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This paper presents a novel structure of multi-cell tube filled with auxetic structures with the aim of improving the crashworthiness performances. The energy absorbing performances of the multi-cell tubes filled with auxetic structures are investigated by finite element analysis and validated experimentally. Compared with other typical energy absorbers, the multi-cell tubes filled with auxetic structures have better energy absorption performance. A parametric study is performed to analyze the effects of beam thickness, beam angle, and tube thickness on the crashworthiness performances. It is found that the tube and beam thicknesses and beam angles have great effects on the energy absorbing performances. An analytical model is also established to predict the energy absorption of multi-cell tubes filled with auxetic structures under axial impact loadings. The analytical predictions agree well with the numerical simulations indicating the analytical model is accurate to predict the energy absorption performances of the proposed structures.

The photocatalytic water splitting kinetics has been analyzed in this paper. The experimental data are taken from the published works and fitted with different theoretical models. From the results, we find that the photocatalytic kinetics of water splitting can be described by Capelas-Mainardi–Vaz (CMV) model very well. This suggests that the water splitting kinetics can be regarded as a fractional first-order kinetics of the chemical reaction. Also, we notice that photocatalytic water splitting is not always completely a monotone kinetics process.

Multi-axis additive manufacturing enables high flexibility of material deposition along dynamically varied directions. The Cartesian motion platforms of these machines include three parallel axes and two rotational axes. Singularity on rotational axes is a critical issue to be tackled in motion planning for ensuring high quality of manufacturing results. The highly nonlinear mapping in the singular region can convert a smooth toolpath with uniformly sampled waypoints defined in the model coordinate system into a highly discontinuous motion in the machine coordinate system, which leads to over-extrusion/under-extrusion of materials in filament-based additive manufacturing. The problem is challenging as both the maximal and the minimal speeds at the tip of a printer head must be controlled in motion. Moreover, collision may occur when sampling-based collision avoidance is employed. In this letter, we present a motion planning method to support the manufacturing realization of designed toolpaths for multi-axis additive manufacturing. Problems of singularity and collision are considered in an integrated manner to improve the motion therefore the quality of fabrication.

3例精氨酸联合可乐定复合激发试验患儿于药物激发第2天出现肉眼血尿，激发后6 d内快速消退，尿红细胞形态学分析提示肾小球性来源。该血尿是良性、一过性的，预后良好；临床医师在矮身材儿童诊治中应严格把握激发试验适应证。.

In this letter, we presented a data-driven framework to optimize the out-of-plane stiffness for soft grippers to achieve mechanical properties as hard-to-twist and easy-to-bend. The effectiveness of this method is demonstrated in the design of a soft pneumatic bending actuator (SPBA). First, a new objective function is defined to quantitatively evaluate the out-of-plane stiffness as well as the bending performance. Then, sensitivity analysis is conducted on the parametric model of an SPBA design to determine the optimized design parameters with the help of Finite Element Analysis (FEA). To enable the computation of numerical optimization, a data-driven approach is employed to learn a cost function that directly represents the out-of-plane stiffness as a differentiable function of the design variables. A gradient-based method is used to maximize the out-of-plane stiffness of the SPBA while ensuring specific bending performance. The effectiveness of our method has been demonstrated in physical experiments taken on 3D-printed grippers.

To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients.We reviewed 82 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP.A total of 22(26.8%) patients developed grade 2 RP and 5(6.1%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.213;95%CI,1.099-1.339; P0.001) and V20(OR,1.435;95%CI,1.166-1.765; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V523% (AUC=0.819, sensitivity:0.701, specificity:0.832) and V208% (AUC=0.812, sensitivity:0.683, specificity:0.811). Additionally, grade≥3 RP did not occur when V530%, V2013% and MLD751.2cGy, respectively.Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV530%, V2013% and MLD751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.

Synthetic hydroxyapatite (HA) and its related materials have made great progress in basic research and clinical application in spinal repair and reconstruction. However, the effect of HA and its composites used in spinal fusion still remained controversial. This meta-analysis aimed at evaluating the efficacy and safety of HA compared with autologous bone.A systematic search in PubMed, MEDLINE, China National Knowledge Internet, EMBASE, and the Cochrane Library was conducted for relevant studies from inception until May 2021. Studies investigating the application of HA and its related composites in spinal fusion were selected for analysis.The operation time of patients treated with artificial bone containing HA was less than that of patients with autologous bone (p = 0.02). The amount of operative blood loss in patients in the HA group was less than that in the autograft group (p = 0.007). Patients treated with autologous bone got a more significant advantage in fusion rate at 6 months (p = 0.009). Nevertheless, there was no significant difference in the fusion rate between patients in the two groups at 12 months or no less than 24 months postoperatively (p = 0.24; p = 0.87). Compared to the autograft group, the HA group significantly decreased postoperative adverse events (p = 0.03). Furthermore, there was no significant difference in the Oswestry Disability Index (p = 1.00) nor the Visual Analogue Scale score (p = 0.94) between the two groups.This meta-analysis suggests that the clinical application of HA and its related composite materials in spinal reconstruction is comparable to that of autologous bone, with satisfactory efficacy and safety.

