Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs)

Recent generation of patient-specific induced pluripotent stem cells (PS-iPSCs) provides significant advantages for cell- and gene-based therapy. Establishment of iPSC-based therapy for skin diseases requires efficient methodology for differentiating iPSCs into both keratinocytes and fibroblasts, the major cellular components of the skin, as well as the reconstruction of skin structures using these iPSC-derived skin components. We previously reported generation of keratinocytes from human iPSCs for use in the treatment of recessive dystrophic epidermolysis bullosa (RDEB) caused by mutations in the COL7A1 gene. Here, we developed a protocol for differentiating iPSCs into dermal fibroblasts, which also produce type VII collagen and therefore also have the potential to treat RDEB. Moreover, we generated in vitro 3D skin equivalents composed exclusively human iPSC-derived keratinocytes and fibroblasts for disease models and regenerative therapies for skin diseases, first demonstrating that iPSCs can provide the basis for modeling a human organ derived entirely from two different types of iPSC-derived cells

Molecular cloning and functional characterization of BcTSA in the biosynthesis of indole alkaloids in Baphicacanthus cusia

Baphicacanthus cusia (Nees) Bremek (B. cusia) is an essential traditional Chinese herb that is commonly used to treat colds, fever, and influenza. Indole alkaloids, such as indigo and indirubin, are the primary active constituents of B. cusia. The indole-producing reaction is crucial for regulating the flow of indole alkaloids metabolites along the pathways and coordinating primary and secondary product biosynthesis in plants. The tryptophan synthase alpha-subunit (TSA) can catalyse a process that produces indole, which is free to enter secondary metabolite pathways; however, the underlying potential mechanism of regulating indigo alkaloids synthesis remains unknown. Here, a BcTSA was cloned from the transcriptome of B. cusia. The BcTSA has a significant degree of similarity with other plant TSAs according to bioinformatics and phylogenetic analyses. Quantitative real-time PCR (RT-qPCR) research showed that BcTSA was dramatically enhanced in response to treatment with methyl jasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA), and was predominantly expressed in the stems as opposed to the leaves and rhizomes. Subcellular localization revealed that BcTSA is localized in chloroplasts, which is compatible with the fact that the conversion of indole-3-glycerol phosphate (IGP) to indole occurs in chloroplasts. The complementation assay results showed that BcTSA was functional, demonstrating that it was capable of catalyzing the conversion of IGP to indole. BcTSA was shown to stimulate the manufacture of indigo alkaloids including isatin, indigo, and indirubin when the gene was overexpressed in the hairy roots of Isatis indigotica. In conclusion, our research provides novel perspectives that might be applied to manipulating the indole alkaloid composition of B. cusia

Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells

Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells

Lanthanide doping induced electrochemical enhancement of Na2Ti3O7 anodes for sodium-ion batteries

Na2Ti3O7 is considered as a promising anode material for sodium ion batteries (SIBs) due to its excellent high-rate performance compared with hard carbons. However, the electrochemical performance of Na2Ti3O7 is heavily limited by its low electrical conductivity. In this study, we synthesized a series of lanthanide (Ln = La, Ce, Nd, Sm, Gd, Er, and Yb) doped microsized Na2Ti3O7 anode materials and systematically studied the electrochemical performance. Compared with pristine Na2Ti3O7, all the doped samples show superior electrochemical performance. Especially, the Yb3+ doped sample not only delivers a high reversible capacity of 89.4 mA h g−1 at 30C, but also maintains 71.6 mA h g−1 at 5C after 1600 cycles, nearly twice that of pristine Na2Ti3O7. It is found for the first time that the enhancement in doped samples is attributed to the introduction of lanthanides which induces lattice distortion and oxygen vacancies

Resistive switching memories in MoS2 nanosphere assemblies

A resistive switching memory device consisting of reduced graphene oxide and indium tin oxide as top/bottom two electrodes, separated by dielectric MoS2 nanosphere assemblies as the active interlayer, was fabricated. This device exhibits the rewritable nonvolatile resistive switching with low SET/RESET voltage (∼2 V), high ON/OFF resistance ratio (∼10 4), and superior electrical bistability, introducing a potential application in data storage field. The resistance switching mechanism was analyzed in the assumptive model of the electron tunneling across the polarized potential barrier

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes

Machine Learning-Aided Crystal Facet Rational Design with Ionic Liquid Controllable Synthesis

Crystallographic facets in a crystal carry interior properties and proffer rich functionalities in a wide range of application areas. However, rational prediction, on-demand customization, and accurate synthesis of facets and facet junctions of a crystal are enormously desirable but still challenging. Herein, a framework of machine learning (ML)-aided crystal facet design with ionic liquid controllable synthesis is developed and then demonstrated with the star-material anatase TiO2. Aided by employing ML to acquire surface energies from facet junction datasource, the relationships between surface energy and growth conditions based on the Langmuir adsorption isotherm are unveiled, enabling to develop controllable facet synthetic strategies. These strategies are successfully verified after applied for synthesizing TiO2 crystals with custom crystal facets and facet junctions under tuning ionic liquid [bmim][BF4] experimental conditions. Therefore, this innovative framework integrates data-intensive rational design and experimental controllable synthesis to develop and customize crystallographic facets and facet junctions. This proves the feasibility of an intelligent chemistry future to accelerate the discovery of facet-governed functional material candidates.F.L. and Z.S. contributed equally to this work. This work was supported by the National Natural Science Foundation of China (Nos. 51706114 and 51302166), Functional Materials Interfaces Genome (FIG) project, Doctoral Fund of Ministry of Education of China (20133108120021), the Australian National University (ANU) Future Scheme (Q4601024), and the Australian Research Council (DP190100295 and LE190100014

Preparation, characterization, and photoswitching/light-emitting behaviors of coronene nanowires

Coronene nanowires were prepared through the reprecipitation method. The as-prepared one-dimensional (1D) nanostructures were characterized by UV-vis, fluorescence spectra, X-ray diffraction (XRD), optical microscopy, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM). We found that coronene nanowires in aqueous solution emitted strong green light instead of blue light for coronene molecules in THF solution. Moreover, the thin film of coronene nanowires on rGO/SiO2/Si electrode produced a strong photocurrent response upon irradiation. In addition, a heterojunction light emitting diode (LED) device with the structure of quartz/ITO/p-coronene nanowires/n-SiC/Ti (10 nm)/Au (120 nm) has been fabricated. The strong electroluminescence (EL) emission centered at 430 nm was detected with a forward bias at 20 V. Our result showed that the use of organic nanowires as the p-type hole injection layer could produce diodes with performance better than those with only inorganic thin-film structures.Accepted versio