Development of an mRNA vaccine against a panel of heterologous H1N1 seasonal influenza viruses using a consensus hemagglutinin sequence.

Seasonal influenza, causes hundreds of thousands of deaths annually, posing a severe threat to human health. Currently available influenza vaccines are targeted only at specific strains or conserved epitopes; however, these vaccines are not completely efficacious because influenza viruses can undergo mutation during circulation, leading to antigenic mismatch between recommended strains and circulating strains and elusion from the immune system. Therefore, developing an influenza vaccine that is quick, effective, and broadly protective has become crucial, and the integral part of hemagglutinin (HA) remains an ideal target for vaccine development. This study developed a lipid nanoparticle-encapsulated nucleoside-modified mRNA vaccine (mRNA-LNPs) encoding a consensus full-length HA sequence (H1c) and evaluated its protective efficacy and immunogenicity through in vitro and in vivo assays. Following two intramuscular immunizations (2, 10 µg, or 20 µg) at a 3-week interval in BALB/c mice, H1c-mRNA-LNP vaccine induced strong antibodies as shown in the hemagglutination-inhibition test and protective neutralizing antibodies against numerous heterologous H1N1 influenza viruses as shown in the microneutralization assay. Additionally, both Th1- and Th2-biased cellular immune responses were elicited, with the Th1-biased response being stronger. Two doses of the H1c-mRNA-LNP vaccine could neutralize a panel of heterologous H1N1 influenza viruses and could confer protection in mice. Taken together, these findings suggest that the H1c-mRNA-LNP vaccine encoding a consensus full-length HA is a feasible strategy for developing a cross-protective vaccine against a panel of heterologous H1N1 influenza viruses.

Asymmetric Total Syntheses of (-)-Fennebricin A, (-)-Renieramycin J, (-)-Renieramycin G, (-)-Renieramycin M, and (-)- Jorunnamycin A via C-H Activation.

Collective total synthesis of five tetrahydroisoquinoline alkaloids including the first total synthesis of (-)-fennebricin A and (-)-renieramycin J has been accomplished. The synthesis features employing a single common amino acid to symmetrically construct the pentacycle of title alkaloids. The palladium-catalyzed arylation of alanine-derived amide developed by Yu was tactically utilized to afford unnatural amino acid building block rapidly and practically. The structure of synthetic (-)-renieramycin M has been confirmed by single crystal X-ray analysis for the first time.

Total Synthesis of (-)-Actinophyllic Acid Enabled by a Key Dual Ir/Amine-Catalyzed Allylation.

A synthetic strategy for the catalytic asymmetric total synthesis of (-)-actinophyllic acid is described. This highly efficient and enantioselective approach allows the rapid installation of the four contiguous chiral centers (C16, C15, C20, and C19) by way of a dual Ir/amine catalytic allylation of 2-indolyl vinyl carbinol 6 and an aldol reaction of resultant chiral aldehyde 4a with 2-pyrrolidinone 5. The key indol-3-ylmethanamine moiety and 1-azabicyclo[4.2.1]nonane ring system were readily generated through a selective Mannich-like cyclization and an intramolecular N-alkylation, respectively.

[Value of multidetector CT on aiding intraoperative judgement of serosal invasion of gastric cancer].

OBJECTIVE: To explore the value of multidetector CT on aiding intraoperative judgement of serosal invasion of gastric cancer. METHODS: Clinical data of 206 cases of gastric cancer undergoing radical surgery in the First Hosptial of China Medical University from August 2009 to June 2011 were analyzed retrospectively. Preoperative CT findings and intraoperative judgement of serosal invasion in gastric cancer were compared with pathological results in order to investigate their values. RESULTS: The sensitivity and specificity of preoperative CT findings and intraoperative judgement of serosal invasion were 88.5%, 81.5% and 98.9%, 61.3%, respectively. The accuracy of preoperative CT in diagnosing serosal invasion was higher than that of intraoperative judgement, while the difference was not statistically significant (84.5% vs. 77.2%, P=0.060). The rates of serosal invasion of normal type, reactive type, nodular type, tendonoid type and color-diffused type were 0 (0/29), 2.5% (1/40), 40.5% (15/37), 59.2% (29/49), and 82.4% (42/51) respectively. The accuracy of preoperative CT in diagnosing serosal invasion of gastric cancer with tendonoid type was higher than that of intraoperative judgement, and the difference was statistically significant (61.2% vs. 87.8%, P=0.002). CONCLUSIONS: Multidetector CT plays an important role in aiding intraoperation judgement of serosal invasion of gastric cancer. For gastric cancer with tendonoid and color-diffused macroscopic serosal appearance, surgeons should pay attention to the value of preoperative CT findings.

[Clinical analysis of autoimmune pancreatitis: a single center study of 14 consecutive cases].

OBJECTIVE: To investigate the characteristic findings of autoimmune pancreatitis (AIP) to increase the recognition of AIP. METHODS: From February 2002 to April 2008, a total of 14 cases of AIP were reviewed by clinical, imaging, serologic, histopathologic features and treatment response. There were 13 male and 1 female, with a mean age of 53 years. The main clinical manifestations included progressive obstructive jaundice in 11 cases, upper abdomen pain in 3 cases. RESULTS: Diffuse enlargement of pancreas and diffuse narrowing of the main pancreatic duct (MPD) were observed in 11 cases, while 3 patients showed localized pancreatic head enlargement and focal narrowing of the MPD. Distal common bile duct stenosis was found in all cases. Increased expression of serum immunoglobulin G was found in 7 patients. Autoantibody test was positive in 5 of 12 patients. Nine of 14 patients with AIP had extrapancreatic organ involvement. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Seven earlier patients were treated initially with surgical laparotomy or resection for suspected malignancy. Steroid therapy was given to the other patients and was responsive. There were 4 recurrences after initial treatment. CONCLUSION: AIP should be a differential diagnosis in pancreatic head mass in order to avoid unnecessary resection.