DNA methylation was one of the earliest discovered epigenetic modifications in vertebrates, and is an important epigenetic mechanism involved in the expression of genes in many biological processes, including muscle growth and development. Its effects on economically important traits are evidenced in reported differences in meat quality traits between Chinese indigenous pig breeds (Wannanhua pig) and Western commercial pig breeds (Yorkshire pig), and this presents a unique model for analyzing the effects of DNA methylation on these traits. In the present study, a whole genome DNA methylation analysis was performed on the two breeds using methylated DNA immunoprecipitation. GO functional enrichment and pathway enrichment analyses identified differentially methylated genes primarily associated with fatty acid metabolism, biological processes of muscle development and signaling pathways related to muscle development and pork quality. Differentially methylated genes were verified by sodium pyrosequencing, and the results were consistent with the sequencing results. The results of the integrative analysis between DNA methylation and gene expression revealed that the DNA methylation levels showed a significantly negative correlation with gene expression levels around the transcription start site of genes. In total, 41 genes were both differentially expressed and methylated; these genes were related to fat metabolism, lipid metabolism and skeletal muscle development. This study could help further explore the molecular mechanisms and phenotypic differences in pig growth and development among different breeds.

The anisotropy of mechanical strength on a 3D printed model can be controlled in a multi-axis 3D printing system as materials can be accumulated along dynamically varied directions. In this paper, we present a new computational framework to generate specially designed layers and toolpaths of multi-axis 3D printing for strengthening a model by aligning filaments along the directions with large stresses. The major challenge comes from how to effectively decompose a solid into a sequence of strength-aware and collision-free working surfaces. We formulate it as a problem to compute an optimized governing field together with a selected orientation of fabrication setup. Iso-surfaces of the governing field are extracted as working surface layers for filament alignment. Supporting structures in curved layers are constructed by extrapolating the governing field to enable the fabrication of overhangs. Compared with planar-layer based Fused Deposition Modeling (FDM) technology, models fabricated by our method can withstand up to 6 . 35× loads in experimental tests.

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".青年是社会和经济发展的核心力量，青年卒中一旦发生将对社会和家庭造成极大的负担。然而我国卒中防控对象主要针对的是中老年患者，青年卒中是脑卒中防治中比较容易被忽略的部分。本文重点阐述了青年卒中的特点、研究进展及防控现状，指出关注青年卒中的重要性，并且希望业界聚焦青年卒中的防治，未来能精准施策，制定出针对青年卒中病因及危险因素的二级预防指南以完善卒中的全面防控体系。在此基础上提高全民健康水平，延长居民预期寿命，从而推动“健康中国2030”战略目标的实现。.

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We report the single-crystal growth of Mn2V2O7and the results of magnetic susceptibility, high-field magnetization up to 55 T and high-frequency electric spin resonance (ESR) measurements for its low-temperatureαphase. Two antiferromagnetic (AFM) ordering at 17.5 K and 3 K and obvious magnetic anisotropy are observed inα-Mn2V2O7upon cooling. In pulsed high magnetic fields, the compound reaches the saturation magnetic moment of ∼10.5μBfor each molecular formula at around 45 T after two undergoing AFM phase transitions atHc1≈ 16 T,Hc2≈ 34.5 T forH//[11ˉ0] andHsf1= 2.5 T,Hsf2= 7 T forH//[001]. In these two directions, two and seven resonance modes are detected by ESR spectroscopy, respectively. Theω1andω2modes ofH//[11ˉ0] can be well described by two-sublattice AFM resonance mode with two zero-field gaps at 94.51 GHz and 169.28 GHz, indicating a hard-axis feature. The seven modes forH//[001] are partially separated by the critical fields ofHsf1andHsf2, displaying the two signs of spin-flop transition. The fittings ofωc1andωc2modes yield zero-field gaps at 69.50 GHz and 84.73 GHz forH//[001], confirming the axis-type anisotropy. The saturated moment and gyromagnetic ratio indicate the Mn2+ion inα-Mn2V2O7is in a high spin state with orbital moment completely quenched. A quasi-one-dimensional magnetism with a zig-zag-chain spin configuration is suggested inα-Mn2V2O7, due to the special neighbor interactions caused by a distorted network structure with honeycomb layer.

