In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed "angiotrophism." We found that polarizing macrophages toward a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has multiplicative effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.S

Expression of Human Frataxin Is Regulated by Transcription Factors SRF and TFAP2

Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia

Elastic wave harvesting in piezoelectric-defect-introduced phononic crystal microplates

International audienc

Elastic foundation-introduced defective phononic crystals for tunable energy harvesting

International audienceDefective phononic crystals offer the advantage of concentrating elastic waves, thereby enhancing the potential for piezoelectric energy harvesting (PEH). However, a key limitation is their reliance on a fixed operating frequency, rendering them susceptible to the prevailing vibration environment. To surmount this constraint, this study introduces a novel approach involving a tunable elastic foundation system for defective phononic crystal structures. The newly developed phononic crystal is fashioned by integrating a periodically elastic foundation beneath a uniform beam. A defect is induced by selectively removing specific elastic foundations and integrating piezoelectric components. Explicit analytical solutions are established through the transfer matrix method and the spectral element method, which are subsequently corroborated via comparison with finite element results. The findings underscore that the periodic elastic foundations impart bandgaps in the elastic wave band structure. The absence of specific elastic foundations results in the emergence of distinct defect modes. Additionally, frequency response analysis exposes the potential for energy enhancement, albeit with inherent variations. Noteworthy is the revelation that manipulating the stiffness of the elastic foundation triggers shifts in the resonant frequency of the output voltage. Therefore, the proposed tunable elastic foundation system exhibits promising potential to engender versatile and adaptive phononic crystal configurations, thereby advancing the domain of PEH

Safety analysis of early oral feeding after esophagectomy in patients complicated with diabetes

Abstract Objective To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma. Methods The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time of starting postoperative oral feeding, the patients were divided into early oral feeding group (EOF, 67 cases) and late oral feeding group (LOF, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional index (ALB, PA, TRF, Hb), immune indexes (IgA, IgG, IgM), inflammatory indexes(CRP, IL-6), normalized T12-SMA, and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups. Results There was no statistical difference in preoperative nutritional index and postoperative complication rates between the two groups (p&gt;0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p&lt;0.05), and the inflammatory indicators (CRP, IL-6) of the EOF group were significantly lower than those of the LOF group (p&lt;0.05). Moreover, postoperative T12-SMA variation and QLQ-C30 scores of the EOF group were better than those in LOF group (p&lt;0.05). Conclusions Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.</jats:p