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Mycoheterotrophs are non-photosynthetic plants that obtain all of their carbon requirements through parasitizing mycorrhizal fungi. They originated from the autotrophic ancestors and usually have more specific relationships with fungi than that of green plants, for reasons that are largely unknown. Determining the factors that lead to specificity in mycoheterotrophs could provide insights on the constraints to mycoheterotrophic evolution. Here we assess the fungal diversities in mycoheterotrophic plants and their co-occurring plants to determine the roles of ecological factors on the specific fungal associations in mycoheterotrophic plants. We investigated mycorrhizal fungal communities in 16 populations of seven Burmannia species with different trophic modes and their co-occurring plants using high-throughput sequencing to assess the tripartite relationships of fungi, mycoheterotrophs and co-occurring autotrophs. We found that mycoheterotrophic species have similar fungal richness to their chlorophyllous relatives, indicating that they are not associated with a reduced set of fungal partners. The preference of mycoheterotrophic species toward specialized fungal assemblages is consistent with the pattern found in the green autotrophic plants within forest habitats, suggesting a coupling of the fungal phylogenetic constraints between mycoheterotrophs and their co-occurring autotrophs. We furthermore show that the turning to fungal communities having closer phylogenetic relationships during habitat shifts from open grasslands to shaded forests might provide the basis for the specialization of mycorrhizal associations in mycoheterotrophic species of Burmannia. Our findings suggest that fungal niche shifts may have promoted fungal partner changes and specialization in mycoheterotrophic plants. Our results provide new insights into the ecological factors leading to the specialized interactions between mycoheterotrophic plants and their fungal partners, expanding our unde

Zhengjun Ma,1 Yanmei Zhang,1 Yupu Zhu,2 Minxuan Cui,2 Yutao Liu,2 Yun-You Duan,1 Li Fan,2 Li Zhang1 1Department of Ultrasound Medicine, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Chemistry and Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Li Fan; Li Zhang, Email xxfanny@fmmu.edu.cn; lilyzhang319_20@hotmail.comIntroduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection.Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo.Results: The results show that IR783-SiO2NPs@NB had a “donut-type” composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability.Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.Keywords: ultrasound contrast agents, nanobubbles, CEUS, scattering cross-section, SiO2 NPs

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimers disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.

Di Zhang,1,&ast; Yu Guan,1,&ast; Xiuxiu Zhou,1 Mingzi Zhang,2 Yu Pu,1 Pengchen Gu,2 Yi Xia,1 Yang Lu,2 Jia Chen,2 Wenting Tu,1 Kunyao Huang,2 Jixin Hou,2 Hua Yang,2 Chicheng Fu,2 Qu Fang,2 Chuan He,2 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Scientific Research Department, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan; Shiyuan Liu, Department of Radiology, Second Affiliated Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +13564684699 ; +13761304518, Fax +86 21 63587668, Email czyxfl@smmu.edu.cn; radiology_cz@163.comPurpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD.Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted.Results: The RSA and RSA% were significantly different among the three groups (p< 0.05) and related to FEV1/FVC (r = − 0.70, p < 0.001; r = − 0.67, p < 0.001), FEV1% predicted (r = − 0.60, p = 0.002; r = − 0.57, p = 0.004), MEF50% predicted (r = − 0.64, p = 0.001; r = − 0.64

Wenjie Huang,1,2 Ting Luo,1,2 Mengqiu Lan,3 Wenting Zhou,1,2 Ming Zhang,1,2 Lihong Wu,3 Zhenni Lu,3 Li Fan1,2 1Department of Reproductive Medicine, Guangzhou Women and Children’s Medical Center Liuzhou Hospital, Liuzhou, Guangxi, 545616, People’s Republic of China; 2Department of Reproductive Medicine, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, Guangxi, 545001, People’s Republic of China; 3Clinical Laboratory Science, Liuzhou Municipal Liutie Central Hospital, Liuzhou, Guangxi, 545007, People’s Republic of ChinaCorrespondence: Wenjie Huang, Email a17377552242@163.comPurpose: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide, characterized by intense lung infiltrations of immune cells (macrophages and monocytes). While existing studies have highlighted the crucial role of the competitive endogenous RNA (ceRNA) regulatory network in COPD development, the complexity and characteristics of the ceRNA network in monocytes remain unexplored.Methods: We downloaded messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) microarray data from GSE146560, GSE102915, and GSE71220 in the Gene Expression Omnibus (GEO) database. This data was used to identify differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs). Predicted miRNAs that bind to DElncRNAs were intersected with DEmiRNAs, forming a set of intersecting miRNAs. This set was then used to predict potential binding mRNAs, intersected with DEmRNAs, and underwent functional enrichment analysis using R software and the STRING database. The resulting triple regulatory network and hub genes were constructed using Cytoscape. Comparative Toxicomics Database (CTD) was utilized for disease correlation predictions, and ROC curve analysis assessed diagnostic accuracy.Results: Our study identified 5 lncRNAs, 4 miRNAs, and 149 mRNAs as differentially expressed. A lncRNA-miRNA-mRNA regulatory network was constructed, and hub genes

