The transcription nuclear factor-erythroid factor 2-related factor 2 (Nrf2) plays a key role in inflammation that is involved in depression. We previously reported that Nrf2 knock-out (KO) mice exhibit depression-like phenotypes through systemic inflammation. (R)-ketamine, an enantiomer of ketamine, has rapid-acting and long-lasting antidepressant-like effects in rodents. We investigated whether (R)-ketamine can produce antidepressant-like effects in Nrf2 KO mice. Effects of (R)-ketamine on the depression-like phenotypes in Nrf2 KO mice were examined. Furthermore, the role of TrkB in the antidepressant-like actions of (R)-ketamine was also examined. In the tail-suspension test (TST) and forced swimming test (FST), (R)-ketamine (10 mg/kg) significantly attenuated the increased immobility times of TST and FST in the Nrf2 KO mice. In the sucrose preference test (SPT), (R)-ketamine significantly ameliorated the reduced preference of SPT in Nrf2 KO mice. Decreased expression of synaptic proteins (i.e., GluA1 and PSD-95) in the medial prefrontal cortex (mPFC) of Nrf2 KO mice was significantly ameliorated after a single injection of (R)-ketamine. Furthermore, the pre-treatment with the TrkB antagonist ANA-12 (0.5 mg/kg) significantly blocked the rapid and long-lasting antidepressant-like effects of (R)-ketamine in Nrf2 KO mice. Furthermore, ANA-12 significantly antagonized the beneficial effects of (R)-ketamine on decreased expression of synaptic proteins in the mPFC of Nrf2 KO mice. These findings suggest that (R)-ketamine can produce rapid and long-lasting antidepressant-like actions in Nrf2 KO mice via TrkB signaling.To investigate the genetic variation and forensic efficiency of 16 X-chromosomal short tandem repeat (X-STR) loci (DX6795, DXS9902, DXS8378, HPRTB, GATA165B12, DXS7132, DXS7424, DXS6807, DXS6803, GATA172D05, DXS6800, DXS10134, GATA31E08, DXS10159, DXS6789, and DXS6810) in the Bai minority, we calculated allele frequencies, forensic parameters, and haplotype frequencies in 424 (202 males and 222 females) unrelated, healthy Bai individuals from Dali Bai Autonomous Prefecture in Yunnan Province, China. We observed a total of 132 alleles; 5-19 alleles were detected in each locus, and the corresponding allele frequencies ranged from 0.0016 to 0.7589. All of the loci detected were highly polymorphic in the Bai population in Yunnan Province, except DXS6800. The values for the combined power of discrimination in females (PDf) and males (PDm) were 0.999999999999996 and 0.999999997487061, respectively. According to a phylogenetic tree, neighboring populations and different nationalities in the same area appeared to have relatively close evolutionary relationships. This study provides and complements X-chromosome genetic polymorphism data for the Bai people in Yunnan Province, Southwest China, and enriches the available reference materials for this Chinese minority population.In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples.The shape of the length frequency distribution (LFD) is an important input for stock assessments and one of the most important features in studies of fish population dynamics, providing estimates of growth parameters. read more In practice, oversampling may occur when sampling commercially important species. At times of more and more limited resources, the length sample size can be optimized at some stages of national or regional sampling programmes, without reducing the quality of stock assessments. The main objective of this study is to demonstrate a general distribution-free methodological approach for an optimization of sample size developed as an alternative to both analytical and bootstrap approaches. A novel framework to identify the reduced but still informative sample and to quantify the (dis) similarity between reduced and original samples is proposed. The identification procedure is based on the concept of reference subsample, which represents a theoretical minimal representative subsample that despite smaller sample size still preserves a reasonably precise LFD for certain species. The difference between the original sample and the reference subsample called admissible dissimilarity value (ADV) serves as the upper threshold and can be used to quantify the reliability of derived subsamples. Monte Carlo simulations were conducted to validate the approach under various LFD shapes. We illustrate in case studies how ADV can support to evaluate adequate sampling effort. The case studies focus on length samples from the German commercial vessels fishing for North Sea cod (Gadus morhua).Proprotein convertase subtilisin/Kexin type 9 (PCSK9) and pyroptosis both play important roles in myocardial infarction. This study was designed to test the hypothesis that PCSK9 regulates pyroptosis in cardiomyocytes during chronic myocardial ischemia. Primary cardiomyocytes were isolated from WT and PCSK9-/- mice. HL-1 cardiomyocytes were used to set up PCSK9-deficient (PCSK9-/-) and PCSK9-upregulated (PCSK9CRISPRa) cardiomyocyte cell line with CRISPR/Cas9 knockout or activation plasmid. Additional studies were performed with chronic myocardial ischemia in WT and PCSK9-/- mice. We observed that PCSK9 initiates mitochondrial DNA (mtDNA) damage, activates NLRP3 inflammasome signaling (NLRP3, ASC, Caspase-1, IL-1β, and IL-18), and subsequently induces Caspase-1-dependent pyroptosis. There was an intense expression of PCSK9 and pyroptosis marker, GSDMD-NT, in the zone bordering the infarct area. PCSK9-/- significantly suppressed expression of NLRP3 inflammasome signaling, GSDMD-NT, and LDH release. Furthermore, serum levels of PCSK9, NLPR3 inflammasome signaling, and pyroptosis (GSDMD and LDH release) were significantly elevated in patients with chronic myocardial ischemia as compared to those in age-matched healthy subjects.