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Cellular immunity in Mycobacteria tuberculosis (Mtb) infection is important for the pathogenesis and final clearance of intracellular Mtb infection. In addition, it is valuable for the diagnosis of tuberculosis. In this pioneering work, we tested in vitro and in vivo antigen presentation and diagnostic application of a recombinant overlapping peptide-protein derived from two Mtb RD1 antigens ESAT-6 and CFP-10 (ROP-TB). The overlapping peptide sequence of ROP-TB is cleaved by the cathepsin S enzyme and covers the entire length of the two proteins. ROP-TB can be expressed and purified from E. coli. Once taken in by antigen-presenting cells, ROP-TB can be cleaved into a peptide pool by cathepsin S within the cells. We found that in dendritic cells, ROP-TB can be processed in 6 hours of co-culture, while the ESAT-6/CFP-10 fusion protein remained in the endosomal compartment. In Mtb-infected mice, ROP-TB stimulated stronger specific T cell responses than pooled synthetic peptides derived from ESAT-6 and CFP-10. With regard to the presentation of in vivo antigens, in a guinea pig model infected with Mtb, ROP-TB induced delayed type hypersensitivity (DTH) responses comparable to those of the tuberculin purified protein derivative (PPD) and ESAT-6/CFP-10 fusion protein. In Mycobacterium bovis (Bovine TB)-infected cattle, ROP-TB elicited DTH responses. Finally, in Mtb infected patients, ROP-TB stimulated cellular immune responses in majority of patients (16/18) of different HLA phenotypes while a single peptide derived from the same proteins did not elicit the immune responses in all patients. In summary, in vitro and in vivo data suggest that ROP-TB stimulates a strong cellular immune response irrespective of HLA phenotypes and is therefore suitable for use in vitro and in vivo diagnostics.

Quorum sensing (QS) has been reported to be involved in bacterial food spoilage. Acetylated homoserine lactones (AHLs) are QS signals of Gram-negative bacteria. AHL lactonases AiiAAI96 is a QS inhibitor, and thus can theoretically be applied to control the Gram-negative bacteria caused sturgeon spoilage by inhibiting their AHL-based QS system. As Gram-negative bacteria and Gram-positive bacteria were both found in spoilage sturgeon, the combination of AiiAAI96 and nisin, which is an effective bactericide to control the Gram-positive bacteria, was used to control the bacteria spoilage of sturgeon. The results showed that AiiAAI96 at 6.6 × 10−2, 6.6 × 10−1 and 6.6 U/mL could suppress the growth of microflora and delayed the increase of TVB-N, sensory score and biogenic amine levels of sturgeon. In addition, 6.6 U/mL AiiAAI96 coupled with 2000 AU/mL nisin exhibited the strongest inhibition effect on spoilage and extended their shelf life by about 5 days. In conclusion, AiiAAI96 combined with nisin could be used as a suitable biological preservative for chilled sturgeon fillets.

The applied research in remote sensing images has been pushed by convolutional neural network (CNN). Because of the fixed size of the perceptual field, CNN is unable to model global semantic relevance. Modeling global semantic information is possible with the self-attentive Transformer-based model. However, the method of patch computation used by Transformer for self-attentive computation ignores the spatial information inside each patch. To address these issues, we offer the STransFuse model as a new semantic segmentation method for remote sensing images. It is a model that combines the benefits of Transformer with CNN to improve the segmentation quality of various remote sensing images. We employ a staged model to extract coarse-grained and fine-grained feature representations at various semantic scales, unlike earlier techniques based on Transformer model fusion. In order to take full advantage of the features acquired at different stages, we designed an adaptive fusion module. This module adaptively fuses the semantic information between features at different scales employing a self-attentive mechanism. The overall accuracy (OA) of our proposed model on the Vaihingen dataset is 1.36% higher than the baseline, and 1.27% improvement in OA over baseline on the Potsdam dataset. When compared to other advanced models, the STransFuse model performs admirably.

Inspired by the impressive achievements of convolutional neural networks in various computer vision tasks and the effective role of attention mechanisms, this article proposes a two-branch fusion network based on attention feature fusion (AFF) called Attention_FPNet to solve the pansharpening problem. We reconstruct the spatial information of the image in the high-pass filter domain and fully consider the spatial information in the multispectral (MS) and panchromatic (PAN) images. At the same time, the input PAN image and the upsampled MS image are directly transmitted to the reconstructed image through a long skip connection. The spectral information of the PAN and MS images is considered to improve the spectral resolution of the fused image. It also supplements the loss of spatial information that may be caused by network deepening. Moreover, an AFF method is used to replace the existing simple channel concatenation method commonly used in pansharpening, which fully considers the relationship between different feature maps and improves the fusion quality. Through experiments on image datasets acquired by the Pleiades, SPOT-6 and Gaofen-2 satellites, the results show that this method can effectively fuse PAN and MS images and generate a fused image and outperforms existing methods.

Multidimensional photography has traditionally been restricted by their static optical architectures and measurement schemes. Here, the authors present a tunable multidimensional photography approach employing active optical mapping, which allows them to adapt the acquisition schemes to the scene.

Abstract Topology Optimization (TO) is a powerful numerical technique to determine the optimal material layout in a design domain, which has accepted considerable developments in recent years. The classic Finite Element Method (FEM) is applied to compute the unknown structural responses in TO. However, several numerical deficiencies of the FEM significantly influence the effectiveness and efficiency of TO. In order to eliminate the negative influence of the FEM on TO, IsoGeometric Analysis (IGA) has become a promising alternative due to its unique feature that the Computer-Aided Design (CAD) model and Computer-Aided Engineering (CAE) model can be unified into a same mathematical model. In the paper, the main intention is to provide a comprehensive overview for the developments of Isogeometric Topology Optimization (ITO) in methods and applications. Finally, some prospects for the developments of ITO in the future are also presented.

Traditional feature dimensionality reduction (FDR) algorithms can extract features by reducing feature dimensions. However, it may lose some useful information and affect the accuracy of classification. Normally, in traditional defect feature extraction, it first obtain the defect area of the defect image by image preprocessing and defect segmentation, select the original feature set of defects by prior knowledge, and extract the optimal features by traditional FDR algorithms to solve the problem of "curse of dimensionality". In this paper, a feature extraction and classification algorithm based on improved sparse auto-encoder (AE) is proposed. We adopt three traditional FDR algorithms at the same time, combine the defect features obtained in pairs, take the merged defect features as the input of sparse AE, then use the "bottleneck" of sparse AE to conduct the defects classification by Softmax classifier. The experimental results show that the proposed algorithm can extract the optimal features of round steel surface defects with less network training time than individual sparse AE, finally get higher classification accuracy than individual FDR algorithm in the actual production line.

