The ExpiCHO-S expression system consistently produced high-yield recombinant NLRP3 inflammasome proteins which led to a further understanding of ASC oligomerization.Obesity is associated with increased risk of oxidative stress in humans and laboratory animals but information regarding obesity-induced oxidative stress in birds is lacking. Therefore, this study aimed to investigate the influence of high-energy diets (HED) on obesity and oxidative stress in domestic pigeons. Forty-five adult clinically healthy-domestic male pigeons were randomly assigned to three equal dietary groups including low (2,850 kcal/kg), medium (3,150 kcal/kg) and high (3,450 kcal/kg) energy diets (named low energy diet, medium-energy diet and HED, respectively). All birds received formulated diets for 60 consecutive days. Several parameters such as feed intake, body weight (BW), average weight gain (AWG) and total weight gain were determined. Serum concentrations of triglyceride (TG), total cholesterol (TC), high-, low- and very-low-density lipoprotein cholesterols, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were evaluated at days 0, 30 and 60; and serum levels of total antioxidant capacity (T-AOC), malondialdehyde (MDA) and cortisol were also measured at day 60. On day 60, five pigeons from each group were randomly euthanized and some parameters such as weight and relative weight of liver, breast muscle, and abdominal fat were determined. Furthermore, hepatic total fat content was also evaluated. BW, AWG, total weight, and circulating TG, TC, ALT, AST, ALP, MDA and cortisol in HED were significantly higher than other groups. Serum T-AOC in HED was significantly lower than the other groups. In conclusion, this study showed that increasing dietary energy up to 3,450 kcal/kg in pigeons led to obesity and oxidative stress in them. Accordingly, it could be stated that HED and obesity induce oxidative stress in pigeon and controlling the dietary energy intake of pigeons is necessary to prevent oxidative stress in them.
  In high grade serous ovarian cancer (HGSOC), there is a spectrum of sensitivity to first line platinum-based chemotherapy. This study molecularly characterizes HGSOC patients from two distinct groups of chemotherapy responders (good vs. poor).
 
  Following primary debulking surgery and intravenous carboplatin/paclitaxel, women with stage III-IV HGSOC were grouped by response.  https://www.selleckchem.com/ALK.html  Patients in the good response (GR) and poor response (PR) groups respectively had a progression-free intervals (PFI) of ≥12 and ≤6months. Analysis of surgical specimens interrogated genomic and immunologic features using whole exome sequencing. RNA-sequencing detected gene expression outliers and inference of immune infiltrate, with validation by targeted NanoString arrays. PD-L1 expression was scored by immunohistochemistry (IHC).
 
  A total of 39 patient samples were analyzed (GR=20; PR=19). Median PFI for GR and PR patient cohorts was 32 and 3months, respectively. GR tumors were enriched for loss-of-function BRCA2 mutations and had a significantly higher nonsynonymous mutation rate compared to PR tumors (p=0.001). Samples from the PR cohort were characterized by mutations in MGA and RAD51B and trended towards a greater rate of amplification of PIK3CA, MECOM, and ATR in comparison to GR tumors. Gene expression analysis by NanoString correlated increased PARP4 with PR and increased PD-L1 and EMSY with GR. There was greater tumor immune cell infiltration and higher immune cell PD-L1 protein expression in the GR group.
 
  Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.
 Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.
  Accurate and swift tissue diagnosis is extremely important for the timely initiation of treatment in pediatric oncology. In our department, ultrasound-guided core needle biopsy (US-guided CNB) is used for tissue diagnosis. In 2016, we added on-site cytology, allowing for an immediate primary diagnosis. We retrospectively reviewed our performance in terms of safety and accuracy for CNBs and on-site cytology.
 
  All pediatric biopsies performed in our hospital between February 2016 and December 2020, were included. Patient clinical, procedural and follow-up data were collected. CNB pathology and cytology results were compared to the final pathologic diagnosis.
 
  We included 71 patients for which 72 biopsies with on-site touch imprint (TI) cytology were performed; the average latency time to biopsy was 1 day. Altogether, we had 61 tumors, (58 malignant, 3 benign) and 11 other lesions. On-site cytology diagnosed 58 malignant tumors, 3 benign tumors and 11 non-tumor tissues. The cytologist correctly differentiated tumor from inflammation in all cases, and diagnosed the precise tumor type in 57 cases, with an accuracy of 94% for final diagnosis. We had no complications related to the procedure or sedation.
 
  US-guided CNB with on-site TI cytology for suspected malignancy in the pediatric population is highly available, safe, and accurate, with real-time diagnosis in most cases. This accelerated diagnostic route has a huge impact on patient care.
 US-guided CNB with on-site TI cytology for suspected malignancy in the pediatric population is highly available, safe, and accurate, with real-time diagnosis in most cases. This accelerated diagnostic route has a huge impact on patient care.In plants, clade A type 2C protein phosphatases (PP2CAs) have emerged as major players in abscisic acid (ABA)-regulated stress responses by inhibiting protein kinase activity. However, how different internal and external environmental signals modulate the activity of PP2CAs are not well known. The transmembrane kinase (TMK) protein 4 (TMK4), one member of a previously identified receptor kinase subfamily on the plasma membrane that plays vital roles in plant cell growth, directly interacts with PP2CAs member (ABA-Insensitive 2, ABI2). tmk4 mutant is hypersensitive to ABA in both ABA-inhibited seed germination and primary root growth, indicating that TMK4 is a negative regulator in ABA signaling pathway. Further analyses indicate that TMK4 phosphorylates ABI2 at three conserved Ser residues, thus enhancing the activity of ABI2. The phosphorylation-mimic ABI2S139DS140DS266D can complement but non-phosphorylated form ABI2S139AS140AS266A cannot complement ABA hypersensitive phenotype of the loss-of-function mutant abi1-2abi2-2.