The semiconductor–liquid junction (SCLJ), the dominant place in photoelectrochemical (PEC) catalysis, determines the interfacial activity and stability of photoelectrodes, whcih directly affects the ...viability of PEC hydrogen generation. Though efforts dedicated in past decades, a challenge remains regarding creating a synchronously active and stable SCLJ, owing to the technical hurdles of simultaneously overlaying the two advantages. The present work demonstrates that creating an SCLJ with a unique configuration of the dual interfacial layers can yield BiVO4 photoanodes with synchronously boosted photoelectrochemical activity and operational stability, with values located at the top in the records of such photoelectrodes. The bespoke dual interfacial layers, accessed via grafting laser‐generated carbon dots with phenolic hydroxyl groups (LGCDs‐PHGs), are experimentally verified effective, not only in generating the uniform layer of LGCDs with covalent anchoring for inhibited photocorrosion, but also in activating, respectively, the charge separation and transfer in each layer for boosted charge‐carrier kinetics, resulting in FeNiOOH–LGCDs‐PHGs–MBVO photoanodes with a dual configuration with the photocurrent density of 6.08 mA cm−2 @ 1.23 VRHE, and operational stability up to 120 h @ 1.23 VRHE. Further work exploring LGCDs‐PHGs from catecholic molecules warrants the proposed strategy as being a universal alternative for addressing the interfacial charge‐carrier kinetics and operational stability of semiconductor photoelectrodes.
Dual interfacial layers, composed of a top covalent anchored carbon dots layer and a Mo:BiVO4 shallow layer with enriched oxygen vacancies, are constructed to synchronously boost charge‐carrier kinetics and inhibit photocorrosion, which results in a BiVO4 photoanode with a photocurrent density of 6.08 mA cm−2, and operational stability up to 120 h at 1.23 VRHE.
Objective
Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether ...miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor β receptor 2 (TGFβR).
Methods
We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial–mesenchymal transition (EMT) were assessed, while its effects on
TGFβR2
expression were analyzed using bioinformatics and a dual luciferase reporter assay.
Results
Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis
.
In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFβR2.
Conclusion
The miRNA miR-17-5p can negatively regulate the expression of TGFβR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC.
Background
The relationship between the ratio of blood urea nitrogen to creatinine (BUN/Cr) and physical frailty in elderly patients remains unclear. The study aims to investigate the association ...between the BUN/Cr ratio and physical frailty in the elderly Chinese population.
Methods
In this cross-sectional analysis, the clinical data of 5213 participants from 2015 were selected from the China Health and Retirement Longitudinal Study (CHARLS). The demographic variables (including age and gender) and health behavior (including smoking and drinking history), anthropometric (including systolic and diastolic blood pressure, waist circumference (WC), etc.), physical performances (i.e., grip strength, repeated chair stands, etc.), and biochemical indicators (i.e., blood urea nitrogen (BUN), creatinine(Cr), total cholesterol (TC), triglycerides (TG), etc.) were measured. The association between the BUN/Cr ratio and physical frailty was analyzed.
Results
After adjusting for potential confounding factors, smooth curve fitting showed a linear relationship between the BUN/Cr ratio and grip strength, a non-linear relationship between the BUN/Cr ratio, and repeated chair-rising time. The fully adjusted linear regression results showed a negative association between the BUN/Cr ratio and grip strength. In the multivariate, piecewise linear regression, when the BUN/Cr ratio was greater than 18.60, the repeated chair-rising time increased with the increase in BUN/Cr ratio (
β
= 0.046, 95%CI 0.025, 0.066;
p
< 0.001). However, we did not observe a significant correlation when the BUN/Cr ratio was less than 18.60 (
β
= −0.007, 95%CI −0.046, 0.032;
p
= 0.717).
Conclusion
This study demonstrated that the BUN/Cr ratio might be associated with physical frailty in older-aged Chinese, and this association requires further investigation.
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Vasorin (VASN) has been reported to be critical in tumor development and angiogenesis. However, VASN has not been ...reported in CRC, and its role is unclear. In this study, VASN expression is upregulated in CRC compared with the normal tissues, and VASN expression positively correlates with N stage and poor overall survival by analysis of different datasets and 32 CRC clinicopathologic samples. Overexpression of VASN significantly promotes CRC cell progression, including proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT), while knockdown of VASN inhibits CRC progression. We found that VASN was associated with the YAP/TAZ and PI3K/AKT pathways by gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Notably, western blotting, immunofluorescence staining and co‐immunofluorescence (co‐IP) confirmed that VASN could interact with YAP and activate the YAP/TAZ and PTEN/PI3K/AKT pathways, and knockdown of YAP reversed this effect. Importantly, our findings indicate that VASN interacts with YAP to inhibit YAP phosphorylation and stimulates CRC proliferation, migration, and invasion through activation of the YAP/TAZ‐TEAD target gene CTGF and PTEN/PI3K/AKT pathways. Our results also show that knockdown of YAP reverses the cellular phenotype induced by increased VASN. In conclusion, our study reveals that VASN acts as an oncogene to stimulate tumor progression in CRC, providing new insights into the molecular mechanisms of CRC development and representing a possible novel biomarker for CRC.