Abstract Background Horseshoe kidney (HSK) is a common renal fusion anomaly, occurring in about 1 in 400–600 individuals. In addition, the incidence of duplicated collecting system is about 0.8%. Case presentation This report documents an extremely rare case, which was treated by multiple procedures in the same operative session to accomplish laparoscopic amputation of the HSK isthmus, resection of duplicate kidney and ureteroscopic lithotripsy. Conclusion Results showed that minimally invasive surgery with use of multiple endoscopes may be a feasible choice for this patient population with complicated comorbid renal conditions.

Abstract Recent researches show that there are some anomalies, which are not satisfied with common sense, appearing in some special permutation flow shop scheduling problems (PFSPs). These anomalies can be divided into three different types, such as changing the processing time of some operations, changing the number of total jobs and changing the number of total machines. This paper summarizes these three types of anomalies showing in the special PFSPs and gives some examples to make them better understood. The extended critical path is proposed and the reason why these anomalies happen in special PFSPs is given: anomalies will occur in these special PFSPs when the time of the operations on the reverse critical path changes. After that, the further reason for these anomalies is presented that when any one of these three types of anomalies happens, the original constraint in the special PFSPs is destroyed, which makes the anomalies appear. Finally, the application of these anomalies in production practice is given through examples and also with the possible research directions. The main contribution of this research is analyzing the intial reason why the anomalies appear in special PFSPs and pointing out the application and the possible research directions of all these three types of anomalies.

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

Abstract Background To investigate predictors of postoperative acute intracranial hemorrhage (AIH) and recurrence of chronic subdural hematoma (CSDH) after burr hole drainage. Methods A multicenter retrospective study of patients who underwent burr hole drainage for CSDH between January 2013 and March 2019. Results A total of 448 CSDH patients were enrolled in the study. CSDH recurrence occurred in 60 patients, with a recurrence rate of 13.4%. The mean time interval between initial burr hole drainage and recurrence was 40.8 ± 28.3 days. Postoperative AIH developed in 23 patients, with an incidence of 5.1%. The mean time interval between initial burr hole drainage and postoperative AIH was 4.7 ± 2.9 days. Bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independent predictors of recurrence in the multiple logistic regression analyses. Preoperative headache was an independent risk factor of postoperative AIH in the multiple logistic regression analyses, however, intraoperative irrigation reduced the incidence of postoperative AIH. Conclusions This study found that bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independently associated with CSDH recurrence. Clinical presentation of headache was the strongest predictor of postoperative AIH, and intraoperative irrigation decreased the incidence of postoperative AIH.

ObjectiveHydrocephalus is common after ventriculitis. This study explores hydrocephalus's clinical characteristics following pyogenic ventriculitis due to multidrug-resistant and extensively drug-resistant Acinetobacter baumannii and Klebsiella pneumoniae.Patients and MethodsWe retrospectively reviewed patients with post-neurosurgical pyogenic ventriculitis due to multidrug-resistant and extensively drug-resistant A. baumannii and K. pneumoniae in our department between January 2014 and June 2020. Once diagnosed, patients received intraventricular lavage followed by daily intraventricular administration of Colistin (polymyxin-E). The patient's clinical/radiographic findings were analyzed and evaluated 6 months after discharge.ResultsIn total, 48 cases were included in this study, and 25% were female. The median age was 45 (SD ± 15) years old. Median intraventricular Colistin administration to acquire sterile cerebrospinal fluid (CSF) was 20 days. Forty-one patients developed hydrocephalus; among them, 18 (43%) had multiloculated hydrocephalus (MLH), 23 (56%) had uni/non-loculated hydrocephalus (ULH/NLH), and 7 (17%) did not develop hydrocephalus. The patients with MLH had (15 days) delayed initiation of intraventricular irrigation (p < 0.022). They had (32 days) longer intraventricular Colistin (p < 0.003) and showed worse outcomes in terms of Glasgow outcome score (GOS) at 6 months follow-up than those without hydrocephalus. The mean score of the MLH group was 1.67 (SD1.23), and ULH/NLH was 2.61 (SD1.4) at p < 0.008.ConclusionMultiloculated hydrocephalus is common in patients receiving delayed intraventricular administration of Colistin and required a longer duration on intraventricular Colistin to treat the pyogenic ventriculitis caused by multidrug/extensive drug-resistant A. baumannii and K. pneumoniae. It is associated with worse clinical outcomes.

BackgroundsAlthough there are a certain number of studies dedicated to the disturbances of the dopaminergic system induced by traumatic brain injury (TBI), the associations of abnormal dopaminergic systems with post-traumatic anxiety and depressive disorders and their underlying mechanisms have not been clarified yet. In the midbrain, dopaminergic neurons are mainly situated in the substantia nigra (SN) and the ventral tegmental area (VTA). Thus, we selected SN and VTA as regions of interest and performed a seed-based global correlation to evaluate the altered functional connectivity throughout the dopaminergic system post-TBI.MethodsThirty-three individuals with TBI and 21 healthy controls were recruited in the study. Anxiety and depressive symptoms were examined by the Hospital Anxiety and Depression Scale. All MRI data were collected using a Siemens Prisma 3.0 Tesla MRI system. The volume of SN and the global functional connectivity of the SN and VTA were analyzed.ResultsIn the present study, patients with TBI reported more anxiety and depressive symptoms. More importantly, some structural and functional alterations, such as smaller SN and reduced functional connectivity in the left SN, were seen in individuals with TBI. Patients with TBI had smaller substantia nigra on both right and left sides, and the left substantia nigra was relatively small in contrast with the right one. Among these findings, functional connectivity between left SN and left angular gyrus was positively associated with post-traumatic anxiety symptoms and negatively associated with depressive symptoms.ConclusionsThe TBI causes leftward lateralization of structural and functional alterations in the substantia nigra. An impaired mesocortical functional connectivity might be implicated in post-traumatic anxiety and depression.

