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C10H11NO, monoclinic, P21/c (no. 14), a = 5.901(2) Å, b = 13.380(4) Å, c = 11.537(3) Å, β = 95.760(5)°, V = 906.3 Å3, Z = 4, Rgt(F) = 0.0488, wRref(F2) = 0.1222, T = 298 K.

All-inorganic tin halide perovskite compounds, such as CsSnI3, have attracted attention in the field of solar cells due to their eco-friendly properties. It is quite a challenge to fabricate high-quality CsSnI3 perovskite films with low defect density due to the low defect tolerance and overquick crystallization growth rate. Herein, we propose a simple yet effective method to modulate the dynamic balance between the growth and nucleation of perovskite crystals for black orthorhombic phase CsSnI3. We found that well-crystallized CsSnI3 thin films can be easily obtained through two-step thermal annealing at low temperatures of 40 °C and 70 °C. We further introduced 1-(4-carboxyphenyl)-2-thiourea to coordinate with surface undercoordinated Sn2+ cations of CsSnI3 thin films through C＝S and C＝O functional groups, significantly decreasing the defect density. The CsSnI3 perovskite solar cells based on a printable c-TiO2/m-TiO2/Al2O3/NiO/carbon mesoporous framework achieved a power conversion efficiency of 8.03% with high reproducibility, which is the best efficiency among those reported for all-inorganic CsSnI3 mesoporous perovskite solar cells to date. Furthermore, the corresponding devices retained 90% of the initial efficiency after 3000 hours of storage in a N2-filled glovebox. [ABSTRACT FROM AUTHOR]

Gene-knockout pigs have important applications in agriculture and medicine. Compared with CRISPR/Cas9, Adenine base editor (ABE) convert single A·T pairs to G·C pairs in the genome without generating DNA double-strand breaks, and this method has higher accuracy and biosafety in pig genetic modification. However, the application of ABE in pig gene knockout is limited by protospacer-adjacent motif sequences and the base-editing window. Alternative mRNA splicing is an important mechanism underlying the formation of proteins with diverse functions in eukaryotes. Spliceosome recognizes the conservative sequences of splice donors and acceptors in a precursor mRNA. Mutations in these conservative sequences induce exon skipping, leading to proteins with novel functions or to gene inactivation due to frameshift mutations. In this study, adenine base-editing-mediated exon skipping was used to expand the application of ABE in the generation of gene knockout pigs. We first constructed a modified "all-in-one" ABE vector suitable for porcine somatic cell transfection that contained an ABE for single-base editing and an sgRNA expression cassette. The "all-in-one" ABE vector induced efficient sgRNA-dependent A-to-G conversions in porcine cells during single base-editing of multiple endogenous gene loci. Subsequently, an ABE system was designed for single adenine editing of the conservative splice acceptor site (AG sequence at the 3′ end of the intron 5) and splice donor site (GT sequence at the 5′ end of the intron 6) in the porcine gene GHR; this method achieved highly efficient A-to-G conversion at the cellular level. Then, porcine single-cell colonies carrying a biallelic A-to-G conversion in the splice acceptor site in the intron 5 of GHR were generated. RT-PCR indicated exon 6 skipped at the mRNA level. Western blotting revealed GHR protein loss, and gene sequencing showed no sgRNA-dependent off-target effects. These results demonstrate accurate adenine base-editing-mediated exon skipping and gene knockout in porcine cells. This is the first proof-of-concept study of adenine base-editing-mediated exon skipping for gene regulation in pigs, and this work provides a new strategy for accurate and safe genetic modification of pigs for agricultural and medical applications. [ABSTRACT FROM AUTHOR]

