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Objective To investigate the effect and potential mechanism of miR-761 on calcified aortic valve disease (CAVD). Methods Normal (n=6) and calcified (n=8) valve tissues were collected from Department of Cardiothoracic Surgery of the First Affiliated Hospital of Chongqing Medical University between January 2022 and January 2023. The changes of autophagy, osteogenesis, GABARAP protein or miR-761 expression in calcified valve tissues were detected by Western blotting, immunohistochemical staining and RT-qPCR. Double luciferase assay verified miR-761 binding to GABARAP 3′-UTR region. The phenotypes of porcine aortic valve interstitial cells (pVICs) were identified by immunofluorescence assay. pVICs were transfected with miR-761 mimic, inhibitor and corresponding control to construct pVICs cell lines with over-expression or knockdown of miR-761. After adding GFP-LC3 adenovirus, the number of autophagosomes was observed. Western blotting, alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of pVICs before and after osteogenic medium(OM) treatment. Results Compared with normal tissues, the prdein levels of Beclin 1, ULK1, α-SMA, RUNX2 and GABARAP were up-regulated in calcified valve tissue tissues, while the levels of p62 and miR-761 were down-regulated (P < 0.05). Dual luciferase assay verified the binding of miR-761 to GABARAP 3′-UTR region (P < 0.05). The isolated pVICs expressed interstitial cell markers (α-SMA, Vimentin). Confocal microscopy showed that overexpression of miR-761 reduced autophagosome production in pVICs. The protein results, alkaline phosphatase staining and alizarin red S staining showed that knockdown of miR-761 significantly increased the expression of GABARAP in pVICs, significantly decreased the expressions of OPN, α-SMA, Collagen Ⅰ and RUNX2 (P < 0.05), and inhibited the calcium salt deposition in the cells induced by OM. Conclusion MiR-761 may inhibit autophagy and promote cardiac valve calcification by inhibiting GABARAP expression.

A Brønsted acid‐catalyzed aza‐Mannich reaction between 3‐hydroxyisoindolin‐1‐ones and N‐tert‐butyl hydrazones was developed. Under the catalysis of the racemic phosphoric acid or trifluoroacetic acid and mild reaction conditions, this domino reaction allows for efficient synthesis of 3‐(hydrazono)isoindolin‐1‐one derivatives in excellent yields with high chemoselectivities. The E‐configuration of the hydrazone products was determined by X‐ray single‐crystal diffraction of 5w. 3‐(Hydrazono)isoindolin‐1‐one derivatives were synthesized in excellent yields and high chemoselectivities by a Brønsted acid‐catalyzed domino reaction between 3‐hydroxyisoindolin‐1‐ones and N‐tert‐butyl hydrazones. The E‐configuration of the hydrazone products was determined by X‐ray single‐crystal diffraction. [ABSTRACT FROM AUTHOR]

The eradication of recalcitrant bacterial biofilm infections necessitates the development of speedy diagnostics and prompt therapeutics. However, constructing a portable versatile platform that enables in situ monitoring of biofilm infections accompanied by potent antibiofilm activity remains challenging. To address this conundrum, a microneedle theranostic patch (Mn: C/G@MN) is devised by incorporating an innovative biophotonic probe (manganese‐doped carbon dots, Mn: CDs) into methacrylated gelatin for visual monitoring of biofilm infection and on‐demand photo‐therapy. The Mn: C/G@MN patch penetrates the physical barrier of biofilms to track their acidic microenvironment, exhibiting a visualized fluorescence color change (from yellow to turquoise) to enable naked‐eye monitoring of biofilm infection. Furthermore, the Mn: C/G@MN patch can drastically eradicate biofilm on‐demand through the synergy of local hyperthermia and hydroxyl radical (•OH) storm under 808 nm near‐infrared light illumination, enabling the damaging of extracellular polymeric substances (EPS) matrix to disperse biofilms and subsequently kill detached bacteria. Both in vitro and in vivo findings authenticate that biofilm infection monitoring‐and‐treating can be achieved. Moreover, the versatile Mn: C/G@MN patch is conducive to suppressing inflammatory responses, expediting collagen deposition, stimulating angiogenesis, and accelerating biofilm‐infected wound healing. As envisaged, this work highlights the potential of such a versatile platform for application in integrated theranostics for biofilm infection. [ABSTRACT FROM AUTHOR]