The assembly of colloids under directional interactions is a powerful way to create 1D chain-like structures (colloidal polymers). However, these colloidal polymers usually disassociate into separate colloids when the surrounding conditions are changed, and additional solidification treatments are required. Herein, we report an in situ welding of colloidal polymers simultaneous with assembly process in solution. When dispersed in a solution containing trace amounts of water, iron oxide dipolar cubes self-associate into chains, and the simultaneous in situ hydrolysis-condensation of tetraethylorthosilicate welds these chains into permanent colloidal polymers. With low water contents, the 1D colloidal assembly is directed by self-induced dipolar interactions via the step-growth mechanism, and the water content has no significant effect on the assembly process but changes the silica shell thickness on the colloidal polymers. With higher water contents, 2D and 3D structures are formed due to the nondirectional attraction of the water on the colloids.

Pyroptosis is defined as an inflammatory form of programmed cell death. Increasing studies have demonstrated that pyroptosis is closely related to tumor development and antitumor process. However, the role of pyroptosis in kidney renal papillary cell carcinoma (KIRP) remains obscure. In this study, we analyzed the expression of 52 pyroptosis-related genes (PRGs) in KIRP, of which 20 differentially expressed PRGs were identified between tumor and normal tissues. Consensus clustering analysis based on these PRGs was used to divided patients into two clusters, from which a significant difference in survival was found (p = 0.0041). The prognostic risk model based on six PRGs (CASP8, CASP9, CHMP2A, GPX4, IL6, and IRF1) was built using univariate Cox regression and LASSO–Cox regression analysis, with good performance in predicting one-, three-, and five-year overall survival. Kaplan–Meier survival analysis showed that the high-risk group had a poor survival outcome (p < 0.001) and risk score was an independent prognostic factor (HR: 2.655, 95% CI 1.192–5.911, p = 0.016). Immune profiling revealed differences in immune cell infiltration between the two groups, and the infiltration of M2 macrophages was significantly upregulated in the tumor immune microenvironment, implying that tumor immunity participated in the KIRP progression. Finally, we identified two hub genes in tumor tissues (IL6 and CASP9), which were validated in vitro. In conclusion, we conducted a comprehensive analysis of PRGs in KIRP and tried to provide a pyroptosis-related signature for predicting the prognosis.

Background Gluteal muscle contracture (GMC) may cause abnormal spinal alignment as well as hip and pelvic deformities. The spine-pelvis alignment of GMC patients is unclear. This study aimed to describe the spine-pelvis sagittal alignment in patients with GMC and to explore the impact of GMC on the pathogenesis of low back pain (LBP). Methods Radiological analysis was performed in 100 patients with GMC and 100 asymptomatic volunteers who acted as the control group. Sagittal parameters were measured by two independent raters and their averages were presented on lateral radiographs of the whole spine, including pelvic incidence (PI), sagittal vertical axis (SVA), pelvic tilt (PT), lumbar lordosis (LL), sacral slope (SS), thoracic kyphosis (TK), and the relationship between PI and LL (expressed as PI-LL). All cases were categorized into one of three classes based on the apex position of lumbar lordosis and were further divided into three groups by the PI value. The GMC and control parameters were compared and the correlations between the parameters in the GMC group were analysed. Results The PI value of the GMC group was significantly less than that of the control group (42.38 ± 10.90° vs 45.68 ± 7.49°, P < 0.05). There was no difference found between the key parameters (SVA, PT, and PI-LL), which correlated with outcomes in adult deformity. No differences of SS were found between the two groups (P > 0.05). The GMC group showed lower average LL (42.77 ± 10.97° vs 46.41 ± 9.07°) and TK (17.34 ± 9.50° vs 20.45 ± 8.02°) compared with the control group (P < 0.05). LL was correlated with PI, SS, PT, TK (P < 0.01) and SVA (P < 0.05). TK and SVA were not correlated with any parameters except LL and pairwise correlations were found among PI, SS, and PT. There were no differences found between the distributions of the lumbar lordosis apex of GMC and the control but the range of SS in apex groups 3 and 4 did differ. GMC patients had the most small-PI value (44%) while approximately 64% of asymptomatic individuals had a normal PI. Interobserver variability was sufficient for all parameters calculated by the intraclass correlation coefficient (ICC). Conclusions Gluteal muscle contracture causes a low PI which may contribute to low back pain. Patients with GMC present the same global sagittal spinal-pelvic balance as asymptomatic individuals due to a compensatory mechanism through excessive flat lumbar and thoracic curves. Future studies on the relationship between spinal-pelvic sagittal and coronal alignment and low back pain are needed to understand the mechanical forces involved in the onset of GMC.

Compared with conventional sandwich structures with two identical face sheets, geometrically asymmetric porous sandwich structures (GAPSSs) can achieve better dynamic performances under certain load and boundary condition, since they provide more choices for geometric design. However, current studies regarding the GAPSSs are mainly analytical- and experimental-based methods with predefined face sheet thicknesses and core configurations, few works investigate the GAPSSs by optimization method. This paper presents a multiscale topology optimization method of the GAPSSs, which is capable of designing both thicknesses of two solid face sheets at macroscale and configurations of porous core at microscale for minimizing dynamic compliance. Specifically, at macroscale, a variable thickness sheet method is employed to optimize the thicknesses of two solid face sheets. Then, at microscale, a parametric level-set method integrated with a numerical homogenization approach is applied to topologically optimize the configuration of the periodic unit cell. The method of moving asymptotes is adopted to update the design variables at both scales. Several 2D and 3D numerical examples are illustrated to show the effectiveness and advantages of the proposed method for designing the GAPSSs. The results indicate that the dynamic compliance of the optimized GAPSSs show superior advantages over the conventional sandwich structures with identical face sheet thicknesses and predefined lattice core.

