NP in all of the three giant surfactant systems. These findings provide the guideline for the preparation of polymer-nanoparticle composites with controllable morphologies, desirable feature sizes, and precise NP distributions in experiments.

Microstructural asymmetry of the brain can provide more direct causal explanations of functional lateralization than can macrostructural asymmetry. We performed a cross-sectional diffusion imaging study of 314 patients treated for childhood acute lymphoblastic leukemia (ALL) at a single institution and 92 healthy controls. An asymmetry index based on diffusion metrics was computed to quantify brain microstructural asymmetry. The effects of age and the asymmetry metrics of the two cohorts were examined with t-tests and linear models. We discovered two new types of microstructural asymmetry. Myelin-related asymmetry in controls was prominent in the back brain (89% right), whereas axon-related asymmetry occurred in the front brain (67% left) and back brain (88% right). These asymmetries indicate that white matter is more mature and more myelinated in the left back brain, potentially explaining the leftward lateralization of language and visual functions. The asymmetries increase throughout childhood and adolescence (P = 0.04) but were significantly less in patients treated for ALL (P

Background Breast intraductal papilloma (IP) is mainly caused by the abnormal proliferation of ductal epithelial cells. Tree shrews have potential as an animal model for the study of breast tumours; however, little is known regarding the transcriptome and DNA methylome landscapes of breast IP in tree shrews. In this research, we conducted whole-genome DNA methylation and transcriptome analyses of breast IP and normal mammary glands in tree shrews. Methods DNA methylation profiles were generated from the whole-genome bisulfite sequencing and whole-transcriptome landscapes of IP and control groups of tree shrews through strand-specific library construction and RNA sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses and gene set enrichment analysis were performed. Spearman's correlation analysis was used to identify statistical relationships between gene expression and DNA methylation. Results A genome-wide perspective of the epigenetic regulation of protein-coding genes in breast IP in tree shrews was obtained. The methylation levels at CG sites were considerably higher than those at CHG or CHH sites, and were highest in gene body regions. In total, 3,486, 82 and 361 differentially methylated regions (DMRs) were identified in the context of CG, CHG, and CHH, respectively, and 701 differentially methylated genes (DMGs) were found. Further, through transcriptomic analysis, 62 differentially expressed genes, 50 long noncoding RNAs, and 32 circular RNAs were identified in breast IP compared to normal mammary glands. Correlation analysis between the DNA methylation and transcriptome data revealed that 25 DMGs were also differentially expressed genes, among which the expression levels of 9 genes were negatively correlated with methylation levels in gene body regions. Importantly, integrated analysis identified 3 genes (PDZ domain-containing 1, ATPase plasma membrane Ca2+ transporting 4 and Lymphocyte cytosolic protein 1) that could serve as candidates for further study of breast IP in tree shrews. Conclusions This research has unearthed the comprehensive landscape of the transcriptome and DNA methylome of spontaneous IP in tree shrews, as well as candidate tumorigenesis related genes in IP. These results will contribute to the use of tree shrews in animal models of breast tumours.

In this work, bifunctional 3D flower-like CaMoO4: Eu3+/AgBr composites were successfully prepared using a two-step hydrothermal process. The as-prepared samples were characterized by SEM, XRD, FT-IR and EIS technologies, and their catalytic and photoluminescence properties were investigated in detail. The results showed that flower-like CaMoO4: Eu3+/AgBr composites exhibited high catalytic activity for 4-nitrophenol reduction. The reduction reaction can be completed within 5 min at room temperature, and the calculated apparent rate constant is 0.607 min−1. Furthermore, CaMoO4: Eu3+/AgBr composites could be developed as an inorganic sensor for nitroaromatic compound assay, due to the competitive adsorption mechanism. Thus, this work provided a new thought in the design of multifunctional materials for the monitoring and removal of organic pollutants.

In this present work, a room temperature coprecipitation method for the synthesis of CaMoO4@SiO2:Ln (Eu3+, Tb3+, Dy3+) phosphors was reported. These particles were characterized using X-ray diffraction (XRD), Energy dispersive spectrometer (EDS), Fourier Transform IR spectroscopy (FTIR), scanning electron microscope (SEM), UV-visible spectrophotometer and photoluminescence (PL) respectively. The results indicated that emission intensity of SiO2 modified samples increased by about 2 times, compared with no-silica modified samples. Multicolor phosphors were also designed by changing the lattice activators (Eu3+, Tb3+, Dy3+). To further explore its applications, the transparent photoluminescent film was developed through the incorporation of polyvinyl alcohol (PVA), and selective and sensitive detection performance on dichromate was demonstrated in detail. In addition, red emission LED devices was assembled with as-prepared phosphors. The present results provide not only the high-performance phosphors modified by silica, but also a deep explanation of the structure-property relationship of the as-prepared sample. Based on these findings, it can be foreseen that these microparticles will be applied in versatile filed.