Yu Pu,&ast; Xiuxiu Zhou,&ast; Di Zhang, Yu Guan, Yi Xia, Shiyuan Liu, Li Fan Department of Radiology, Second Affiliated Hospital of PLA Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; +86 21 81886011, Fax +86 21 63587668, Email radiology_cz@163.com; fanli0930@163.comPurpose: To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters.Patients and Methods: A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA.Results: The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P< 0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P< 0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than

Fully-supervised airway segmentation has accomplished significant triumphs over the years in aiding pre-operative diagnosis and intra-operative navigation. However, full voxel-level annotation constitutes a labor-intensive and time-consuming task, often plagued by issues such as missing branches, branch annotation discontinuity, or erroneous edge delineation. label-efficient solutions for airway extraction are rarely explored yet primarily demanding in medical practice. To this end, we introduce a novel skeleton-level annotation (SkA) tailored to the airway, which simplifies the annotation workflow while enhancing annotation consistency and accuracy, preserving the complete topology. Furthermore, we propose a skeleton-supervised learning framework to achieve accurate airway segmentation. Firstly, a dual-stream buffer inference is introduced to realize initial label propagation from SkA, avoiding the collapse of direct learning from SkA. Then, we construct a geometry-aware dual-path propagation framework (GDP) to further promote complementary propagation learning, composed of hard geometry-aware propagation learning and soft geometry-aware propagation guidance. Experiments reveal that our proposed framework outperforms the competing methods with SKA, which amounts to only 1.96% airways, and achieves comparable performance with the baseline model that is fully supervised with 100% airways, demonstrating its significant potential in achieving label-efficient segmentation for other tubular structures, such as vessels.

In recent years, the potential applications of Large Multimodal Models (LMMs) in fields such as healthcare, social psychology, and industrial design have attracted wide research attention, providing new directions for human factors research. For instance, LMM-based smart systems have become novel research subjects of human factors studies, and LMM introduces new research paradigms and methodologies to this field. Therefore, this paper aims to explore the applications, challenges, and future prospects of LMM in the domain of human factors and ergonomics through an expert-LMM collaborated literature review. Specifically, a novel literature review method is proposed, and research studies of LMM-based accident analysis, human modelling and intervention design are introduced. Subsequently, the paper discusses future trends of the research paradigm and challenges of human factors and ergonomics studies in the era of LMMs. It is expected that this study can provide a valuable perspective and serve as a reference for integrating human factors with artificial intelligence., Comment: 14 pages, journal paper

Zhe Zhao,1,&ast; Yinghui Gao,2,&ast; Junling Lin,3,&ast; Ruyi Xu,4 Zijun He,5 Libo Zhao,1 Fengfeng Fang,5 Weimeng Cai,6 Kaibin Chen,7 Li Fan,1 Lin Liu6 1Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2PKU-Upenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of China; 4Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Medical College, Yan’an University, Yan’an, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 7Sleep Center, The Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Fan, Cardiology Department of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13301100573, Email fl6698@163.com Lin Liu, Department of Respiratory and Critical Care Medicine of the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13263189578, Email liulin715@qq.comIntroduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Depression is a crucial factor among the various factors that are associated with OSA and CVD.Purpose: This study was conducted with an aim to

