Inhalational anthrax is caused by B. anthracis, a virulent sporeforming bacterium which secretes anthrax toxins consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF). LF is a Zn-dependent metalloprotease and is the main determinant in the pathogenesis of anthrax. Here we report the identification of a lead small-molecule inhibitor of anthrax lethal factor by screening an available synthetic small-molecule inhibitor library using fluorescence-based high-throughput screening (HTS) approach. Seven small molecules were found to have inhibitory effect against LF activity, among which SM157 had the highest inhibitory activity. All theses small molecule inhibitors inhibited LF in a noncompetitive inhibition mode. SM157 and SM167 are from the same family, both having an identical group complex, which is predicted to insert into S1' pocket of LF. More potent small-molecule inhibitors could be developed by modifying SM157 based on this identical group complex. [BMB reports 2011; 44(12): 811-815]

Multiple high-powered magnetic Buckyball ingestions may lead to a high risk of severe complications. Great concerns have been raised by public health workers, and it remains challenging for clinicians to solve this troublesome problem. We report a large case series of children with Buckyball ingestion from six tertiary medical centers. The clinical data, including demographics, medical history, diagnosis tools, management options, intraoperative or endoscopic findings, and outcomes, were retrospectively analyzed. Seventy-one children aged 1–13 years ingested 2–41 Buckyballs. Among them, Buckyballs passed spontaneously on 2–10 days post-ingestion in seven cases; gastroscopic removal was performed in 14 cases; laparoscopic removal in 13 cases; laparoscopic-assisted surgical removal in 6 cases; and open surgical removal in 31 cases. Surgical indications included small bowel obstruction, perforation, peritonitis, acute abdominal pain, or along with ingestion of other metallic foreign bodies. Among those who underwent a surgical procedure, primary intestinal repair was performed in 44 cases, enterectomy with primary anastomosis in 6 cases. The postoperative hospital stay ranged from 5 to 28 days. No major complications occurred. In unwitnessed cases, a vague medical history and nonspecific symptoms usually make the diagnosis difficult. The treatment options should include the watch-and-wait approach, endoscopic, laparoscopic-assisted, or open surgical removal of Buckyballs, with primary intestinal repair or anastomosis. Preventive measures, including children's not having access to Buckyballs, are essential to protect children from this kind of unintentional injury.

Nasal augmentation is a popular modern technique requested by many Asian people. There are two kinds of autologous cartilage used to augment the nose at present: carved as a monobloc or diced into pieces. Each approach has its pros and cons. The authors performed their surgical technique on a group of 28 patients. Twenty of these patients had undergone rhinoplasties performed before referral to our hospital; eight of these patients had undergone a primary rhinoplasty. Bilateral conchal, nasal septum, or rib cartilage was harvested; deep temporal fascia or abdominal muscle fascia to be prepared for packing stripped cartilage was also removed at this time. The cartilage was placed on a plastic cutting board and cut into strips with a transverse section of 1 × 1 mm. Then, these strips were packed and covered by fascia to form the grafts. The median follow-up was 23 months (range, 12 to 48 months). Twenty-two patients were satisfied with their augmented noses. Through examinations, biopsies, and magnetic resonance imaging scans, less resorption was observed with the multistrip autologous cartilage technique. Junctional stepoffs, excessive prominence, and slanting grafts occurred in three patients, two of whom had revisions. Using multistrip autologous cartilage grafts is an easier method to perform and could be another alternative technique for augmentative and reconstructive rhinoplasties.

Context 46,XY, disorders of sexual development (46,XY, DSD) is a congenital genetic disease whose pathogenesis is complex and clinical manifestations are diverse. The existing molecular research has often focused on single-centre sequencing data, instead of prediction based on big data. Aims This work aimed to fully understand the pathogenesis of 46,XY, DSD, and summarise the key pathogenic genes. Methods Firstly, the potential pathogenic genes were identified from public data. Secondly, bioinformatics was used to predict pathogenic genes, including hub gene analysis, protein–protein interaction (PPI) and function enrichment analysis. Lastly, the genomic DNA from two unrelated families were recruited, next-generation sequencing and Sanger sequencing were performed to verify the hub genes. Key results A total of 161 potential pathogenic genes were selected from MGI and PubMed gene sets. The PPI network was built which included 144 nodes and 194 edges. MCODE 4 was selected from PPI which scored the most significant P-value. The top 15 hub genes were ranked and identified by Cytoscape. Furthermore, three variants were found on SRD5A2 gene by genome sequencing, which belonged to the prediction hub genes. Conclusions Our results indicate that occurrence of 46,XY, DSD is attributed to a variety of genes. Bioinformatics analysis can help us predict the hub genes and find the most core network MCODE model. Implications Bioinformatic predictions may provide a novel perspective on better understanding the pathogenesis of 46,XY, DSD.