The induction of polyploidy is an efficient technique for creating a diversity of genetic, phenotypic, and phytochemical novelties in plant taxa. Sage (Salvia officinalis L.) is a well-known medicinal plant rich of valuable bioactive molecules such as triterpenic and phenolic acids. In the present study, the effect of in vitro and in vivo polyploidization on morphological characteristics, anatomical structures, phytochemical traits, and expression level of the genes involved in the biosynthesis of major triterpenic acids (ursolic, betulinic, and oleanolic acids) of the plant was studied. The sterile seeds treated with different concentrations (0, 0.05, 0.1, and 0.2%) of colchicine for 24 and 48 h were considered for polyploidy induction. Flow cytometry and chromosome counting were used to confirm the ploidy level of diploid (2n = 2x = 14, 2C DNA = 1.10 pg) and tetraploid (2n = 4x = 28, 2C DNA = 2.12 pg) plants after seven months. The highest polyploidy induction was obtained by applying 0.1% (w/v) colchicine for 48 h with an efficiency of 19.05% in vitro tetraploidy. Polyploids showed differences in leaf shape and color, leaf and stem thickness, trichrome density, root length, plant height, and number of leaves compared to diploid plants. There was also a significant decrease in rosmarinic acid content in polyploid (plants) as compared to diploid plants. Although a significant decrease in ursolic acid content was observed in polyploids, betulinic acid content associated with the expression levels of genes encoding enzymes being active in triterpene biosynthesis such as squalene epoxidase (SQE) and lupeol synthase (LUS). The expression of SQE and LUS was significantly increased in in vitro tertaploids (2.9-fold) and in vivo mixoploids (2.4-fold). The results confirm the idea that induced polyploidy can randomly alter breeding traits of plants as well as the content of bioactive compounds.There is substantial evidence that GABAB agonist, baclofen, prevents somatic and motivational responses induced by nicotine withdrawal and may target drug cue vulnerabilities in humans. In this context, we explored different aspects associated with the possible mechanisms whereby the GABAB receptors might influence nicotine withdrawal. Male mice received nicotine (2.5 mg/kg, s.c.) 4 times daily, for 7 consecutive days. Nicotine-treated mice received the nicotinic acetylcholine receptor antagonist, mecamylamine (MEC, 2 or 3.5 mg/kg, s.c.), to precipitate the withdrawal state. A second group of dependent mice received 2-hydroxysaclofen (GABAB receptor antagonist, 1 mg/kg, s.c.) before MEC-precipitated abstinence. Somatic signs of nicotine withdrawal were measured for 30 min. Anxiogenic-like response associated to nicotine withdrawal was assessed by the elevated plus maze test. The dysphoric/aversive effect induced by nicotine withdrawal was evaluated using conditioned place aversion paradigm. Dopamine, serotonin and its metabolites concentrations were determined by HPLC in the striatum, cortex and hippocampus. Finally, α4β2 nicotinic acetylcholine receptor density was determined in several brain regions using autoradiography assays. The results showed that MEC-precipitated nicotine withdrawal induced somatic manifestations, anxiogenic-like response and dysphoric/aversive effect, and 2-hydroxysaclofen potentiated these behavioral responses. Additionally, 2-hydroxysaclofen was able to change striatal dopamine levels and α4β2 nicotinic acetylcholine receptor density, both altered by MEC-precipitated nicotine withdrawal. These findings provide important contributions to elucidate neurobiological mechanisms implicated in nicotine withdrawal. We suggest that GABAB receptor activity is necessary to control alterations induced by nicotine withdrawal, which supports the idea of targeting GABAB receptors to treat tobacco addiction in humans. Immune checkpoint inhibitors (ICIs) are standard of care in advanced non-small cell lung cancer (NSCLC), however their status in patients with poor performance status (PS) is poorly defined. We aimed to evaluate the efficacy and safety of ICIs in NSCLC patients with PS ≥ 2. We conducted a systematic review and meta-analysis of interventional and observational studies, which reported efficacy and safety data on ICIs in PS ≥ 2 comparing to PS ≤ 1 NSCLC patients. Efficacy endpoints included Objective Response Rate (ORR), Disease-Control Rate (DCR), Overall Survival (OS), Progression-Free Survival (PFS). Safety endpoint was the incidence of severe (grade≥3) Adverse Events (AE). Random-effects model was applied for meta-analysis. Heterogeneity was assessed using I . The review is registered on PROSPERO (CRD42020162668). Sixty-seven studies (n = 26,442 patients) were included. In PS ≥ 2 vs. PS ≤ 1 patients, the pooled odds ratios were for ORR 0.46 (95 %CI 0.39-0.54, I 0 %); for DCR 0.39 (95 %CI 0.33-0.48, Idies are indispensable to determine whether poor PS patients derive benefit from ICIs.Compared to others, individuals living in communities of socioeconomic disadvantage experience more atherosclerotic cardiovascular disease (CVD) and a greater extent of preclinical atherosclerosis. Although the mechanisms underlying these associations remain unclear, it is widely hypothesized that alterations in normative cortisol release from the Hypothalamic Pituitary Adrenal (HPA) axis may play a role in linking lower community socioeconomic position (C-SEP) to CVD risk. The current study examined this hypothesis in relation to a marker of preclinical atherosclerosis among 488 healthy midlife adults (30-54 years, Mean age= 43, 52% Female, 81% White). All participants were employed and without clinical CVD. C-SEP was estimated from census tract data, and atherosclerosis was measured as intima-medial thickness of the carotid arteries (cIMT) by duplex ultrasonography. https://www.selleckchem.com/products/piperlongumine.html Four indicators of HPA activity [cortisol at awakening and the cortisol awakening response (CAR), rate of diurnal decline in cortisol (diurnal to -0.004). These results suggest that low C-SEP associations with preclinical atherosclerosis may be due in part to correlated variation in adrenocortical activity.