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The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.
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Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations.
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Objective: To evaluate the efficacy of Tuina (Chinese therapeutic massage) manipulation plus horse-riding squat exercise in treating knee osteoarthritis (KOA) and optimize the combining protocol. Methods: Based on a 2×2 factorial design, 120 eligible KOA patients were randomized into a manipulation group (group A1B2), a manipulation plus horse-riding squat group (group A1B1), a sitting knee-adjustment group (group A2B2 group), and a sitting knee-adjustment plus horse-riding squat group (group A2B1), with 30 cases in each group. The intervention was conducted three times a week, lasting for four weeks. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was taken as the major measure for efficacy evaluation (including three component scores, pain, stiffness, and daily function, and total score). Results: The three component scores (pain, stiffness, and daily function) and the total score of WOMAC showed significant differences after the intervention in the four groups (P<0.05). There were significant inter-group differences in the WOMAC stiffness score amongst the four groups after the intervention (P<0.05). In group A1B1, the step length, stride, walking speed, and knee joint flexion angle changed significantly after treatment (P<0.05). After the intervention, the step length changed significantly in group A1B2 (P<0.05), and the walking speed changed significantly in group A2B1 (P<0.05). There were no significant differences in the step length, stride, walking speed, or knee joint flexion angle among the four groups (P>0.05). The extensor peak torque at 180 °/s changed significantly in group A1B2 after treatment (P<0.05). Neither the intra-group nor the inter-group comparisons of the four groups revealed significant differences in the other isokinetic muscle strength parameters (P>0.05). The main effect of manipulation showed significant in affecting the WOMAC pain and total scores (P<0.05). The main effect of horse-riding squat exercise showed significant in affecting the WOMAC pain and stiffness scores (P<0.05). Conclusion: The four treatment protocols all can improve the symptoms of KOA, for instance, relieving pain and stiffness, and enhancing daily function. Group A2B1 produces the most eminent effect in relieving joint stiffness. The main effects of both manipulation and horse-riding squat exercise are significant in reducing pain. Besides, the main effect of horse-riding squat exercise is significant in relieving joint stiffness.
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3D reconstruction technologies have been widely used in medical diagnostic assist, surgical simulation, anatomy teaching, etc. The resolution of traditional imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI) cannot meet the needs of life science research. Continuous sectioning technology can provide accurate and high-resolution information for the vast majority of tissues, which make it become a valuable method in the research and exploration of microstructures studies. With the development of microscopy and image processing techniques, significant advances have been made in the small-scale serial sections-based 3D reconstruction technologies. This enables the analysis of sample morphology and tissue function, as well as a more complete assessment of the structure of the tissue. Therefore, this technology has led to profound changes in the fields of cell and tissue biology. In this paper, the common small-scale serial sections-based 3D reconstruction technologies were compared and reviewed.
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The lymphatic system plays an important role in human health and disease. In addition to a role in the immune response, the lymphatics can also serve as a pathway for cancer metastasis.Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers.In the case where the primary focus has been controlled, cervical lymph node metastasis is one of the most important factors affecting the prognosis of head and neck cancer.Thus, understanding the anatomy of the lymphatic system is of paramount importance in predicting cancer metastasis and to perform proper lymph node dissection in cancer patients.The objective of this review is to summarize current imaging approaches that facilitate both basic science and clinical investigations of lymphatic vasculature.Mutation analysis of the laryngeal lymphatic system may provide a theoretical basis for the diagnosis and treatment of HNSCC.
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BACKGROUND: With the extensive application of small animal imaging and imaging studies, it requires the investigators to master the cross-sectional anatomy of mice, but the anatomy of mouse nasal cavity and sinuses cannot be obtained through vivisection.OBJECTIVE: To establish a highly precise serial colorful sectional image data set of mice using digital virtual human technology.METHODS: An adult male Balb/c mouse was killed for freezing embedded using modified Kawamoto's method and was then serially scanned at 5 μm of thickness by Leica CM3600XP cryostat microtome. The sectional images were photographed with a 24 million pixels Nikon D750 camera and stored as JPG files. All images were preliminarily registered by manually cropping the images based on the edge of block surface using software photoshop 7.0. Then, the image size, brightness and registration were corrected and adjusted, and the format of the images was unified as TIFF. The data set was imported to Amira 6.0 and was registered again with least square method. The quality of the data set was evaluated by three-dimensional reconstruction. RESULTS AND CONCLUSION: A total of 6034 original images with a size of 87 GB were captured. After cropping, adjusting and registration, the final size was 184 G. The mouse three-dimensional reconstruction model was satisfactory. To conclude, the data set established using the method and system mentioned above is characterized by high resolution and high-fidelity, which might facilitate the further study of the precise anatomy of mice and other fundamental experiments.