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. Our aim was to identify a novel miRNA that can predict prognosis of childhood ALL patients and explore its potential mechanism. The miRNA expression profiles of childhood ALL were analyzed using GEO database and HiSeq instruments. The expression of miR-155 was examined by RT–PCR in 42 ALL patients. To investigate the role of miR-155 in ALL, four ALL cell lines (CEM-C1, Jurkat, MOLT-3 and MOLT-4) were transfected with miR-155 mimics, miR-155 inhibitors or corresponding controls. Dual-luciferase reporter system was applied to confirm the miR-155 target ZNF238. Moreover, proliferation and apoptosis were evaluated by MTT and flow cytometry. Dataset GSE56489 and GSE23024 demonstrated that miR-155 was up-regulated and ZNF238 was down-regulated at diagnosis status of ALL. High miR-155 expression was associated with poor outcome. Overexpressed miR-155 promoted ALL cell proliferation and inhibited apoptosis. Dual-luciferase reporter result showed that miR-155 directly regulated ZNF238. Silencing ZNF238 promoted cell proliferation in ALL cells. Our research indicating that miR-155 might possess potential value as a biomarker for predicting the prognosis of individuals. However, the role of ZNF238 in childhood ALL remain unknown. In the present study, we found the possible role of ZNF238 as a new tumor suppressor in ALL, which might be necessary for the antiproliferative functions of normal cells to counteract ALL formation. Our results propose that miR-155 is in association with poor prognosis of childhood ALL. Furthermore, miR-155 could promote cell proliferation targeting ZNF238. [ABSTRACT FROM AUTHOR]

Patients with Parkinson's disease (PD) have a higher incidence rate of duodenal ulcers. The mucus barrier provides the first line of defense for duodenal mucosal protection. However, it is unknown whether duodenal mucus secretion is affected in PD. In the present study, we used the rats microinjected 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra to investigate duodenal mucus secretion and potential therapeutic targets in duodenal ulcer in PD. Alcian blue-periodic acid-Schiff, transmission electron microscopy, immunofluorescence, duodenal mucosal incubation, and enzyme-linked immunosorbent assays were used. The 6-OHDA rats exhibited mucin accumulation and retention in duodenal goblet cells. Mucin granules were unable to fuse with the apical membranes of goblet cells, and the exocytosis ratio of goblet cells was significantly reduced. Moreover, decreased acetylcholine and increased muscarinic receptor 2 (M2R) levels were detected in the duodenal mucosa of 6-OHDA rats. Bilateral vagotomy rats were also characterized by defective duodenal mucus secretion and decreased acetylcholine with increased M2R levels in the duodenal mucosa. Application of the cholinomimetic drug carbachol or blocking M2R with methoctramine significantly promoted mucus secretion by goblet cells and increased MUC2 content in duodenal mucosa-incubated solutions from 6-OHDA and vagotomy rats. We conclude that the reduced acetylcholine and increased M2R contribute to the impaired duodenal mucus secretion of 6-OHDA rats. The study provides new insights into the mechanism of duodenal mucus secretion and potential therapeutic targets for the treatment of duodenal ulcers in PD patients. [ABSTRACT FROM AUTHOR]

In response to hypoxic-ischemic brain damage (HIBD), microglia activation and its mediated inflammation contribute to neuronal damage. Inhibition of over-activated microglia is deemed to be a potential therapeutic strategy. Our previous studies showed that gastrodin efficiently depressed the neuroinflammation mediated by activated microglia in HIBD neonatal rats. The underlying mechanisms through which gastrodin acts on activated microglia have not been fully elucidated. This study is designed to determine whether gastrodin would regulate the Notch signaling pathway and Sirtuin3 (Sirt3), which are implicated in regulating microglia activation. The present results showed that gastrodin markedly suppressed the expression of members of Notch signaling pathway (Notch-1, NICD, RBP-JK and Hes-1) in activated microglia both in vivo and in vitro. Conversely, Sirt3 expression was enhanced. In BV-2 microglia treated with a γ-secretase inhibitor of Notch pathway- DAPT, the expression of RBP-JK, Hes-1, and NICD was suppressed in activated microglia. Treatment with DAPT and gastrodin further decreased NICD and Hes-1 expression. Sirt3 expression was also decreased after DAPT treatment. However, Sirt3 expression in activated BV-2 microglia given a combined DAPT and gastrodin treatment was not further increased. In addition, combination of DAPT and Gastrodin cumulatively decreased tumor necrosis factor-α (TNF-α) expression. The results suggest that gastrodin regulates microglia activation via the Notch signaling pathway and Sirt3. More importantly, interference of the Notch signaling pathway inhibited Sirt3 expression, indicating that Sirt3 is a downstream gene of the Notch signaling pathway. It is suggested that Notch and Sirt3 synergistically regulate microglia activation such as in TNF-α production. [ABSTRACT FROM AUTHOR]

