Rapid characterization of spike variants via mammalian cell surface display

The SARS-CoV-2 spike (S) protein is a critical component of subunit vaccines and a target for neutralizing antibodies. Spike is also undergoing immunogenic selection with clinical variants that increase infectivity and partially escape convalescent plasma. Here, we describe spike display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed [~]200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by thirteen neutralizing antibodies (nAbs). An alanine scan of all five N-terminal domain (NTD) loops highlights a public class of epitopes in the N1, N3, and N5 loops that are recognized by most of the NTD-binding nAbs. Some clinical NTD substitutions abrogate binding to these epitopes but are circulating at low frequencies around the globe. NTD mutations in variants of concern B.1.1.7 (United Kingdom), B.1.351 (South Africa), B.1.1.248 (Brazil), and B.1.427/B.1.429 (California) impact spike expression and escape most NTD-targeting nAbs. However, two classes of NTD nAbs still bind B.1.1.7 spikes and neutralize in pseudoviral assays. B.1.351 and B.1.1.248 include compensatory mutations that either increase spike expression or increase ACE2 binding affinity. Finally, B.1.351 and B.1.1.248 completely escape a potent ACE2 peptide mimic. We anticipate that spike display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.

Clinical and dermoscopic manifestations of nail damage in 12 cases of hand, foot and mouth disease / 中华皮肤科杂志

Objective:To investigate clinical and dermoscopic manifestations of nail damage secondary to hand, foot and mouth disease.Methods:Clinical data were collected from 12 patients with nail damage secondary to hand, foot and mouth disease in Department of Dermatology, Shandong Provincial Hospital from June to November 2015, and characteristics of nail damage were analyzed.Results:The clinical manifestations of nail damage following hand, foot and mouth disease included dryness of periungual skin (12 cases) , nail plate cavities (11 cases) , nail fractures (11cases) and Beau′s lines (4 cases) . Dermoscopy showed nail discoloration (12 cases) , nail delamination (12 cases) , horizontal streaks (10 cases) , longitudinal streaks (8 cases) , brown background of the nail matrix (11 cases) , telangiectasia (7 cases) , periungual desquamation (12 cases) and red background (10 cases) .Conclusion:The clinical manifestations of nail damage following hand, foot and mouth disease are mainly dryness of periungual skin, nail plate cavities and fractures, and its dermoscopic manifestations include nail discoloration, delamination, horizontal and longitudinal streaks, brown background of the nail matrix, telangiectasia, periungual desquamation and red background.

Three-dimensional reconstruction reduction and design of digital plates for proximal tibia fracture / 中国组织工程研究

BACKGROUND:In three-dimensional CT reconstruction model, fracture virtual reduction and internal fixation cannot be achieved, and reasonable operation scheme cannot be formulated. It cannot fuly meet the needs of clinical orthopedics physicians. OBJECTIVE:To explore the methods to perform three-dimensional reconstruction, reduction on proximal tibial fracture and to design digital plate using software. METHODS:Nine specimens of knee joint were built to be A1-3, B1-3 and C1-3 types of proximal tibial fracture according to the AO standard. Al specimens were treated with CT scan. Three-dimensional reconstruction and reduction on nine types of bone fracture models were performed in Mimics. The digital plates and screws were designed in Solidworks. Virtual internal fixation on the reduced three-dimensional models was performed. RESULTS AND CONCLUSION:Al bone fracture models received three-dimensional reconstruction and reduction, and the design for internal fixational plates and screws as wel as virtual internal fixation were accomplished. A3, B3 and C3 types were presented. These results suggest that the digital plates for proximal tibial fracture could be designed in Mimics and Solidworks with a personal computer. Our experience could be used in the real operation.

Laterodorsal tegmentum and pedunculopontine tegmental nucleus circuits regulate renal functions: Neuroanatomical evidence in mice models / 华中科技大学学报（医学）（英德文版）

Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney.

Manifestation of dynamic contrast-enhanced CT of hepatic injury in rabbits / 中华创伤杂志

Objective To analyze the features of dynamic contrast-enhanced CT of blunt hepatic injury in rabbits. Methods The model of blunt hepatic injury was established in 40 New Zealand white rabbits with a steel ball falling down to the xiphoid process of the animals. Plain CT scan and dynamic contrast-enhanced CT scan (Hispeed spiral CT/2i, GE, America) of the liver were performed. Arterial,portal and balanced phases were respectively at 8-10 s, 35-40 s and 120-150 s after initiation of the contrast medium injection. The non-enhanced and enhanced images were compared in aspects of location and range of injury, tear of the liver capsule, active bleeding, involvement of the main hepatic veins and CT features of abdominal hemorrhage, which was further compared with the results of gross anatomy. Results The rate of plain CT scan was obviously lower than that of dynamic contrast-enhanced CT scan,which defined single tear in 13 patients, multiple lacerations in 18, liver subcapsular hematoma in seven,liver hematoma in nine, liver coated gap in 17, active bleeding in nine and main hepatic vein injury in five, with coincidence rates with the results of gross observation for 13/13,18/18,7/9,9/9,25/30,9/5and 5/4 respectively. According to Moore' s classification, CT/Laparotomy performed from grade Ⅰ to grade Ⅵ were 5/4 patients at grade Ⅰ , 15/13 at grade Ⅱ, 9/11 at grade, 5/6 at grade Ⅳ, 1/2 at grade Ⅴ, O at grade respectively. Conclusion Dynamic contrast-enhanced CT scan, especially at portal and balanced phases, is of great value for diagnoses of liver injuries and determination of injury severity.