Iron was used as the catalyst for the direct C-H functionalization/C-S bond formation under mild conditions. Various substrates could afford benzothiazoles in moderate to excellent yields. Preliminary mechanistic studies revealed that pyridine played a crucial role for the high yields and selectivities.
Parkinson's disease (PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-124) is abundantly expressed in the DA neurons and its expression level decreases in the 1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine (MPTP) model of PD. However, whether the upregulation of miR-124 could attenuate neurodegeneration remains unknown. Here, we employed miR-124 agomir and miR-124 mimics to upregulate miR-124 expression in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells, respectively. We found that loss of DA neurons and striatal dopamine in MPTP-treated mice was significantly reduced by upregulating miR-124. In addition, we identified a target of miR-124, Bim that mediated the neuroprotection of miR-124. Indeed, treatment of miR-124 agomir in MPTP-treated mice inhibited Bim expression, thus suppressing Bax translocation to mitochondria. Moreover, impaired autophagy process in MPTP-treated mice and MPP(+) -intoxicated SH-SY5Y cells characterized as autophagosomes (AP) accumulation and lysosomal depletion were alleviated by the upregulation of miR-124. Taken together, these results indicate that upregulation of miR-124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons.
We investigated immune-related long non-coding RNAs (lncRNAs) that may be exploited as potential therapeutic targets in anaplastic gliomas. We obtained 572 lncRNAs and 317 immune genes from the Chinese Glioma Genome Atlas microarray and constructed immune-related lncRNAs co-expression networks to identify immune-related lncRNAs. Two additional datasets (GSE16011, REMBRANDT) were used for validation. Gene set enrichment analysis and principal component analysis were used for functional annotation. Immune-lncRNAs co-expression networks were constructed. Nine immune-related lncRNAs (SNHG8, PGM5-AS1, ST20-AS1, LINC00937, AGAP2-AS1, MIR155HG, TUG1, MAPKAPK5-AS1, and HCG18) signature was identified in patients with anaplastic gliomas. Patients in the low-risk group showed longer overall survival (OS) and progression-free survival than those in the high-risk group (P < 0.0001; P < 0.0001). Additionally, patients in the high-risk group displayed no-deletion of chromosomal arms 1p and/or 19q, isocitrate dehydrogenase wild-type, classical and mesenchymal TCGA subtype, G3 CGGA subtype, and lower Karnofsky performance score (KPS). Moreover, the signature was an independent factor and was significantly associated with the OS (P = 0.000, hazard ratio (HR) = 1.434). These findings were further validated in two additional datasets (GSE16011, REMBRANDT). Low-risk and high-risk groups displayed different immune status based on principal components analysis. Our results showed that the nine immune-related lncRNAs signature has prognostic value for anaplastic gliomas.
Vibrational sum frequency generation (VSFG) spectroscopy has been a powerful technique to probe molecular structures at non-centrosymmetric media. Recent developed heterodyne (HD) detection can further reveal spectral phase and molecular orientations. Adding imaging capability to an HD VSFG signal can bring spatial visualization capability into this non-linear optical technique. However, it has been a challenge to build an HD VSFG microscope that is both easy to align and has good spectral phase stability -two necessary criterions for the broad application of this technique into various areas of science. Here, we report a fully-collinear HD VSFG microscope, which meets both phase stability and optical alignment requirements that can spatially resolve images of molecular interfaces and domains, with chemical and structural sensitivities. The phase stability is more than nine times better than a Michelson Interferometric HD VSFG microscope. Using this HD VSFG microscope, we study the structures of molecular selfassembly films. Because of the superior phase sensitivity, we successfully identify two molecular domains with different molecular orientations, which we show is not possible to extract from an ensemble-averaged VSFG spectrum or homodyne-detected VSFG image.
Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines. Uni and Multivariate Cox regression analysis revealed that HOXA-AS3 was an independent prognostic factor in glioma patients. Gene set enrichment analysis indicated that the gene sets correlated with HOXA-AS3 expression were involved in cell cycle progression and E2F targets. Functionally, HOXA-AS3 silencing resulted in proliferation arrest by altering cell cycle progression and promoting cell apoptosis, and impaired cell migration in glioma cells. Furthermore, the growth-inhibiting effect of HOXA-AS3 knockdown was also demonstrated in Xenograft mouse model. Our results highlight the important role of HOXA-AS3 in glioma progression, and indicate that HOXA-AS3 may be served as a valuable prognostic biomarker for glioma.
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