Wenting Tu,1,&ast; Taohu Zhou,1,2,&ast; Xiuxiu Zhou,1,&ast; Yanqing Ma,3 Shaofeng Duan,4 Yun Wang,1 Xiang Wang,1 Tian Liu,1 HanXiao Zhang,5 Yan Feng,1 Wenjun Huang,2 Xinang Jiang,1 Yi Xiao,1 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4GE Healthcare, Precision Health Institution, Shanghai, 210000, People’s Republic of China; 5School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu, 221018, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, Second Affiliated Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; +86 21 81886018, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: This study aimed to screen out computed tomography (CT) morphological features and clinical characteristics of patients with lung cancer to identify chronic obstructive pulmonary disease (COPD). Further, we aimed to develop and validate different diagnostic nomograms for predicting whether lung cancer is comorbid with COPD.Patients and Methods: This retrospective study examined data from 498 patients with lung cancer (280 with COPD, 218 without COPD; 349 in training cohort, 149 in validation cohort) from two centers. Five clinical characteristics and 20 CT morphological features were evaluated. Differences in all variables were assessed between COPD and non-COPD groups. Models were developed using multivariable logistic regression to identify COPD, including clinical, imag

Airway segmentation, especially bronchioles segmentation, is an important but challenging task because distal bronchus are sparsely distributed and of a fine scale. Existing neural networks usually exploit sparse topology to learn the connectivity of bronchioles and inefficient shallow features to capture such high-frequency information, leading to the breakage or missed detection of individual thin branches. To address these problems, we contribute a new bronchial segmentation method based on Group Deep Dense Supervision (GDDS) that emphasizes fine-scale bronchioles segmentation in a simple-but-effective manner. First, Deep Dense Supervision (DDS) is proposed by constructing local dense topology skillfully and implementing dense topological learning on a specific shallow feature layer. GDDS further empowers the shallow features with better perception ability to detect bronchioles, even the ones that are not easily discernible to the naked eye. Extensive experiments on the BAS benchmark dataset have shown that our method promotes the network to have a high sensitivity in capturing fine-scale branches and outperforms state-of-the-art methods by a large margin (+12.8 % in BD and +8.8 % in TD) while only introducing a small number of extra parameters., Comment: Submitted to MICCAI2023

We study a federated linear bandits model, where $M$ clients communicate with a central server to solve a linear contextual bandits problem with finite adversarial action sets that may be different across clients. To address the unique challenges of adversarial finite action sets, we propose the FedSupLinUCB algorithm, which extends the principles of SupLinUCB and OFUL algorithms in linear contextual bandits. We prove that FedSupLinUCB achieves a total regret of $\tilde{O}(\sqrt{d T})$, where $T$ is the total number of arm pulls from all clients, and $d$ is the ambient dimension of the linear model. This matches the minimax lower bound and thus is order-optimal (up to polylog terms). We study both asynchronous and synchronous cases and show that the communication cost can be controlled as $O(d M^2 \log(d)\log(T))$ and $O(\sqrt{d^3 M^3} \log(d))$, respectively. The FedSupLinUCB design is further extended to two scenarios: (1) variance-adaptive, where a total regret of $\tilde{O} (\sqrt{d \sum \nolimits_{t=1}^{T} \sigma_t^2})$ can be achieved with $\sigma_t^2$ being the noise variance of round $t$; and (2) adversarial corruption, where a total regret of $\tilde{O}(\sqrt{dT} + d C_p)$ can be achieved with $C_p$ being the total corruption budget. Experiment results corroborate the theoretical analysis and demonstrate the effectiveness of FedSupLinUCB on both synthetic and real-world datasets., Comment: Accepted to NeurIPS 2023, camera-ready version

The analysis of Synthetic Aperture Radar (SAR) imagery is an important step in remote sensing applications, and it is a challenging problem due to its inherent speckle noise. One typical solution is to model the data using the $G_I^0$ distribution and extract its roughness information, which in turn can be used in posterior imaging tasks, such as segmentation, classification and interpretation. This leads to the need of quick and reliable estimation of the roughness parameter from SAR data, especially with high resolution images. Unfortunately, traditional parameter estimation procedures are slow and prone to estimation failures. In this work, we proposed a neural network-based estimation framework that first learns how to predict underlying parameters of $G_I^0$ samples and then can be used to estimate the roughness of unseen data. We show that this approach leads to an estimator that is quicker, yields less estimation error and is less prone to failures than the traditional estimation procedures for this problem, even when we use a simple network. More importantly, we show that this same methodology can be generalized to handle image inputs and, even if trained on purely synthetic data for a few seconds, is able to perform real time pixel-wise roughness estimation for high resolution real SAR imagery.