Reconstruction of high-fidelity 3D objects or scenes is a fundamental research problem. Recent advances in RGB-D fusion have demonstrated the potential of producing 3D models from consumer-level RGB-D cameras. However, due to the discrete nature and limited resolution of their surface representations (e.g., point or voxel based), existing approaches suffer from the accumulation of errors in camera tracking and distortion in the reconstruction, which leads to an unsatisfactory 3D reconstruction. In this article, we present a method using on-the-fly implicits of Hermite Radial Basis Functions (HRBFs) as a continuous surface representation for camera tracking in an existing RGB-D fusion framework. Furthermore, curvature estimation and confidence evaluation are coherently derived from the inherent surface properties of the on-the-fly HRBF implicits, which are devoted to a data fusion with better quality. We argue that our continuous but on-the-fly surface representation can effectively mitigate the impact of noise with its robustness and constrain the reconstruction with inherent surface smoothness when being compared with discrete representations. Experimental results on various real-world and synthetic datasets demonstrate that our HRBF-fusion outperforms the state-of-the-art approaches in terms of tracking robustness and reconstruction accuracy.

This article presents a novel soft robotic system for a deformable mannequin that can be employed to physically realize the 3-D geometry of different human bodies. The soft membrane on a mannequin is deformed by inflating several curved chambers using pneumatic actuation. Controlling the freeform surface of a soft membrane by adjusting the pneumatic actuation in different chambers is challenging as the membrane’s shape is commonly determined by the interaction between all chambers. Using vision feedback provided by a structured-light based 3-D scanner, we developed an efficient algorithm to compute the optimized actuation of all chambers, which could drive the soft membrane to deform into the best approximation of different target shapes. Our algorithm converges quickly by including pose estimation in the loop of optimization. The time-consuming step of evaluating derivatives on the deformable membrane is avoided by using the Broyden update when possible. The effectiveness of our soft robotic mannequin with controlled deformation has been verified in experiments.

目的 基于多中心数据，分析成人噬血细胞综合征（HLH）预后的影响因素。 方法 收集2014年3月至2020年7月淮海淋巴瘤协作组8个医疗中心确诊的124例成人HLH患者的临床资料。基于Maxstat算法、X-Tile软件和限制立方样条获取连续变量的最佳截断值。采用Cox比例风险回归模型构建成人HLH风险预测模型并通过列线图实现模型的可视化，采用Bootstrap重抽样的方法进行验证，使用一致性指数（C-index）和校正曲线验证列线图，检查预测精度。采用Kaplan-Meier法分析计算生存率并绘制生存曲线，组间比较使用Log-rank检验。 结果 124例患者的中位年龄为55（18～84）岁，男性61例（49.19％）。最常见的病因是感染，血清铁蛋白增高者110例（88.71％），肝脾肿大者57例（45.97％）。124例患者中77例（62.10％）死亡，患者的中位生存期为7.07个月，单因素分析结果表明成人HLH的预后受性别、年龄、纤维蛋白原、血肌酐、ALT和白蛋白的影响（P

Neutron–gamma discrimination (NGD) for gadolinium-containing scintillators is a challenging issue which prevents them from being used in highly efficient neutron detectors with high signal-to-noise ratios. Pulse-shape based digital-signal processing has been selected to tackle this issue, with an emphasis on the dimensionality reduction of the raw data and capability to mitigate the influence of noise, unwanted variations, and outliers on the accuracy of classification. We present two graph-embedded non-negative matrix factorization digital classifiers in which an event graph (or a network) is introduced to find a low-dimensional structure hidden in the high-dimensional experimental data. Utilizing energy-independent normalized features of waveforms and a graph composed of mixed-source reference events, the smooth or sparse low-dimensional representation of detector signals from a Ce:Gd3Al2Ga3O12 scintillator leads to a high thermal neutron detection efficiency (77%–80%) and a high NGD ratio (neutron–gamma efficiency ratio, ∼109) simultaneously. Moreover, excellent discrimination between neutron and ambient background events has been achieved. The proposed graph-embedded algorithms may be applied not only for thermal-neutron position-sensitive detectors and single-channel detectors but also for other radiation detectors that need excellent particle (or crystal) discrimination capabilities and high detection efficiencies in many applications, including medical imaging, nondestructive testing, and security scans.

The COVID-19 pandemic shows the defects of current public health law system and the necessity of the amendment to Law on Prevention and Treatment of Infectious Diseases. The institutional design of the prevention and control of emerging communicable disease shall be modified and Principle of Preventive Legislation shall be determined. Following the multicultural coordination in the pandemic prevention and control, the responsibilities of the central and local government shall be clarified and the functions of the experts and the public need to work fully and effectively. Current pandemic information release system shall be reformed to solve the conflict of laws and the information direct system shall be optimized. Principle of proportionality shall be obeyed to protect the appropriateness, necessity and balance of the pandemic prevention and control measures.新型冠状病毒肺炎疫情显示出当前公共卫生法治体系的缺陷，应尽快修改完善《传染病防治法》：完善新发传染病防治的制度设计，确立新发传染病监测的风险预防原则，加强流行病学调查的法治保障；坚持疫情防控的多元协同，厘清中央和地方政府的责任，充分发挥专家和公众的作用；改革疫情信息发布制度，解决法律冲突问题，优化信息直报制度和直报系统；遵循疫情防控中的比例原则，保障防疫措施的妥当性、必要性和均衡性。.

