Recent advances in immunotherapy are raising hope to treat clear cell renal cell carcinoma (ccRCC) with PD-L1 inhibitors, but only a small portion of patients are PD-L1 positive. The heterogeneous expression pattern of PD-L1 in patient population suggests that PD-L1 expression is under the control of diverse regulatory mechanisms. Although recent studies have identified numerous novel PD-L1 regulators, reports on microRNAs which modulate PD-L1 expression are much scarce. In this study, we confirmed that PD-L1 expression was up-regulated in ccRCC compared to paired normal tissues. Using miRDB and miRTarBase, 11 microRNAs were predicted to target PD-L1. After measuring the microRNA panel with TaqMan assays, we found that microRNA-497-5p down-regulation was associated with PD-L1 up-regulation. In TCGA-KIRC dataset, microRNA-497-5p down-regulation was also associated with PD-L1 up-regulation as well as shorter survival. We further validated that PD-L1 was a direct target of microRNA-497-5p in two RCC cell lines. In addition, microRNA-497-5p inhibited cell proliferation, clone formation and migration, while promoted apoptosis in in-vitro assays. Our study reveals a novel regulatory mechanism of PD-L1 expression and the potential of miR-497-5p as therapeutic target and biomarker deserves further investigation.

Electrospinning is a type of electrohydrodynamics that utilizes high-voltage electrostatic force to stretch a polymer solution into nanofibers under the influence of an electric field, with most of the fibers falling onto a collector. This technology is favored by researchers across various fields due to its simple and inexpensive device for producing nanofibers in a straightforward manner. Nanofibers prepared through electrospinning have a high specific surface area and high porosity. Electrospinning technology shows extensive potential, especially within biomedical sensors. This article provides a systematic overview of the factors influencing electrospinning, the parameters of the electrospinning process, the types of electrospun nanofibers, and the applications of electrospinning technology in the field of sensors, including wearable sensors, pressure sensors, and glucose sensors. The paper summarizes the research progress in this field and points out the direction of development for electrospinning technology, as well as the future challenges.

Retinoblastoma protein-interacting zinc-finger gene 1 (RIZ1) displays strong tumor suppressive activities, and its expression is often silenced in many types of human tumors. However, the relationship between RIZ1 expression and glioma prognosis remains unclear. The dysregulation of RIZ1 was evaluated using real-time polymerase chain reaction, western blot, and immunohistochemical analysis of gliomas from 51 patients. Correlation analysis was performed to examine relationships between RIZ1 immunoreactivity, clinicopathological features, and patient prognosis. Also, human malignant glioma U87 and U251 cell lines were stably transduced with ectogenic RIZ1 using a lentiviral vector to investigate the effects of induced expression of RIZ1 on cell proliferation, cell cycle, and apoptosis. Real-time polymerase chain reaction and western blot analysis showed that RIZ1 was downregulated in high-grade gliomas compared with low-grade gliomas and normal brain tissue. Immunohistochemistry showed less RIZ1 labeling in high-grade gliomas than in low-grade gliomas. There was a negative correlation between RIZ1 and Ki-67 immunoreactivity. Clinicopathological evaluation revealed that RIZ1 expression was negatively correlated with tumor grade and patient age. Kaplan-Meier survival analysis showed a positive correlation between RIZ1 immunoreactivity level and progression-free and overall survival times. Multivariate analysis showed that high RIZ1 expression was an independent prognostic factor for patients with gliomas. Induced expression of RIZ1 in U87 and U251 cells reduced cell proliferation and increased apoptosis, and cell cycle analysis revealed that a majority of cells were arrested at G2-M. Moreover, transfection with a RIZ1 expression vector increased p53 and caspase-3 expression and decreased p-IKBα and p-AKT protein levels, suggesting that RIZ1 may stimulate p53-mediated apoptosis and inhibit p-IKBα and p-AKT signaling pathways. Our results suggest that high RIZ1 labeling is indicative of lower grades of gliomas and is associated with better progression-free and overall survival rates. Therefore, RIZ1 may be a promising therapeutic target for patients with gliomas.

Smart drug delivery, through which the drug molecules are delivered according to the requests of human biological rhythms or by maximizing drug therapeutic effects, is highly desired in pharmaceutics. Many biomacromolecules have been exploited for this application in the past few decades, both in industry and laboratories. Biphasic release, with an intentional pulsatile release and a following extended release stage, represents a typical smart drug delivery approach, which aims to provide fast therapeutic action and a long time period of effective blood drug concentration to the patients. In this study, based on the use of a well-known biomacromolecule, i.e., cellulose acetate (CA), as the drug (acetaminophen, ATP)-based sustained release carrier, a modified coaxial electrospraying process was developed to fabricate a new kind of core–shell nanoparticle. The nanoparticles were able to furnish a pulsatile release of ATP due to the shell polyvinylpyrrolidone (PVP). The time cost for a release of 30% was 0.32 h, whereas the core–shell particles were able to provide a 30.84-h sustained release of the 90% loaded ATP. The scanning electron microscope and transmission electron microscope results verified in terms of their round surface morphologies and the obvious core–shell double-chamber structures. ATP presented in both the core and shell sections in an amorphous state owing to its fine compatibility with CA and PVP. The controlled release mechanisms of ATP were suggested. The disclosed biomacromolecule-based process–structure–performance relationship can shed light on how to develop new sorts of advanced nano drug delivery systems.

Background: Recent studies regarding the effects of erythropoietin (EPO) for treating traumatic brain injury (TBI) have been inconsistent. This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess the safety and efficacy of EPO for TBI patients at various follow-up time points. Methods: A literature search was performed using PubMed, Web of Science, MEDLINE, Embase, Google Scholar and the Cochrane Library for RCTs studying EPO in TBI patients published through March 2019. Non-English manuscripts and non-human studies were excluded. The assessed outcomes include mortality, neurological recovery and associated adverse effects. Dichotomous variables are presented as risk ratios (RR) with a 95% confidence interval (CI). Results: A total of seven RCTs involving 1197 TBI patients (611 treated with EPO, 586 treated with placebo) were included in this study. Compared to the placebo arm, treatment with EPO did not improve acute hospital mortality or short-term mortality. However, there was a significant improvement in mid-term (6 months) follow-up survival rates. EPO administration was not associated with neurological function improvement. Regarding adverse effects, EPO treatment did not increase the incidence of thromboembolic events or other associated adverse events. Conclusions: This meta-analysis indicates a slight mortality benefit for TBI patients treated with EPO at mid-term follow-up. EPO does not improve in-hospital mortality, nor does it increase adverse events including thrombotic, cardiovascular and other associated complications. Our analysis did not demonstrate a significant beneficial effect of EPO intervention on the recovery of neurological function. Future RCTs are required to further characterize the use of EPO in TBI.