Myricetin is a flavonoids compound extracted from edible myrica rubra. We aimed to evaluate the efficacy of Myricetin on colonic chronic inflammation and inflammation-driven tumorigenesis in mice. ...Myricetin was administrated by gavage for 4 consecutive weeks. Mice were sacrificed and the number of colonic polyps was counted. Myricetin significantly inhibited AOM/DSS-induced colitis and colorectal tumorigenesis. Myricetin prevented the incidence of colorectal tumorigenesis and reduced the size of colorectal polyps. Histopathologic analysis showed that Myricetin could attenuate the degree of colonic inflammation and colorectal tumorigenesis. Further analysis showed that Myricetin strongly reduced the levels of inflammatory factors TNF-α, IL-1β, IL-6, NF-κB, p-NF-κB, cyclooxygenase-2 (COX-2), PCNA and Cyclin D1 in the colonic tissues as analyzed by the assays of immunohistochemical staining, Western blotting and Q-RT-PCR. Our results demonstrated that Myricetin possesses the biological activities of chemoprevention colonic chronic inflammation and inflammation-driven tumorigenesis. We suggest that Myricetin could be developed as a promising chemopreventive drug for reducing the risk of colorectal cancer.
AKT serves as an epigenetic modulator that links epigenetic regulation to cell survival and proliferation while the epigenetic mediator OCT4 critically controls stem cell pluripotency and ...self-renewal. Emerging evidence indicated their complicated interplays in cancer cells and cancer stem cells (CSCs), and inhibiting either one may activate the other. Thus, in this study, we propose a strategy to targeting both factors simultaneously. Firstly, a combination of an OCT4-specific shRNA and the specific AKT inhibitor Akti-1/2 potently suppressed the propagation of human embryonal carcinoma cells, adherent cancer cells and stem-like cancer cells, establishing the proof-of-concept that dual inhibiting OCT4 and AKT can effectively target various cancer cells. Next, we combined Akti-1/2 with metformin, a widely-prescribed drug for treating type 2 diabetes, which was reported to down-regulate OCT4 expression. The metformin + Akti-1/2 combo significantly altered multiple signaling and epigenetic pathways, induced growth arrest and cell death of adherent and stem-like glioblastoma U87 cells, and attenuated their tumorigenicity in vivo. Taken together, we demonstrate here that simultaneously targeting an epigenetic mediator and an epigenetic modulator, by dual inhibiting OCT4 and AKT, can have significantly improved efficacies over single treatment in suppressing the propagation of CSCs as well as the entire bulk of differentiated cancer cells.
Many imaging studies have reported structure alterations in patients with type 1 diabetes mellitus (T1DM) by using voxel-based morphometry (VBM). Nevertheless, the results reported were inconsistent ...and had not been reviewed quantitatively. Accordingly, the quantitative meta-analysis which including VBM studies of patients with T1DM was conducted.
The gray matter volume alterations in patients with T1DM was estimated by using the software seed-based d mapping. Meantime, the meta-regression was applied to detect the effects of some demographics and clinical characteristics.
Six studies were finally included, which with 6 datasets comprising 414 T1DM patients and 216 healthy controls. The pooled meta-analyses detected that patients with T1DM showed robustly increased gray matter volume in the left dorsolateral superior frontal gyrus and middle frontal gyrus and a decreased gray matter volume in the right lingual gyrus, cerebellum, precuneus, the left inferior temporal gyrus, and middle temporal gyrus. The meta-regression showed that the mean age, the female patient's ratio, duration of illness and HbAlc% for T1DM patients were not linearly related with gray matter alterations.
This meta-analysis demonstrates that gray matter volume decreases in T1DM patients were mainly locates in the cortical regions and cerebellum.
Chronic methamphetamine (MA) use is associated with psychiatric symptoms. This study explored pattern of co-occurring psychiatric symptoms in MA users and their relationship to duration of MA use. A ...cross-sectional study was conducted among MA users at the Shenzhen Compulsory Drug Detoxification Center from April 2012 to October 2015. The Positive and Negative Syndrome Scale, Hamilton Anxiety Scale, and Beck Depression Inventory were used to assess psychiatric symptoms. Among 1277 MA users, 57.6% participants had any type of psychiatric symptoms including depressive, anxiety and psychotic symptoms. A dose-response relationship was found between duration of MA use and risk of psychiatric symptoms. The odds ratios (OR) of depressive symptoms increased with the duration of MA use (1–5 years vs. < 1 year: 1.74 95% CI, 1.24–2.42; ≥ 5 years vs. < 1 year: 2.07 1.19–3.61), so did the ORs of co-occurring anxiety and depressive symptoms (1–5 years: 1.74 1.20–2.51; ≥ 5 years: 3.09 1.76–5.40). Methamphetamine-dependent individuals were four-times more likely to experience any type of psychiatric symptoms than non-dependent users. The prevalence of psychiatric symptoms was high in chronic MA users and increased with MA use duration. Early prevention and treatment strategies targeting both MA use and associated psychiatric symptoms are needed.
•Over half of the MA users were present with psychiatric symptoms covering psychosis, depression and anxiety.•The co-occurrence of multiple psychiatric symptoms in chronic MA users was common.•A dose-response relationship between duration of MA use and the risk of psychiatric symptoms was observed in chronic MA users.•Early intervention and effective treatment are urgently needed to address both MA dependence and associated psychiatric problems.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed ...to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.
Fluorescent carbon dots (FCDs) have received considerable attention because of the great potential for a wide range of applications, from bioimaging to optoelectronic devices. In this work, we ...reported the synthesis of nitrogen-doped FCDs with an average size of 2 nm in a subcritical water apparatus by using biomass waste (i.e., expired milk) as the precursor. The obtained FCDs were highly dispersed in aqueous solution because of the presence of O-containing functional groups on their surfaces. Under the excitation of ultraviolet and blue light, the FCDs exhibited excitation wavelength-dependent fluorescence in the emission range of 400–550 nm. The FCDs could be easily taken up by HeLa cells without additional surface functionalization, serving as fluorescent nanoprobes for bioimaging. The applications of FCDs as sensing agents for the detection of Fe3+, solid-state fluorescent patterning, and transparent hybrid films were also performed, demonstrating their potential for solid-state fluorescent sensing, security labeling, and wearable optoelectronics.
PDF