Click chemistry is not a single specific reaction, but describes ways of generating products which emulate examples in nature. Click reactions occur in one pot, are not disturbed by water, generate minimal and inoffensive byproducts, and are characterized by a high thermodynamic driving force, driving the reaction quickly and irreversibly towards a high yield of a single reaction product. As a result, over the past 15 years it has become a very useful bio-orthogonal method for the preparation of chemical cross-linked biopolymer-based hydrogel, in the presence of e.g. growth factors and live cells, or in-vivo. Biopolymers are renewable and non-toxic, providing a myriad of potential backbone toolboxes for hydrogel design. The goal of this review is to summarize recent advances in the development of click chemistry-based biopolymeric hydrogels, and their applications in regenerative medicine. In particular, various click chemistry approaches, including copper-catalyzed azide-alkyne cycloaddition reactions, copper-free click reactions (e.g. the Diels–Alder reactions, the strain-promoted azide-alkyne cycloaddition reactions, the radical mediated thiol-ene reactions, and the oxime-forming reactions), and pseudo-click reactions (e.g. the thiol-Michael addition reactions and the Schiff base reactions) are highlighted in the first section. In addition, numerous biopolymers, including proteins (e.g. collagen, gelatin, silk, and mucin), polysaccharides (e.g. hyaluronic acid, alginate, dextran, and chitosan) and polynucleotides (e.g. deoxyribonucleic acid), are discussed. Finally, we discuss biopolymeric hydrogels, cross-linked by click chemistry, intended for the regeneration of skin, bone, spinal cord, cartilage, and cornea. This article provides new insights for readers in terms of the design of regenerative medicine, and the use of biopolymeric hydrogels based on click chemistry reactions.

BACKGROUND Recently published data demonstrated proton therapy (PRT) significantly reduced cognitive decline relative to photons for pediatric medulloblastoma. These findings imply that reductions in dose to critical CNS structures during the boost phase may account for better outcomes over time. Here, we examine differences in dosimetric data for medulloblastoma patients treated on ACNS0331 with photon (Intensity Modulated Radiation Therapy, 3D-Conformal Radiation Therapy) vs PRT to identify potential structures responsible for cognitive benefit. METHODS COG ACNS0331 was a randomized trial examining the impact of reduced craniospinal irradiation (CSI) dose (standard vs low dose, in patients aged 3–7) and volume (whole posterior fossa vs involved field) in pediatric medulloblastoma patients. We identified 136 patients (IMRT=95, 3DCRT=28, Proton=13) enrolled on ACNS0331 with complete radiation and imaging data and re-contoured 10 critical brain structures to calculate dose. RESULTS Proton therapy significantly reduced the dose to critical structures. For example, temporal lobe mean dose and V30 were 30Gy/38% (PRT), 40Gy/89% (IMRT), 41Gy/84% (3DCRT)), hippocampi mean dose were 51 Gy (IMRT), 52 Gy (3DCRT), and 44Gy (PRT) and cochlear mean dose were 43 Gy (IMRT), 49 Gy (3DCRT), and 31Gy (PRT). Dose to several other critical structures were also significantly reduced including the whole brain, supratentorium, cerebellum, and pituitary. CONCLUSIONS Proton therapy greatly reduces dose to critical CNS structures when compared to IMRT or 3DCRT. Further studies are needed to correlate dose reductions in these structures with improved cognitive outcomes.

Protein–ligand interaction detection without disturbances (e.g., surface immobilization, fluorescent labeling, and crystallization) presents a key question in protein chemistry and drug discovery. The emergent technology of transient induced molecular electronic spectroscopy (TIMES), which incorporates a unique design of microfluidic platform and integrated sensing electrodes, is designed to operate in a label-free and immobilization-free manner to provide crucial information for protein–ligand interactions in relevant physiological conditions. Through experiments and theoretical simulations, we demonstrate that the TIMES technique actually detects protein–ligand binding through signals generated by surface electric polarization. The accuracy and sensitivity of experiments were demonstrated by precise measurements of dissociation constant of lysozyme and N-acetyl-d-glucosamine (NAG) ligand and its trimer, NAG3. Computational fluid dynamics (CFD) computation is performed to demonstrate that the surface’s electric polarization signal originates from the induced image charges during the transition state of surface mass transport, which is governed by the overall effects of protein concentration, hydraulic forces, and surface fouling due to protein adsorption. Hybrid atomistic molecular dynamics (MD) simulations and free energy computation show that ligand binding affects lysozyme structure and stability, producing different adsorption orientation and surface polarization to give the characteristic TIMES signals. Although the current work is focused on protein–ligand interactions, the TIMES method is a general technique that can be applied to study signals from reactions between many kinds of molecules., NAG-binding changes lysozyme adsorption orientation on Au(111) surface in water and introduces different surface electric polarization signals in transition state, which is used to detect protein−ligand interactions.