A new type of light steel-wood-plastic residential structure in rural has popular in recent years in rural Yunnan, China. The application of light steel, wood, and new plastic materials in practical engineering is gradually increasing due to its advantages of green ecology and waste utilization, and its response characteristics under earthquakes have attracted great attention. In this paper, seismic-resistant models, seismic-isolated models, and seismic-damped models for multistorey light steel-wood-plastic structures were established using the SAP2000 finite element software based on different seismic response methods. The seismic-isolated model is divided into five schemes, namely, LRB400, LRB500, LRB600, high damped, and friction pendulum-isolated bearings, and the seismic-damped model is divided into three schemes, namely, ordinary bracing, soft-steel bracing, and BRB bracing at the same locations around the 2nd floor of the building. Nonlinear time analysis was carried out for the nine schemes, comparing the period, structural interstorey displacement, base shear, top displacement, top acceleration, and economy of the structure under the action of an 8-degree earthquake. Results show that the period of the seismic-isolated system increased by approximately 130% compared to the seismic-resistant system, and the period of the damped system decreased slightly compared to the seismic system, the interstorey displacement, base shear, and top acceleration of both the seismic-isolated system and the damped system were smaller than those of the seismic-resistant system, and the seismic-isolated system decreased by approximately 40% compared to the damped system, and the seismic-isolated system was more effective than the damped system. From the comparison of postearthquake damage cost and full-cycle cost, the economic performance of the seismic-isolated structure is better than that of the damped and seismic-resistant structures. The conclusions of this paper can provide a scientific reference for promoting the use of new light steel-wood-plastic residential buildings.

The joints in the rock mass are essential for the stability of rocky slopes, and the destabilization damage of the slope is often directly related to the joints. In this study, in order to reveal the instability process and mechanism of rock slopes from a microscale perspective, the DEM simulations for rocky slopes of the K88 + 400∼K88 + 540 section of Zhongkai Expressway are carried out considering the influence of joints. Based on the findings of the on-site jointed structural surfaces, a rocky slope model containing two sets of intermittent joints was constructed, and the linear parallel bond model and the smooth joint model are used to characterize the rock body and joints, respectively. The evolution of microfracture, contact force chain, and particle displacement are analyzed to explore the micromechanism of slope instability. Finally, the triple reinforcement scheme of anchor cable frame and grass planting is proposed. The research results can provide a reference for stability analysis and reinforcement of similar rocky slope projects.

Digital twins are applied in smart manufacturing towards a smarter cyber-physical manufacturing system for effective analysis, fault diagnosis, and system optimization of a physical system. In this paper, a framework applying a digital twin to industrial robots is proposed and realizes the real-time monitoring and performance optimization of industrial robots. This framework includes multi-domain modeling, behavioral matching, control optimization, and parameter updating. The properties of the industrial robot are first modeled in a digital environment to realize the strong interactive and all-around 3D visual monitoring. Then, behavioral matching is performed to map the virtual system to the physical system in real time. Furthermore, the control performance of the system is improved by using a fractional order controller based on the improved particle swarm optimization algorithm. This framework is applied to the experimental verification of real-time control optimization on an industrial robot. The time-domain performance is improved in the simulation and experimental results, where the overshoot is promoted at least 42%, the peak time is promoted at least 32%, and the settling time is promoted at least 33%. The simulation and experimental results demonstrate the effectiveness of the proposed framework for a digital twin combined with fractional order control (FOC).

Biped locomotion provides more mobility and effectiveness compared with other methods. Animals have evolved efficient walking patterns that are pursued by biped robot researchers. Current researchers have observed that symmetry is a critical criterion to achieve efficient natural walking and usually realize symmetrical gait patterns through morphological characteristics using simplified dynamic models or artificial priors of the center of mass (CoM). However, few considerations of symmetry and energy consumption are introduced at the joint level, resulting in inefficient leg motion. In this paper, we propose a full-order biped gait planner in which the symmetry requirement, energy efficiency, and trajectory smoothness can all be involved at the joint level, and CoM motion is automatically determined without any morphological prior. In order to achieve a symmetrical and efficient walking pattern, we first investigated the characteristic of a completely symmetrical gait, and a group of nearly linear slacked constraints was designed for three phases of planning. Then a Constrained Direct Collocation (DIRCON)-based full-order biped gait planner with a weighted cost function for energy consumption and trajectory smoothness is proposed. A dynamic simulation with our newly designed robot model was performed in CoppliaSim to test the planner. Physical comparison experiments on a real robot device finally validated the symmetry characteristic and energy efficiency of the generated gait. In addition, a detailed presentation of the real biped robot is also provided.

The heat dissipation capability of the battery thermal management system (BTMS) is a prerequisite for the safe and normal work of the battery. Currently, many researchers have designed and studied the structure of BTMS to better control the battery temperature in a specific range and to obtain better temperature uniformity. This allows the battery to work safely and efficiently while extending its life. As a result, BTMS has been a hot topic of research. This work investigates the impact of pin-fins on the heat dissipation capability of the BTMS using the computational fluid dynamics (CFD) approach, designs several BTMS schemes with different pin-fin structures, simulates all schemes for fluid-structure interaction, and examines the impact of different distribution, number, and shape of pin-fins on heat dissipation capability and pressure drop. Analyzing the effect of cooling plates with different pin-fins on the thermal capability of the BTMS can provide a basis for the structural design of this BTMS with pin-fin cooling plates. The findings demonstrate that the distribution and quantity of pin-fin shapes might affect heat dissipation. The square-section pin-fins offer better heat dissipation than other pin-fin shapes. As the pin-fins number increases, the maximum battery temperature decreases, but the pressure drop increases. It has been observed that uniform pin-fin distribution has a superior heat dissipation effect than other pin-fin distribution schemes. In summary, the cooling plate with a uniform distribution of 3 × 6 square section pin-fins has better heat dissipation capability and less power consumption, with a maximum battery temperature of 306.19 K, an average temperature of 304.20 K, a temperature difference of 5.18 K, and a pressure drop of 99.29 Pa.

Deeply understanding the dynamic operating characteristics of high-speed railway (HSR) systems is of essential significance in theory and practice for the planning, construction, and operational management of HSR systems. In this paper, the HSR system is described as a temporal network, and the evolution of connected clusters in the system is considered as a percolation process. The critical integration time Tc of the percolation process can determine the formation of a globally connected cluster and measure the transport performance of the HSR system. The appearance time of critical edges identified at Tc can significantly affect the reliability of the transport performance of an HSR system. Compared to random percolation in the static HSR network, it can be found that the critical fraction pc of the percolation process in a temporal HSR network is almost always larger. This indicates that the global connectivity and the transport performance of HSR systems is overestimated by the static network abstraction. This paper provides a promising way of understanding the dynamic characteristics of HSR systems, evaluating their transport performance, and improving their reliability.