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sengupta, T., Koonce, N. L., Vazquez-Martinez, N., Moyle, M. W., Duncan, L. H., Emerson, S. E., Han, X., Shao, L., Wu, Y., Santella, A., Fan, L., Bao, Z., Mohler, W. A., Shroff, H., & Colon-Ramos, D. A. Differential adhesion regulates neurite placement via a retrograde zippering mechanism. Elife, 10, (2021): e71171, https://doi.org/10.7554/eLife.71171., During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles., National Institutes of Health (R24-OD01647) Zhirong Bao William Mohler Daniel A Colón-Ramos National Institutes of Health (R01NS076558) Daniel A Colón-Ramos National Institutes of Health (DP1NS111778) Daniel A Colón-Ramos Howard Hughes Medical Institute (Faculty Scholar Award) Daniel A Colón-Ramos Marine Biological Laboratory (Whitman and Fellows program) Hari Shroff Daniel A Colón-Ramos Gordon and Betty Moore Foundation (Moore Grant) Hari Shroff Daniel A Colón-Ramos Gruber Foundation (Gruber Science Fellowship) Titas Sengupta National Institutes of Health (Predoctoral Training Program in Genetics NIH 2020 T32 GM.) Noelle L Koonce National Institutes of Health (F32-NS098616) Mark W Moyle National Institutes of Health (NIBIB Intramural Research Program) Hari Shroff National Institutes of Health (P30CA008748) Zhirong Bao

The supercooling effect is deemed to be a crucial issue for thermal energy storage using phase change materials (PCMs). The exploration of promising additives plays a decisive role in effective suppression efforts for suppressing the supercooling effect of a PCM. The present work proposed a potential additive, polyvinylpyrrolidone (PVP), to reduce the supercooling of erythritol, which is the most promising polyol PCM candidate for medium temperature range. PVP with various loadings was dispersed in erythritol to make composites for the proof-of-concept tests. It was shown that the degree of supercooling of erythritol can be reduced significantly from over 64 ? to about 21 ? in the presence of only 1.0 wt.% PVP. Along with the mitigated supercooling effect, the addition of PVP also leads to an increase of the retrievable latent heat during crystallization, from ~187 J/g to ~224 J/g at the same minute PVP loading of 1.0 wt.%, by increasing the crystallinity of erythritol. The PVP-loaded erythritol composites exhibit little sacrifice in latent heat of fusion, i.e., only ~15% loss when the PVP loading reaches 6.0 wt.%. In addition, multiple tests confirmed that PVP can be dissolved in erythritol, thus desirable compatibility was obtained and the composites would have long-term reliability. This proposed additive enables an efficient and cost-effective way for improving the crystallization behaviors of erythritol (and other polyol PCMs) towards real-world applications., QC 20220503

This work proposes a novel transformation termed the conformal navigation transformation to achieve collision-free navigation of a robot in a workspace populated with arbitrary polygonal obstacles. The properties of the conformal navigation transformation in the polygonal workspace are investigated in this work as well as its capability to provide a solution to the navigation problem. %The properties of the conformal navigation transformation are investigated, which contribute to the solution of the robot navigation problem in complex polygonal environments. %which facilitates the navigation of robots in complex environments. The definition of the navigation function is generalized to accommodate non-smooth obstacle boundaries. Based on the proposed transformation and the generalized navigation function, a provably correct feedback controller is derived for the automatic guidance and motion control of the kinematic mobile robot. Moreover, an iterative method is proposed to construct the conformal navigation transformation in a multi-connected polygonal workspace, which transforms the multi-connected problem into multiple single-connected problems to achieve fast convergence.In addition to the analytic guarantees, the simulation study verifies the effectiveness of the proposed methodology in a workspace with non-trivial polygonal obstacles., Comment: arXiv admin note: substantial text overlap with arXiv:2208.06876

Navigation functions provide both path and motion planning, which can be used to ensure obstacle avoidance and convergence in the sphere world. When dealing with complex and realistic scenarios, constructing a transformation to the sphere world is essential and, at the same time, challenging. This work proposes a novel transformation termed the conformal navigation transformation to achieve collision-free navigation of a robot in a workspace populated with obstacles of arbitrary shapes. The properties of the conformal navigation transformation, including uniqueness, invariance of navigation properties, and no angular deformation, are investigated, which contribute to the solution of the robot navigation problem in complex environments. Based on navigation functions and the proposed transformation, feedback controllers are derived for the automatic guidance and motion control of kinematic and dynamic mobile robots. Moreover, an iterative method is proposed to construct the conformal navigation transformation in a multiply-connected workspace, which transforms the multiply-connected problem into multiple simply-connected problems to achieve fast convergence. In addition to the analytic guarantees, simulation studies verify the effectiveness of the proposed methodology in workspaces with non-trivial obstacles.