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Objective To analyze and discuss the clinical effect of the four-hands technique mode of doctor-nurse collaboration in endoscopic sinus surgery. Methods Convenient sampling method was used to select 50 cases of patients with nasal endoscopic surgery who met the inclusion criteria and agreed to participate in this study in the period between January to May in 2016. Designing one side of the nasal cavity of patients with traditional surgery mode, the other side of the nasal cavity to carry out the four-hands operation mode. The operation time and amount of bleeding were recorded. Results The operation time, amount of bleeding of traditionalsingle hand operationside and the other side of four-hands operation respectively were (39.30 ± 21.96) min, (143.86 ± 15.01) ml and (31.60 ± 19.27) min, (102.98 ± 12.85) ml, with significant differences between the two groups (t=2.096, 14.625, P<0.01). Conclusions The four-hands technique of doctor-nurse collaboration can significantly reduce the operation time, reduce the amount of bleeding and get a better surgical field, clinical nurse and doctor′s cooperation is more closely and also improve the quality of patient care.
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Increasing incidence of musculoskeletal injuries coupled with limitations in the current treatment options have necessitated tissue engineering and regenerative medicine- based approaches. Moving forward from engineering isolated musculoskeletal tissues, research strategies are now being increasingly focused on repairing and regenerating the interfaces between dissimilar musculoskeletal tissues with the aim to achieve seamless integration of engineered musculoskeletal tissues. This article reviews the state-of-the-art in the tissue engineering of musculoskeletal tissue interfaces with a focus on Singapore's contribution in this emerging field. Various biomimetic scaffold and cellbased strategies, the use of growth factors, gene therapy and mechanical loading, as well as animal models for functional validation of the tissue engineering strategies are discussed.
Subject(s)
Humans , Cell- and Tissue-Based Therapy , Genetic Therapy , Intercellular Signaling Peptides and Proteins , Musculoskeletal Diseases , Rehabilitation , Therapeutics , Orthopedic Procedures , Methods , Osteogenesis , Regenerative Medicine , Methods , Singapore , Stem Cells , Stress, Mechanical , Tissue Engineering , Methods , Tissue Scaffolds , Weight-BearingABSTRACT
Objective To study the effect of Fructus Aurantii Immaturus Decoction on defecating function of constipated mice.Methods Constipation mice models were induced by Compound Diphenoxylate.Defecating effects of Fructus Aurantii Immaturus on normal and constipation mice were observed.Results Middle and high dose of Fructus Aurantii Immaturus decoction could increase impelling rate of small intestine,shorten the time for the first dark stools(P<0.05 or P<0.01).and add the amount of dark stools within 6 hours(P<0.01).Conclusion Fructus Aurantii Immaturus has the functions of loosening bowel to relieve constipation.
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Objective Explore the value of video-assisted thoracoscopic extended thymectomy in the treatment of myasthenia gravis.Methods This is a prospective randomized control study.Fifty-four patients who were confirmed to be MG preoperatively from 2005 to 2008 were divided into VATS group(27 cases)and thoracotomy group(27cases).Thymectomy and dissection of all faity tissue anterior to pericardium were performed in both groups.Results When compared with thoacotomy group,VATS group had less blood loss,shorter postoperative hospital stay and time of postoperative chest drainge tube left.One patient was converted to open surgery because of the injury to the brachiocephalic vein.During a period of followed-up 624 months,symptom was improved in 81% of the patients in VATS group and 85% in thoractomy group(P>0.05).Conclusion Extened thymectomy with VATS is safe and feasible with the advantage of less invasion,less surgical trauma and pain,lower rate of complication and good curative effect.
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A single factor duplicate test was designed to investigate whether bovine recombinded resistin impacts the expression of pyruvate carboxylase (PC) mRNA and the activity of PC in vitro culture bovine hepatocyte.Bovine recombinded resistin was added to the media with 0,25,50,100,200 and 400 ng/L.Abundance of PC mRNA in bovine hepatocyte,which was cultured with bovine recombinded resistin for 12 hours,was determined by real-time fluorescence quantitative RT-PCR,and activity of PC was determined by colourimetry.The results showed that bovine recombinded resistin could downregulate the expression of PC mRNA and the activity of PC in vitro culture bovine hepatocyte.
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Objective To study the application of VATS and gasless laparoscopy to the treatment of portal hepertension Methods 12 operations of the splenectomy combined with ligation of pericardial vein and lower part of lung covered by omentum majus were performed throngh the thoracoscopy and laparascopy Results All of the 12 operations were successful. The procedures lasted (2.5～5.2) hours with mean time being 3.3 hours. Gastrointestinal function recovered in (48-72) hours after operation. The duration of hospitalization was (9～11)days. No postoperative thoracic and abdominal cavity complications were found. The average duration of hospitalization after operation was 10.3 days.12 cases were followed up for 2 month to 4 years and no rebleeding was found. Conclusions The procedures including ligation of pericardial vein under VATS combined with gasless laparoscopy assisted splenectomy and lower part of lung covered by omentum majus for the treatment of portal hypertension is passable.