Degenerate behavior (i.e., forming different self-assembled structures for a given block copolymer (BCP) under the same confinement) commonly exists in various confined systems. Understanding degenerate behavior is crucial for precise control over the structures formed by self-assembly systems under confinement. In this study, the degenerate behavior of a self-assembled AB diblock copolymer/nanoparticle (NP) mixture in a cylindrical pore is studied using Monte Carlo simulation. We find that the degenerate behavior of such a mixture depends on the introduction of the NP. Under different pore sizes, four typical degenerate structures [i.e., single helices (S-helices), double helices (D-helices), parallel cylinders, and stacked toroids] can be obtained if the NP content is zero. However, when the NP content in the mixture is increased, it is found that the number of degenerate structures decreases, that is, only blocky structures can be obtained in the case of high NP content. Moreover, the probability of forming S-helices decreases, whereas the probability of forming D-helices increases with increase in the NP content. Analysis of the interactive enthalpy densities and the chain conformation of the systems indicates that entropy plays an important role in the degenerate structure formation. This study provides some new insights into the degenerate behavior of a BCP/NP mixture under confinement, which can offer a theoretical reference for further experiments.

The spacially confined environment can greatly affect the self-assembly behavior of block copolymers, which provides an effective way for fabricating nanomaterials with novel structures and functionalities. Understanding the self-assembly behavior of block copolymers under various confined environments is of great importance for both fundamental studies and practical applications. In this work, the self-assembly behavior of tetragonal-packed cylinder-forming linear ABC triblock copolymers in cylindrical pore is studied using Monte Carlo simulation. Simulation results show that the self-assembly structures of the triblock copolymers depend on the pore size. In larger pore, the self-assembly structure is independent of the initial state of the system, only complex lariat structures are formed. While in smaller pore, the self-assembly structures depend on the initial state of the system. Double helices, parallel pillars and stacked disks can be obtained from different initial states. Further investigations indicate that when the pore size is incommensurate with the equilibrium period of the system in bulk, the occurring probability of the structure with higher interactive energy is high. However, when the pore size is commensurate with the equilibrium period, the occurring probability of the structure with higher interactive energy is low. Moreover, the statistical analysis at the level of micro-scale for the same double helices reveals that with the increase in the pore size, the mean-square end-to-end distance of the polymer chains in cylindrical pore increases, and the orientation of the polymer chains changes from the direction that is perpendicular to the pore axis to the direction that is parallel to the pore axis. The simulation results not only offer new insights into the self-assembly behavior of block copolymers under confined environment, but also provide a theoretical basis for corresponding experiments.

Previous researches found that apigenin exerted antidepressant-like effects in rodents. However, it is unclear whether the neurotrophic system is involved in the antidepressant-like effects of apigenin. Our present study aimed to explore the neurotrophic related mechanism of apigenin in depressive-like mice induced by chronic corticosterone treatment. Mice were repeatedly injected with corticosterone (40 mg/kg) subcutaneously (s.c) once daily for consecutive 21 days. Apigenin (20 and 40 mg/kg) and fluoxetine (20 mg/kg) were administered 30 min prior to the corticosterone injection. The behavioral tests indicated that apigenin reversed the reduction of sucrose preference and the elevation of immobility time in mice induced by chronic corticosterone treatment. In addition, the increase in serum corticosterone levels and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) levels in corticosterone-treated mice were also ameliorated by apigenin administration. Taken together, our findings intensively confirmed the antidepressant-like effects of apigenin and indicated that the antidepressant-like mechanism of apigenin was mediated, at least partly by up-regulation of BDNF levels in the hippocampus.

A well-defined ceria nanocube with six (100) planes was successfully prepared by a facile hydrothermal method. Hydrogenation tests on the carbon dioxide, and several advanced analysis techniques, were used to investigate the catalytic performance of ceria nanocube for reverse water–gas shift (RWGS) and understand the governing reaction mechanism. The results demonstrated that the obtained ceria was a typical mesoporous material with a fluorite structure, and mainly had cerium with + 4 valence oxidation state. As-obtained ceria nanocube showed good performance for RWGS reaction, while nickel on ceria evidently promoted the hydrogenation of CO2. An oxygen-transformation and metal-dissociation mechanism for RWGS reaction was proposed. The dissociation of carbon dioxide over ceria by directly oxidized oxygen vacancy was considered as a main reaction pathway of RWGS. Meanwhile, dissociated adsorption of CO2 and hydrogen over nickel surface directly formed CO and supplied spillover hydrogen to nearby oxygen vacancies, respectively. The neighboring oxygen vacancies at the interface of nickel and ceria were considered as efficient active sites for CO2 hydrogenation.

