Precise and label-free tumour cell recognition based on a black phosphorus nanoquenching platform

Breast cancer is a type of heterogeneous disease, which manifests as different molecular subtypes due to the complex nature of tumour initiation, progression, and metastasis. Accurate identification of a breast cancer subtype plays crucial roles in breast cancer management. Herein, taking advantage of the efficient quenching properties of black phosphorus nanosheets (BPNSs), in combination with the high specificity of ssDNA (or RNA) aptamer, a fluorometric duplexed assay that is capable of the simultaneous detection of two tumour markers within one run is developed. When mixed with BPNSs, the fluorescence of both FAM and Cy3 labelled aptamers was quenched. The presence of different subtypes of breast cancer cells restored the FAM and Cy3 fluorescence in distinct patterns according to their intrinsic features. The proposed assay can precisely recognise label-free breast cancer subtypes, providing an efficient method for cell type identification and guidance for subsequent breast cancer treatment. The significance of the proposed study is two-fold. First, we provide a simple method for sensitive and specific tumour cell detection; secondly, and more importantly, the proposed dual assay allows precise recognition of tumour cells and thus opens a door for rapid characterization and sorting of a wide range of tumours without using expensive instruments

Genome-wide and single-base resolution DNA methylomes of the Pacific oyster <i>Crassostrea gigas</i> provide insight into the evolution of invertebrate CpG methylation

BACKGROUND: Studies of DNA methylomes in a wide range of eukaryotes have revealed both conserved and divergent characteristics of DNA methylation among phylogenetic groups. However, data on invertebrates particularly molluscs are limited, which hinders our understanding of the evolution of DNA methylation in metazoa. The sequencing of the Pacific oyster Crassostrea gigas genome provides an opportunity for genome-wide profiling of DNA methylation in this model mollusc. RESULTS: Homologous searches against the C. gigas genome identified functional orthologs for key genes involved in DNA methylation: DNMT1, DNMT2, DNMT3, MBD2/3 and UHRF1. Whole-genome bisulfite sequencing (BS-seq) of the oyster’s mantle tissues revealed that more than 99% methylation modification was restricted to cytosines in CpG context and methylated CpGs accumulated in the bodies of genes that were moderately expressed. Young repeat elements were another major targets of CpG methylation in oysters. Comparison with other invertebrate methylomes suggested that the 5’-end bias of gene body methylation and the negative correlation between gene body methylation and gene length were the derived features probably limited to the insect lineage. Interestingly, phylostratigraphic analysis showed that CpG methylation preferentially targeted genes originating in the common ancestor of eukaryotes rather than the oldest genes originating in the common ancestor of cellular organisms. CONCLUSIONS: Comparative analysis of the oyster DNA methylomes and that of other animal species revealed that the characteristics of DNA methylation were generally conserved during invertebrate evolution, while some unique features were derived in the insect lineage. The preference of methylation modification on genes originating in the eukaryotic ancestor rather than the oldest genes is unexpected, probably implying that the emergence of methylation regulation in these 'relatively young’ genes was critical for the origin and radiation of eukaryotes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-1119) contains supplementary material, which is available to authorized users

Identification of lipid droplet structure-like/resident proteins in Caenorhabditis elegans.

The lipid droplet (LD) is a cellular organelle that stores neutral lipids in cells and has been linked with metabolic disorders. Caenorhabditis elegans has many characteristics which make it an excellent animal model for studying LDs. However, unlike in mammalian cells, no LD structure-like/resident proteins have been identified in C. elegans, which has limited the utility of this model for the study of lipid storage and metabolism. Herein based on three lines of evidence, we identified that MDT-28 and DHS-3 previously identified in C. elegans LD proteome were two LD structure-like/resident proteins. First, MDT-28 and DHS-3 were found to be the two most abundant LD proteins in the worm. Second, the proteins were specifically localized to LDs and we identified the domains responsible for this targeting in both proteins. Third and most importantly, the depletion of MDT-28 induced LD clustering while DHS-3 deletion reduced triacylglycerol content (TAG). We further characterized the proteins finding that MDT-28 was ubiquitously expressed in the intestine, muscle, hypodermis, and embryos, whereas DHS-3 was expressed mainly in intestinal cells. Together, these two LD structure-like/resident proteins provide a basis for future mechanistic studies into the dynamics and functions of LDs in C. elegans

