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The hepatopancreas is the key organ involved in energy storage, immune response, and metabolism during crustacean molting, yet the underlying molecular mechanisms in the hepatopancreas that regulate molting remain unknown. In the present study, we conducted a comprehensive proteomic analysis in the hepatopancreas and quantified 1527 proteins, of which 193 changed significantly in abundance among three molting stages (pre-molt PrM, post-molt PoM, and inter-molt InM) of Scylla paramamosain using iTRAQ-coupled LC-MS/MS. Ten exoskeleton and cuticle reconstruction proteins, such as chitinase, cuticle protein and myosin heavy chain, were found change significantly in abundance between PoM and PrM. Six energy metabolism proteins such as mitochondrial cytochrome c oxidase, cytochrome b-c1 and cAMP-dependent protein kinase with positive loadings showed a higher abundance in InM than PoM. In addition, all differentially abundance proteins (DAPs) were annotated for GO function and KEGG pathway analysis. GO analysis demonstrated function subcategories mainly including thiamine metabolism, complement and coagulation cascades, endocrine, shigellosis, salmonella infection, and other factor-regulated calcium reabsorption. The KEGG pathway enrichment analysis indicated that the DAPs were mainly involved in reconstruction of the exoskeleton and cuticle, energy reserves, metabolism, and immune response during the molting process. The results for the proteins and key pathways involved in the molting process provide fundamental molecular evidence that will improve our understanding of morphological and metabolism variation in the molting cycle and will serve as a potential blueprint for future study on molecular mechanism of molting in crustaceans.The indole side chain of tryptophan is a versatile π-donor that can participate in various types of cation-π interactions. An understanding of how it may contribute as an auxiliary binding group in mercury(II) complexes can provide valuable insights toward the design of effective chelators for optimal mercury immobilization. In this study, we investigate how the incorporation of two tryptophan residues in model dicysteinyl peptides might participate in peptide-mercury(II) complex stabilization. Two pentapeptides consisting of a Cys-Trp-Cys sequence motif containing a second tryptophan residue at the N-terminal (BT1) or C-terminal (BT2) were designed. Cyclosporin A solubility dmso An analogous cyclohexapeptide (BT3) was included to evaluate how tryptophan residues, restricted in constrained peptidic turn motifs, might take part in mercury(II) complexation. Their interactions with mercury(II) were investigated by spectroscopic methods and computational modeling. UV-vis studies indicate the formation of 11 dithiolated mercury(II) complex, which is corroborated by ESI-MS analysis. Spectroscopic studies reveal that the tryptophan indole group(s) in BT1 and BT3 can participate in mercury(II) cation-π interactions. Optimized 11 mercury(II)-BT3 structures indicate that both indole rings are very close to the mercury(II) coordination site and could stabilize it by shielding it from ligand exchange. These findings provide some useful insights toward use of aromatic donor groups as hydrophobic shields in designing more effective metal chelating agents.
To develop and validate a simple delirium-predicting scoring system in patients undergoing major abdominal surgery by incorporating preoperative risk factors and intraoperative surgical Apgar score (SAS).

Observational retrospective cohort study.

A tertiary general hospital in China.

1055 patients who received major abdominal surgery from January 2015 to December 2019.

We collected data on preoperative and intraoperative variables, and postoperative delirium. A risk scoring system for postoperative delirium in patients after major open abdominal surgery was developed and validated based on traditional logistic regression model. The elastic net algorithm was further developed and evaluated.

The incidence of postoperative delirium was 17.8% (188/1055) in these patients. They were randomly divided into the development (n=713) and validation (n=342) cohorts. Both the logistic regression model and the elastic net regression model identified that advanced age, arrythmia, hypoalbuminemia, coagulation dyslly useful predictive model for postoperative delirium in patients undergoing major open abdominal surgery.
The prognostic scoring system, which used both preoperative risk factors and surgical Apgar score, serves as a good first step toward a clinically useful predictive model for postoperative delirium in patients undergoing major open abdominal surgery.
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility.

Cochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance.

Of 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p<0.001) and tumor/immune cells (30.1% vs 14.6% p<0.001), but not in tumor cells (18.7% vs 17.8% p=0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p<0.001).

The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
The observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
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