Enhancing grain boundary ionic conductivity in mixed ionic electronic conductors

The emergent properties arising from the interactions of phases including interfacial contributions and phase evolution at the mesoscale present new opportunities, as well as challenges, for materials performance and functionality. Mixed ionic-electronic conductors are widely used in devices for energy conversion and storage. Grain boundaries in these materials have nanoscale spatial dimensions, which can generate substantial resistance to ionic transport due to dopant segregation. Here, we report a concept of targeted phase formation in a Ce0.8Gd0.2O2-δ-CoFe2O4 (CGO-CFO) composite that serves to enhance the grain boundary ionic conductivity. Using spatially resolved electron microscopy, we probed the grain boundary charge distribution and chemical environments altered by the phase reaction between the two constituents. The formation of an emergent phase successfully avoided segregation of the Gd dopant and depletion of oxygen vacancies at the Ce0.8Gd0.2O2-δ-Ce0.8Gd0.2O2-δ grain boundary. This resulted in superior grain boundary ionic conductivity as demonstrated by the enhanced oxygen permeation flux. This work illustrates the control of mesoscale level transport properties in mixed ionic-electronic conductor composites through processing induced modifications of the grain boundary defect distribution. Implications for controlling grain boundary composition in diverse applications of ceramic-ceramic composites such as nuclear waste immobilization will be discussed

Design of Adaptive Switching Controller for Robotic Manipulators with Disturbance

Two adaptive switching control strategies are proposed for the trajectory tracking problem of robotic manipulator in this paper. The first scheme is designed for the supremum of the bounded disturbance for robot manipulator being known; while the supremum is not known, the second scheme is proposed. Each proposed scheme consists of an adaptive switching law and a PD controller. Based on the Lyapunov stability theorem, it is shown that two new schemes can guarantee tracking performance of the robotic manipulator and be adapted to the alternating unknown loads. Simulations for two-link robotic manipulator are carried out and show that the two schemes can avoid the overlarge input torque, and the feasibility and validity of the proposed control schemes are proved

Epigenetic and Phenotypic Profile of Fibroblasts Derived from Induced Pluripotent Stem Cells

Human induced pluripotent stem (hiPS) cells offer a novel source of patient-specific cells for regenerative medicine. However, the biological potential of iPS-derived cells and their similarities to cells differentiated from human embryonic stem (hES) cells remain unclear. We derived fibroblast-like cells from two hiPS cell lines and show that their phenotypic properties and patterns of DNA methylation were similar to that of mature fibroblasts and to fibroblasts derived from hES cells. iPS-derived fibroblasts (iPDK) and their hES-derived counterparts (EDK) showed similar cell morphology throughout differentiation, and patterns of gene expression and cell surface markers were characteristic of mature fibroblasts. Array-based methylation analysis was performed for EDK, iPDK and their parental hES and iPS cell lines, and hierarchical clustering revealed that EDK and iPDK had closely-related methylation profiles. DNA methylation analysis of promoter regions associated with extracellular matrix (ECM)-production (COL1A1) by iPS- and hESC-derived fibroblasts and fibroblast lineage commitment (PDGFRβ), revealed promoter demethylation linked to their expression, and patterns of transcription and methylation of genes related to the functional properties of mature stromal cells were seen in both hiPS- and hES-derived fibroblasts. iPDK cells also showed functional properties analogous to those of hES-derived and mature fibroblasts, as seen by their capacity to direct the morphogenesis of engineered human skin equivalents. Characterization of the functional behavior of ES- and iPS-derived fibroblasts in engineered 3D tissues demonstrates the utility of this tissue platform to predict the capacity of iPS-derived cells before their therapeutic application

Fibroblasts derived from human embryonic stem cells direct development and repair of 3D human skin equivalents

