Moreover, increased adjuvant TMZ cycles corresponded with improved volumetric response only among more nodular tumors, and this volumetric response was associated with improved survival outcomes. Finally, in a subcohort of patients with known MGMT methylation status, methylated tumors were more diffusely invasive than unmethylated tumors, suggesting the improved response in nodular tumors is not driven by a preponderance of MGMT methylated tumors. CONCLUSIONS Our finding that less diffusely invasive tumors are associated with greater volumetric response to TMZ suggests patients with these tumors may benefit from additional adjuvant TMZ cycles, even for those without MGMT methylation.INTRODUCTION Epidemiologically, cigarette smoking is a well-known risk factor for the pathogenesis of rheumatoid arthritis (RA). However, there has been few plausible explanations why cigarette smoking aggravated RA. We investigated the causal effect of smoking in experimental model of arthritis development. METHODS During induction of experimental arthritis with collagen challenge, mice were exposed to a smoking environment with 3R4F cigarettes. Generated smoke was delivered to mice through a nose-only exposure chamber (ISO standard 3308). Human cartilage pellet was challenged by cigarette smoke extract to identify citrullinating potential in vitro. RESULTS Cigarette smoke exacerbated arthritis in a collagen-induced arthritis (CIA) model. Exposure to smoke accelerated the onset of arthritis by 2 weeks compared to the conventional model without smoke. Citrullination of lung tissue as well as tarsal joints were revealed in smoke-aggravated CIA mice. Interestingly, tracheal cartilage was a core organ regarding intensity and area size of citrullination. The trachea might be an interesting organ in viewpoint of sharing cartilage with joint and direct smoke exposure. Anti-CCP antibodies were barely detected in the serum of CIA mice, they were significantly elevated in cigarette smoke group. Citrullinated antigens were increased in the serum of smoke-exposed mice. Lastly, a cigarette smoke extract enhanced human cartilage citrullination in vitro. CONCLUSIONS Missing link of arthritic mechanism between smoke and RA could be partially explained by tracheal citrullination. To control tracheal cartilage citrullination may be beneficial for preventing arthritis development or aggravation if cigarette smoke is becoming a risk factor to pre-arthritic individual.BACKGROUND To estimate the potential gain in life expectancy from addressing modifiable risk factors for all-cause mortality (excluding suicide and deaths from accidents or violence) across specific serious mental illness (SMI) subgroups, namely schizophrenia, schizoaffective disorders, and bipolar disorders in a Western population. METHODS We have used relative risks from recent meta-analyses to estimate the population attribution fraction (PAF) due to specific modifiable risk factors known to be associated with all-cause mortality within SMI. The potential gain in life expectancy at birth, age 50 and age 65 years were assessed by estimating the combined effect of modifiable risk factors from different contextual levels (behavioural, healthcare, social) and accounting for the effectiveness of existing interventions tackling these factors. Projections for annual gain in life expectancy at birth during a two-decade was estimated using the Annual Percentage Change (APC) formula. The predicted estimates were based on mortality rates for year 2014-2015. RESULTS Based on the effectiveness of existing interventions targeting these modifiable risk factors, we estimated potential gain in life expectancy at birth of four (bipolar disorders), six (schizoaffective disorders), or seven years (schizophrenia). The gain in life expectancy at age 50 years was three (bipolar disorders) or five (schizophrenia and schizoaffective disorders) years. The projected gain in life expectancy at age 65 years was three (bipolar disorders) or four (schizophrenia and schizoaffective disorders) years. CONCLUSIONS The implementation of existing interventions targeting modifiable risk factors could narrow the current mortality gap between the general and the SMI populations by 24% (men) to 28% (women). These projections represent ideal circumstances and without the limitation of overestimation which often comes with PAFs.Lentinula edodes is one of the most popular edible mushrooms worldwide and contains important medicinal components such as lentinan, ergosterol, and eritadenine. Mushroom metabolism is regulated by the mycelia and fruit body using light; however, in mushrooms, the underlying molecular mechanisms controlling this process as well as light-induced gene expression remain unclear. Therefore, in this study, we compared morphological changes and gene expression in the fruit bodies of L. edodes cultivated under blue light and continuous darkness. Our results showed that blue light primarily induced pileus growth (diameter and thickness) compared to dark cultivation. Alternatively, stipe length development was promoted by dark cultivation.  https://www.selleckchem.com/products/apcin.html  We also performed RNAseq on L. edodes under the blue light/dark cultivation conditions. A total of 12,051 genes were used for aligning the Illumina raw reads and 762 genes that showed fold change cut-offs of >|2| and significance p-values of less then 0.05 were selected under blue light condition. Among the genes which showed two-fold changed genes, 221 were upregulated and 541 were downregulated. In order to identify blue light induced candidate genes, differentially expressed genes (DEGs) were selected according to 4-fold changes and validated by RT-PCR. We identified 8 upregulated genes under blue light condition, such as DDR48-heat shock protein, Fasciclin-domain-containing protein and carbohydrate esterase family 4 protein, FAD NAD-binding domain-containing protein that are involved in morphological development of primordium and embryonic muscle development, cell adhesion and affect the structure of cellulosic and non-cellulosic cell walls of fruit body development, and photoreceptor of blue light signaling for fruit body and pigment development, respectively. This study provides valuable insights into the molecular mechanisms underlying the role of blue light in mushroom growth and development and can thus contribute to breeding programs to improve mushroom cultivation.