Although a flow cytometer, being one of the most popular research and clinical tools for biomedicine, can analyze cells based on the cell size, internal structures such as granularity, and molecular markers, it provides little information about the physical properties of cells such as cell stiffness and physical interactions between the cell membrane and fluid. In this paper, we propose a computational cell analysis technique using cells' different equilibrium positions in a laminar flow. This method utilizes a spatial coding technique to acquire the spatial position of the cell in a microfluidic channel and then uses mathematical algorithms to calculate the ratio of cell mixtures. Most uniquely, the invented computational cell analysis technique can unequivocally detect the subpopulation of each cell type without labeling even when the cell type shows a substantial overlap in the distribution plot with other cell types, a scenario limiting the use of conventional flow cytometers and machine learning techniques. To prove this concept, we have applied the computation method to distinguish live and fixed cancer cells without labeling, count neutrophils from human blood, and distinguish drug treated cells from untreated cells. Our work paves the way for using computation algorithms and fluidic dynamic properties for cell classification, a label-free method that can potentially classify over 200 types of human cells. Being a highly cost-effective cell analysis method complementary to flow cytometers, our method can offer orthogonal tests in companion with flow cytometers to provide crucial information for biomedical samples.

We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium-bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique.

The problem of globally asymptotic stability for nonnegative equilibrium points of genetic regulatory networks (GRNs) with time-varying discrete delays and unbounded distributed delays is considered. So far, there are very few results concerning the problem; and in which the nonnegativity of equilibrium points is neglected. In this paper, the existence of nonnegative equilibrium points is firstly presented. Then, by using the nonsingular M-matrix theory and the functional differential equation theory, M-matrix-based sufficient conditions are proposed to guarantee that the kind of GRNs under consideration here has a unique nonnegative equilibrium point which is globally asymptotically stable. The M-matrix-based stability criteria derived here can be easily verified, since they are to check whether a constant matrix is a nonsingular M-matrix. Several numerical examples are offered to illustrate the effectiveness of the approach proposed in this paper.

In this study, elucidation of protein adsorption mechanism is performed using dual polarization interferometry (DPI) and quartz crystal microbalance with dissipation (QCM-D) to study adsorption behaviors of bovine serum albumin (BSA) and lysozyme (LYZ) on poly (ethylene glycol) (PEG) layers. From the analysis of DPI, PEG2000 and PEG5000 show tight and loose mushroom conformations, respectively. Small amount of LYZ could displace the interfacial water surrounding the tight mushroomed PEG2000 chains by hydrogen bond attraction, leading to protein adsorption. The loose mushroomed PEG5000 chains exhibit a more flexible conformation and high elastic repulsion energy that could prevent protein adsorption of all BSA and most of LYZ. From the analysis of QCM, PEG2000 and PEG5000 show tight and extended brush conformations. The LYZ adsorbed mass has critical regions of PEG2000 (0.19 chain/nm(2)) and PEG5000 (0.16 chain/nm(2)) graft density. When graft density of PEG is higher than the critical region (brush conformations), the attraction of hydrogen bonds between PEG and LYZ is the dominant factor. When graft density of PEG is lower than the critical region (mushroom conformations), elastic repulsion between PEG and proteins is driven by the high conformation entropy of PEG chains, which is the dominant force of steric repulsion in PEG-protein systems. Therefore, the adsorption of BSA is suppressed by the high elastic repulsion energy of PEG chains, whereas the adsorption of LYZ is balanced by the interactions between the repulsion of entropy elasticity and the attraction of hydrogen bonds.

Accurately monitor SO2 derivatives in agricultural crop leaf tissues is imperative, but it is still limited. A fluorescent sensing system with the characteristic of ratiometric near-infrared (NIR) fluorescence response to analyte is conducive to applying in agricultural crop leaf tissues. Herein, we rationally constructed 7-diethyl-amino-aza-coumarin conjugated quinolinium hybrid, CQ-1, as the first fluorescent sensing system to monitor SO2 derivatives in ratiometric NIR response manner in agricultural crop leaf tissues. CQ-1 exhibited specific and sensitive ratiometric NIR response to SO2 derivatives, with detection limits calculated to be 0.016 μM. Moreover, the fluorescence ratios (I516/I714) of the CQ-1 displayed linear relationship with the concentrations of introduced SO2 derivatives from 0 to 300 μM. Fluorescence imaging experiments revealed that CQ-1 was able to detect pre-treated SO2 derivatives in agricultural crop leaf tissues. Significantly, quantitative detection of SO2 derivatives in leaf tissues which were assimilated by stomata from SO2 polluted air was successfully conducted. The sensing system developed herein will be used as an effective tool to accurately monitor the subtle changes of SO2 derivative level in various agricultural crops.