本例为59岁恶性黑色素瘤一线化疗失败出现肝转移的中年男性患者，治疗上予3次以顺铂60 mg为基础的肝动脉灌注化疗，进一步予卡瑞利珠单抗200 mg标准剂量每2周1次免疫治疗，规律用药2周期后复查腹部CT。经过选择性肝动脉灌注化疗及程序性死亡受体-1抗体抑制剂联合治疗后，整体疗效达到部分缓解，肝功能指标较前明显好转，未出现任何明显不良反应。.

Room temperature ferromagnetism (RTFM) was observed in unirradiated ZnO single crystal owing to zinc vacancy (VZn) defects. D-D neutron irradiation was used to regulate the defect concentration and types avoiding interference of impurity elements. D-D neutron mainly collides elastically with ZnO single crystals, producing VZn, oxygen vacancy (VO), and other point defects, the density and kind of defect associated with neutron irradiation fluence. It can be found the saturation magnetization (Ms) first increases and then decreases with the irradiation fluence increases, meaning there is an optimum value for VZn concentration. When the neutron fluence is greater than 5× 109 n/cm2, more unstable VZn combined with VO to form zinc-oxygen divacancy (VZnO), indicating neutron irradiation changes the defect types. VZnO induces a smaller magnetic moment; thus, the Ms decreased. To further verify the origin of RTFM, the CASTEP module was employed to calculate the magnetic and structural properties of native vacancy defects in ZnO. VZn induces 2.12 μB magnetic moment, and only VZnO formed by the nearest VZn and VO has 2.09 μB magnetic moment, while 3VO cluster introduces a magnetic moment of $\sim $1 μB. Combined experiment and CASTEP calculation results, VZn is the most likely origin of RTFM.

The fabrication flexibility of 3D printing has sparked a lot of interest in designing structures with spatially graded material properties. In this paper, we propose a new type of density graded structure that is particularly designed for 3D printing systems based on filament extrusion. In order to ensure high-quality fabrication results, extrusion-based 3D printing requires not only that the structures are self-supporting, but also that extrusion toolpaths are continuous and free of self-overlap. The structure proposed in this paper, called CrossFill, complies with these requirements. In particular, CrossFill is a self-supporting foam structure, for which each layer is fabricated by a single, continuous and overlap-free path of material extrusion. Our method for generating CrossFill is based on a space-filling surface that employs spatially varying subdivision levels. Dithering of the subdivision levels is performed to accurately reproduce a prescribed density distribution. We demonstrate the effectiveness of CrossFill on a number of experimental tests and applications., Comment: Submission to Symposium on Solid and Physical Modeling 2019

International audience; We present an inverse design tool for fabric formwork - a process where flat panels are sewn together to form a fabric container for casting a plaster sculpture. Compared to 3D printing techniques, the benefit of fabric formwork is its properties of low-cost and easy transport. The process of fabric formwork is akin to molding and casting but having a soft boundary. Deformation of the fabric container is governed by force equilibrium between the pressure forces from liquid fill and tension in the stretched fabric. The final result of fabrication depends on the shapes of the flat panels, the fabrication orientation and the placement of external supports. Our computational framework generates optimized flat panels and fabrication orientation with reference to a target shape, and determines effective locations for external supports. We demonstrate the function of this design tool on a variety of models with different shapes and topology. Physical fabrication is also demonstrated to validate our approach.

This letter tackles the problem of energy-efficient coverage path planning for exploring general surfaces by an autonomous vehicle. Efficient algorithms are developed to generate paths on freeform 3-D surfaces according to a special design pattern as height extremity aware Fermat spiral for this purpose. By using the exact boundary-sourced geodesic distances, the method for generating Fermat spiral paths is first introduced to cover a general surface. Then, heuristics for energy efficiency are incorporated to add peak points of a height field as sources for geodesic computation. The paths generated by our method can significantly reduce the cost caused by gravity. Physical experiments have been taken on different terrain surfaces to demonstrate the effectiveness of our approach.

We tackle the problem of dense reconstruction with a practical system, in which near point lighting (NPL) is employed. Different from the conventional formulation of photometric stereo (PS) that assumes parallel lighting, PS under the NPL condition is a nonlinear problem as the local surface normals are coupled with its distance to the camera as well as the light sources. After obtaining the locations of point lights by a calibration process, we develop a new framework to solve this nonlinear reconstruction problem via mesh deformation, in which each facet is corresponding to a pixel in the image captured by the camera. In our framework, mesh deformation is decoupled into an iteration of interlaced steps of local projection and global blending. Experimental results verify that our method can generate accurate estimation of surface shape under NPL in a few iterations. Besides, this approach is robust to errors on the positions of light sources and is easy to be implemented.

