Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts.Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107–10–5 M) or Sac/Val (107–105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry.Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively.Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.

Novel near-infrared (NIR) phosphors are in demand for light-emitting diode (LED) devices to extend their suitability for new applications and, in turn, support the sustainable and healthy development of the LED industry. The Cr3+ has been used as an activator in the development of new NIR phosphors. However, one main obstacle for the Cr3+-activated phosphors is the low luminescence efficiency due to the spin-forbidden d-d transition of Cr3+. The rare-earth (RE) huntite minerals that crystallize in the form of REM3(BO3)4 (M = Al, Sc, Cr, Fe, Ga) have a large family of members, including the rare-earth scandium borates of RESc3(BO3)4. Interestingly, in our research, we found that the luminescence efficiency of Cr3+ in the CeSc3(BO3)4 host, whose quantum yield was measured at 56%, is several times higher than that in GdSc3(BO3)4, TbSc3(BO3)4, and LuSc3(BO3)4 hosts. Hereby, the energy conversion and transfer in the luminescence of CeSc3(BO3)4:Cr3+ phosphor were examined. The Stokes shift of electron energy conversion within the Cr3+ 4T2g level for the emission at 818 nm and excitation at 625 nm in CeSc3(BO3)4 host was evaluated to be 3775.1 cm−1, and the super-large splitting energy of the 2F5/2 and 2F72 sub-states of the Ce3+ 4f1 state, about 3000 cm−1, was found in CeSc3(BO3)4 host. The typical electronic thermal vibration peaks were observed in the excitation spectra of CeSc3(BO3)4:Cr3+. On this basis, the smallest phonon energy, around 347.7 cm−1, of the CeSc3(BO3)4 host was estimated. Finally, the energy transfer that is responsible for the far higher photoluminescence of Cr3+ in CeSc3(BO3)4 than in other hosts was proven through the way of Ce3+ emission and Cr3+ reabsorption.