BACKGROUND Retinoblastoma (RB) seriously endangers the vision and even the life of patients. This study aimed to explore the endoplasmic reticulum stress (ERS) and drug resistance of RB and verify the effect of miR-512-3p as a regulator of XBP-1 shearing mechanism on ERS, proliferation, apoptosis, and autophagy levels of RB cells. MATERIAL AND METHODS Y79, weri-RB1, and HXO-RB44 cells were treated with cisplatin (DDP) gradient concentration to construct DDP-resistant cells. The drug inhibition rate and cell proliferation were assessed by CCK-8 assay. The cell transfection and cell apoptosis were detected by RT-qPCR analysis and TUNEL assay, respectively. The protein expression was detected by Western blot analysis. Dual-luciferase reporter assay confirmed the combination of miR-512-30p and XBP-1 transcript 1/2. RESULTS DDP inhibition rates for DDP-resistant RB cells were lower than that for RB cells. The XBP-1 expression was increased in DDP-resistant RB cells, and Y79 cells were chosen for the subsequent experiments. After transfection, miR-512-3p overexpression obviously inhibited the proliferation of DDP-resistant Y79 cells (Y79/DDP cells). miR-512-3p overexpression increased the DDP inhibition rate for Y79/DDP cells and apoptosis of Y79/DDP cells. miR-512-3p overexpression downregulated the expression of LC3 II/I in Y79/DDP cells. The effect of miR-512-3p inhibition on Y79/DDP cells was not as obvious as the effect of miR-512-3p overexpression on Y79/DDP cells. Furthermore, miR-512-3p was confirmed to be combined with XBP-1 transcript variant 1. CONCLUSIONS miR-512-3p improved the DDP resistance of RB cells by promoting ERS-induced apoptosis and inhibiting the proliferation and autophagy of RB cells.

Classification of cell types and isolation of targeted cells according to their imaging and spatial characteristics, beyond traditional fluorescently labeled biomarkers, enable the development of new biological insight and establishment of connections between phenotypical and morphological, and genomic cell information in normal and diseased states. Here, we demonstrate a microfluidic flow cytometer cell sorter that uses fast scanning laser excitation sources and photomultiplier tubes (PMTs), coupled with real-time image processing, to image and sort cells based on user-defined spatial features. Dozens of features, including label-free characteristics such as size, shape, scattering pattern, morphology, as well as the spatial distribution of fluorescently labeled biomarkers, greatly expand the available information space in cell analysis. The use of a disposable microfluidic cartridge that is compatible with the imaging system contributes to size reduction and lowered risk of cross contamination. The so-called cameraless design that uses PMTs to replace CCD makes the system more compatible with conventional fluorescence-activated cell sorters and user friendly, while enjoying the sensitivity and benefits of PMTs. The cell image features can be directly extracted from the temporal waveforms or from the reconstructed cell images via temporal–spatial transformation.

Utilizing the non-covalent π-π stacking of pyrene functionalized molecules onto graphene surfaces has achieved great success in the detection of various bio-objects, while the fundamental investigations on surface modifications stills remain rarely exploited. Here, we report the nano and atomic scale analysis of the π-π stacking functionalized graphene surface regarding to its surface topography, molecular self-assembly as well as process optimizations. The ‘amphipathic’ molecule, pyrene-maltose, is used for the non-covalent functionalization of graphene and systematical analysis is performed to understand the influence of different solvents on the molecular surface arrangement. Atomic force microscopy (AFM) and spectroscopy analysis indicate the successful formation of pyrene-maltose layer on graphene surface and it is further confirmed by scanning tunneling microscopy, depicting the self-assembled and densely packed pyrene-maltose layer that give distinguished and ordered diamond-shape lattice as compared to triangular lattice in pristine graphene. We also demonstrated that the interfacial adhesion forces between the AFM probe and the functionalized surfaces allow the detection of the lectin protein Concavalin A through selective absorption. This work provides essential evidence of the π-π interactions between pyrene molecules and graphene, and the AFM based adhesion measurement also has the potential to be employed in a variety of bio-detection applications.

AimsTo identify the common and specific molecular mechanisms of three well-defined subtypes of endometriosis (EMs): ovarian endometriosis (OE), peritoneal endometriosis (PE), and deep infiltrating endometriosis (DIE).MethodsFour microarray datasets:GSE7305andGSE7307for OE,E-MTAB-694for PE, andGSE25628for DIE were downloaded from public databases and conducted to compare ectopic lesions (EC) with eutopic endometrium (EU) from EMs patients. Differentially expressed genes (DEGs) identified by limma package were divided into two parts: common DEGs among three subtypes and specific DEGs in each subtype, both of which were subsequently performed with the Kyoto Encyclopedia of Genes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed by common DEGs and five hub genes were screened out from the PPI network. Besides, these five hub genes together with selected interested pathway-related genes were further validated in an independent OE RNA-sequencing datasetGSE105764.ResultsA total of 54 EC samples from three EMs subtypes (OE, PE, DIE) and 58 EU samples were analyzed, from which we obtained 148 common DEGs among three subtypes, and 729 specific DEGs in OE, 777 specific DEGs in PE and 36 specific DEGs in DIE. The most enriched pathway of 148 shared DEGs was arachidonic acid (AA) metabolism, in which most genes were up-regulated in EC, indicating inflammation was the most common pathogenesis of three subtypes. Besides, five hub genes AURKB, RRM2, DTL, CCNB1, CCNB2 identified from the PPI network constructed by 148 shared DEGs were all associated with cell cycle and mitosis, and down-regulated in EC, suggesting a slow and controlled proliferation in ectopic lesions. The KEGG pathway analysis of specific DEGs in each subtype revealed that abnormal ovarian steroidogenesis was a prominent feature in OE; OE and DIE seems to be at more risk of malignant development since both of their specific DEGs were enriched in the pathways in cancer, though enriched genes were different, while PE tended to be more associated with dysregulated peritoneal immune and inflammatory microenvironment.ConclusionBy integrated bioinformatic analysis, we explored common and specific molecular signatures among different subtypes of endometriosis: activated arachidonic acid (AA) metabolism-related inflammatory process and a slow and controlled proliferation in ectopic lesions were common features in OE, PE and DIE; OE and DIE seemed to be at more risk of malignant development while PE tended to be more associated with dysregulated peritoneal immune and inflammatory microenvironment, all of which could deepen our perception of endometriosis.