Ar+ post-irradiation effects on magnetic behavior of Cu+-implanted ZnO single crystals were studied. It was found that Cu+-implanted and Ar+-irradiated samples, even the primary sample, showed a magnetic moment (MM), but the saturation magnetization (MS) of Ar+ post-irradiated on Cu+ as-implanted one drastically decreased. Based on the first-principle method, it was drawn to the incomplete filling electronic configuration of the substituted Cu ion whose 3d orbital hybridized with O-2p contributing to the magnetism. The MM induced by the substituted Cu+ ion was much less than that induced by the substituted Cu2+ and Cu3+ ion, so the ratio of Cu2+,3+/Cu+ decreased after Ar+ post-irradiation, leading to the decrease of MS. The excessive concentration of O vacancy induced by post-irradiation also weakened the MM by their compensating electrons, and decreased the effective magnetic exchange coupling interaction. Cu-related clusters dissolution was also a critical reason for the reduction of MS.

Microstructures with spatially-varying properties such as trabecular bone are widely seen in nature. These functionally graded materials possess smoothly changing microstructural topologies that enable excellent micro and macroscale performance. The fabrication of such microstructural materials is now enabled by additive manufacturing (AM). A challenging aspect in the computational design of such materials is ensuring compatibility between adjacent microstructures. Existing works address this problem by ensuring geometric connectivity between adjacent microstructural unit cells. In this paper, we aim to find the optimal connectivity between topology optimized microstructures. Recognizing the fact that the optimality of connectivity can be evaluated by the resulting physical properties of the assemblies, we propose to consider the assembly of adjacent cells together with the optimization of individual cells. In particular, our method simultaneously optimizes the physical properties of the individual cells as well as those of neighbouring pairs, to ensure material connectivity and smoothly varying physical properties. We demonstrate the application of our method in the design of functionally graded materials for implant design (including an implant prototype made by AM), and in the multiscale optimization of structures.

According to a document issued by the General Office of National Health Commission, "one person, one diagnosis, and one room" is required in the process of outpatient consultation. However, the patient will need to go to another room for dressing change after the doctor checks the wound if sticking to the conventional layout of current wound repair specialist outpatient clinic in hospitals and following the regulation of "separation of diagnosis and treatment". To allow a patient walking back and forth with the exposed wounds to different clinics or going to another clinic for dressing change with the original dressing reapplied to the wound is against the regulation of nosocomial infection control and the principle of sterility. To ensure that the layout of the outpatient clinic in the wound repair outpatient department not only conforms to the principle of "one person, one diagnosis, and one room", but also meets the characteristics of the diagnosis and treatment process of chronic wounds, this paper proposes the layout of "large space and small partition" in the wound repair clinic.依据国家卫生健康委办公厅的文件规定，在门诊接诊过程中，需要做到“一人一诊一室”。 但是，如果按目前医院创面修复专科门诊的常规布局，当医师查看创面后，照 “诊疗要分离”的规定，患者需到另外一个空间换药。让患者裸露着创面来回于各个诊室，或采用原敷料再次覆盖创面后，患者至其他诊室换药，均不符合医院感染控制的规定和无菌原则。为让创面修复科的门诊诊室布局既遵守“一人一诊一室”的原则，又符合慢性创面诊疗流程的特点，本文提出创面修复门诊“大空间、小隔断”布局的建议。.