Yu Pu,1,&ast; Xiuxiu Zhou,1,&ast; Di Zhang,1,&ast; Yu Guan,1,&ast; Yi Xia,1 Wenting Tu,1 Yang Lu,2 Weidong Zhang,2 Chi-Cheng Fu,2 Qu Fang,2 Geertruida H de Bock,3 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Scientific Research, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China; 3Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, ChangZheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; Tel +86 21 81886012, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: To explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.Patients and Methods: A total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.Results: Machine learning-based PRM

Yu Hu,1,&ast; Li-Jun Fan,2,3,&ast; Yue-Ming Jiang,1 Hong Liu,4 Hui Yong,5 Chong Peng1 1Department of Anesthesiology, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Department of Anesthesiology, Xuzhou, Jiangsu, People’s Republic of China; 4Heping Women and Children’s Hospital, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Cardiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chong Peng, Department of Anesthesiology, Xuzhou Maternity and Child Health Care Hospital, No. 46 Heping Road Xuzhou, Xuzhou, Jiangsu, People’s Republic of China, 221010, Email pc15895228357@163.comPurpose: Neuraxial (spinal and epidural) anesthesia is the cornerstone of ensuring the satisfaction rate of painless delivery; however, whether it prolongs the first stage of labor remains controversial. Although current clinical research results tend to be negative, the conclusions are not convincing due to the lack of basic research. This study was conducted to provide a theoretical reference for this controversy through basic research.Materials and Methods: A spinal anesthesia model was established by the intrathecal injection of 0.1% ropivacaine in late-pregnant rats (day 22). The cervical resistance test was used to measure the tension of different groups of isolated cervical tissues. Western blotting and cervical tissue cyclic AMP (cAMP) enzyme-linked immunosorbent assay were performed to clarify the possible related mechanisms.Results: Cervical resistance experiments showed that the intrathecal injection of ropivacaine decreased the c

Fan Lai,1,&ast; Xin Li,1,&ast; Qi Wang,1,&ast; Yingjuan Luo,1 Xin Wang,1 Xiuhua Huang,1 Jiajia Zhang,1 Jieru Peng,1 Qin Wang,1 Li Fan,1 Wen Li,1 Junrong Huo,1 Tianjiao Liu,1 Yalan Li,2 Yonghong Lin,1 Xiao Yang1 1Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2The Fourth People’s Hospital of Chengdu, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Yang; Yonghong Lin, Chengdu Women’s and Children’s Central Hospital, 1617 Riyue Avenue, Qingyang District, Chengdu, 611731, Sichuan, People’s Republic of China, Tel +86 13882288881 ; +86 13808031895, Email yangxiaocwcch@aliyun.com; linyonghongcwcch@aliyun.comPurpose: Fever is one of the most typical clinical symptoms of coronavirus disease 2019 (COVID-19), and non-contact infrared thermometers (NCITs) are commonly used to screen for fever. However, there is a lack of authoritative data to define a “fever” when an NCIT is used and previous studies have shown that NCIT readings fluctuate widely depending on ambient temperatures and the body surface site screened. The aim of this study was to establish cut-off points for normal temperatures of different body sites (neck, forehead, temples, and wrist) and investigate the accuracy of NCITs at various ambient temperatures to improve the standardization and accuracy of fever screening.Patients and Methods: A prospective investigation was conducted among 904 participants in the outpatient and emergency departments of Chengdu Women’s and Children’s Central Hospital. Body temperature was measured using NCITs and mercury axillary thermometers. A receiver operating characteristic curve was used to determine the accuracy of body temperature detection at the four body surface sites.

Activation of plant pattern-triggered immunity (PTI) relies on the recognition of microbe-derived structures, termed patterns, through plant-encoded surface-resident pattern recognition receptors (PRRs). We show that proteobacterial translation initiation factor 1 (IF1) triggers PTI in Arabidopsis thaliana and related Brassicaceae species. Unlike for most other immunogenic patterns, IF1 elicitor activity cannot be assigned to a small peptide epitope, suggesting that tertiary fold features are required for IF1 receptor activation. We have deployed natural variation in IF1 sensitivity to identify Arabidopsis leucine-rich repeat (LRR) receptor-like protein 32 (RLP32) as IF1 receptor using a restriction site-associated DNA sequencing approach. RLP32 confers IF1 sensitivity to rlp32 mutants, IF1-insensitive Arabidopsis accessions and IF1-insensitive Nicotiana benthamiana, binds IF1 specifically and forms complexes with LRR receptor kinases SOBIR1 and BAK1 to mediate signaling. Similar to other PRRs, RLP32 confers resistance to Pseudomonas syringae, highlighting an unexpectedly complex array of bacterial pattern sensors within a single plant species.