INTRODUCTION: Pluripotent, human stem cells hold tremendous promise as a source of progenitor and terminally differentiated cells for application in future regenerative therapies. However, such therapies will be dependent upon the development of novel approaches that can best assess tissue outcomes of pluripotent stem cell-derived cells and will be essential to better predict their safety and stability following in vivo transplantation. METHODS: In this study we used engineered, human skin equivalents (HSEs) as a platform to characterize fibroblasts that have been derived from human embryonic stem (hES) cell. We characterized the phenotype and the secretion profile of two distinct hES-derived cell lines with properties of mesenchymal cells (EDK and H9-MSC) and compared their biological potential upon induction of differentiation to bone and fat and following their incorporation into the stromal compartment of engineered, HSEs. RESULTS: While both EDK and H9-MSC cell lines exhibited similar morphology and mesenchymal cell marker expression, they demonstrated distinct functional properties when incorporated into the stromal compartment of HSEs. EDK cells displayed characteristics of dermal fibroblasts that could support epithelial tissue development and enable re-epithelialization of wounds generated using a 3D tissue model of cutaneous wound healing, which was linked to elevated production of hepatocyte growth factor (HGF). Lentiviral shRNA-mediated knockdown of HGF resulted in a dramatic decrease of HGF secretion from EDK cells that led to a marked reduction in their ability to promote keratinocyte proliferation and re-epithelialization of cutaneous wounds. In contrast, H9-MSCs demonstrated features of mesenchymal stem cells (MSC) but not those of dermal fibroblasts, as they underwent multilineage differentiation in monolayer culture, but were unable to support epithelial tissue development and repair and produced significantly lower levels of HGF. CONCLUSIONS: Our findings demonstrate that hES-derived cells could be directed to specified and alternative mesenchymal cell fates whose function could be distinguished in engineered HSEs. Characterization of hES-derived mesenchymal cells in 3D, engineered HSEs demonstrates the utility of this tissue platform to predict the functional properties of hES-derived fibroblasts before their therapeutic transplantation

Safety and effectiveness of indocyanine green fluorescence imaging-guided laparoscopic hepatectomy for hepatic tumor: a systematic review and meta-analysis

IntroductionPrevious clinical investigations have reported inconsistent findings regarding the feasibility of utilizing indocyanine green fluorescence imaging (ICGFI) in laparoscopic liver tumor removal. This meta-analysis aims to comprehensively evaluate the safety and effectiveness of ICGFI in laparoscopic hepatectomy (LH).MethodsA systematic search of pertinent clinical studies published before January 30th, 2023 was conducted in databases including PubMed, Embase, Cochrane, and Web of Science. The search strategy encompassed key terms such as “indocyanine green fluorescence,” “ICG fluorescence,” “laparoscopic hepatectomy,” “hepatectomies,” “liver Neoplasms,” “hepatic cancer,” and “liver tumor.” Additionally, we scrutinized the reference lists of included articles to identify supplementary studies. we assessed the quality of the incorporated studies and extracted clinical data. Meta-analysis was performed using STATA v.17.0 software. Either a fixed-effects or a random-effects model was employed to compute combined effect sizes, accompanied by 95% confidence intervals (CIs), based on varying levels of heterogeneity.ResultsThis meta-analysis encompassed eleven retrospective cohort studies, involving 959 patients in total. Our findings revealed that, in comparison to conventional laparoscopic hepatectomy, patients receiving ICGFI-guided LH exhibited a higher R0 resection rate (OR: 3.96, 95% CI: 1.28, 12.25, I2 = 0.00%, P = 0.778) and a diminished incidence of intraoperative blood transfusion (OR: 0.42, 95% CI: 0.22, 0.81, I2 = 51.1%, P = 0.056). Additionally, they experienced shorter postoperative hospital stays (WMD: −1.07, 95% CI: −2.00, −0.14, I2 = 85.1%, P = 0.000). No statistically significant differences emerged between patients receiving ICGFI-guided LH vs. those undergoing conventional LH in terms of minimal margin width and postoperative complications.ConclusionICGFI-guided LH demonstrates marked superiority over conventional laparoscopic liver tumor resection in achieving R0 resection and reducing intraoperative blood transfusion rates. This technique appears to hold substantial promise. Nonetheless, further studies are needed to explore potential long-term benefits associated with patients undergoing ICGFI-guided LH.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD 42023398195

Transcriptome profile analysis in spinal cord injury rats with transplantation of menstrual blood-derived stem cells

IntroductionMenstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats.MethodsMenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene co-expression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships.ResultsA total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges.DiscussionIn summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI

Integrin-Blocking Antibodies Delay Keratinocyte Re-Epithelialization in a Human Three-Dimensional Wound Healing Model

The α6β4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, α6β4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE), which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting β4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different β4 epitopes, one adhesion-blocking (ASC-8) and one non-adhesion blocking (ASC-3), and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where β4 is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate β4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process

TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, <it>TFPI-2 </it>was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether <it>TFPI-2 </it>was inactivated epigenetically in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Transcriptional expression levels of <it>TFPI-2 </it>was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of <it>TFPI-2 </it>as a tumor suppressor gene in NPC was addressed by re-introducing <it>TFPI-2 </it>expression into the NPC cell line CNE2.</p> <p>Results</p> <p><it>TFPI-2 </it>mRNA transcription was inactivated in NPC cell lines. <it>TFPI-2 </it>was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. <it>TFPI-2 </it>expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration.</p> <p>Conclusions</p> <p>Epigenetic inactivation of <it>TFPI-2 </it>by promoter hypermethylation is a frequent and tumor specific event in NPC. <it>TFPI-2 </it>might be considering as a putative tumor suppressor gene in NPC.</p