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FMRFamide (Phe-Met-Arg-Phe-NH 2 )-activated sodium channel (FaNaC) is an amiloride-sensitive sodium channel activated by endogenous tetrapeptide in invertebrates, and belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. The ENaC/DEG superfamily differs markedly in its means of activation, such as spontaneously opening or gating by mechanical stimuli or tissue acidosis. Recently, it has been observed that a number of ENaC/DEG channels can be activated by small molecules or peptides, indicating that the ligand-gating may be an important feature of this superfamily. The peptide ligand control of the channel gating might be an ancient ligand-gating feature in this superfamily. Therefore, studying the peptide recognition of FaNaC channels would advance our understanding of the ligand-gating properties of this superfamily of ion channels. Here we demonstrate that Tyr-131, Asn-134, Asp-154, and Ile-160, located in the putative upper finger domain of Helix aspersa FaNaC (HaFaNaC) channels, are key residues for peptide recognition of this ion channel. Two HaFaNaC specificinsertion motifs among the ENaC/DEG superfamily, residing at the putative ␣4-␣5 linker of the upper thumb domain and the ␣6-␣7 linker of the upper knuckle domain, are also essential for the peptide recognition of HaFaNaC channels. Chemical modifications and double mutant cycle analysis further indicated that those two specific inserts and key residues in the upper finger domain together participate in peptide recognition of HaFaNaC channels. This ligand recognition site is distinct from that of acid-sensing ion channels (ASICs) by a longer distance between the recognition site and the channel gate, carrying useful information about the ligand gating and the evolution of the trimeric ENaC/DEG superfamily of ion channels.The epithelial sodium channel/Degenerin (ENaC/DEG) 4 superfamily, cloned in the early 1990s, is nonvoltage-gated, amiloride-sensitive, and sodium-selective ion channels, including ASIC, ENaC, DEG, FaNaC, bile acid-sensitive ion channel (BASIC), and pickpocket (PPK) channels, etc. (1, 2). ENaC/DEG ion channels are implicated in many physiological and pathological functions such as synaptic plasticity, learning and memory, emotion regulation, neurodegenerative diseases, epileptic seizures, pain sensation, mechano-sensation, blood pressure regulation, and cystic fibrosis (1-3), which makes them potential drug targets for those disorders. The members of the ENaC/ DEG superfamily differ markedly by means of activation. For example, DEG channels are mechano-sensitive; ENaC channels open spontaneously; ASIC channels are capable of sensing tissue acidosis, while FaNaC is activated by RFamide peptides, etc. (4). Recently, great advances have been made in the exploration of the activation mechanism of this superfamily. For example, it is now known that ENaC, ASIC3, BASIC, and ASIC1a channels can be activated by the small molecules S3969 (5), GMQ (6), bile acid (7), and peptide toxin (8, 9) respectively. These new findings sugge...

Our results suggested that IDO gene expression correlates with the severity of acute rejection and that IFN-γ-induced IDO-positive DCs may attenuate acute rejection and catalyze local tryptophan metabolism via IDO enzyme expression, leading to immune tolerance after liver transplantation.

Objectives We aimed to evaluate the values of neutrophil‐to‐lymphocyte ratio (NLR) and white blood cell (WBC) in predicting severity of acute pancreatitis (AP) with different etiologies. Methods We compared NLR and WBC levels in patients with different etiologies and AP severity. The optimal cutoff value for them to predict severe acute pancreatitis (SAP) was determined by receiver operating characteristic (ROC) curve analysis. Results Both NLR and WBC were elevated in patients with SAP. After subgrouping AP by etiology, NLR was predictive of SAP only in hypertriglyceridemia‐induced AP (HTG‐AP), while WBC could effectively predict severity in both gallstone and HTG‐AP. The best cutoff value of WBC for predicting SAP in gallstone AP patients was 12.81 × 109/L, with sensitivity and specificity of 78.9% and 70.2%. The best cutoff value for NLR and WBC to differentiate HTG‐SAP was more than 5.88 and 15.89 × 109/L, respectively, with sensitivity and specificity of 87% and 50% for NLR and 56.5% and 75.76% for WBC. Conclusions Our study firstly demonstrated that NLR selectively played a role in HTG‐AP, while WBC could predict the severity of both gallstone and HTG‐AP. Furthermore, we firstly elucidated that NLR was more sensitive and accurate in judging the severity of HTG‐AP compared with WBC.