This study aimed to determine whether cyclo-oxygenase-1 (COX-1) mediates dilatation of mouse arteries via synthesis of prostacyclin (PGI 2 ) and, if so, how PGI 2 (IP) receptors contribute and whether thromboxane prostanoid (TP) receptors are implicated in the process. Mesenteric arteries were isolated from wild-type mice or mice with COX-1 deficiency (COX-1 −/− ). The vasomotor reaction to the COX substrate arachidonic acid (AA) was determined with isometric force measurement, while the in vitro production or the plasma level of the PGI 2 metabolite 6-keto-PGF 1α was analysed with high-performance liquid chromatography-mass spectroscopy or enzyme immunoassay, respectively. Results showed that AA, which evoked endotheliumdependent 6-keto-PGF 1α production, elicited relaxation that was inhibited or enhanced by antagonizing IP or TP receptors, respectively. Also, IP receptor blockade resulted in contraction in response to AA (following NO synthase inhibition), which was prevented by a concomitant TP receptor antagonism. Meanwhile, COX-1 −/− or COX-1 inhibition abolished the in vitro 6-keto-PGF 1α production and reduced the relaxation or contraction observed with AA. Real-time PCR showed that whereas TP receptor mRNAs were detected at similar levels, IP receptor mRNAs were present at higher levels in the branches than in the main stem of the mesenteric artery. In addition, antagonizing the IP receptors enhanced the contraction evoked by PGI 2 in the carotid artery. Also, we noted that COX-1 −/− mice had a reduced basal plasma 6-keto-PGF 1α level. These results demonstrate an explicit vasodilator role for COX-1-mediated endothelial PGI 2 synthesis and suggest that the functionally opposing IP and TP receptors concomitantly mediate the vasomotor reaction to PGI 2 , with the dilator activity of IP receptors being compromised by the vasoconstrictor effect of TP receptors and vice versa.

Breast cancer (BC) is the most frequently diagnosed type of cancer, and the leading cause of cancer-associated mortality in females worldwide. The aim of the present study was to investigate the prognostic and therapeutic potential of NUF2 in BC. The expression levels of NUF2 in BC tissues and cell lines were evaluated via bioinformatics, reverse transcription-quantitative PCR, western blot analysis and immunohistochemistry (IHC). In addition, the effect of NUF2 knockdown on BC cell proliferation and apoptosis was investigated using small interfering RNA (siRNA) technology. Bioinformatics and IHC analysis showed that NUF2 was overexpressed in BC tissues. Furthermore, western blot and RT-qPCR analyses demonstrated that NUF2 was upregulated in BC cells. In addition, BC cells transfected with NUF2 siRNA exhibited significantly decreased proliferation and colony formation, and increased apoptosis, compared with the control. Additionally, cell cycle analysis revealed that NUF2 induced G0/G1 cell cycle arrest by inhibiting cyclin B1 expression. Collectively, the present study suggested that NUF2 may represent a promising prognostic biomarker and a potential therapeutic target for BC.

For SERS analysis in living cells, the inevitable desorption of Raman molecule on the substrate surface is a key challenge. To ensure high stability, SERS systems with Raman molecules protected inside the core–Raman molecule–shell (C–M–S) structures have been designed, but at the expense of sacrificed sensing performances. Here a shell-switchable SERS blocking strategy is developed for the reliable SERS analysis in living cells, relying on the shell blockers to regulate the SERS sensing signal without affecting the internal Raman molecules. After several C–M–S structures were investigated, the SERS blocking mechanism confirmed that thick shells (Au, Ag, ZnO, and MnO2) can cause a significant reduction in the internal SERS signal by obstructing the penetration of the laser or signal. The CAu–Mpy–SAu–SMnO2 nanoprobe is designed for the ratiometric SERS sensing in living cells, which retains sensing performances even though the Raman molecule is protected inside the nanostructure. This SERS strategy makes the turn-on sensing achievable in living cells with the MnO2 shell as a signal switch and a Raman reference. Additionally, it allows for accurate monitoring of the degradation of MnO2 carriers in living cells, even without fluorescent labels.

A nanoflare, a conjugate of Au nanoparticles (NPs) and fluorescent nucleic acids, is believed to be a powerful nanoplatform for diagnosis and therapy. However, it highly suffers from the nonspecific detachment of nucleic acids from the AuNP surface because of the poor stability of Au−S linkages, thereby leading to the false-positive signal and serious side effects. To address these challenges, we report the use of covalent amide linkage and functional Au@graphene (AuG) NP to fabricate a covalent conjugate system of DNA and AuG NP, label-rcDNA-AuG. Covalent coating of abundant amino groups (−NH 2 ) onto the graphitic shell of AuG NP efficiently facilitates the coupling with carboxyl-labeled capture DNA sequences through simple, but strong, amide bonds. Importantly, such an amidebonded nanoflare possesses excellent stability and anti-interference capability against the biological agents (nuclease, DNA, glutathione (GSH), etc.). By accurately monitoring the intracellular miR-21 levels, this covalent nanoflare is able to identify the positive cancer cells even in a mix of cancer and normal cells. Moreover, it allows for efficient photodynamic therapy of the targeted cancer cells with minimized side effects on normal cells. This work provides a facile approach to develop a superstable nanosystem showing promising potential in clinical diagnostics and therapy.