CD73 aggravates alcohol-related liver fibrosis by promoting autophagy mediated activation of hepatic stellate cells through AMPK/AKT/mTOR signaling pathway.

CD73 is a membrane-bound glycoprotein that can dephosphorylate AMP to adenosine. Increasing evidence has shown that CD73 is involved in the occurrence and development of liver fibrosis. However, the potential mechanism by which CD73 affects the progression of alcohol-related liver fibrosis (ALF) remains unknown. This study aimed to examine the role and mechanism of CD73 in autophagy in HSC-T6 cells and its role in ALF in mice that treated with alcohol plus CCl4. We found that CD73 knockout reduced serum alanine aminotransferase and aspartate aminotransferase levels and decreased liver injury and collagen deposition. Furthermore, autophagy-related indicators were downregulated in the liver fibrosis tissues of CD73-/- (EtOH + CCl4) mice. In vitro, the expression of CD73 and autophagy increased in activated HSC-T6 cells. Autophagy inhibitor, 3-methyladenine, reduced autophagy and activation of acetaldehyde-induced HSC-T6 cells. When using CD73-siRNA, autophagy in HSC-T6 cells was found to be downregulated. However, the CD73 plasmid increased the activation and autophagy of hepatic stellate cells (HSCs). In addition, CD73 induced autophagy through the AMPK/AKT/mTOR pathway, which is characterized by an increase in the ratio of P-AMPKα/AMPKα and a decrease in the ratio of P-AKT/AKT and P-mTOR/mTOR. Our study found that CD73 promotes HSCs activation by regulating autophagy through the AMPK/AKT/mTOR signaling pathway.

High sensitivity pH sensing by using a ring resonator laser integrated into a microfluidic chip.

We present a chip-scale integrated pH sensor with high sensitivity by using an optofluidic ring resonator (OFRR) laser. An optical fiber with a high refractive index (RI) is employed both as an optical cavity and the sensing reactor along a microchannel, while disodium fluorescein (DSF) aqueous solution with a low RI is served as the cladding gain medium and fluorescent probes. The pump light is introduced along the fiber axis and guided by the total internal reflection at the fiber/cladding interface. The evanescent field of the pump light extends out of the fiber surface and efficiently excites the dye molecules residing in the evanescent field region of the Whispering Gallery Modes (WGMs) of the OFRRs to produce lasing emission. This pumping scheme provides a uniform excitation to the gain medium and significantly increases the signal-to-noise ratio, ensuring a low lasing threshold and highly sensitive sensing. The lasing threshold property under different pH conditions is experimentally and theoretically conducted to evaluate the sensing performance, which shows that the lasing threshold highly depends on the pH value of the cladding solution due to the increasing deprotonation process. We further verify that the intensity of the lasing emission and the pH value shows good linearity in the pH range 6.51-8.13, with a 2-order-of-magnitude sensitivity enhancement compared to fluorescence measurement. The proposed OFRR lasing platform shows excellent robustness and low sample consumption, providing a powerful sensing strategy in medicine, and hazardous/toxic/volatile sensing, which require label-free, real-time, and in situ detection.

Sexual, physical, and overall adverse effects in patients treated with 5α-reductase inhibitors: a systematic review and meta-analysis.

Postfinasteride syndrome (PFS) is a term coined to characterize a constellation of reported undesirable sexual, physical, and neuropsychiatric side effects. In the present study, we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors (5ARIs) increases the risk of PFS-like adverse effects. A search of studies published until May 10, 2020, was performed using PubMed, EMBASE, and the Cochrane Library. We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia (BPH) or androgenetic alopecia (AGA), and identified 34 studies from 28 articles that met our eligibility criteria. In the random-effects model, the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial (95% confidence interval [CI]: 1.64-2.14). Regarding specific types of adverse effects, the use of 5ARIs had a 1.89-fold risk of sexual adverse effects (95% CI: 1.74-2.05) and was associated with an increased risk of physical adverse effects (relative risk [RR]: 1.31, 95% CI: 0.80-2.15), albeit without statistical significance. This meta-analysis helped to better define the adverse effects caused by 5ARIs. We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment. Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.