In-Situ Growth of One-Dimensional Blocking Layer to Mitigate Deficient Surface of Single-Crystal Perovskites.

Organic-inorganic halide perovskite (OIHP) single crystals are promising for optoelectronic application, but their high surface trap density and associated ion migration hinders device performance and stability. Herein, a one-dimensional (1D) perovskites are designed and proposed as blocking layer at the crystal/electrode interface to mitigate the surface issues. As a model system, the interface ion migration in Cs0.05FA0.95PbI3 (FA=formamidinium) single-crystal perovskite solar cells (PSCs) is obviously suppressed, leading to increase of T90 lifetime from 260 to 1000 hours, five times better than previously reported results. Besides, the reduction of surface iodide ion vacancies inhibits nonradiative recombination, thus increasing the efficiency from 22.1% to 23.8%, which is one of the highest values for single-crystal PSCs. Since the deficient crystal surface is a universal and open issue, our strategy is instructive for optimizing diverse single-crystal perovskite devices.

Perovskite Single Crystals with Self-Cleaning Surface for Efficient Photovoltaics.

Metal halide perovskite single crystals are promising for diverse optoelectronic applications. As a universal issue of solution-grown perovskite single crystals, surface contamination causes adverse effect on material properties and device performance. Herein, learning from the self-cleaning effect of lotus leaf, we address the surface contamination issue by introducing an amphiphilic long-chain organic amine into the perovskite crystal growth solution. Self-assembly of CTAC provides a hydrophobic crystal surface, inducing spontaneous removal of residual growth solution, which results in clean surface and better optoelectronic properties of perovskite single crystals. An impressive efficiency of 23.4 % is obtained, setting a new record for FAx MA1-x PbI3 single-crystal perovskite solar cells (PSCs). Moreover, our strategy also applies to perovskite single crystals with different morphology and composition, which may contribute to improvement of other single-crystal perovskite optoelectronic devices.

Chiral pharmacokinetics of ibuprofen enantiomers in Chinese preterm neonates with patent ductus arteriosus using a validated UHPLC-MS/MS method.

Persistent patent ductus arteriosus (PDA) is generally observed in preterm neonates. Oral ibuprofen is the standard treatment for closing PDA in China. To investigate the chiral pharmacokinetics of ibuprofen enantiomers in Chinese premature infants with PDA, a simple, fast, and sensitive analytical enantioselective technology was developed with ultra-performance liquid chromatography (UPLC) - tandem mass spectrometry (MS/MS). Chromatographic separation of (R)-ibuprofen and (S)-ibuprofen was accomplished on a Lux® 3 µm Cellulose-3 (150 mm × 2.0 mm, 3 µm) at a flow rate of 0.2 mL/min within 6 min. UPLC separation was achieved by isocratic elution with a mobile phase consisting of formic acid:water (75:1000000, v/v) and acetonitrile:methanol (1:1, v/v). Only 50 µL of plasma samples were pre-treated with acetonitrile precipitation. Ibuprofen-d3 was used as an internal standard. The standard curves of both enantiomers were linear over a concentration range of 0.0500 µg/mL to 50.00 µg/mL. The method has been validated for selectivity, carryover effect, lower limit of quantification, precision, accuracy, matrix effect, extraction recovery, dilution integrity, and stability based on the existing guidelines of the National Medical Products Administration, the United States Food and Drug Administration, and the European Medicines Agency. This method has been successfully applied to investigate the pharmacokinetics of ibuprofen enantiomers in 9 preterm infants with PDA. Our results showed that a high chiral inversion ratio of (R)- to (S)-ibuprofen exists in Chinese preterm neonates. Further studies should be conducted to monitor drug concentration following oral administration of ibuprofen and to consider the effect of individual variations and ethnic differences in metabolizing enantiomers of ibuprofen in premature neonates with PDA.

Hyperoxia-induced miR-342-5p down-regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3.

BACKGROUND AND PURPOSE: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation. EXPERIMENTAL APPROACH: Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis. KEY RESULTS: Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets. CONCLUSION AND IMPLICATIONS: These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD.

MiR-148a promotes myocardial differentiation of human bone mesenchymal stromal cells via DNA methyltransferase 1 (DNMT1).