Study question How do endometrium OCT image characteristics during peri-implantation window correlate with histomorphometry and associate with implantation outcomes in women with reproductive failure? Summary answer Endometrium OCT intensity correlated with stromal cell density and gland size. Endometrium with recurrent implantation failure had low OCT intensity but reversed in successful implantation. What is known already OCT is a non-invasive imaging technique using low energy near-infrared light to capture micrometer-scale resolution images from optical scattering media. An image produced by OCT resembles tissue architecture observed in histology, so OCT imaging has been regarded as “optical biopsy”. Our previous findings demonstrated OCT is better than ultrasound to identify endometrial pathology. We also showed association of OCT signal with microvessel density in peri-implantation endometrium. However, other histomorphometry were not evaluated. It is still unclear whether endometrium OCT image characteristics are different in reproductive failure and can predict implantation outcomes. Study design, size, duration This was a prospective study conducted at teaching hospital of The Chinese University of Hong Kong from Jan 2018 to Dec 2019. 46 infertile women with or without recurrent miscarriage (RM) and implantation failure (RIF) were recruited in this study. Endometrium OCT imaging and subsequent biopsy were performed on the seventh day after luteal hormone surge (LH + 7) in natural cycle prior to the consecutive natural conception or embryo transfer (ET) cycle. Participants/materials, setting, methods At least 5 systematic random endometrium OCT images from uterine fundus, body and lower segment of each subject were included for intensity analysis by two independent observers. OCT intensity of each image was classified as low, moderate, high based on optical range and then average OCT intensity in each uterine region was calculated for group comparison. Endometrium glandular epithelial, stromal, endothelial, uNK cells were defined by standard H&E and specific immunostaining for histomorphometry and correlation. Main results and the role of chance OCT intensity significantly correlated with endometrial cell and gland parameters regardless classifications of reproductive failure and implantation outcome. Higher OCT intensity indicated higher stromal cell density, gland to stromal (G/S) ratio and average gland area, but fewer microvessel and uNK cells. None of the endometrium histomorphometry were significantly different among different reproductive failure types and implantation outcomes, suggesting it may not be sensitive enough to detect the abnormal histological features. However, OCT intensity was significantly lower in the uterine fundus and body of RIF group than in that of infertile and RM groups. There was no significant difference of OCT intensity in the lower part of the endometrium among three groups. It indicates that OCT intensity is a sensitive marker to differentiate endometrium with RIF from the endometrium with other conditions and also endometrium with RIF is characterized with less stromal cells and smaller glands. Compared with infertile group with unsuccessful implantation, OCT intensity was higher in all three parts of the uterus from the infertile group with successful implantation, but the results were not statistically different. The results further implied that endometrial cells and gland size may potentially contribute to the endometrium receptivity for implantation. Limitations, reasons for caution Current endometrium OCT imaging depth is within 3mm, change beyond this thickness is inaccessible but still the most important layer for implantation. This is a pilot and small study with lack of normal fertile control. Endometrium OCT imaging in the same natural conception or ET cycle will be more accurate. Wider implications of the findings: OCT imaging could be used as a potential noninvasive modality to evaluate peri-implantation window endometrium. It enables real-time and in-situ visualization of endometrium structure and pathology with no additional biopsy risk and examination delay. Larger clinical trials are needed to confirm its clinical applications and utilities. Trial registration number CREC 2016.160

Study question To investigate the different metabolomic profiling in serum between pregnant and non-pregnant women during early implantation period. Summary answer Metabolomics of progesterone-related hormones enhances from ET day3 for pregnancy women compared with non-pregnancy women. What is known already Metabolomics is based on high-throughput analytical methods to identify and quantify metabolites. Compared to other omics study, metabolomics is the closest one to the phenotype, allowing the observation of dynamic changes in phenotype at specific timepoints. So far there is no published work about the metabolomics profile in human early implantation period. Study design, size, duration: Study design: comparative study. Size: 14 pregnancy women and 14 non-pregnancy women. duration: time-course. Participants/materials, setting, methods Participants: pregnancy women and unpregnancy women after embryo transfer (ET). Setting: university-based study. Methods: Peripheral blood were collected at ET day0, 3, 6 and 9. metabolomic profiling in serum by platforms of capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry (LC-MS). Main results and the role of chance There were no statistical difference of the age, BMI, basal FSH level, endometrium thickness on the day of embryo transfer, distribution of primary and secondary fertility, embryo transfer cycle as well as the infertile types between the two groups. After deleting those with over 50% missing data, we finally have 310 metabolites into statistical analysis. Among the 310 metabolite, lipid metabolites account the largest percentage, nearly half of all metabolites. The second biggest class of metabolites in our data was organic acids. Combined results in repeated measurement ANOVA (RM-ANOVA) and ANOVA-simultaneous component analysis (ASCA) as well as multivariate empirical Bayes time-series analysis (MEBA), we finally found that progesterone-related hormones were the most important metabolites for the whole time-series data. Those significant metabolites showed a significant down regulation from ET day0 to ET day3 and up regulation from ET day3 to ET day9. Limitations, reasons for caution we have limited sample size for this study and further validation is necessary for confirmation. Wider implications of the findings: The phenomenon of upregulation of progesterone-related hormones from day3 in pregnancy group might be related to the embryo-originated hcg. Because the embryo has entered into endometrium at day3 and produced cytokines, hcg and other interaction with endometrium. Trial registration number NA