Objective: Myocardial injury is a severe complication in population exposed to high altitude. As a new biomarker for inflammatory response, neutrophil to lymphocyte ratio (NLR) has been widely used to predict the prognosis of various diseases. In this study, we intend to explore the risk factors for myocardial injury at high altitude and examine the relationship between NLR level and development of myocardial injury.Methods: Consecutive patients admitted to a secondary general hospital at high altitude from June 2019 to May 2020 were selected into this retrospective study. Clinical and biochemical data were collected. According to the results of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzymes (CK-MB), and aspartate amino transferase (AST), patients were divided into myocardial injury group and normal group.Results: A total of 476 patients were enrolled in this study. Myocardial injury occurred in 158 patients (33.2%). We found that altitude, NLR, hemoglobin, total bilirubin, total cholesterol, and lipoprotein A in myocardial injury group were significantly higher than that in normal group (P < 0.05), while platelet count in myocardial injury group was significantly lower than that in normal group (P < 0.05). Logistic multivariate regression analysis revealed that there was an independent relationship between myocardial injury and smoke, NLR, hemoglobin (P < 0.05). By using Spearman correlation analysis, NLR was proved to have a significant positive correlation with LDH, CK, and CK-MB (P < 0.05) instead of AST. A receiver operating characteristic (ROC) curve was drawn to demonstrate that NLR could significantly predict the occurrence of myocardial injury with an area under the curve (AUC) of 0.594 (95% CI: 0.537–0.650, P < 0.05), and the level of 2.967 (sensitivity = 38.0%, specificity = 83.6%) was optimal cutoff value.Conclusion: The incidence of myocardial injury is high in population at high altitude. Smoke, hemoglobin, and NLR are independent factors related to myocardial injury. As a convenient and efficient marker, NLR is found to be closely associated with myocardial enzymes and have a predict role in the occurrence of myocardial injury. This study will provide a theoretical basis on NLR for the early diagnosis of myocardial injury at high altitude.

Lumbar disc herniation (LDH) with radicular pain is a common and complicated musculoskeletal disorder. Our previous study showed that LDH-induced methylglyoxal (MG) accumulation contributed to radicular pain. The underlying mechanisms through which MG accumulates are poorly understood. In the present study, we found that both MG and tumor necrosis factor-alpha (TNF-ɑ) levels in the herniated disc of patients with radicular pain were significantly increased, and the activity of Glyoxalase 1 (GLO1), the rate-limiting enzyme that metabolizes MG, was decreased. In rats, the LDH model was mimicked by implantation of autologous nucleus pulposus (NP) to the left lumbar five spinal nerve root. The mechanical allodynia was observed in LDH rats. Besides, MG and TNF-ɑ levels were increased, and GLO1 activity was significantly decreased in the implanted NP. In cultured rat NP cells, stimulation with the inflammatory mediator TNF-ɑ reduced GLO1 activity and expression. These results suggested that TNF-ɑ-induced GLO1 activity decrease contributed to MG accumulation in the herniated disc of patients with radicular pain.

Bone marrow mesenchymal stem cells (BMSCs) play a critical role in bone formation and are extremely sensitive to external mechanical stimuli. Mechanical signals can regulate the biological behavior of cells on the surface of titanium-related prostheses and inducing osteogenic differentiation of BMSCs, which provides the integration of host bone and prosthesis benefits. But the mechanism is still unclear. In this study, BMSCs planted on the surface of TiO2 nanotubes were subjected to cyclic mechanical stress, and the related mechanisms were explored. The results of alkaline phosphatase staining, real-time PCR, and Western blot showed that cyclic mechanical stress can regulate the expression level of osteogenic differentiation markers in BMSCs on the surface of TiO2 nanotubes through Wnt/β-catenin. As an important member of the histone acetyltransferase family, GCN5 exerted regulatory effects on receiving mechanical signals. The results of the ChIP assay indicated that GCN5 could activate the Wnt promoter region. Hence, we concluded that the osteogenic differentiation ability of BMSCs on the surface of TiO2 nanotubes was enhanced under the stimulation of cyclic mechanical stress, and GCN5 mediated this process through Wnt/β-catenin.

Permanent magnet synchronous motors (PMSM) have been substantially used in electric vehicles (EVs) due to their advantages such as low loss, large torque, and high power density. With the continuous improvement of the PMSM performance requirements, its heat dissipation has also attracted increasing attention. This paper proposes a cooling system to realize the heat dissipation of the motor through internal oil circulation and external water circulation. Meanwhile, to obtain the best cooling system parameters, an optimization framework is developed for heat dissipation optimization of the motor. First, the most suitable Latin hypercube sampling (LHS) method is selected for sampling through the Coordinates exchange algorithm. Second, we separately study the modeling accuracy of thirteen surrogate models and finally select the back propagation (BP) neural network model. Then, we use six multi-objective optimization algorithms (MOOAs) to optimize the model, and select the optimal solution via the utopian point method. Finally, the motor heat dissipation situation is effectively improved, and the effectiveness and reliability of the optimization framework are proved, which provides an alternative mean for the heat dissipation design optimization of the motor and has prominent practical significance.

The vulnerability of current face recognition systems to presentation attacks significantly limits their application in biometrics. Herein, we present a passive presentation attack detection method based on a complete plenoptic imaging system which can derive the complete plenoptic function of light rays using a single detector. Moreover, we constructed a multi-dimensional face database with 50 subjects and seven different types of presentation attacks. We experimentally demonstrated that our approach outperforms the state-of-the-art methods on all types of presentation attacks.

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.

Reduced-dimensional halide perovskites are promising for light-emitting diodes but suffer from photo-degradation. Here Quan et al. identify the edge of the perovskite nanoplatelets as the degradation channels and use phosphine oxides to passivate the edges and boost device performance and lifetime.

