Cytochrome P450 1A2 (CYP1A2) is one of the main hepatic CYPs involved in metabolism of carcinogens and clinically used drugs. Nonsynonymous single nucleotide polymorphisms (nsSNPs) of this enzyme could affect cancer susceptibility and drug efficiency. Hence, identification of human CYP1A2 pathogenic nsSNPs could be of great importance in personalized medicine and pharmacogenetics. Here, 176 nsSNPs of human CYP1A2 were evaluated using a variety of computational tools, of which 18 nsSNPs were found to be associated with pathogenicity. Further analysis suggested possible association of 9 nsSNPs (G73R, G73W, R108Q, R108W, E168K, E346K, R431W, F432S and R456H) with the risk of hepatocellular carcinoma. Molecular dynamics simulations revealed higher overall flexibility, decreased intramolecular hydrogen bonds and lower content of regular secondary structures for both cancer driver variants G73W and F432S when compared to the wild-type structure. In case of F432S, loss of the conserved hydrogen bond between Arg137 and heme propionate oxygen may affect heme stability and the observed significant rise in fluctuation of the CD loop could modify CYP1A2 interactions with its redox partners. Together, these findings propose CYP1A2 as a possible candidate for hepatocellular carcinoma and provide structural insights into how cancer driver nsSNPs could affect protein structure, heme stability and interaction network.Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial lung disease of unknown cause. It has a high risk of rapid progression and mortality. We conducted a systematic review and meta-analysis to evaluate the risk factor of IPF. We searched Medline, Embase, and the Cochrane library from the earliest record to March, 2020. Case-control studies on occupational and environmental risk factors or on jobs with a risk of IPF were searched for. From 2490 relevant records, 12 studies were included. Any occupational or environmental exposure to metal dust (OR 1.83, 95% CI 1.15-2.91, I2 = 54%), wood dust (OR 1.62 5% CI 1.04-2.53, I2 = 5%) and pesticide (OR 2.07, 95% CI 1.24-3.45, I2 = 0%) were associated with an increased risk of IPF. Farming or agricultural work (OR 1.88, 95% CI 1.17-3.04, I2 = 67%) was also associated with an increased risk of IPF. Moreover, smoking increased IPF risk with an odds ratio of 1.39 (95% CI 1.01-1.91, I2 = 29%). In conclusion, metal dust, wood dust, pesticide, occupational history of farming or agriculture and ever smoking increased the risk of IPF.Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the basal ganglia (BG) and thalamocortical circuitry. While defective motor control has long been considered the defining symptom of PD, mounting evidence indicates that the BG are fundamentally important for a multitude of cognitive, emotional, and motivational processes in addition to motor function. Here, we review alterations in moral decision-making in people with PD, specifically in the context of deceptive behavior. We report that PD patients exhibit two opposite behavioral patterns hyper- and hypo-honesty. https://www.selleckchem.com/products/tak-243-mln243.html The hyper-honest subgroup engages in deception less often than matched controls, even when lying is associated with a monetary payoff. This behavioral pattern seems to be linked to dopaminergic hypo-activity, implying enhanced harm avoidance, risk aversion, non-impulsivity, and reduced reward sensitivity. On the contrary, the hypo-honest subgroup-often characterized by the additional diagnosis of impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS)-deceives more often than both PD patients without ICDs/DDS and controls. This behavioral pattern appears to be associated with dopaminergic hyperactivity, which underpins enhanced novelty-seeking, risk-proneness, impulsivity, and reward sensitivity. We posit that these two complementary behavioral patterns might be related to dysfunction of the dopaminergic reward system, leading to reduced or enhanced motivation to deceive. Only a few studies have directly investigated moral decision-making in PD and other neurodegenerative disorders affecting the BG, and further research on the causal role of subcortical structures in shaping moral behavior is needed.Density functional theory method combined with docking and molecular dynamics simulations are used to understand the interaction of carmustine with human glutathione reductase enzyme. The active site of the enzyme is evaluated by docking simulation is used for molecular dynamics simulation to deliver the carmustine molecule by (5,5) single walled carbon nanotube (SWCNT). Our model of carmustine in the active site of GR gives a negative binding energy that is further refined by QM/MM study in gas phase and solvent phase to confirm the stability of the drug molecule inside the active site. Once released from SWCNT, carmustine forms multiple polar and non-polar hydrogen bonding interactions with Tyr180, Phe209, Lys318, Ala319, Leu320, Leu321, Ile350, Thr352 and Val354 in the range of 2-4 Å. The SWCNT vehicle itself is held fix at its place due to multiple pi-pi stacking, pi-amide, pi-sigma interactions with the neighboring residues. These interactions in the range of 3-5 Å are crucial in holding the nanotube outside the drug binding region, hence, making an effective delivery. This study can be extended to envisage the potential applications of computational studies in the modification of known drugs to find newer targets and designing new and improved controlled drug delivery systems.Despite the widespread applications of C-H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-C-H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C-H functionalization introduction of DG prior to C-H activation and removal of DG post-functionalization. Here we report a temporary directing group (TDG) for meta-C-H functionalization via reversible imine formation. By overruling facile ortho-C-H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C-C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored.