The consistencies and inconsistencies between distal cholangiocarcinoma and pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

Objective: To evaluate the consistencies and inconsistencies between distal cholangiocarcinoma (DCCA) and pancreatic ductal adenocarcinoma (PDCA) regarding their biological features and long-term prognosis. Methods: PubMed, the Cochrane Library, and EMBASE were searched to find comparative studies between DCCA and PDCA. RevMan5.3 and Stata 13.0 software were used for the statistical analyses. Results: Eleven studies with 4,698 patients with DCCA and 100,629 patients with PDCA were identified. Pooled results indicated that patients with DCCA had a significantly higher rate of preoperative jaundice (p = 0.0003). Lymphatic metastasis (p < 0.00001), vascular invasion (p < 0.0001), and peri-neural invasion (p = 0.005) were more frequently detected in patients with PDCA. After curative pancreaticoduodenectomy (PD), a significantly higher R0 rate (p < 0.0001) and significantly smaller tumor size (p < 0.00001) were detected in patients with DCCA. Patients with DCCA had a more favorable overall survival (OS) (p < 0.00001) and disease-free survival (DFS) (p = 0.005) than patients with PDCA. However, postoperative morbidities (p = 0.02), especially postoperative pancreatic fistula (POPF) (p < 0.00001), more frequently occurred in DCCA. Conclusion: Patients with DCCA had more favorable tumor pathological features and long-term prognosis than patients with PDCA. An early diagnosis more frequently occurred in patients with DCCA. However, postoperative complications, especially POPF, were more frequently observed in patients with DCCA.

Aedes aegypti HPX8C modulates immune responses against viral infection.

Mosquitoes act as vectors of numerous pathogens that cause human diseases. Dengue virus (DENV) transmitted by mosquito, Aedes aegypti, is responsible for dengue fever epidemics worldwide with a serious impact on human health. Currently, disease control mainly relies on vector targeted intervention strategies. Therefore, it is imperative to understand the molecular mechanisms underlying the innate immune response of mosquitoes against pathogens. In the present study, the expression profiles of immunity-related genes in the midgut responding to DENV infection by feeding were analyzed by transcriptome and quantitative real-time PCR. The level of Antimicrobial peptides (AMPs) increased seven days post-infection (d.p.i.), which could be induced by the Toll immune pathway. The expression of reactive oxygen species (ROS) genes, including antioxidant genes, such as HPX7, HPX8A, HPX8B, HPX8C were induced at one d.p.i. and peaked again at ten d.p.i. in the midgut. Interestingly, down-regulation of the antioxidant gene HPX8C by RNA interference led to reduction in the virus titer in the mosquito, probably due to the elevated levels of ROS. Application of a ROS inhibitor and scavenger molecules further established the role of oxygen free radicals in the modulation of the immune response to DENV infection. Overall, our comparative transcriptome analyses provide valuable information about the regulation of immunity related genes in the transmission vector in response to DENV infection. It further allows us to identify novel molecular mechanisms underlying the host-virus interaction, which might aid in the development of novel strategies to control mosquito-borne diseases.

CTL14, a recognition receptor induced in late stage larvae, modulates anti-fungal immunity in cotton bollworm Helicoverpa armigera.

C-type lectin (CTL) is usually considered as pattern recognition receptors in insect innate immunity. Here we found that CTL14 of Helicoverpa armigera was only activated in the fifth instar larvae not in the second instar by entomopathogen Beauveria bassiana infection. Recombinant CTL14 protein was found to form aggregates with zymosan and B. bassiana in vitro. Immunoprecipitation studies demonstrated that CTL14 interacted with serine proteinases (SP), serine proteinase inhibitor (serpin), prophenoloxidases (PPO) and vitellogenin (Vg) in the larval hemolymph. Furthermore, depletion of CTL14 using dsRNA led to dramatic decrease in the expression level of PPO1. Additionally, CTL14 depleted H. armigera decreased the resistance to fungal challenge. Taken together, our study showed the direct involvement of CTL14 in the anti-fungal immunity of H. armigera, which further explained the stronger immune responses in the fifth instar compared to the second instar larvae.

Functional study on the mutations in the silkworm (Bombyx mori) acetylcholinesterase type 1 gene (ace1) and its recombinant proteins.

The acetylcholinesterase of Lepidoptera insects is encoded by two genes, ace1 and ace2. The expression of the ace1 gene is significantly higher than that of the ace2 gene, and mutations in ace1 are one of the major reasons for pesticide resistance in insects. In order to investigate the effects of the mutations in ace1's characteristic sites on pesticide resistance, we generated mutations for three amino acids using site-directed mutagenesis, which were Ala(GCG)303Ser(TCG), Gly(GGA)329Ala(GCA) and Leu (TCT)554Ser(TTC). The Baculovirus expression system was used for the eukaryotic expression of the wild type ace1 (wace1) and the mutant ace1 (mace1). SDS-PAGE and Western blotting were used to detect the targeting proteins with expected sizeof about 76 kDa. The expression products were purified for the determination of AChE activity and the inhibitory effects of physostigmine and phoxim. We observed no significant differences in the overall activity of the wild type and mutant AChEs. However, with 10 min of physostigmine (10 µM) inhibition, the remaining activity of the wild type AChE was significantly lower than that of the mutant AChE. Ten min inhibition with 33.4 µM phoxim also resulted in significantly lower remaining activity of the wild type AChE than that of the mutant AChE. These results indicated that mutations for the three amino acids reduced the sensitivity of AChE to physostigmine and phoxim, which laid the foundation for future in vivo studies on AChE's roles in pesticide resistance.