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Alpha-fetoprotein (AFP) is a serum biomarker mainly for early stage diagnosis and prognosis of primary liver cancer in clinical analysis. As a label-free analyte-specific biosensor with ultrahigh sensitivity and broad detection range, photoelectrochemical (PEC) sensor is promising for AFP detection. A unique feature of the PEC sensor, the separation of its excitation source and the detection signal, offers a great opportunity in the spatial and temporal domains to enhance its performance. For the spatial domain, AuNPs/TiO2/Au (in short, ATA) sandwiched structure was designed for magnetic resonance generation and light absorption enhancement. The strong light–matter interaction due to the dipole image effect has achieved an over 20 times increase in the sensitivity of the designed sensor. Instead of the typical method that manually switches the light source for photocurrent, lock-in amplification (LIA) was proposed to modulate the light source in the temporal domain. Such modulated signal can be coherently amplified and extracted from a strong noise background, which improves the signal-to-noise ratio (SNR) of the photocurrent signal and leads to a larger measurement range. This designed AFP biosensor exhibited one-order-of-magnitude wider linear detection range from 10 pg mL $^{-{1}}$ to $1~\mu \text{g}$ mL $^{-{1}}$ with a detection limit of 4.5 pg mL $^{-{1}}$ .

ABSTRACTCardiac hypertrophy (CH) is a result of the physiological adaptation of the heart to coronary heart disease, hypertension, and other cardiovascular diseases. Sinomenine is extracted from Caulis Sinomenii. This study aimed to explore the specific mechanism of the action of sinomenine in cardiac hypertrophy (CH) via Nrf2/ARE signaling pathway in vivoand in vitro. To establish a model of CH, H9C2 cells were treated with angiotensin II (Ang II) and intraperitoneally injected with isoproterenol. Then the cells were treated with 50 and 100 μM sinomenine. TUNEL, HE, rhodamine-labeled phalloidin, and immunohistochemical staining were performed. Flow cytometry was used to measure apoptosis rates. mRNA expression of ANP, BNP, and β-MHC was determined by qRT-PCR. Furthermore, western blotting was performed to analyze protein expression. After sinomenine treatment, the surface area and apoptosis rates were decreased. Furthermore, the mRNA expression of ANP, BNP, and β-MHC, levels of reactive oxygen species and malondialdehyde, and protein expression of Caspase3 and Bax were down-regulated, and the protein expression of Bcl-2 was upregulated. Sinomenine activates the Nrf2/ARE signaling pathway, and inhibition of this signaling pathway reversed the effects of sinomenine. In animal experiments, sinomenine decreased the heart weight and left ventricular weight indices, as well as the expression of ANP, BNP, and β-MHC. Furthermore, sinomenine reduced the apoptosis rate and relieved CH-related oxidative stress by activating the Nrf2/ARE signaling pathway. Together, these findings reveal that sinomenine is a potential candidate drug for CH treatment and further research is required to generalize the result in human subjects.

Background Hemodialysis (HD) patients have altered free triiodothyronine (fT3) levels. A low fT3 level is a strong and inverse mortality predictor in HD patients. However, little is known about the relationship between fT3 and left ventricular function in HD patients.Methods A total of 128 maintenance HD patients were enrolled in this study. A thyroid function test with blood sampling and echocardiography was conducted. Low-T3 syndrome was defined as fT3 level <3.62 pmol/L and normal thyroid stimulating hormone (TSH). Overall mortality and rate of cardiovascular (CV) events were assessed during 48 months of follow-up.Results Low-T3 syndrome was detected in 57 (44.5%) of the 128 patients. Patients with low-T3 syndrome had a shorter duration of HD (49.1 vs. 73.3, p = 0.01), and lower serum albumin (35.1 vs. 40.4 g/L, p<0.001), left ventricular ejection fraction (LVEF; 54.7% vs. 63.9%, p<0.001), and fractional shortening at endocardial levels (endoFS; 29.3% vs. 34.8%, p = 0.001) compared to those with normal fT3 levels. In multivariate linear regression, LVEF, albumin, and duration of HD were independently correlated with fT3 levels. In addition, fT3 was also correlated with LVEF. During the study period, 13 (10.1%) patients died, CV events occurred in 15 (11.7%) patients. In Cox regression analysis, low fT3 level and elevated high-sensitivity C-reactive protein (hs-CRP) were associated with mortality and CV events.Conclusions In HD patients, fT3 level is positively correlated with LVEF. Low fT3 level and elevated hs-CRP predicted all-cause mortality and CV events.