Abstract Background The supercapsular percutaneously-assisted total hip arthroplasty (SuperPath) was proposed to be minimally invasive and tissue sparing with possible superior postoperative outcomes to traditional approaches of total hip arthroplasty (THA). Here, we compared the short-term outcomes of staged THA with the SuperPath or through posterolateral approach (PLA) for bilateral osteonecrosis of the femoral head (ONFH). Methods Patients with bilateral late-stage ONFH were prospectively recruited from our department from March 2017 to March 2018. Staged bilateral THAs with one side SuperPath and the other side PLA were performed consecutively in the same patients with right and left hips alternating within approaches. The average time interval between the staged THAs was 3 months. Perioperative status (operation time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay) and postoperative function (range of motion, pain, and hip function) were recorded and compared between the SuperPath and PLA approaches within 12-month postoperatively. Results Four male patients (age, 51.00 ± 4.54; BMI, 21.49 ± 1.73) with bilateral alcohol-induced ONFH (Ficat III/IV) were followed up over 12 months postoperatively. Compared with the PLA, the SuperPath yielded shorter incision length (7.62 vs. 11.12 cm), longer operation time (103.25 vs. 66.50 min), more blood loss (1108.50 vs. 843.50 ml), deficient abduction angle of the acetabular cup (38.75° vs. 44.50°), and inferior early-term hip function (Harris hip score, 72.50 vs. 83.25) at 12-month postoperatively. Soft tissue damage, length of hospital stay, postoperative pain, postoperative range of motion, and 12-month patient satisfaction were comparable between both approaches. Conclusion The SuperPath may be a minimally invasive technique but the present study shows less favorable short-term outcomes than PLA for total hip arthroplasty in osteonecrosis of the femoral head. More investigations are required to provide convincing favorable evidences of the SuperPath over other traditional THA approaches. Trial registration information The trial was retrospectively registered in https://www.researchregistry.com (No. Researchregistry4993) on July 04, 2019. The first participant was enrolled on March 13, 2017.

Abstract Background Articular cartilage lesions generated by trauma or osteoarthritis are the most common causes of pain and disability in patients. Abstract The development of photopolymerizable hydrogels has allowed for significant advances in cartilage repair procedures. Such three-dimensional (3D) networks of polymers that carry large amounts of water can be created to resemble the physical characteristics of the articular cartilage and be delivered into ill-defined cartilage defects as a liquid solution prior to polymerization in vivo for perfect fit with the surrounding native tissue. These hydrogels offer an adapted environment to encapsulate and propagate regenerative cells in 3D cultures for cartilage repair. Among them, mesenchymal stem cells and chondrocytes may represent the most adapted sources for implantation. They also represent platforms to deliver therapeutic, biologically active factors that promote 3D cell differentiation and maintenance for in vivo repair. Conclusion This review presents the benefits of photopolymerization of hydrogels and describes the photoinitiators and materials in current use for enhanced cartilage repair.

An energy-storage system comprised of lithium-ion battery modules is considered to be a core component of new energy vehicles, as it provides the main power source for the transmission system. However, manufacturing defects in battery modules lead to variations in performance among the cells used in series or parallel configuration. This variation results in incomplete charge and discharge of batteries and non-uniform temperature distribution, which further lead to reduction of cycle life and battery capacity over time. To solve this problem, this work uses experimental and numerical methods to conduct a comprehensive investigation on the clustering of battery cells with similar performance in order to produce a battery module with improved electrochemical performance. Experiments were first performed by dismantling battery modules for the measurement of performance parameters. The k-means clustering and support vector clustering (SVC) algorithms were then employed to produce battery modules composed of 12 cells each. Experimental verification of the results obtained from the clustering analysis was performed by measuring the temperature rise in the cells over a certain period, while air cooling was provided. It was found that the SVC-clustered battery module in Category 3 exhibited the best performance, with a maximum observed temperature of 32 °C. By contrast, the maximum observed temperatures of the other battery modules were higher, at 40 °C for Category 1 (manufacturer), 36 °C for Category 2 (manufacturer), and 35 °C for Category 4 (k-means-clustered battery module). Keywords: Clustering algorithm, Battery module, Equalization, Electric vehicle

Abstract Applications of graphene as transparent conductive electrodes (TCE) have been hindered either by high cost of single crystal graphene or balance between transparency and sheet resistance of polycrystalline graphene. In this work, we propose to fabricate multilayer graphene film grids (MGFG) to enhance transparency and keep low sheet resistance through IR laser tailoring. It is proved that the transparency of MGFG could be increased by 200 times while remaining its competitive sheet resistance as low as 340 Ω sq−1 through adjusting the tailoring grid, and the corresponding figures of merit (FoM) is increased from 0.1 to 3.6. As-obtained MGFG is demonstrated in generating controllable local thermal field and defogging efficiently. The strategy of laser-tailoring grid will greatly advance the applications of graphene for transparent electrodes in industry.

With the development of the smart manufacturing, data-driven fault diagnosis has receiving more and more attentions from both academic and engineering fields. As one of the most important data-driven fault diagnosis method, deep learning (DL) has achieved remarkable applications. However, the DL based fault diagnosis methods still have the following two drawbacks: 1) One of the most major branch of deep learning is to construct the deeper structures, however the deep learning models in fault diagnosis is very shadow. 2) As stated by the no-free-lunch theorem, no single model can perform best on every dataset, and the individual deep learning model still suffers from the generalization ability. In this research, a new negative correlation ensemble transfer learning method (NCTE) is proposed. Firstly, the transfer learning based ResNet-50 is proposed to construct a deep learning structure that has 50 layers. Secondly, several fully-connected layers and softmax classifiers are trained cooperatively using negative correlation learning (NCL). Thirdly, the hyper-parameters of the proposed NCTE are determined by cross validation. The proposed NCTE is conducted on the KAT Bearing Dataset, and the prediction accuracy of NCTE is as high as 98.73%. This results show that NCTE has achieved a good results compared with other machine learning and deep learning method.

Optics-free circularly-polarized light detection has suffered from extremely low responsivity. Here Chen et al. demonstrate chiral organic–inorganic hybrid perovskite based detectors to distinguish circularly-polarized light with high responsivity of 797 mA/W.

Abstract The flexible job shop scheduling problem (FJSP) is considered as an important problem in the modern manufacturing system. It is known to be an NP-hard problem. Most of the algorithms used in solving FJSP problem are categorized as metaheuristic methods. Some of these methods normally consume more CPU time and some other methods are more complicated which make them difficult to code and not easy to reproduce. This paper proposes a modified iterated greedy (IG) algorithm to deal with FJSP problem in order to provide a simpler metaheuristic, which is easier to code and to reproduce than some other much more complex methods. This is done by separating the classical IG into two phases. Each phase is used to solve a sub-problem of the FJSP: sequencing and routing sub-problems. A set of dispatching rules are employed in the proposed algorithm for the sequencing and machine selection in the construction phase of the solution. To evaluate the performance of proposed algorithm, some experiments including some famous FJSP benchmarks have been conducted. By compared with other algorithms, the experimental results show that the presented algorithm is competitive and able to find global optimum for most instances. The simplicity of the proposed IG provides an effective method that is also easy to apply and consumes less CPU time in solving the FJSP problem.