Study question To compare the changing peripheral levels of inflammation-related cytokine profile during a 9-day period after blastocyst transfer between women who did and did not conceive. Summary answer:Successful implantation is associated with transient increase in serum pro-inflammatory cytokine profile followed by a switch to anti-inflammatory cytokine profile prior to confirmation of pregnancy.What is known already: Immunomodulation is thought to be important for the prevention of rejection of the implanting semi-allograft embryo and successful establishment of pregnancy. A successful pregnancy is characterized by a dominance of anti-inflammatory cytokine profile in the peripheral blood in the first and second trimesters of pregnancy. It is achieved by a complex interplay between various immune cells and cytokines at the fetal-maternal interface, among which the key-players are interleukine–10 (IL–10) and transforming growth factor-β1 (TGF-β1). The circulating inflammatory response in the first few days after embryo transfer to the pathophysiology of implantation failure remains unclear. Study design, size, duration: This prospective observational and longitudinal study on 47 women with infertility was performed in an in vitro fertilization unit from December 2018 to August 2019. The amounts of a range of cytokines was measured on serial blood samples obtained during a 9-day period after blastocyst transfer. Participants/materials, setting, methods Serial blood samples were obtained on the day of embryo transfer, and 3, 6, and 9 days afterward for measurement of serum interferon gamma (IFN-γ), tumor necrosis factor alpha, interleukin (IL)–2, IL–4, IL–10, IL–12, IL–13, IL–17, IL–18, and IL–22 using cytometric bead arrays; transforming growth factor beta 1 (TGF-β1) was measured using commercial enzyme-linked immunosorbent assay kits. Main results and the role of chance The cytokine profile was similar between the women who conceived and those who did not on the day of blastocyst transfer. In women who conceived, IFN-γ and IL–17 (pro-inflammatory cytokines) exhibited a transient and significant increase on day 3 after blastocyst transfer, which decreased to the baseline levels by day 6. Meanwhile, IL–10 (anti-inflammatory cytokine) was increased significantly on days 6 and 9, and TGF-β1 (anti-inflammatory cytokine) was increased significantly on day 9 after blastocyst transfer. In women who did not conceive, there was a more pronounced increase in IFN-γ and IL–17 (pro-inflammatory cytokines) on day 3, which was sustained on days 6 and 9 without a switch to an anti-inflammatory cytokine profile. Among women who conceived after blastocyst embryo transfer, there was a transient and modest increase in serum pro-inflammatory cytokine profile (IFN-γ and IL–17) 3 days after blastocyst transfer, which was followed by a switch to anti-inflammatory cytokine profile (increase IL–10 and TGF-β1) by 6 days after blastocyst transfer and the latter increase was sustained 9 days after blastocyst transfer, when pregnancy was confirmed. Limitations, reasons for caution This is an observational study on peripheral blood cytokine levels, so it is not possible to draw conclusions if the implantation failure is due primarily to failure of the embryo to elicit a trigger for the switch or failure of maternal response to a normal trigger released by the embryo. Wider implications of the findings: The characteristic change in peripheral cytokine profile during successful implantation, well before confirmation of pregnancy, may provide an opportunity to develop serum biomarkers to monitor implantation and to understand the mechanism of its failure, especially in women who experience recurrent implantation failure after IVF. Trial registration number Not applicable

Study question Whether the changing peripheral levels of Tim–3/Galectin–9 (Gal–9) and PD–1/PL–1 over 4 weeks after ET in ongoing pregnancies is different from pregnancies destined to miscarry. Summary answer A significant and sustained increase of Tim–3 in pNK cells was observed in pregnancies which were ongoing but not in pregnancies which later miscarried. What is known already The importance of maternal immune adaptation and tolerance to the implanting embryo, an allograft, has been extensively investigated for decades. Immune checkpoint molecules, like T-cell immunoglobulin mucin–3 (Tim–3) and programed cell death–1 (PD–1), are co-stimulatory receptors negatively regulating immune responses. During pregnancy, Tim–3 and PD–1 are expressed by several immune cells in the decidua and participate in the maternal-fetal immune interactions to mediate maternal immune tolerance through binding to their ligands Gal–9 and progressed death-ligand 1 (PD-L1) produced by trophoblast and immune cells. In addition to the implantation site, Tim–3 and PD–1 expressions in peripheral lymphocytes are modified during pregnancy. Study design, size, duration A prospective observational study includes 81 women who achieved ongoing pregnancy and 17 women who suffered from miscarriage after single day–5 blastocyst transfer. All the subjects were recruited from November 2018 to January 2020 in a university teaching hospital. Participants/materials, setting, methods Women undergoing single blastocyst transfer after in-vitro-fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment were recruited on the day of ET following informed, written consent. They had serial blood samples taken on the day of ET, and 4, 5, 6 and 7 weeks of gestation for measurement of (1) membranous Tim–3 and PD–1 expression on various peripheral lymphocytes by flow cytometry; and (2) serum concentrations of ligands Gal–9 and PD-L1 by ELISA. Main results and the role of chance The comparisons between two groups showed there was no significant difference between the 2 groups in baseline levels among all the parameters measured. In women who achieved ongoing pregnancy, a significant and sustained increase of Tim–3 in either peripheral NK (pNK) subsets was observed at 4-week, 5-week, 6-week and 7-week gestations compared to the baseline (Tim–3+CD56dimNK 39.14±1.51%, 41.14±1.62%, 41.34±1.94%, and 41.69±2.12% vs. 30.27±1.49%; Tim–3+CD56brihgtNK cells, 24.54±1.71%, 25.43±1.54%, 27.26±1.88% and 24.70±1.64% vs. 19.08±1.13%), and the concentration of serum PD-L1 was significantly increased at 6-week and 7-week gestations (48.33±17.78 pg/ml, 52.53±20.60 pg/ml) when compared to the day of blastocyst transfer (41.40±16.01 pg/ml). The expressions of Tim–3 in T, NKT cells and PD–1 in NK, T, NKT cells were not significantly changed across the 5 time points. In women who conceived but later miscarried, all the parameters examined from 4–7 weeks of gestation were not significantly different when compared with the baseline measurement. The only measurement which showed a significant difference between the 2 groups and across all time points after ET was the proportion of Tim–3+CD56dimNK cells which was significantly higher in women who achieved ongoing pregnancies compared with women who destined to miscarry from 4 to 7 weeks of gestation. Limitations, reasons for caution It is uncertain if the observation would be different between miscarriage associated with aneuploid embryo or euploid embryo as we had not been able to obtain karyotyping result in most of the miscarriage cases. Wider implications of the findings: Our preliminary observation suggests that the proportion of Tim–3+pNK cells as early as 4-week gestation could be a potential immuno-bio-marker to predict if a pregnancy is likely to progress normally or result in a miscarriage. Clearly, the finding in this study needs to be confirmed in a larger cohort study Trial registration number not applicable.