Understanding the thermodynamic phase transition of black holes can provide the deep insight into the fundamental properties of black hole gravity to establish the quantum gravity. In this work, we investigate the phase transition and its dynamics for the charged EPYM AdS black hole. Through reconstructing the Maxwell's equal-area law, we find there exists the high-/low-potential black hole (HPBH/LPBL) phase transition, not only the pure large/small one. The Gibbs free energy landscape ($G_L$) is treated as a function of the black hole horizon, which is the order parameter of the phase transition due to the thermal fluctuation. From the view point of $G_L$, the stable HPBH/LPBL states are corresponding to two wells of $G_L$, which have the same depth. The unstable intermediate-potential black hole state corresponds to the local maximum of $G_L$. Then we focus on the probability evolution governed by the Fokker-Planck equation. Through solving the Fokker-Planck equating with different reflection/aborption boundary conditions and initial conditions, the dynamics of switching between the coexistent HPBH and LPBL phases is probed within the first passage time. Furthermore, the effect of temperature on the dynamic property of phase transition is also investigated., Comment: arXiv admin note: substantial text overlap with arXiv:2104.10309

BackgroundBone loss is the most common reason for broken bones among the elderly. An ideal agent for the treatment of bone loss should have both osteoclast inhibitory and osteoblast stimulatory functions. Leucine-rich repeat kinase 1 (LRRK1) is a novel target for alternative antiresorptive drugs to treat osteoporosis and osteoporotic fractures. Recently a chemical IN04, Methyl 3-[({([5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-thio}-acetyl)-amino]-benzoate, has been identified as a potential LRRK1 inhibitor.ObjectiveThe aim of this work is to investigate how the chemical IN04 interacts with LRRK1 and inhibits its activity.MethodsA structural model of the LRRK1 kinase domain was constructed with SWISS-MODEL. The human protein kinase ROCO4 (PDB ID: 4YZN) was chosen as the template based on sequence homology, structural and phylogenetic analysis. In addition, a homology model of the LRRK1 ROC domain was also prepared based on the LRRK2 ROC domain structure (PDB ID: 2ZEJ). The interactions of IN04 with the active sites in the LRRK1 kinase domain and ROC domain were investigated by SwissDock.ResultsIN04 was docked into the active site of the LRRK1 kinase domain with similar interactions as ATP comparable to the ligand bound to homologous kinases. Many rational binding modes of IN04 to LRRK1 kinase domain were investigated and the most likely binding pose containing multiple hydrogen bonds and a salt bridge was discovered. However, IN04 cannot fit into the GDP-binding site of the ROC domain.ConclusionChemical IN04 inhibits LRRK1 by binding to the active site of the kinase domain but not the ROC domain.

We present a combined analytical and numerical investigation to show how an optimal control field can be designed to generate maximum field-free orientation of molecules for three populated rotational states. Based on a model involving pure rotational ladder-climbing excitation between rotational states, a set of optimal amplitude and phase conditions are analytically derived for the applied control fields. The maximum degree of orientation can be achieved when the field satisfies amplitude and phase conditions at the two transition frequencies. Multiple optimal solutions exist, and to examine these conditions, we devise a quantum coherent control scheme using two terahertz pulses and successfully apply it to the linear polar molecule HCN at ultracold temperature. The sensitivity of both populations and phases of rotational states to control field parameters, i.e., the detuning, bandwidth, and time delay, is analyzed so as to understand the optimal orientation mechanism. This work thus examines the frequency-domain landscape belonging to optimal pulses.