Turbojet engines have a slow response and require mechanical assistance to perform vertical take-offs and landings. In this paper, we propose a vertical take-off and landing (VTOL) aircraft that contains one-dimensional thrust vectoring nozzle modules to solve the problem of dependence on the response of the turbojet. The turbojet engine is placed horizontally in the module, the rotational speeds are fixed, and the force along the turbojet axis remains constant as the nozzle rotates from the horizontal to the vertical position. The aircraft is composed of four modules, whose position and attitude control are realized by using the thrust difference caused by the different angles of the four vector nozzles. The modules no longer rely on the response speed of the turbojet engine, and controlling the angles of four nozzles makes it easier to operate the aircraft. The horizontal placement of the turbojet can reduce the thickness of the aircraft fuselage and decrease air resistance. The process of moving the nozzle from a horizontal to a vertical position prevents the engine from blowing directly on the ground and, thus, reduces the ground effect.

Bearing fault diagnosis is important to ensure safe operation and reduce loss for most rotating machinery. In recent years, deep learning (DL) has been widely used for bearing fault diagnosis and has achieved excellent results. Continuous wavelet transform (CWT), which can convert original sensor data to time–frequency images, is often used to preprocess vibration data for the DL model. However, in time–frequency images, some frequency components may be important, and some may be unimportant for DL models for fault diagnosis. So, how to choose a frequency range of important frequency components is needed for CWT. In this paper, an Integrated Gradient-based continuous wavelet transform (IG-CWT) method is proposed to address this issue. Through IG-CWT, the important frequency components and the component frequency range can be detected and used for data preprocessing. To verify our method, experiments are conducted on four famous bearing datasets using 3 DL models, separately, and compared with CWT, and the results are compared with the original CWT. The comparisons show that the proposed IG-CWT can achieve higher fault diagnosis accuracy.

Various constraints exist in bipedal movement. Due to the natural ability of effectively handling constraints, trajectory optimization has become one of the mainstream methods in biped gait planning, especially when constraints become much more complex on non-flat terrain. In this paper, we propose a multi-modal biped gait planner based on DIRCON, which can generate different gaits for multiple, non-flat terrains. Firstly, a virtual knot is designed to model the state transitions when the swing foot contacts terrain and is inserted as the first knot of the target trajectory of the current support phase. Thus, a complete gait or multi-modal gaits sequence can be generated at one time. Then, slacked complementary constraints, which can avoid undesired trajectories, are elaborated to describe the coupling relationships between terrain information and bipedal motion for trajectory optimization based gait planning. The concrete form of the gait planner is also delivered. Finally, we verify the performance of the planner, as well as the structural design of our newly designed biped robot in CoppeliaSim through flat terrain walking, stairs terrain walking and quincuncial piles walking. The three experiments show that the gaits planned by the proposed planner can enable the robot to walk stably over non-flat terrains, even through simple PD control.

A metal–graphene metamaterial device exhibiting a tunable, electromagnetically induced transparency (EIT) spectral response at terahertz frequencies is investigated. The metamaterial structure is composed of a strip and a ring resonator, which serve as the bright and dark mode to induce the EIT effect. By employing the variable conductivity of graphene to dampen the dark resonator, the response frequency of the device shifts dynamically over 100 GHz, which satisfies the convenient post-fabrication tunability requirement. The slow-light behavior of the proposed device is also analyzed with the maximum group delay of 1.2 ps. The sensing performance is lastly studied and the sensitivity can reach up to 100 GHz/(RIU), with a figure of merit (FOM) value exceeding 4 RIU−1. Therefore, the graphene-based metamaterial provides a new miniaturized platform to facilitate the development of terahertz modulators, sensors, and slow-light applications.

Printed circuit board (PCB) defect detection plays a crucial role in PCB production, and the popular methods are based on deep learning and require large-scale datasets with high-level ground-truth labels, in which it is time-consuming and costly to label these datasets. Semi-supervised learning (SSL) methods, which reduce the need for labeled samples by leveraging unlabeled samples, can address this problem well. However, for PCB defects, the detection accuracy on small numbers of labeled samples still needs to be improved because the number of labeled samples is small, and the training process will be disturbed by the unlabeled samples. To overcome this problem, this paper proposed a semi-supervised defect detection method with a data-expanding strategy (DE-SSD). The proposed DE-SSD uses both the labeled and unlabeled samples, which can reduce the cost of data labeling, and a batch-adding strategy (BA-SSL) is introduced to leverage the unlabeled data with less disturbance. Moreover, a data-expanding (DE) strategy is proposed to use the labeled samples from other datasets to expand the target dataset, which can also prevent the disturbance by the unlabeled samples. Based on the improvements, the proposed DE-SSD can achieve competitive results for PCB defects with fewer labeled samples. The experimental results on DeepPCB indicate that the proposed DE-SSD achieves state-of-the-art performance, which is improved by 4.7 mAP at least compared with the previous methods.

