OBJECTIVEThe aim of this study is to analyze the three-dimensional crystal structure of SMU.2055 protein, a putative acetyltransferase from the major caries pathogen Streptococcus mutans (S. mutans). The design and selection of the structure-based small molecule inhibitors are also studied.

METHODSThe three-dimensional crystal structure of SMU.2055 protein was obtained by structural genomics research methods of gene cloning and expression, protein purification with Ni²⁺-chelating affinity chromatography, crystal screening, and X-ray diffraction data collection. An inhibitor virtual model matching with its target protein structure was set up using computer-aided drug design methods, virtual screening and fine docking, and Libdock and Autodock procedures.

RESULTSThe crystal of SMU.2055 protein was obtained, and its three-dimensional crystal structure was analyzed. This crystal was diffracted to a resolution of 0.23 nm. It belongs to orthorhombic space group C222(1), with unit cell parameters of a = 9.20 nm, b = 9.46 nm, and c = 19.39 nm. The asymmetric unit contained four molecules, with a solvent content of 56.7%. Moreover, five small molecule compounds, whose structure matched with that of the target protein in high degree, were designed and selected.

CONCLUSIONProtein crystallography research of S. mutans SMU.2055 helps to understand the structures and functions of proteins from S. mutans at the atomic level. These five compounds may be considered as effective inhibitors to SMU.2055. The virtual model of small molecule inhibitors we built will lay a foundation to the anticaries research based on the crystal structure of proteins.

Bacterial Proteins ; chemistry ; Cloning, Molecular ; Crystallization ; Crystallography, X-Ray ; Dental Caries ; Humans ; Streptococcus mutans ; chemistry ; X-Ray Diffraction

The interaction between genetic and environmental factors influences the onset,development and prognosis of cerebral ischemia.Recently,epigenetic regulation is increasingly becoming a research focus on cerebral ischemia,and there has been great progress in research on DNA methylation,histone modification and miRNA network.Epigenetic regulation provides a new idea for identifying potential therapeutic targets of cerebral ischemia.

Purpose To investigate MRI features of encephalitis in children with severe hand-foot-mouth disease (HFMD). Materials and Methods The MR images of 85 cases of clinically diagnosed encephalitis in severe HFMD patients were retrospectively reviewed. Results In 85 patients, plain MRI was negative in 28;57 cases were positive including 10 cases showing punctate or patchy lesions in cerebral hemisphere, callosum, thalamus and cerebellar vermis with isointensity or slightly hypointensity on T1WI, isointensity or slightly hyperintensity on T2WI, and hyperintensity on T2FLAIR and DWI. In 47 cases, the lesions were located in the brainstem, tegmentum of pons and medulla oblongata. MRI features included symmetric high signal on DWI in posterior portions of brainstem, hypointensity or isointensity on T1WI and hyperintensity or isointensity on T2WI and T2FLAIR (n=17);patchy long T1, long T2 signal in posterior portions of brainstem, normal or mild hyperintensity on DWI, hyperintensity on T2FLAIR (n=30); lesion extending around the fourth ventricle in 9 patients, one of which involved bilateral cerebral peduncles. Conclusion Encephalitis in children with severe HFMD has characteristic MRI features. The lesions are mostly located in the posterior portion of the brainstem. DWI and T2FLAIR can better detection lesions.

Objective: To investigate the vascular anatomy of the stomach, especially the right gastroepiploic artery for the reconstruc-tion of a gastric tube during esophagectomy. Methods: The vascular anatomy of the stomach was studiing in 28 embalmed human specimens provided by the Department of Anatomy, Shanghai Medical College, Fudan University, included 10 female and 18 male spec-imens. The length and diameter of gastric vessels were measured. The ratio of the length of the right gastroepiploic artery to the length of the greater curvature was calculated. Anastomosis between the left and right gastroepiploic arteries was also assessed. Re-sults: Twenty-five left gastric arteries were observed in the autopsies, with the mean diameter of 3.40 (2.10-6.40) mm. Twenty-one right gastric arteries were measured, with the mean diameter of 1.97 (0.68-3.56) mm. Twenty-six left gastroepiploic arteries were ob-served, with the mean diameter of 1.87 (0.80-2.96) mm. Twenty-eight right gastroepiploic arteries were measured, with the mean di-ameter of 2.82 (1.58-4.80) mm. The mean lengths of the 28 right gastroepiploic arteries and their greater curvatures were 216.71 (120-318) mm and 356.39 (248-487) mm, respectively. The ratio of the length of right gastroepiploic arteries and greater curvatures was 0.61 (0.45-0.82). The anastomosis between the left and right gastroepiploic arteries was observed in 60.7% (17/28) of the specimens. Conclusions: The length and diameter of gastric vessels were calculated. It was assumed that the right gastroepiploic artery provides an average of 61% of the blood supply for the great curvature. In addition, the anastomotic branch of the right and left gastroepiploic arteries was observed in 60.7% specimens. These anatomical data allow surgeons to estimate the blood supply and to choose an opti-mal method of gastric tube reconstruction during esophagectomy.

Extranodal natural killer/T-cell lymphoma (ENKTCL) is the subtype of non-Hodgkin lymphoma with high heterogeneity and invasiveness. Though most ENKTCL patients are present as early-stage at diagnosis, clinical prognosis significantly differs due to the limitations of clinical staging. Radiotherapy (RT) and chemotherapy (CT) are the first-line treatments for early ENKTCL patients. However, there is no consensus on the combined modalities of RT and CT, and their optimal strategy. With the continuous renewal of clinical staging and prognostic models, early-stage ENKTCL patients tend to accept risk-adapted treatment with proper stratification. In this review, the latest research progresses on clinical staging, prognostic models and treatment were retrospectively analyzed, aiming to provide references for clinical decision-making.

Endoplasmic reticulum stress refers to a cellular stress response triggered when cells are stimulated, which is manifested as the disruption of endoplasmic reticulum homeostasis and dysfunction in various pathological conditions, resulting in the accumulation of a large number of misfolded and unfolded proteins within the endoplasmic reticulum and an imbalance of calcium ions. Macrophages are the most abundant immune cells in the liver and play an important role in maintaining liver homeostasis and various liver diseases. Recent studies have confirmed that the unfolded protein response caused by endoplasmic reticulum stress plays an important role in regulating macrophage immune response. This article reviews the mechanisms of endoplasmic reticulum stress regulating macrophage immune response and its role in liver diseases such as ischemia-reperfusion injury during organ transplantation, liver fibrosis, and hepatocellular carcinoma, in order to deepen the understanding of the mechanism of macrophage immune regulation and provide new ideas for research and interventional treatment related to liver diseases.