System components were evaluated in various scenarios including different environmental and weather conditions.This study aims to evaluate the risk assessment approach of the REACH legislation in industrial chemical departments with a focus on the use of three models to calculate exposures, and discuss those factors that can determine a bias between the estimated exposure (and therefore the expected risk) in the extended safety data sheets (e-SDS) and the expected exposure for the actual scenario. To purse this goal, the exposure estimates and risk characterization ratios (RCRs) of registered exposure scenarios (ES; "communicated exposure" and "communicated RCR") were compared with the exposure estimates and the corresponding RCRs calculated for the actual, observed ES, using recommended tools for the evaluation of exposure assessment and in particular the following tools (i) the European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment v.3.1 (ECETOC TRA), (ii) STOFFENMANAGER® v.8.0 and (iii) the Advanced REACH Tool (ART). We evaluated 49 scenarios in three companies handling chemicals. Ries of chemical risk.Ca2+-signaling-which requires the presence of calcium sensors such as calmodulin (CaM) and calmodulin-like (CML) proteins-is crucial for the regulation of plant immunity against pathogen attack. However, the underlying mechanisms remain elusive, especially the roles of CMLs involved in plant immunity remains largely uninvestigated. In the present study, CaCML13, a calmodulin-like protein of pepper that was originally found to be upregulated by Ralstonia solanacearum inoculation (RSI) in RNA-seq, was functionally characterized in immunity against RSI. CaCML13 was found to target the whole epidermal cell including plasma membrane, cytoplasm and nucleus. We also confirmed that CaCML13 was upregulated by RSI in pepper roots by quantitative real-time PCR (qRT-PCR). The silencing of CaCML13 significantly enhanced pepper plants' susceptibility to RSI accompanied with downregulation of immunity-related CaPR1, CaNPR1, CaDEF1 and CabZIP63. In contrast, CaCML13 transient overexpression induced clear hypersensitivity-reaction (HR)-mimicked cell death and upregulation of the tested immunity-related genes. In addition, we also revealed that the G-box-containing CaCML13 promoter was bound by CabZIP63 and CaCML13 was positively regulated by CabZIP63 at transcriptional level. selleck chemical Our data collectively indicate that CaCML13 act as a positive regulator in pepper immunity against RSI forming a positive feedback loop with CabZIP63.Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-γ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-β) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures.Background and objectives Diabetes mellitus (DM) stands out among the most important public health problems worldwide since it represents a high burden on health systems and is associated with higher hospitalization rates, and a higher incidence of cardiovascular diseases. Amputations are among the most common complications, leading to disability and increasing care costs. This research aims to analyze the prevalence of DM-related amputations, comorbidities and associated risk factors in the diabetic population residing in the State of Espírito Santo, Brazil. Materials and Methods This is a quantitative, exploratory, cross-sectional study with a time series design and the use of secondary data registered and followed by the system of Registration and Monitoring of Hypertension and Diabetes-SisHiperdia. Results The sample consisted of 64,196 diabetic patients, out of them, 3.9% had type 1 DM, 10.9% with type 2 DM, and 85.2% with DM coexisting with hypertension. Most were female (66.6%), aged 40 to 59 years (45.6%), and 60 years and older (45.2%). The prevalence of DM-related amputations in the analyzed sample was 1.2% in type 1 DM, 1.5% in type 2 DM, and 2.2% in concomitant DM and hypertension. Higher amputation rates were observed in males in the age group above 60 years in type 1 DM and type 2 DM and were slightly higher in the age groups up to 29 years in DM with hypertension. A higher prevalence of amputation was related to smoking, physical inactivity, acute myocardial infarction (AMI), stroke, chronic kidney disease (CKD), and diabetic foot (DF) in all types of DM. Conclusions The present study showed a significant prevalence of DM-related amputations. An increased prevalence was evidenced when correlated with smoking, physical inactivity, AMI, stroke, CKD, and DF with significant statistical associations, except for a sedentary lifestyle in type 1 DM.