The small optical bandgap of a CsSnI3‐based inorganic perovskite film makes it a hopeful candidate as an absorber layer in solar cell applications. Herein, a coadditive 2‐aminopyrazine (APZ) in the precursor solution to form SnF2−APZ complex with the aim to restrain Sn2+ oxidation and thus improve the CsSnI3‐based device performance is proposed. It is found that the amino group of APZ significantly suppresses oxidation of Sn2+ through a Lewis acid–base addition reaction. Consequently, the CsSnI3‐based mesoporous perovskite solar cells that use a printable c‐TiO2/m‐TiO2/Al2O3/NiO/carbon framework with high reproducibility achieve a power conversion efficiency of 5.12%. This is a champion efficiency for fully inorganic CsSnI3‐based mesoporous devices reported up to now. Furthermore, after 60 days of storage in a N2‐filled glovebox, the device still maintains an initial efficiency of 92%. [ABSTRACT FROM AUTHOR]

Objective *To investigate the therapeutic efficacy of metformin (MF) on glucose dysregulation and dyslipidaemia induced by quetiapine in patients with schizophrenia (SZ). Methods *A total of 83 SZ patients from Shanghai Hongkou District Mental Health Center and Shanghai Yangpu District Mental Health Center were enrolled, and randomly divided into treatment group (MF group, n=38) and control group (n=45). The control group received oral quetiapine therapy, and the MF group additionally received metformin on the basis of oral quetiapine therapy. The serum levels of glucose (GLU), total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small density low-density lipoprotein cholesterol (sd-LDL-C) and homocysteine (HCY) were determined before treatment and 2, 4 and 8 weeks after treatment. Results *There were no statistic differences in ages, courses, body mass index, the levels of GLU, TC, TAG, HDL-C, LDL-C, sd-LDL-C and HCY between the control and MF group before treatment (all P>0.05). After 8 weeks of treatment, levels of all biomarkers elevated in the control group. The levels of GLU, TC, TAG, LDL-C, sd-LDL-C and HCY were lower after treatment, and the level of HDL-C elevated higher in the MF group. The variations of levels of HDL-C after treatment showed statistically no significant difference between the two groups (P=0.247), while statistical differences existed in other biomarkers, which indicated that the glucose-lowering and lipid-lowering efficacies in the MF group were significantly better than those in the control group. The analysis of variance suggested that, in the control group, the level of HDL-C elevated significantly after 4 and 8 weeks' treatment, having statistical differences (P=0.005 and P=0.003). The level of LDL-C elevated significantly after 2, 4 and 8 weeks' treatment (P=0.005, P= 0.019 and P=0.026), and no statistical differences were observed in other biomarkers. In the MF group, the levels of GLU, TC, TAG and sd-LDL-C were lower 2, 4 and 8 weeks after treatment, the levels of LDL-C and HCY descended 4 and 8 weeks after treatment, and no statistical differences were observed in other biomarkers. The level of HDL-C was higher after 2 weeks, treatment, but showed statistically no significant differences 4 and 8 weeks after treatment, compared to the level determined before treatment. Conclusion *Administration of MF in the SZ patients having glucose dysregulation and dyslipidaemia induced by quetiapine can significantly lower serum level of GLU, and improve the serum lipid profiles. [ABSTRACT FROM AUTHOR]