Our single-center study with a large number of patients provided evidence regarding the epidemiology of AC. Preoperative nutritional support and intestinal stenting significantly reduced postoperative complications and, more importantly, increased postoperative satisfaction.

The human DEAD box protein 3 (DDX3) has been implicated in different processes contributing to gene expression. Interestingly, DDX3 is required as an essential host factor for the replication of HIV and hepatitis C virus (HCV) and is therefore considered a potential drug target. On the other hand, DDX3 interacts with IB kinase (IKK) and TANK-binding kinase 1 (TBK1) and contributes to the induction of antiviral type I interferons (IFNs). However, the molecular mechanism by which DDX3 contributes to IFN induction remains unclear. Here we show that DDX3 mediates phosphorylation of interferon regulatory factor 3 (IRF3) by the kinase IKK. DDX3 directly interacts with IKK and enhances its autophosphorylation and activation. IKK then phosphorylates several serine residues in the N terminus of DDX3. Phosphorylation of DDX3 at serine 102 (S102) is required for recruitment of IRF3 to DDX3, facilitating its phosphorylation by IKK. Mutation of S102 to alanine disrupted the interaction between DDX3 and IRF3 but not that between DDX3 and IKK. The S102A mutation failed to enhance ifnb promoter activation, suggesting that the DDX3-IRF3 interaction is crucial for this effect. Our data implicates DDX3 as a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKK. DDX3 might thus be involved in pathway-specific activation of IRF3. The human DEAD box RNA helicase DDX3 is a multifunctional cellular protein which has been implicated in various processes linked to gene expression (1). Its RNA helicase activity is coopted by viruses that require DDX3 as an essential host factor for their replication, such as HIV and HCV (2-4). In contrast, we and others have previously demonstrated that DDX3 contributes to antiviral innate immune signaling pathways leading to ifnb induction (5-9). This function of DDX3 is independent of its ATPase and helicase activity (6, 7). ifnb promoter induction requires activation of the transcription factors IRF3 and IRF7, which occurs only downstream of certain, mostly antiviral, pattern recognition receptors (PRRs). Antiviral PRRs comprise the endosomal Toll-like receptors TLR3, TLR7, TLR8, and TLR9, cytosolic RIG-like helicases (RLHs), and several newly discovered cytosolic DNA receptors (10). These receptors recognize different species of viral nucleic acids and induce type I IFNs in response (11). TLR3 and TLR4 engage the TRIF (TIR domain-containing adaptor inducing IFN-␤)-dependent pathway for activation of IRF3 (12). In this pathway, phosphorylation-dependent activation of IRF3 is mediated by the IKK-related kinases TBK1 and IKKε (13,14). The RLHs also utilize TBK1 and IKKε for IRF3 activation after engaging the adaptor molecule MAVS (mitochondrial antiviral signaling) (15, 16). DNA receptors activate IRF3 through TBK1 and the adaptor molecule STING (stimulator of IFN genes).While these signaling pathways converge on IKKε and TBK1 for IRF3 activation, not all receptors that activate IKKε and/or TBK1 lead to IRF3 activation (17). This suggests that additional factors are required for li...

In flowering plants, pollen tubes are guided into ovules by multiple attractants from female gametophytes to release paired sperm cells for double fertilization. It has been well-established that Ca2+ gradients in the pollen tube tips are essential for pollen tube guidance and that plasma membrane Ca2+ channels in pollen tube tips are core components that regulate Ca2+ gradients by mediating and regulating external Ca2+ influx. Therefore, Ca2+ channels are the core components for pollen tube guidance. However, there is still no genetic evidence for the identification of the putative Ca2+ channels essential for pollen tube guidance. Here, we report that the point mutations R491Q or R578K in cyclic nucleotide-gated channel 18 (CNGC18) resulted in abnormal Ca2+ gradients and strong pollen tube guidance defects by impairing the activation of CNGC18 in Arabidopsis. The pollen tube guidance defects of cngc18-17 (R491Q) and of the transfer DNA (T-DNA) insertion mutant cngc18-1 (+/−) were completely rescued by CNGC18. Furthermore, domain-swapping experiments showed that CNGC18’s transmembrane domains are indispensable for pollen tube guidance. Additionally, we found that, among eight Ca2+ channels (including six CNGCs and two glutamate receptor-like channels), CNGC18 was the only one essential for pollen tube guidance. Thus, CNGC18 is the long-sought essential Ca2+ channel for pollen tube guidance in Arabidopsis.