Valley-polarized Exitonic Mott Insulator in WS2/WSe2 Moir\'e Superlattice

Strongly enhanced electron-electron interaction in semiconducting moir\'e superlattices formed by transition metal dichalcogenides (TMDCs) heterobilayers has led to a plethora of intriguing fermionic correlated states. Meanwhile, interlayer excitons in a type-II aligned TMDC heterobilayer moir\'e superlattice, with electrons and holes separated in different layers, inherit this enhanced interaction and strongly interact with each other, promising for realizing tunable correlated bosonic quasiparticles with valley degree of freedom. We employ photoluminescence spectroscopy to investigate the strong repulsion between interlayer excitons and correlated electrons in a WS2/WSe2 moir\'e superlattice and combine with theoretical calculations to reveal the spatial extent of interlayer excitons and the band hierarchy of correlated states. We further find that an excitonic Mott insulator state emerges when one interlayer exciton occupies one moir\'e cell, evidenced by emerging photoluminescence peaks under increased optical excitation power. Double occupancy of excitons in one unit cell requires overcoming the energy cost of exciton-exciton repulsion of about 30-40 meV, depending on the stacking configuration of the WS2/WSe2 heterobilayer. Further, the valley polarization of the excitonic Mott insulator state is enhanced by nearly one order of magnitude. Our study demonstrates the WS2/WSe2 moir\'e superlattice as a promising platform for engineering and exploring new correlated states of fermion, bosons, and a mixture of both

Microbial Community Succession and Response to Environmental Variables During Cow Manure and Corn Straw Composting

In composting system, the composition of microbial communities is determined by the constant change in the physicochemical parameters. This study explored the dynamics of bacterial and fungal communities during cow manure and corn straw composting using high throughput sequencing technology. The relationships between physicochemical parameters and microbial community composition and abundance were also evaluated. The sequencing results revealed the major phyla included Proteobacteria, Bacteroidetes, Firmicutes, Chloroflexi and Actinobacteria, Ascomycota, and Basidiomycota. Linear discriminant analysis effect size (LEfSe) illustrated that Actinomycetales and Sordariomycetes were the indicators of bacteria and fungi in the maturation phase, respectively. Mantel test showed that NO3--N, NH4+-N, TN, C/N, temperature and moisture content significantly influenced bacterial community composition while only TN and moisture content had a significant effect on fungal community structure. Structural equation model (SEM) indicated that TN, NH4+-N, NO3--N and pH had a significant effect on fungal abundance while TN and temperature significantly affected bacterial abundance. Our finding increases the understanding of microbial community succession in cow manure and corn straw composting under natural conditions

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Background/Aims: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways. Methods: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca2+]o) and/or 1 μM nifedipine, 0.1 μM BAPTA-AM, 1 μM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca2+]i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed. Results: In vitro, [Ca2+]o stimulated pBMSCs adipogenesis by increasing [Ca2+]i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca2+]o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca2+]o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca2+]i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT. Conclusion: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control

CMRxRecon: An open cardiac MRI dataset for the competition of accelerated image reconstruction

Cardiac magnetic resonance imaging (CMR) has emerged as a valuable diagnostic tool for cardiac diseases. However, a limitation of CMR is its slow imaging speed, which causes patient discomfort and introduces artifacts in the images. There has been growing interest in deep learning-based CMR imaging algorithms that can reconstruct high-quality images from highly under-sampled k-space data. However, the development of deep learning methods requires large training datasets, which have not been publicly available for CMR. To address this gap, we released a dataset that includes multi-contrast, multi-view, multi-slice and multi-coil CMR imaging data from 300 subjects. Imaging studies include cardiac cine and mapping sequences. Manual segmentations of the myocardium and chambers of all the subjects are also provided within the dataset. Scripts of state-of-the-art reconstruction algorithms were also provided as a point of reference. Our aim is to facilitate the advancement of state-of-the-art CMR image reconstruction by introducing standardized evaluation criteria and making the dataset freely accessible to the research community. Researchers can access the dataset at https://www.synapse.org/#!Synapse:syn51471091/wiki/.Comment: 14 pages, 8 figure