Wenjie Huang,1,&ast; Li Fan,1,&ast; Yongmei Tang,1 Yinxiu Chi,2 Jingjing Li1 1Department of Reproductive Medicine, Liuzhou Maternity and Child Healthcare Hospital, Affiliated Women and Children’s Hospital of Guangxi University of Science and Technology, Liuzhou, Guangxi, 545001, People’s Republic of China; 2School of Basic Medicine, Central South University, Changsha, Hunan, 410078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingjing Li; Wenjie Huang Email 7407lijingjing@163.com; a17377552242@163.comBackground: Integrin beta4 (ITGB4) is a transmembrane receptor that plays a key role in tumorigenesis and tumor development. However, there are no pan-cancer analyses of ITGB4.Methods: This study demonstrates the first potential oncogenic roles of ITGB4 across 33 tumors based on the dataset of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).Results: ITGB4 is highly expressed in many cancers, and distinct correlations exist between ITGB4 expression and the prognosis of tumor patients. We also found that the methylation and genetic alteration level of ITGB4 was associated with some cancer prognosis. Furthermore, we found a reduced phosphorylation of ITGB4 at S1457 in several tumors, such as breast and ovarian cancers. Finally, ITGB4 expression was correlated with cancer-associated fibroblasts in liver hepatocellular carcinoma and prostate adenocarcinoma, and the infiltration level of NK cells and neutrophils was observed in other cancers, such as breast invasive carcinoma and lung adenocarcinoma. Moreover, RNA metabolism and protein processing-associated functions are involved in the functional mechanism of ITGB4.Conclusion: Our first pan-cancer study may offer a relatively comprehensive understanding of the oncogenic roles of ITGB4 across different tumors.Keywords: ITGB4, cancer, prognosis, methylation, phosphorylation

Image guided depth completion is the task of generating a dense depth map from a sparse depth map and a high quality image. In this task, how to fuse the color and depth modalities plays an important role in achieving good performance. This paper proposes a two-branch backbone that consists of a color-dominant branch and a depth-dominant branch to exploit and fuse two modalities thoroughly. More specifically, one branch inputs a color image and a sparse depth map to predict a dense depth map. The other branch takes as inputs the sparse depth map and the previously predicted depth map, and outputs a dense depth map as well. The depth maps predicted from two branches are complimentary to each other and therefore they are adaptively fused. In addition, we also propose a simple geometric convolutional layer to encode 3D geometric cues. The geometric encoded backbone conducts the fusion of different modalities at multiple stages, leading to good depth completion results. We further implement a dilated and accelerated CSPN++ to refine the fused depth map efficiently. The proposed full model ranks 1st in the KITTI depth completion online leaderboard at the time of submission. It also infers much faster than most of the top ranked methods. The code of this work is available at https://github.com/JUGGHM/PENet_ICRA2021., Comment: Accepted by ICRA 2021

Transcriptome differences between Hodgkin's lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and mantle cell lymphoma (MCL), which are all derived from B cell, remained unclear. This study aimed to construct lymphoma-specific diagnostic models by screening lymphoma marker genes. Transcriptome data of HL, DLBCL, and MCL were obtained from public databases. Lymphoma marker genes were screened by comparing cases and controls as well as the intergroup differences among lymphomas. A total of 9 HL marker genes, 7 DLBCL marker genes, and 4 MCL marker genes were screened in this study. Most HL marker genes were upregulated, whereas DLBCL and MCL marker genes were downregulated compared to controls. The optimal HL-specific diagnostic model contains one marker gene (MYH2) with an AUC of 0.901. The optimal DLBCL-specific diagnostic model contains 7 marker genes (LIPF, CCDC144B, PRO2964, PHF1, SFTPA2, NTS, and HP) with an AUC of 0.951. The optimal MCL-specific diagnostic model contains 3 marker genes (IGLV3-19, IGKV4-1, and PRB3) with an AUC of 0.843. The present study reveals the transcriptome data-based differences between HL, DLBCL, and MCL, when combined with other clinical markers, may help the clinical diagnosis and prognosis.

Jun Rao, Lihua Shao, Min Lin, Jin Huang, Li Fan Department of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Li FanDepartment of Gastroenterology, The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University, No. 68 Gehu Road, Wujin District, Changzhou, Jiangsu, 213000, People’s Republic of ChinaEmail lifan226@163.comBackground: Ulcerative colitis (UC) has become one of the fastest-growing severe diseases worldwide with high morbidity. This research aimed to explore the function of lncRNA UCA1 in UC progression.Methods: RT-qPCR analysis was used to examine the expression of UCA1 level in colonic mucosa tissues of UC patients. Then, fetal human cells (FHCs) were stimulated by LPS to induce inflammatory injury. CCK-8, flow cytometry and ELISA were adopted to determine the influence of UCA1 depletion on cell viability, apoptosis and pro-inflammatory factors levels in LPS-induced FHCs. The interaction between UCA1 and miR-331-3p or BRD4 was confirmed by luciferase reporter assay. The expressions of key factors involved in NF-κB pathway were assessed by Western blotting.Results: LncRNA UCA1 level was elevated in colonic mucosa tissues of UC patients. LPS stimulation restrained cell viability and promoted the apoptosis and inflammatory factors levels, thus inducing FHCs inflammatory injury, while these effects were partially abolished by UCA1 knockdown. Moreover, it was found that UCA1 silence improved LPS-triggered cell injury via miR-331-3p. In addition, BRD4 was directly targeted by miR-331-3p, and BRD4 deficiency neutralized the effects of miR-331-3p repression on LPS-triggered injury in LPS-treated FHCs.Conclusion: Our data determined that UCA1 knockdown attenuated UC development via targeting the miR-331-3p/BRD4/NF-κB pathway.Keywords: UCA1, ulcerative colitis, miR-331-3p, BRD4

