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Repeated mechanical and chemical insults cause an irreversible alteration of extracellular matrix (ECM) composition and properties, giving rise to vocal fold scarring that is refractory to treatment. Although it is well known that fibroblast activation to myofibroblast is the key to the development of the pathology, the lack of a physiologically relevant in vitro model of vocal folds impedes mechanistic investigations on how ECM cues promote myofibroblast differentiation. Herein, we describe a bio-orthogonally cross-linked hydrogel platform that recapitulates the alteration of matrix adhesiveness due to enhanced fibronectin deposition when vocal fold wound healing is initiated. The synthetic ECM (sECM) was established via the cycloaddition reaction of tetrazine (Tz) with slow (norbornene, Nb)-and fast (trans-cyclooctene, TCO)-reacting dienophiles. The relatively slow Tz−Nb ligation allowed the establishment of the covalent hydrogel network for 3D cell encapsulation, while the rapid and efficient Tz−TCO reaction enabled precise conjugation of the celladhesive RGDSP peptide in the hydrogel network. To mimic the dynamic changes of ECM composition during wound healing, RGDSP was conjugated to cell-laden hydrogel constructs via a diffusion-controlled bioorthognal ligation method 3 days post encapsulation. At a low RGDSP concentration (0.2 mM), fibroblasts residing in the hydrogel remained quiescent when maintained in transforming growth factor beta 1 (TGF-β1)-conditioned media. However, at a high concentration (2 mM), RGDSP potentiated TGF-β1-induced myofibroblast differentiation, as evidenced by the formation of an actin cytoskeleton network, including F-actin and alpha-smooth muscle actin. The RGDSP-driven fibroblast activation to myofibroblast was accompanied with an increase in the expression of wound healing-related genes, the secretion of profibrotic cytokines, and matrix contraction required for tissue remodeling. This work represents the first step toward the establishment of a 3D hydrogel-based cellular model for studying myofibroblast differentiation in a defined niche associated with vocal fold scarring.

Renal damage is the major cause of SLE associated mortality, and IFIT1expression was elevated in SLE cases in accordance of previous studies. Therefore, we conducted an animal study to identify the role of IFIT1 expression in renal pathological changes.18 female MRL/lpr mice and same number of female BALB/c mice were enrolled in present study. Quantitative analysis of urine protein, Complement C3 and C4, and anti-ds DNA antibody were conducted. HE and PAS staining and TEM analysis were employed to observe the pathological changes in renal tissue. Significant elevation on urine protein and anti-dsDNA and reduction on Complement C3 and C4 were observed in MRL/lpr mice when comparing the controls in same age. Staining and TEM analysis observed several pathological changes in glomerulus among MRL/lpr mice, including cellular enlargement, basement membrane thickening, and increased cellularcasts. The linear regression analysis found the optical density of IFIT1 was inversely associated with F-actin, Nephrin, and Podocin, but not Synatopodin. In summary, IFIT1 expression is associated with podocytes damage, and capable of suppressing some proteins essential to glomerular filtration.

Background: As a common and frequent disease in pediatric patients, pediatric anorexia (PN) poses a serious threat to childhood growth and health. In recent years, societal changes in lifestyle and diet have increased the incidence of this PN, which has attracted extensive attention from both the medical community and parents. It has been shown that massage therapy represents an effective intervention for the treatment of anorexia, but investigation on its mechanism(s) of action remains limited. In this study, we will explore the biological mechanism(s) of PN from the perspective of intestinal flora, to further reveal its site of action and therapeutic mechanism(s). Methods: A total of 60 healthy children will be randomly selected for physical examination. According to a random number generated by a computer, children with anorexia who meet the inclusion criteria will be selected. In strict accordance with the time sequence of inclusion, subjects will be randomly assigned to either the massage or control group (n = 60 per group). The blank group will receive no treatment. Children in the massage group will receive a designated massage protocol. The control group will be administered oral Jianweixiaoshi tablets over 4 weeks. Each group will be compared for intestinal flora structure, fecal short chain fatty acids levels, serum trace elements, urine D-xylose-excretion rates, gastric fluid emptying, gastric motility, and hemoglobin levels before and after treatment. Results: We will review the clinical trial registry in China (http://www.chictr.org.cn/searchprojen.aspx), peer-reviewed journals and academic conferences. Conclusion: This study will verify the intervention mechanism(s) of pediatric massage on intestinal flora and host metabolism in children with anorexia. Trial registration number: ChiCTR2000033274

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