The red emitting composite phosphors Bi2MoO6:Eu3+/C3N4 were prepared via a solid-state method and characterized by different techniques like XRD, SEM, FT-IR, Raman, UV-vis DRS and PL. The effects of reaction temperature and C3N4 amount on the structure and optical properties of Bi2MoO6 were studied in detail. The powder X-ray diffraction patterns showed that the crystal phase structure changed with the increase of temperature. Also, the introduction of C3N4 had a significant impact on photoluminescence properties, which provides a universal strategy for phosphors to improve luminescence performance.

The Human Leukocyte Antigen (HLA) system or complex plays an irreplaceable role in regulating the humans' immune system. Accurate prediction of peptide binding with HLA can efficiently promote to identify those neoantigens, which potentially make a great change in immune drug development. HLA is one of the most polymorphic genetic systems in humans, and thousands of HLA allelic versions exist (Choo, 2007). Owing the high polymorphism of HLA complex, it is still pretty difficult to accurately predict the binding affinity. In this paper, we proposed a novel algorithm which combined convolutional neural network and long short-term memory to solve this problem. Our model has been tested with the experimental benchmark from IEDB and shows the state-of-the-art performance compared with other currently popular algorithms.

Haiyan Zhu,1–3 Xuxia Wang,1,4 Yuanyuan Han,1,2 Wenjuan Zhang,5 Wei Xin,3 Xiaotao Zheng,3 Jun Zhang1,2 1Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 2Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 3Department of Stomatology, Weihai Municipal Hospital, Weihai, Shandong Province, China; 4Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 5Department of Stomatology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China Purpose: In this study, a series of in vitro experiments were performed to investigate the molecular mechanisms underlying cell migration promoted by icariin (ICA) at low concentrations.Materials and methods: Bone marrow stromal cells (BMSCs) were cultured with different concentrations of ICA to verify whether it can enhance the efficiency of BMSCs migration. Western blot was employed to measure the expression of hypoxia-inducible factor-1α (HIF-1α) and C-X-C chemokine receptor type 4 (CXCR4) at different time points in BMSCs treated with ICA. Subsequently, we evaluated the function of HIF-1α in the expression of CXCR4 and the migration of cells by transfecting plasmid HIF-1α small interfering RNA (siHIF-1α) into BMSCs model.Results: Our data indicated that different concentrations of ICA (10, 1, and 0.1 µM) further enhanced the chemotactic capability of SDF-1α, and the most prominent cell migration stimulatory effect was observed with 1 µM ICA. Furthermore, ICA significantly enhanced the protein levels of CXCR4 and HIF-1α, and this effect was blocked by ICI 12,780 (estrogen receptor antagonis). Moreover, transfection of BMSCs with siHIF-1α reduced CXCR4 expression, suggesting that HIF-1α can regulate the migration of cells by influencing the expression of CXCR4.Conclusion: ICA promoted BMSCs migration via the activation of HIF-1α and further regulated the expression of CXCR4, suggesting that ICA might have beneficial effects in stem cell therapy. Keywords: cell migration, CXCR4, HIF-1α, SDF-1α, icariin

Fe-MOFs were successfully synthesized with the dielectric barrier discharge (DBD) plasma method, and applied for degradation of methyl orange by the Fenton process. Fe-MOFs were characterized by XRD, SEM, EDS, BET and FT-IR. A systematic study was carried out to optimize the synthesis conditions, taking into account the Fenton capacity performance for degradation of methyl orange. The optimal synthesis conditions were a discharge time of 100 min, discharge voltage of 18 kV, reactant concentration of 14 g L−1 and reactant mass ratio (TA : FeCl3·6H2O) of 1 : 5, with influence on the crystallization, morphologies and particle size. The degradation rate of methyl orange could reach 85% within 40 min with the MO concentration of 50 mg L−1, Fe-MOF dosage of 0.12 g L−1, pH of 5 and H2O2 at 1 mL L−1. Meanwhile, the Fenton catalytic process was conducted covering a range of catalyst concentrations, initial MO concentrations, pH and H2O2 amounts. Higher catalyst concentration, lower MO initial concentration, pH of 3 and H2O2 amount of 1 mL L−1 were conducive to the degradation efficiency.