MicroRNAs have potential to modulate the differentiation of stem cells. In previous study, we found that miR-148a was up-regulated in myocardial differentiation of human bone mesenchymal stromal cells (hBMSCs) induced by 5'-azacytidine. However, the role of miR-148a in regulating this process still remains unclear. In this study, we investigated the function and molecular mechanism of miR-148a in myocardial differentiation of hBMSCs. We found that miR-148a was significantly increased while DNA methyltransferase 1 (DNMT1) was significantly decreased in myocardial differentiation of hBMSCs. Then, the dual luciferase reporter assays method indicated that DNMT1 was the direct target of miR-148a. In addition, we showed that up-regulation of miR-148a could enhance myocardial differentiation of hBMSCs, while down-regulation of miR-148a could inhibit myocardial differentiation process. Moreover, knockdown of DNMT1 could block the role of miR-148a in promoting myocardial differentiation of hBMSCs. Finally, MiR-148a acted on methylation level of GATA-4 and knockdown of DNMT1 could block this function. Therefore, our results indicate that miR-148a plays a vital role in regulating myocardial differentiation of hBMSCs by targeting DNMT1.

[Regulation and mechanism of miR-148a on cardiomyocyte differentiation induced by 5-aza in mesenchymal stem cells].

OBJECTIVE: To investigate the expression of miR-148a in the process of myocardial differentiation of human mesenchymal stem cells (hMSCs) induced by 5-azacytidine (5-aza) and study the effects of miR-148a on myocardial differentiation of hMSCs. METHODS: The immunofluorescence analysis was used to detect the expressions of the associated mark genes of cardiac specific protein (α-MHC) in the process of myocardial differentiation of hMSCs induced by 5-aza. qRT-PCR and Western blot were used to analysis the expressions of miR-148a and DNA methyltransferase 1 (DNMT1) after myocardial differentiation of hMSCs, respectively. The expression of α-MHC after transfection with synthetic miR-148 mimics and miR-148a inhibitor was examined by Western blot. We used bioinformatics analysis to predict the potential target of miR-148a, and the dual luciferase report gene system was used to verify the predication. After co-transfected with DNMT1 shRNA and miR-148a inhibitors, hMSCs were used to explore the regulatory role and mechnism of miR-148a in the process of myocardial differentiation of hMSCs. RESULTS: α-MHC was increased significantly after induced by 5-azacytidine. miR-148a was increased significantly in cardiomyocyte differentiation of hMSCs, while the gene and protein expression levels of DNMT1 were decreased significantly in this progress (P<0.01). The expression of α-MHC was up-regulated significantly in hMSCs when miR-148a was induced into cardiomyocyte differentiation and overexpressed. Instead, downregulation of miR-148a suppressed α-MHC expression (P<0.01). Knockdown of DNMT1 blocked the role of miR-148a in differentiation of hMSCs. CONCLUSIONS: miR-148a was upregulated in cardiomyocyte differentiation of hMSCs, and miR-148a promoted myocardial differentiation of hMSCs via targeting DNMT1.

DNA Methyltransferase 1: A Potential Gene Therapy Target for Hepatocellular Carcinoma?

BACKGROUND: DNA methyltransferase 1 (DNMT1) mutants display altered methylation patterns that may contribute to oncogenesis. We hypothesized that the silencing or inhibition of DNMT1 may affect the malignancy of hepatocellular carcinoma (HCC) cells. METHODS: The HCC cell line KYN2 was used to construct 3 experimental groups: i) a DNMT1-siRNA group transfected with a green fluorescent protein (GFP) lentiviral vector to silence endogenous DNMT1 gene expression, which was confirmed by real-time quantitative polymerase chain reaction, ii) a 5-Aza-CdR group transfected with a null GFP lentiviral vector and treated with the DNMT1 inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR), and iii) a control group transfected with a null GFP lentiviral vector. Cellomics ArrayScan VTI imaging and MTT assays were conducted to assess cell proliferation. Cell cycle phase arrest and apoptosis were assayed by flow cytometry. Colony formation was assessed by fluorescence microscopy. RESULTS: DNMT1 mRNA expression was significantly inhibited in DNMT1-silenced cells relative to control cells (p < 0.05), indicating successful transfection and gene expression knockdown. Cell proliferation was significantly inhibited in DNMT1-siRNA and 5-Aza-CdR cells relative to control cells (p < 0.05). G1-to-S phase shifts were significantly increased in DNMT1-siRNA and 5-Aza-CdR cells relative to control cells (p < 0.05). Apoptosis was significantly increased in DMNT1-siRNA and 5-Aza-CdR cells relative to control cells (p < 0.05). DMNT1-siRNA and 5-Aza-CdR cells displayed significantly reduced colony formation relative to control cells (p < 0.05). Notably, 5-Aza-CdR had more pronounced effects upon all these parameters than DNMT1 silencing. CONCLUSION: DNMT1 activity appears to positively contribute to the malignancy of HCC cells.