(2011) zVAD-induced autophagic cell death requires c-Src-dependent ERK and JNK activation and reactive oxygen species generation , Autophagy, 7:2, 217-228,
Differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) from its histologic mimickers, especially metastatic adenocarcinomas of gastric and pancreatic origin, is a great challenge for pathologists. In this study, through bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus, we identified C-reactive protein (CRP) as a candidate marker to differentiate iCCA from other adenocarcinomas and validated its diagnostic performance by immunohistochemistry in a large cohort of clinical samples including 103 iCCAs, 384 other adenocarcinomas, and 34 liver metastases of various origins. The sensitivity and specificity of CRP expression in the diagnosis of iCCA were 75.7% and 91.1% when using tissue microarrays and 93.3% and 88.2% when using whole tissue sections, respectively. We also compared the diagnostic performance of CRP with N-cadherin, a previously reported marker for iCCA. The sensitivity and specificity of N-cadherin were 54.4% and 92.2% when using tissue microarrays and 80.0% and 88.2% when using whole tissue sections, respectively. The sensitivity of CRP was higher than that of N-cadherin, whereas their specificity was similar. CRP expression was associated with mass-forming gross type (P<0.001), absence of perineural invasion (P=0.002), and N-cadherin expression (P<0.001). CRP expression was also associated with better overall survival (P=0.002) and longer recurrence-free time (P=0.032) after surgery. Our study suggests that CRP is a promising immunohistochemical marker to differentiate iCCA from other adenocarcinomas. Compared with N-cadherin, CRP showed higher sensitivity and similar specificity. CRP expression was associated with better prognosis in iCCA.
The shallow-water hydrothermal vent (HV) system off Kueishan Island lies at the end of the Okinawa Trough to the northeast of Taiwan. Near its submarine vent openings, aperiodic vent discharges generate a dynamic acidic (pH 5.5-8.1) and sulfidic (9-3000 μM) ecosystem. The dominant metazoan in this unique environment is the brachyuran vent crab, Xenograpsus testudinatus, which has developed robust metabolic strategies and highly adaptive acid-base regulatory mechanisms to maintain its physiological homeostasis. X. testudinatus is considered a holobiont, but the symbiotic mechanisms underlying acid and sulfur tolerance in the host-microbe system remain largely unclear. In this study, we used LoopSeq long-read sequencing of the full-length 16S rRNA gene to identify the bacterial communities present in the gills and carapace surface of X. testudinatus. The alpha diversity analysis, Venn diagram, and principal coordinate analysis (PCoA) indicated that the gills and carapace surface exhibit different bacterial constituents. Further measurements of relative abundance, coupled with functional predictions and fluorescence in situ hybridization (FISH), revealed a predominance of Sulfurovum sp. NBC37-1, a key bacterium that can perform sulfur and hydrogen oxidation to support denitrification processes. Consequently, our findings suggest that the symbiotic bacteria may play a critical role in conferring the extraordinary acid and sulfur tolerances of X. testudinatus, allowing the crustacean holobiont to thrive in its ecological niche within one of the most extreme marine habitats on Earth.
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