Diffuse intrinsic pontine glioma (DIPG) is predominantly diagnosed clinically, with biopsy often reserved for cases with atypical imaging features and/or symptoms. Outcome data and molecular profiling of DIPG have been limited almost entirely to tumors with typical features. We examined the clinicopathologic characteristics and outcomes of 28 patients with pontine-centered lesions who underwent diagnostic biopsy at our institution from 2003 to 2018 because of atypical MRI findings. The median age at diagnosis was 5.2 years (range, 0.7–17.1), and the median symptom duration pre-diagnosis was 1 month (range, 0–24). Common atypical features included pontine asymmetry, tumor extension into the medulla and cerebellar peduncles, and exophytism. Four patients (14.3%) developed transient neurologic symptoms; one (3.6%) experienced a new, permanent cranial neuropathy; and no biopsy-related deaths occurred. Sixteen of the 28 tumors (57%) were confirmed histologically as DIPGs (WHO grade II–IV gliomas; “atypical DIPG”). Of these 16 cases, H3 K27M status was assessed through immunohistochemistry in 14 (88%) and nine were immunopositive (64.3%). The remainder (“atypical non-DIPGs”) were pilocytic astrocytomas (58.3%), gangliogliomas (8.3%), CNS embryonal tumors, NOS (16.7%), or C19MC-altered embryonal tumors with multilayered rosettes (16.7%). With a median follow-up of 28.6 months (range, 3.0 – 173.2), 2-year overall survival (OS) was 72.4%, 83.3%, and 62.2% for the total cohort, atypical non-DIPGs, and atypical DIPGs, respectively (P=NS for all). However, OS with H3 K27M–mutant atypical DIPG was inferior to that with H3 WT atypical DIPG (P=0.003). Compared to OS in a contemporary typical DIPG cohort (N=100), OS was significantly longer for the total atypical cohort, atypical non-DIPGs, and atypical DIPGs (P

The cell membrane glycolipid GD2 is expressed by multiple solid tumors, including 88% of osteosarcomas and 98% of neuroblastomas. However, osteosarcomas are highly heterogeneous with many tumors exhibiting GD2 expression on 99%, p

DNA technology based bio-responsive nanomaterials have been widely studied as promising tools for biomedical applications. Gold nanoparticles (AuNPs) and graphene oxide (GO) sheets are representative zero- and two-dimensional nanomaterials that have long been combined with DNA technology for point-of-care diagnostics. Herein, a cascade amplification system based on duplex-specific nuclease (DSN)-assisted target recycling and electrocatalytic water-splitting is demonstrated for the detection of microRNA. Target microRNAs can form DNA: RNA heteroduplexes with DNA probes on the surface of AuNPs, which can be hydrolyzed by DSN. MicroRNAs are preserved during the reaction and released into the suspension for the digestion of multiple DNA probes. After the DSN-based reaction, AuNPs are collected and mixed with GO to form AuNP/GO nanocomposite on an electrode for the following electrocatalytic amplification. The utilization of AuNP/GO nanocomposite offers large surface area, exceptional affinity to water molecules, and facilitated mass diffusion for the water-splitting reaction. For let-7b detection, the proposed biosensor achieved a limit detection of 1.5 fM in 80 min with a linear detection range of approximately four orders of magnitude. Moreover, it has the capability of discriminating non-target microRNAs containing even single-nucleotide mismatches, thus holding considerable potential for clinical diagnostics.

It is one of the important goals for human-computer interaction to make the robot understand the Chinese instruction. The paper presents a scheme for Chinese instruction processing. After the user's speech instruction is obtained, the first thing to do is to conduct a voice preprocessing and Voice Activity Detection (VAD), and then the speech recognition by means of Baidu Cloud Speech Recognition technology. For recognized sentences, Chinese segmentation is carried out by using the Chinese segmentation algorithm combining dictionary and statistics. Then the professional keyword database is utilized to extract the key words, with the aim of attaining the verbs to perform the task and the nouns related to the places and objects in the task, so that the robot can receive the task semantic analysis. The method proves to achieve high accuracy and meet the task analysis requirement of NAO robot by experiments.

