MiR-210-3p-EphrinA3-PI3K/AKT axis regulates the progression of oral cancer

This study aimed to explore new therapeutic targets to improve the survival rate of patients with oral squamous cell carcinoma (OSCC).MiR-210-3p, EphrinA3 and EMT related indices were evaluated in OSCC tissues and cell lines. In addition, the relationship between differential EphrinA3 expression and tumour progression was explored through molecular biology techniques, in vitro functional experiments and tumour xenotransplantation models. The expression of EphrinA3 (r_s = −0.719, P < .05) and E-cadherin (r_s = −0.856, P < .05) was negatively correlated with the pathological grading in OSCC tissues. Protein clustering shows EphrinA3 may be associated with tumour progression. EphrinA3 also can regulate the biological behaviour of oral cancer cells. And it regulates the EMT by the PI3K/AKT signalling pathway. MiR-210-3p targeted the gen EFNA3. Up-regulation of miR-210-3p expression can decrease the expression of EphrinA3 and further to influence the biological behaviour of OSCC. The miR-210-3p-EphrinA3-PI3K/AKT signalling axis plays an important role in the progress of OSCC. EphrinA3 may serve as a novel target for oral cancer treatment.     

A novel lncRNA PLK4 up‐regulated by talazoparib represses hepatocellular carcinoma progression by promoting YAP‐mediated cell senescence

A growing number of studies recognize that long non‐coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA‐regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo‐like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11‐50D9.3), whose expression was dramatically down‐regulated in hepatocellular carcinoma (HCC) tissues and cells. Interestingly, talazoparib, a novel and highly potent poly‐ADP‐ribose polymerase 1/2 (PARP1/2) inhibitor, could increase lncRNA PLK4 expression in HepG2 cells. Importantly, we showed that talazoparib‐induced lncRNA PLK4 could function as a tumour suppressor gene by Yes‐associated protein (YAP) inactivation and induction of cellular senescence to inhibit liver cancer cell viability and growth. In summary, our findings reveal the molecular mechanism of talazoparib‐induced anti‐tumor effect, and suggest a potential clinical use of talazoparib‐targeted lncRNA PLK4/YAP‐dependent cellular senescence for the treatment of HCC.     

LncRNA TUG1 alleviates cardiac hypertrophy by targeting miR-34a/DKK1/Wnt-β-catenin signalling

The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy.     

Investigation of the Effects of Squalene and Squalene Epoxides on the Homeostasis of Coenzyme Q10 in Rats by UPLC‐Orbitrap MS

Squalene has been used as a dietary supplement for a long history due to its potential cancer‐preventive function. However, the mechanism has not been investigated in detail yet. Therefore, the aim of this study is to see if the plasma coenzyme Q10 (CoQ10) level will be altered by gavage of squalene and oxidosqualenes to rats. In the present work, a sensitive and simple high‐performance analytical method based on ultra‐high‐performance liquid chromatography coupled with an Orbitrap mass spectrometry (UPLC‐Orbitrap‐MS) was developed for the quantification of CoQ10 in rat plasma. Coenzyme Q9 (CoQ9) was employed as the internal standard. CoQ10 was determined after acetonitrile‐mediated plasma protein precipitation using UPLC‐Orbitrap‐MS in negative ion mode. Intragastric administration of squalene and the two squalene epoxides into rats once daily for several days elevated the level of CoQ10 in their plasma, but there was no significant difference between high‐dose (286 mg/kg) and low‐dose (143 mg/kg) groups. Intragastric administration of squalene once a day for 5 consecutive days and oxidosqualenes once a day for 3 consecutive days is necessary for reaching the steady‐state level of CoQ10. Our present findings indicate that squalene and oxidosqualenes may be useful for stimulating the synthesis of CoQ10 in rats.     

Ultrafine Co3Se4 Nanoparticles in Nitrogen‐Doped 3D Carbon Matrix for High‐Stable and Long‐Cycle‐Life Lithium Sulfur Batteries

Lithium–sulfur batteries are a promising high energy output solution for substitution of traditional lithium ion batteries. In recent times research in this field has stepped into the exploration of practical applications. However, their applications are impeded by cycling stability and short life‐span mainly due to the notorious polysulfide shuttle effect. In this work, a multifunctional sulfur host fabricated by grafting highly conductive Co₃Se₄ nanoparticles onto the surface of an N‐doped 3D carbon matrix to inhibit the polysulfide shuttle and improve the sulfur utilization is proposed. By regulating the carbon matrix and the Co₃Se₄ distribution, N‐CN‐750@Co₃Se₄‐0.1 m with abundant polar sites is experimentally and theoretically shown to be a good LiPSs absorbent and a sulfur conversion accelerator. The S/N‐CN‐750@Co₃Se₄‐0.1 m cathode shows excellent sulfur utilization, rate performance, and cyclic durability. A prolonged cycling test of the as‐fabricated S/N‐CN‐750@Co₃Se₄‐0.1 m cathode is carried out at 0.2 C for more than 5 months which delivers a high initial capacity of 1150.3 mAh g^?1 and retains 531.0 mAh g^?1 after 800 cycles with an ultralow capacity reduction of 0.067% per cycle, maintaining Coulombic efficiency of more than 99.3%. The reaction details are characterized and analyzed by ex situ measurements. This work highly emphasizes the potential capabilities of transition‐metal selenides in lithium–sulfur batteries.     

High‐Performance Platinum‐Perovskite Composite Bifunctional Oxygen Electrocatalyst for Rechargeable Zn–Air Battery

Constructing highly active electrocatalysts with superior stability at low cost is a must, and vital for the large‐scale application of rechargeable Zn–air batteries. Herein, a series of bifunctional composites with excellent electrochemical activity and durability based on platinum with the perovskite Sr(Co_0.8Fe_0.2)_0.95P_0.05O_3?δ (SCFP) are synthesized via a facile but effective strategy. The optimal sample Pt‐SCFP/C‐12 exhibits outstanding bifunctional activity for the oxygen reduction reaction and oxygen evolution reaction with a potential difference of 0.73 V. Remarkably, the Zn–air battery based on this catalyst shows an initial discharge and charge potential of 1.25 and 2.02 V at 5 mA cm^?2, accompanied by an excellent cycling stability. X‐ray photoelectron spectroscopy, X‐ray absorption near‐edge structure, and extended X‐ray absorption fine structure experiments demonstrate that the superior performance is due to the strong electronic interaction between Pt and SCFP that arises as a result of the rapid electron transfer via the Pt? O? Co bonds as well as the higher concentration of surface oxygen vacancies. Meanwhile, the spillover effect between Pt and SCFP also can increase more active sites via lowering energy barrier and change the rate‐determining step on the catalysts surface. Undoubtedly, this work provides an efficient approach for developing low‐cost and highly active catalysts for wider application of electrochemical energy devices.     

Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss

Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.     

Global Profiling of Alternative Splicing in Callus Induction of Immature Maize Embryo

In Vitro Cellular & Developmental Biology - Plant - Callus induction in plants is similar to pluripotent stem cell induction in animals and can incite global changes in gene expression....