Vitamin B6 Deficiency Induces Autism-Like Behaviors in Rats by Regulating mTOR-Mediated Autophagy in the Hippocampus.

Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.

Electrochemically Quantifying the Phase Transition of Cesium Lead Halide Perovskite Quantum Dots in Purification.

A good purification strategy for obtaining high-quality and low-cost perovskite QDs ink requires a complete removal of the impurities but with a minimal phase transition of QDs from the perovskite phases to the nonperovskite δ-phase. This pioneering work reports the electrochemical quantification on the phase transition level of CsPbI3 QDs in purification. Cyclic voltammetry of the purified QDs evidenced the formation of a new product in the purification process, which was demonstrated to be the undesired nonperovskite δ-phase by independent structural analysis. The developed electrochemical methodology further enabled the quantification of the extent of the phase transition of the QDs purified using different strategies by simply analyzing the charge associated with the relevant peaks and allowing optimization of the purification. The latter is of vital importance for commercialization and is an essential step for boosting their device performance.

Probing Dynamics of Lead(II) Sulfide Quantum Dots in Solution Ligand Exchange by Voltammetry.

The ligand/quantum dots (QDs) ratio is crucial for the liquid state ligand exchange process to ensure a high-quality surface passivation and stable QDs ink. Herein we report an electrochemical method to investigate the ligand exchanged PbS-PbI2 QDs. It is found that the shell and core Pb(II) are distinguished by their reduction peak position in the cyclic voltammogram and the peak charge ratio gives the shell/core composition of the QDs. Combined with XPS analysis and UV-vis spectroscopy, it is further indicated that the shell/core ratio of PbS-PbI2 QDs varies as the ligand PbI2 concentration changes. Specifically, below a certain concentration, more PbI2 binds to the QD surface, leading to better passivation when the PbI2 concentration increases; however, beyond that concentration, decomposition of QDs likely occurs via an anion exchange process. The presented electrochemical method provides a new and powerful tool to investigate and optimize QD surface chemistry for boosting the scale up applications of QD devices.

Arbutin suppresses osteosarcoma progression via miR-338-3p/MTHFD1L and inactivation of the AKT/mTOR pathway.

Arbutin, a glycoside extracted from the plant Arctostaphylos uva-ursi, has been previously reported to possess antioxidant, anti-inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG-63 and SW1353. Arbutin suppressed OS cell viability in a dose- and time-dependent manner, as shown by Cell Counting Kit-8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated-protein kinase B (AKT)/phosphorylated-mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR-338-3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR-338-3p promoted cell invasion, migration and proliferation in arbutin-treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR-338-3p/MTHFD1L and by inactivating the AKT/mTOR pathway.

MTHFD1L as a folate cycle enzyme correlates with prognostic outcome and its knockdown impairs cell invasive behaviors in osteosarcoma via mediating the AKT/mTOR pathway.

Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.

Long noncoding RNA LINC00461 induced osteoarthritis progression by inhibiting miR-30a-5p.

Mounting studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development and occurrence of several human diseases. However, the role of LINC00461 in osteoarthritis (OA) remains obscure. A CCK-8 assay was performed to detect cell viability, and qRT-PCR analysis was used to measure mRNA expression. The targeting by miR-30a-5p of the LINC00461 3'UTR was detected using a luciferase reporter assay. Our data indicated that the inflammatory mediators IL-6 and TNF-α induced LINC00461 expression in chondrocytes and that the expression of LINC00461 was upregulated in OA tissues. Furthermore, we showed that TNF-α and IL-6 suppressed the expression of miR-30a-5p and that miR-30a-5p expression was lower in OA tissues than in normal samples. The expression level of miR-30a-5p in OA tissues was negatively related to LINC00461 expression. In addition, we showed that LINC00461 directly interacted with miR-30a-5p in chondrocytes. Elevated expression of LINC00461 induced chondrocyte proliferation, cell cycle progression, inflammation, and extracellular matrix (ECM) degradation. However, we demonstrated that ectopic expression of miR-30a-5p suppressed cell growth, cell cycle progression, inflammation and ECM degradation. Finally, we found that overexpression of LINC00461 enhanced chondrocyte proliferation, cell cycle progression, inflammation, and ECM degradation by downregulating miR-30a-5p. These data demonstrated that LINC00461 may modulate the development of OA by suppressing miR-30a-5p expression in chondrocytes. We propose that LINC00461 and miR-30a-5p may be potential therapeutic and diagnostic targets for OA.

miR-137 suppresses cell growth and extracellular matrixdegradation through regulating ADAMTS-5 in chondrocytes.

Osteoarthritis (OA) is the most common degenerative joint disease. microRNAs (miRNAs) have been showen to act critical roles in several diseases including OA. However, the involvement and underlying mechanism of miR-137 in development of OA remains unkown. In our study, we firstly showed that IL-1ß decreased the expression of miR-137 in the chondrocytes and we demonstrated that the miR-37 expression level was lower in the OA cases than in the control patients. Dual-luciferase reporter analysis was performed to confirm that ADAMTS-5 was a direct target gene of miR-137. Furthermore, we indicated that elevated expression of miR-137 decreased the protein expression of ADAMTS-5 in the chondrocytes. In additional, we showed that IL-1ß induces the ADAMTS-5 expression in the chondrocytes. The ADAMTS-5 expression level was higher in the OA cases than in the control patients. We showed that the expression of ADAMTS-5 was negatively correlated with the miR-137 expression level in OA tissues. Overexpression of miR-137 suppressed cell growth, extracellular matrix (ECM) degradation and inflammation in chondrocytes. These preliminary data elucidated that miR-137 suppressed OA progression via inhibiting cell growth, inflammation and ECM degradation.

Aluminum-Doped Cesium Lead Bromide Perovskite Nanocrystals with Stable Blue Photoluminescence Used for Display Backlight.

Bright and stable blue emitters with narrow full-width at half-maxima are particularly desirable for applications in television displays and related technologies. Here, this study shows that doping aluminum (Al3+) ion into CsPbBr3 nanocrystals (NCs) using AlBr3 can afford lead-halide perovskites NCs with stable blue photoluminescence. First, theoretical and experimental analyses reveal that the extended band gap and quantum confinement effect of elongated shape give rise to the desirable blueshifted emission. Second, the aluminum ion incorporation path is rationalized qualitatively by invoking fundamental considerations about binding relations in AlBr3 and its dimer. Finally, the absence of anion-exchange effect is corroborated when green CsPbBr3 and blue Al:CsPbBr3 NCs are mixed. Combinations of the above two NCs with red-emitting CdSe@ZnS NCs result in UV-pumped white light-emitting diodes (LED) with an National Television System Committee (NTSC) value of 116% and ITU-R Recommendation B.T. 2020 (Rec. 2020) of 87%. The color coordinates of the white LED are optimized at (0.32, 0.34) in CIE 1931. The results suggest that low-cost, earth-abundant, solution-processable Al-doped perovskite NCs can be promising candidate materials for blue down-conversion layer in backlit displays.