Classical molecular dynamics simulations were performed to investigate the effects of salt on the lower critical solution temperature (LCST) of Poly (N-isopropylacrylamide) (PNIPAM). PNIPAM is often studied as a protein proxy due to the presence of a peptide bond in its monomer unit. PNIPAM is a temperature sensitive polymer which exhibits hydrophobic-hydrophilic phase transition at its LCST. The presence of salt in the solution will shift its LCST, typically to a lower temperature. This LCST shift follows the so-called Hofmeister series. Molecular dynamics (MD) simulations of PNIPAM in 1 M of NaCl, NaBr, NaI, and KCl were carried out to elucidate the effects of different salt on LCST and protein stability. Our results suggest that direct interactions between the salt cations and the polymer play a critical role in the shift of LCST and subsequently on protein stability. Further, cations have a much stronger affinity with the polymer, whereas anions bind weakly with the polymer. Moreover, the cation-polymer binding affinity is inversely correlated with the cation-anion contact pair association constant in solution.

Dehydration of neutral and protonated glycerol was investigated using quantum mechanical calculations (CBS-QB3). Calculations on neutral glycerol show that there is a high barrier for simple 1,2-dehydration, E(a)=70.9 kcal mol(-1), which is lowered to 65.2 kcal mol(-1) for pericyclic 1,3-dehydration. In contrast, the barriers for dehydration of protonated glycerol are much lower. Dehydration mechanisms involving hydride transfer, pinacol rearrangement, or substitution reactions have barriers between 20 and 25 kcal mol(-1). Loss of water from glycerol via substitution results in either oxirane or oxetane intermediates, which can inter-convert over a low barrier. Subsequent decomposition of these intermediates proceeds via either a second dehydration step or loss of formaldehyde. The computed mechanisms for decomposition of protonated glycerol are supported by the gas-phase fragmentation of protonated glycerol observed using a triple--quadrupole mass spectrometer.

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Background Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. Methods A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/ lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. Result NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. Conclusion In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.