Vesicle size and size uniformity determine whether the vesicle can realize its full potential in a wide range of biological and biomedical applications. Herein, we reported a simple yet general cosolvent method to directly prepare uniform polymeric vesicles with a tunable size ranging from 100 nm to 150 nm formed from the amphiphilic diblock copolymer poly(4-vinylpyridine)-block-polystyrene (P4VP77-b-PS318). The uniform polymeric vesicles can be easily obtained by adding plenty of selective solvent only once into the polymer solution and then resting overnight. It is found that uniform vesicles are formed with a fixed size. There is no further fusion between vesicles. The PDI of the vesicles measured by DLS can be as low as 0.03. Moreover, the size of these uniform vesicles can be controlled by the content of the selective solvent. The higher the content of the selective solvent, the smaller the vesicles that form. Monte Carlo simulation was also performed in this study. The simulation results indicated that the vesicle size indeed decreases with an increase in the content of the selective solvent. Two reasons leading to the decrease in vesicle size are elucidated. In addition, the simulations reveal that the size uniformity of the vesicle is essentially determined by the interactive enthalpy of the system.

Primarily due to concerns about severe neurocognitive sequelae, immediate post-surgical craniospinal radiotherapy (CSRT) is often avoided in young children (

A facile method for the synthesis of a Ln3+ (Eu, Tb) doped BiPO4 (BPO) nanocrystals were developed using an environment-friendly low temperature hydrothermal method assisting with phenol formaldehyde resin (PFr). Structure and surface functional groups of BPO samples were characterized by XRD and IR patterns. Morphology was studied by SEM technology also. Furthermore, doped BPO display strong red and green emissions from Eu3+ and Tb3+ ions respectively, and the BPO suspension is selectively quenched upon addition Fe3+ ions, and there is barely any interference by other metal ions, thus making the nanocrystals as a potential Fe3+ ions Fluorescent Probe, and the detection limit is below micromole level.

Circular RNAs (circRNAs) are a novel type of non-coding RNA expressed across different species and tissues. At present, little is known about the expression and function of circRNAs in the tree shrew brain. In this study, we used RNA-seq to identify 35,007 circRNAs in hippocampus and cerebellum samples from infant (aged 47–52 days), young (aged 15–18 months), and old (aged 78–86 months) tree shrews. We observed no significant changes in the total circRNA expression profiles in different brain regions over time. However, circRNA tended to be downregulated in the cerebellum over time. Real-time RT-PCR analysis verified the presence of circRNAs. KEGG analysis indicated the occurrence of ubiquitin-mediated proteolysis, the MAPK signaling pathway, phosphatidylinositol signaling system, long-term depression, the rap1 signaling pathway, and long-term potentiation in both brain regions. We also observed that 29,087 (83.1%) tree shrew circRNAs shared homology with human circRNAs. The competing endogenous RNA networks suggested novel_circRNA_007362 potential functions as a 24-miRNAs sponge to regulate UBE4B expression. Thus, we obtained comprehensive circRNA expression profiles in the tree shrew brain during postnatal development and aging, which might help to elucidate the functions of circRNAs during brain aging and in age-related diseases.

The Montreal Protocol has succeeded in limiting major ozone-depleting substance emissions, and consequently stratospheric ozone concentrations are expected to recover this century. However, there is a large uncertainty in the rate of regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia-North America dipole mode in the total column ozone over the Northern Hemisphere, showing negative and positive total column ozone anomaly centres over Eurasia and North America, respectively. The positive trend of this mode explains an enhanced total column ozone decline over the Eurasian continent in the past three decades, which is closely related to the polar vortex shift towards Eurasia. Multiple chemistry-climate-model simulations indicate that the positive Eurasia-North America dipole trend in late winter is likely to continue in the near future. Our findings suggest that the anticipated ozone recovery in late winter will be sensitive not only to the ozone-depleting substance decline but also to the polar vortex changes, and could be substantially delayed in some regions of the Northern Hemisphere extratropics., Climate change can exert a significant effect on the ozone recovery. Here, the authors show that the Arctic polar vortex shift associated with Arctic sea-ice loss could slow down ozone recovery over the Eurasian continent.

Different patterns of gray matter volume (GMV) abnormalities have been reported between chronic patients with deficit schizophrenia (DS), relative to nondeficit schizophrenia (NDS) patients. However, it is not clear whether these differences are characteristic to the pathophysiology of DS or due to the effects of medications or illness durations. To address this issue, GMV in 88 first-episode, drug-naive patients with schizophrenia (44 DS and 44 NDS), 67 of their first-degree relatives and 84 healthy controls were assessed using voxel- based morphometry (VBM) and compared between groups. Correlations between GMV and clinical symptoms in patients were also assessed. Compared to controls, DS patients displayed more severe GMV reduction in the cerebellar culmen than NDS patients. GMV reduction in culmen was also observed in the first-degree relatives of DS (but not NDS) patients, suggesting possible different genetic risk in DS and NDS. The left insula was significantly smaller in DS patients than both NDS patients and controls, and smaller GMV of this region was associated with more severe negative symptoms in patients. Our results collectively indicate that DS might represent a distinct subtype of schizophrenia from NDS and the GMV change in left insula may be a morphological signature of DS.