Extreme precipitation events have increasingly happened at global and regional scales as the global climate has changed in recent decades. Accurate quantitative precipitation estimation (QPE) plays an important role in the warning of extreme precipitation events. With hourly rain gauge observations as a reference, this study compares the performance of Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (GPM) mission (IMERG) and Global Satellite Mapping of Precipitation (GSMaP) quantitative precipitation estimation (QPE) products over Northern China in 2021. The Probability of Detection (POD), Relative Bias (RB), Root-Mean-Squared Error (RMSE), and Fractional Standard Error (FSE) are among the assessment metrics, as are the Probability of Detection (POD), False Alarm Ratio (FAR), and Critical Success Index (CSI). We examined the spatial distribution of cumulative precipitation and the temporal distribution of hourly average precipitation for three severe precipitation occurrences using these assessment metrics. The IMERG products capture strong precipitation centers that are compatible with the gauge observations, especially in extreme precipitation events in areas with relatively flat terrain and low-altitude (≤1000 m). Both IMERG (National Aeronautics and Space Administration, NASA) and GSMaP (Japan Aerospace Exploration Agency, JAXA) satellite-based QPE products have precipitation peaks in advance (2–4 h) and generally underestimate (overestimate) precipitation when the actual precipitation is heavy (light). The satellite-based QPE products generally overestimate the heavy rainfall caused by non-typhoons and underestimate the heavy rainfall caused by typhoons. The GSMaP products may have the capacity to detect short-term rainstorm events. The accuracy of satellite-based QPE products may be influenced by precipitation intensity, sensors, terrain, and other variables. Therefore, in accordance with our recommendations, more ground rainfall stations should be used to collect actual precipitation data in regions with high levels of spatial heterogeneity and complex topography. The data programmers should strengthen the weights computation retrieval technique and fully utilize infrared (IR)-based data. Furthermore, this study is expected to give helpful feedback to the algorithm developers of IMERG and GSMaP products, as well as those researchers into the use of IMERG and GSMaP satellite-based QPE products in applications.

Runt-related transcription factors (RUNXs) can serve as both transcription activators and repressors during biological development, including immune cell maturation. RUNX factors have both tumor-promoting and tumor-suppressive roles in carcinogenesis. Immune cell infiltration and the tumor immune microenvironment have been found to be key regulators in breast cancer progression, treatment response, and patient outcome. However, the relationship between the RUNX family and immune cell infiltration in breast cancer remains unclear. We performed a comprehensive analysis to reveal the role of RUNX factors in breast cancer. Analysis of patient data in the Oncomine database showed that the transcriptional levels of RUNX proteins in breast cancer were elevated. Kaplan–Meier plotter (KM plotter) analysis showed that breast cancer patients with higher expression of RUNX proteins had better survival outcomes. Through analysis of the UALCAN database, we found that the transcriptional levels of RUNX factors were significantly correlated with some breast cancer patient characteristics. cBio Cancer Genomics Portal (cBioPortal) analysis showed the proportions of different RUNX genomic alterations in various subclasses of breast cancer. We also performed gene ontology (GO) and pathway analyses for the significantly differentially expressed genes that were correlated with RUNX factors in breast cancer. TIMER database analysis showed that immune cell infiltration in breast cancer could be affected by the transcriptional level, mutation, and gene copy number of RUNX proteins. Using the Gene Set Cancer Analysis (GSCA) database, we analyzed the effects of RUNX gene methylation on the level of immune cell infiltration in breast cancer. We found that the methylation level changes of RUNX2 and RUNX3 had opposite effects on immune cell infiltration in breast cancer. We also analyzed the relationship between the methylation level of RUNX genes and the TGF-β signaling pathway using the TISIDB database. The results showed that the methylation levels of RUNX1 and RUNX3 were correlated with the expression of TGF-β1. In summary, our analysis found that the RUNX family members can influence the infiltration of various immune cells in breast cancer depending on their expression level, mutation, gene copy number, and methylation. The RUNX family is an important regulator of immune cell infiltration in breast cancer and may serve as a potential prognostic biomarker.

In cold areas where the annual rail temperature difference can exceed 90 °C, continuous welded rails (CWRs) on small-radius curves are more likely to buckle or distort owing to the large radial temperature force and large lateral deformation of the rails. To facilitate safe operation of trains in cold areas, a magnetostrictive displacement measurement technique was used to measure the lateral displacement of CWRs in this study. Then, a long-term monitoring system, including a sensor subsystem, a data acquisition and transmission subsystem, and a data analysis and management subsystem, was established for the monitoring of CWRs on small-radius curves and applied in a field test. One year of continuous observation results showed that this monitoring system could effectively realize the functions of real-time acquisition, wireless transmission, and data storage in a cold climate. The collection and analysis of these observation data, including the air temperature, rail temperature, and lateral displacement of the rail, can be further applied for the stability prediction of CWRs on small-radius curves.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose–type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN–expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2–type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19–associated coagulopathy.

Summary: Here, we describe a protocol to construct, calibrate, and operate a versatile tiling light sheet microscope for imaging cleared tissues. The microscope uses adjustable tiling light sheets to achieve higher spatial resolution and better optical sectioning ability than conventional light sheet microscopes and to image cleared tissues with the cellular to the subcellular spatial resolution. It is compatible with all tissue clearing methods and aligned semiautomatically through the phase modulation of the illumination light.For complete details on the use and execution of this protocol, please refer to Chen et al. (2020).

Many studies focused on the annulus fibrosus (AF) injury in rodent tail model for the intervertebral disk degeneration (IDD) research. However, previous studies caused tremendous injury of intervertebral disk (IVD) by penetrating whole disk. This study aimed to build a progressive IDD rodent tail model by a novel device for precise and minimally invasive puncture in AF. A precise puncture device was customized by 3D Printing Technique. 40 rodent tail IVDs were randomly grouped as follows: group A, non-puncture; group B, annulus needle puncture (ANP) for 4 week; group C, ANP for 8 week; and group D, ANP for 12 week. Pre- and post-puncture IVD height on radiographs and IVD signal intensity on T2 magnetic resonance imaging (MRI) were measured. Average bone density (ABD) on the end of coccygeal vertebrae between punctured disk was measured on the radiographs. Hematoxylin and eosin, TUNEL staining methods, immunofluorescence for cleaved-caspas3 and immunohistochemistry for aggrecan and collagen II were performed. Progressively and significantly increasing IVD height loss and degenerative grade were observed following the time points. The ABD was respectively, 81.20 ± 4.63 in group A, 83.93±3.18 in group B, 92.65 ± 4.32 in group C, 98.87 ± 6.69 in group D. In both group C and group D, there were significant differences with group A. In histology, increasing number of AF cells was noted in group B. In both group C and D, the fissures in AF were obviously observed, and a marked reduction of AF cells were also observed. In all ANP groups, there were significant decrease in number of NP cells, as well as aggrecan and collagen II contents. TUNEL assay showed cellular apoptosis were stimulated in all puncture group, especially in group D. A progressive IDD rat model could be standardly established by the micro-injury IVD puncture using a novel 3D printing device. This animal model provided a potential application for research of progressive hyperosteogeny following IDD development.