Real-time proprioception is a challenging problem for soft robots, which have almost infinite degrees-of-freedom in body deformation. When multiple actuators are used, it becomes more difficult as deformation can also occur on actuators caused by interaction between each other. To tackle this problem, we present a method in this paper to sense and reconstruct 3D deformation on pneumatic soft robots by first integrating multiple low-cost sensors inside the chambers of pneumatic actuators and then using machine learning to convert the captured signals into shape parameters of soft robots. An exterior motion capture system is employed to generate the datasets for both training and testing. With the help of good shape parameterization, the 3D shape of a soft robot can be accurately reconstructed from signals obtained from multiple sensors. We demonstrate the effectiveness of this approach on two designs of soft robots -- a robotic joint and a deformable membrane. After parameterizing the deformation of these soft robots into compact shape parameters, we can effectively train the neural networks to reconstruct the 3D deformation from the sensor signals. The sensing and shape prediction pipeline can run at 50Hz in real-time on a consumer-level device., 8 pages, 10 figures

This study aims to explore the correlation between N-acetyltransferase 2 (NAT2) expression in colorectal cancer (CRC) tissues and the progression and prognosis of CRC. Through in vitro and in vivo experiments, the biological functions of NAT2 in the occurrence and development of CRC were explored.Immunohistochemical (IHC) staining, reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot were used to detect the difference of NAT2 expression in CRC tissues and normal tissues. The role of NAT2 in the cell proliferation, apoptosis, migration, invasion, and tumorigenesis and development of CRC was analyzed by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell cell invasion, wound-healing assays and construction of nude mouse xenograft model. The correlation between the expression level of NAT2, and the overall survival and clinicopathological characteristics of CRC patients were statistically analyzed to preliminarily determine the clinical significance of NAT2 in the diagnosis and prognosis of CRC.The expression level of NAT2 was notably upregulated in CRC. NAT2 knockdown inhibited the proliferation, migration, invasion and in vivo tumor formation of CRC cells, and promoted cell apoptosis. High NAT2 expression was associated with TNM stage, differentiation degree, tumor size, distant metastasis, lymph node metastasis and poor prognosis in CRC patients.This study showed that the expression level of NAT2 in CRC tissues was increased and closely related to the metastasis and prognosis of CRC. In addition, NAT2 can be used as a new prognostic biomarker and therapeutic target for CRC.

Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wild-type (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes., Graphical abstract, This research reveals the effect of a1 synonymous mutation in IGF-1 on the gene-expression process and its potential mechanism at both animal and cellular levels and suggests that codon collocation is of great significance in influencing gene function.

成人Ⅱ型瓜氨酸血症（CTLN2）在临床上相对少见，如果对本病缺乏足够的认识，很容易造成误诊和漏诊。本文将报道一例反复误诊为精神疾病长达4年的CTLN2基因确诊病例，系统回顾其临床特点及诊疗进展。.

High-precision powder bed fusion (PBF), together with highly complex geometries necessitate a much more scalable representation of the geometry and an efficient computational pipeline. This paper presents a new digital design and manufacturing paradigm to solve the scalability and efficiency challenges by using the concept of STL-free workflow. It seamlessly integrates implicit solid modelling for design and direct slicing for manufacturing without any intermediate steps related to STL meshes. The presented paradigm has been validated by two case studies involving complex geometries filled with multiscale triply periodic minimal surfaces (TPMS), which are fabricated by PBF with laser beam size 25 µm.