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Rheumatoid arthritis (RA), a chronic inflammatory joint disease causing permanent disability, involves exosomes, nanosized mammalian extracellular particles. Circular RNA (circRNA) serves as a biomarker in RA blood samples. This research screened differentially expressed circRNAs in RA patient plasma exosomes for novel diagnostic biomarkers. In this study, samples of RA patients with insufficient response to methotrexate (MTX-IR), combined use of tumor necrosis factor inhibitors (TNFi) were followed up for half a year, and 56 circRNA samples of self-test data were stratified into training, testing, and external validation cohorts according to whether American College of Rheumatology 20% improvement criteria (ACR20) was achieved. A diagnostic xgboost model was developed using common hub genes identified by random forest and least absolute shrinkage and selection operator (LASSO), with intersection genes derived from overlapping machine learning-selected genes. Diagnostic performance evaluated via receiver operating characteristic (ROC) curves using pROC for area under the curve (AUC). Optimal LASSO model with 4 circRNAs determined, with AUC > 0.6 for key genes. The model validation performed well on the test set, but not significantly on the validation set. Then, circRNA screening was performed in combination with clinical data, and cross-validation identified hsa-circ0002715, hsa-circ0001946, hsa-circ0000836, and rheumatoid factor (RF) as key genes, among which hsa-circ0002715 and hsa-circ0001946 were emphasized as key markers on the training set. In addition, the morphology and size of exosomes and the expression of CD9 and CD81 verified the successful extraction of exosomes. The qPCR analysis of plasma exosomes in TNFi patients found that the expression of hsa-circ0002715 was higher than that in patients who didn't reach ACR20, and the expression of hsa-circ0001946 was lower than that in patients who didn't reach ACR20. The above studies suggested that hsa-circ0002715 and hsa-circ0001946 may become markers for predicting MTX-IR RA patients and TNFi precision treatment. [ABSTRACT FROM AUTHOR]

Silver antimony sulfide (AgSbS2) is considered a promising photovoltaic absorber material because of its suitable bandgap, large absorption coefficient, and environmental friendliness. However, the photovoltaic performance of AgSbS2‐based solar cells is far from expectation and the applications of AgSbS2 are limited by the underdeveloped fabrication technology. Herein, an effective method is developed to improve the photovoltaic performance of devices by adding indium (In) into the Ag–Sb–S system followed by a selenization process. With the addition of In, the morphology uniformity and the crystallinity of the films are simultaneously improved due to the diminished defects such as pinholes and cracks, leading to a better heterojunction interface between Ag1−xIn2xSb1−xSySe2−y and CdS. The Hall effect measurements demonstrate that the carrier concentration of the films effectively increases to 8.16 × 1014 cm−3 on adding In. The optical characterization suggests that In addition significantly enhances the optical absorption and broadens the absorption wavelength range. Furthermore, the conduction band offset between the absorber and the buffer layer is substantially reduced by adding In, which lessens the carrier recombination at the interface, increasing the carriers transport efficiency. The power conversion efficiency of the Ag1−xIn2xSb1−xSySe2−y device is largely improved from 0.74% (In/Sb = 0) to 1.98% (In/Sb = 0.47). [ABSTRACT FROM AUTHOR]

Background: Trk gene fusions are an important driver in the development of cancers, including secretory breast cancer and infantile congenital sarcoma. Since the first-generation of small molecule Trk inhibitors (Larotrectinib and Entrectinib) came to market, research on small molecule TRK inhibitors, especially second-generation inhibitors that break through the resistance problem, has developed rapidly. Therefore, this article focuses on the research progress of first-generation drugs and second-generation drugs that break through drug resistance., Methods: We used the database to search for relevant and cutting-edge documents, and then filtered and selected them based on the content. The appropriate articles were analyzed and classified, and finally, the article was written according to the topics., Results: The phenomenon of Trk protein fusion and its relation to tumors are described, followed by an explanation of the composition and signaling pathways of Trk kinases. The representative Trk inhibitors and the development of novel Trk inhibitors are classified according to whether they overcome drug resistance problems., Conclusion: This paper provides a theoretical reference for the development of novel inhibitors by introducing and summarizing the representative and novel Trk inhibitors that break through the drug resistance problem., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

It has been demonstrated that cyclooxygenase-2 (COX-2) is expressed in melanoma tissues and prostaglandin E(2) (PGE(2)) is produced by melanoma cells in vitro. However, the roles of COX-2/PGE(2) in melanoma are largely unknown. In the present study, we set out to analyze the correlation of endogenous PGE(2) with the expression of macrophage chemoattractant protein-1 (MCP-1) and to identify the signaling pathway involved. It was found that MCP-1 mRNA was heterogeneously expressed in 18 melanoma tissue specimens, and the levels of MCP-1 mRNA were positively correlated with those of COX-2 mRNA. Inhibition of endogenous PGE(2) production by a COX-2 inhibitor, COX-2 siRNA or an NFκB inhibitor suppressed MCP-1 expression, whereas treatment with TNF-α (to stimulate endogenous PGE(2) production) or exogenous PGE(2) enhanced MCP-1 expression in melanoma cells. Both the EP4 antagonist and the p38 MAPK inhibitor reduced MCP-1 production in melanoma cells, and abrogated the increased MCP-1 secretion induced by TNF-α or exogenous PGE(2). Conditioned medium from melanoma cells promoted macrophage migration, which was blocked by inhibitors of the PGE(2)/EP4/p38 MAPK signaling pathway. These results indicate that endogenous PGE(2) induces MCP-1 expression via EP4/p38 MAPK signaling in an autocrinal manner in melanoma, and melanoma cell-derived PGE(2) may be involved in macrophage recruitment in the melanoma microenvironment.

Objective: To explore the promoting effects of cograft of auto-microskin and allo-dermal matrix on burn wound healing., Methods: Forty-six patches of full skin loss wounds were made in the backs of 6 small white swines. Auto-microskin and meshed acellular allo-dermal matrix were simultaneously prepared. The 46 wounds were averagely divided into test (T) and control (C) groups. The wounds in T group were covered with auto-microskin and allo-dermal matrix (1:4) and split-thick allo-porcine skin. While the wounds in C group were grafted with autoskin and allo-dermal matrix., Results: The skin survival rate exhibited no difference between C and T groups (P > 0.05). There was similar histological exhibition in the two groups after skin grafting. The structure of collagen fibres appeared integrated, clear with regular arrangement and steady diameter at 8 - 20 post-operative weeks. Simultaneously, it was revealed by histological examination that normal vascular structure could be identified in the grafted skin and that inflammatory reaction ameliorated gradually and that epithelium combined well with dermis. It was also found that the epidermal papillar across the basement membrane fixed well to allo-dermis. The skin appeared smooth, elastic and functioned well at 5 months after skin grafting., Conclusion: The grafted skin survived well after the cograft of auto-microskin and allo-dermal matrix, which might be ideal covering material for the major deep burn wound healing.