Manganese-Catalyzed Mono-N-Methylation of Aliphatic Primary Amines without the Requirement of External High-Hydrogen Pressure.

The synthesis of mono-N-methylated aliphatic primary amines has traditionally been challenging, requiring noble metal catalysts and high-pressure H2 for achieving satisfactory yields and selectivity. Herein, we developed an approach for the selective coupling of methanol and aliphatic primary amines, without high-pressure hydrogen, using a manganese-based catalyst. Remarkably, up to 98 % yields with broad substrate scope were achieved at low catalyst loadings. Notably, due to the weak base-catalyzed alcoholysis of formamide intermediates, our novel protocol not only obviates the addition of high-pressure H2 but also prevents side secondary N-methylation, supported by control experiments and density functional theory calculations.

Genomic alterations of cerebrospinal fluid cell-free DNA in leptomeningeal metastases of gastric cancer.

BACKGROUND: Leptomeningeal metastases (LM) were rare in gastric cancer (GC), and GC patients with LM (GCLM) generally suffer from poor prognosis. Nevertheless, the clinical utility of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) was underinvestigated in GCLM. METHODS: We retrospectively studied 15 GCLM patients, and all patients had paired primary tumor tissue samples and post-LM CSF samples while 5 patients also had post-LM plasma samples. All samples were analyzed using next-generation sequencing (NGS), and the molecular and clinical features were correlated with clinical outcomes. RESULTS: CSF had higher mutation allele frequency (P = 0.015), more somatic mutations (P = 0.032), and more copy-number variations (P < 0.001) than tumor or plasma samples. Multiple genetic alterations and aberrant signal pathways were enriched in post-LM CSF, including CCNE1 amplification and cell cycle-related genes, and CCNE1 amplification was significantly associated with patients' overall survival (P = 0.0062). More potential LM progression-related markers were detected in CSF samples than in tumor samples, including PREX2 mutation (P = 0.014), IGF1R mutation (P = 0.034), AR mutation (P = 0.038), SMARCB1 deletion (P < 0.001), SMAD4 deletion (P = 0.0034), and TGF-beta pathway aberration (P = 0.0038). Additionally, improvement in intracranial pressure (P < 0.001), improvement in CSF cytology (P = 0.0038), and relatively low levels of CSF ctDNA (P = 0.0098) were significantly associated with better PFS. Lastly, we reported a GCLM case whose CSF ctDNA dynamic changes were well correlated with his clinical assessment. CONCLUSIONS: CSF ctDNA could more sensitively detect molecular markers and metastasis-related mechanisms than tumor tissues in GCLM patients, and our study sheds light on utilizing CSF ctDNA in prognostic estimation and clinical assessment in GCLM.

Establishment of human induced pluripotent stem cell line from dermal fibroblasts of a healthy individual.

Human-induced pluripotent stem cells (hiPSCs) are used to establish patient-specific cell lines and organs which are ideal models to mirror the pathological features of diseases in vitro and also, investigate the underlying mechanisms. It is essential to generate wild-type hiPSCs lines to optimize differentiation protocol and be also used, possibly, for cell therapy. In this study, hiPSCs were generated from the dermal fibroblasts of a 78-year-old healthy female individual using the non-genetic-integrated Sendai virus protocol, and characterized using standard validated methods.

Suppression of lncRNA SNHG15 protects against cerebral ischemia-reperfusion injury by targeting miR-183-5p/FOXO1 axis.

BACKGROUND: Cerebral ischemia/reperfusion (I/R) injury is a severe complication during the treatment of patients with stroke. It has been shown that the expression of SNHG15 was increased in patients with ischemic stroke (IS). However, the function and regulatory mechanism of SNHG15 in IS remains unclear. METHODS: An oxygen glucose deprivation/reoxygenation (OGD/R) cell model was use to establish an in vitro model of I/R injury. RT-qPCR assay was used to detect the level of SNHG15 in OGD/R-treated SH-SY5Y cells. Meanwhile, middle cerebral artery occlusion (MCAO) was used to establish an in vivo model of cerebral I/R injury. RESULTS: The expression of SNHG15 was upregulated in OGD/R-treated SH-SY5Y cells. Downregulation of SNHG15 during reperfusion reduced cell death in OGD/R-treated SH-SY5Y cells. In addition, SNHG15 knockdown suppressed OGD/R-induced apoptosis in SY-SY5Y cells by attenuating intracellular ROS generation and reducing mitochondrial membrane potential (MMP) lost. In addition, SNHG15 knockdown promoted cell cycle transition in SY-SY5Y cells after OGD/R insult accompany with PI3K/Akt signaling activation. Meanwhile, mechanism investigations suggested SNHG15 knockdown downregulated the expression of FOXO1 through acting as a competitive 'sponge' of miR-183-5p. Most importantly, knockdown of SNHG15 expression in vivo inhibited neuronal apoptosis and decreased infarct area in MCAO rats. CONCLUSION: Thus, the present study indicated that SNHG15 knockdown protected against cerebral I/R injury via targeting miR-183-5p/FOXO1 axis, which may represent a potential therapeutic option for the treatment of cerebral IS.