No abstract

Manganese(iii) hexadentate Schiff base complexes ([Mn(sal-N-1,5,8,12)]Y·S, Y = AsF (1); Y = SbF (2); Y = NO, S = CHOH (3) and Y = Cl (4)) have been investigated to determine the impact of anion effects, intramolecular ligand distortions, and intermolecular supramolecular structures on the spin crossover (SCO) behavior. The crystal structure of [Mn(sal-N-1,5,8,12)]PF, a complex known to exhibit an abrupt SCO behavior with an 8 K hysteresis window, reveals that this complex has a temperature-dependent anion order-disorder transition that disrupts the hydrogen-bonding chain upon SCO, indicating that hydrogen bonds between cations and anions greatly influence the magnetic properties. The SCO in 1 is mediated by intermolecular hydrogen-bonding interactions. The subtle balance of these hydrogen bonds induces a cooperative SCO process with a hysteresis width of 18 K, which is the largest one reported in the d SCO chemistry. For 2, crystal structural analysis indicates that changing the anion from AsF to SbF led to close stackings between phenyl groups from ligands. These stackings preclude the spin transition of the [Mn(sal-N-1,5,8,12)] cations. With NO and Cl as counterions, the [Mn(sal-N-1,5,8,12)] cations are arranged more loosely and exhibit gradual SCO in the temperature range of 300-100 K. Careful evaluation of the supramolecular structures of these complexes and similar complexes reported previously revealed strong correlation between the supramolecular packing forces and their magnetic properties.

Nitric oxide (NO)-induced apoptosis in neurons is an important cause of neurodegenerative disease in humans. The cold-inducible protein RBM3 mediates the protective effects of cooling on apoptosis induced by various insults. However, whether RBM3 protects neural cells from NO-induced apoptosis is unclear. This study aimed to investigate the neuroprotective effect of RBM3 on NO-induced apoptosis in human SH-SY5Y neuroblastoma cells. Firstly, we demonstrated that mild hypothermia (32 °C) induces RBM3 expression and confers a potent neuroprotective effect on NO-induced apoptosis, which was substantially diminished when RBM3 was silenced by siRNA. Moreover, overexpression of RBM3 exhibited a strong protective effect against NO-induced apoptosis. Signaling pathway screening demonstrated that only p38 inhibition by RBM3 provided neuroprotective effect, although RBM3 overexpression could affect the activation of p38, JNK, ERK, and AKT signaling in response to NO stimuli. Notably, RBM3 overexpression also blocked the activation of p38 signaling induced by transforming growth factor-β1. Furthermore, both RBM3 overexpression and mild hypothermia abolished the induction of miR-143 by NO, which was shown to mediate the cytotoxicity of NO in a p38-dependent way. These findings suggest that RBM3 protects neuroblastoma cells from NO-induced apoptosis by suppressing p38 signaling, which mediates apoptosis through miR-143 induction.

Background Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal tumor. However, the molecular mechanisms of KIRC pathogenesis remain little known. The purpose of our study was to identify potential key genes related to the occurrence and prognosis of KIRC, which could serve as novel diagnostic and prognostic biomarkers for KIRC. Methods Three gene expression profiles from gene expression omnibus database were integrated to identify differential expressed genes (DEGs) using limma package. Enrichment analysis and PPI construction for these DEGs were performed by bioinformatics tools. We used Gene Expression Profiling Interactive Analysis (GEPIA) database to further analyze the expression and prognostic values of hub genes. The GEPIA database was used to further validate the bioinformatics results. The Connectivity Map was used to identify candidate small molecules that could reverse the gene expression of KIRC. Results A total of 503 DEGs were obtained. The PPI network with 417 nodes and 1912 interactions was constructed. Go and KEGG pathway analysis revealed that these DEGs were most significantly enriched in excretion and valine, leucine, and isoleucine degradation, respectively. Six DEGs with high degree of connectivity ( ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA ) were selected as hub genes, which significantly associated with worse survival of patients. Finally, we identified the top 20 most significant small molecules and pipemidic acid was the most promising small molecule to reverse the KIRC gene expression. Conclusions This study first uncovered six key genes in KIRC which contributed to improving our understanding of the molecular mechanisms of KIRC pathogenesis. ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA could serve as the promising novel biomarkers for KIRC diagnosis, prognosis, and treatment.