Cobalt-catalyzed amination of aziridines and azetidines toward 1,2- and 1,3-diamines.

Diamines play important roles in synthetic organic chemistry and thus facilitate life and materials sciences. Herein we report a cobalt-catalyzed ring opening, nucleophilic amination of aziridines and azetidines with N-fluorosulfonamides toward a wide range of 1,2- and 1,3-diamine derivatives in moderate to good yields under mild conditions.

Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm.

Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.

NKX6-1 Is a Less Sensitive But Specific Biomarker of Chromophobe Renal Cell Carcinoma.

NKX6-1 is a transcription factor that plays a key role in the development, differentiation, and identity maintenance of beta cells of pancreatic islets. Although NKX6-1 expression has also been discovered in pancreatic well-differentiated neuroendocrine tumors (WDNETs) and duodenal WDNETs, its expression in chromophobe renal cell carcinoma (chRCC) is unexplored. Analysis of mRNA expression and immunohistochemistry of NKX6-1 was performed using the kidney cancer cohort from The Cancer Genome Atlas (TCGA) and paraffin-embedded whole-tissue slides from our 196 collected cases, including 48 chRCCs (43 classic and 5 eosinophilic subtypes), 24 renal oncocytomas (ROs), 46 clear cell renal cell carcinomas, 41 papillary renal cell carcinomas, 14 renal urothelial carcinomas, 7 low-grade oncocytic renal tumors (LOTs), 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. NKX6-1 expression was almost exclusively upregulated in chRCC at both the mRNA and protein levels compared with other renal tumors. NKX6-1 was immunohistochemically positive in 39 of 48 (81.3%) chRCCs, but negative in 46 clear cell renal cell carcinomas, 24 ROs, 7 low-grade oncocytic renal tumors, 8 eosinophilic solid and cystic renal cell carcinomas, 3 succinate dehydrogenase-deficient renal cell carcinomas, and 5 renal oncocytic tumors, not otherwise specified. Diffuse, moderate, and focal NKX6-1 staining were seen in 21, 4, and 14 of the 39 chRCCs, respectively. In contrast, NKX6-1 was focally positive in only 1 of 41 (2.4%) papillary renal cell carcinomas and 2 of 14 (14.3%) renal urothelial carcinomas. Therefore, the sensitivity and specificity of NKX6-1 staining were 81.3% and 98% for chRCC, respectively. In conclusion, NKX6-1 may be a novel potential marker for differentiating chRCC from other renal neoplasms, especially from RO.