Background: Available evidence on the comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder (PTSD) in children and adolescents remains uncertain. Objective: We aimed to compare and rank the different types and formats of psychotherapies for PTSD in children and adolescents. Methods: We searched eight databases and other international registers up to 31 December 2020. The pairwise meta-analyses and frequentist network meta-analyses estimated pooled standardised mean differences (SMDs) and ORs with random-effects model. Efficacy at post-treatment and follow-up, acceptability, depressive and anxiety symptoms were measured. Findings: We included 56 randomised controlled trials with 5327 patients comparing 14 different types of psychotherapies and 3 control conditions. For efficacy, cognitive processing therapy (CPT), behavioural therapy (BT), individual trauma-focused cognitive–behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing, and group TF-CBT were significantly superior to all control conditions at post-treatment and follow-up (SMDs between −2.42 and −0.25). Moreover, CPT, BT and individual TF-CBT were more effective than supportive therapy (SMDs between −1.92 and −0.49). Results for depressive and anxiety symptoms were similar to the findings for the primary outcome. Most of the results were rated as ‘moderate’ to ‘very low’ in terms of confidence of evidence. Conclusions: CPT, BT and individual TF-CBT appear to be the best choices of psychotherapy for PTSD in young patients. Other types and different ways of delivering psychological treatment can be alternative options. Clinicians should consider the importance of each outcome and the patients’ preferences in real clinical practice.

Although great success has been achieved in catalytic asymmetric hydroamination of unactivated alkenes using transition metal catalysis and organocatalysis, the development of catalytic desymmetrising hydroamination of such alkenes remains a tough challenge in terms of attaining a high level of stereocontrol over both remote sites and reaction centers at the same time. To address this problem, here we report a highly efficient and practical desymmetrising hydroamination of unactivated alkenes catalysed by chiral Brønsted acids with both high diastereoselectivity and enantioselectivity. This method features a remarkably broad alkene scope, ranging from mono-substituted and gem-/1,2-disubstituted to the challenging tri- and tetra-substituted alkenes, to provide access to a variety of diversely functionalized chiral pyrrolidines bearing two congested tertiary or quaternary stereocenters with excellent efficiency under mild and user-friendly synthetic conditions. The key to success is indirect activation of unactivated alkenes by chiral Brønsted acids via a concerted hydroamination mechanism.

The thermal endurance of four pure and three binary eutectic mixture sugar alcohols were examined as a complementary work to the previous screening efforts based on the phase change behaviors towards latent heat storage. It was shown that both the melting point and latent heat of fusion of these sugar alcohols degrade with increasing the heating duration, and that a higher degree of superheat leads to faster degradation. The melting point drift mainly attributes to the shrinking range of hydrogen bonding, whereas the decay of latent heat is likely resulted from the disruption of hydrogen bond networks and incomplete crystallization. Among the various candidates, erythritol exhibits the best thermal endurance. The infrared spectra demonstrated that sugar alcohols can be oxidized to generate aldehydes upon heating when exposed to air. It was also found that the duration for 10% degradation of the latent heat of fusion of inositol can be extended by similar to 9 times when being protected by nitrogen gas. However, although the introduction of nitrogen gas could efficiently improve the thermal endurance, other complex reactions can still occur in inert gas atmosphere at high temperatures, leaving the room for further improving the thermal endurance of sugar alcohols toward real-world applications., QC 20201201

Graphene oxide (GO) nanosheets were employed as the additive to make composites of erythritol, a promising medium-temperature PCM candidate. GO nanosheets modified with hydroxyl groups were applied to improve the dispersion stability of the composites. A systematic characterization on the latent heat storage performance was performed for both pure and composite erythritol, in order to identify the benefits and challenges of the composites. It was found that the thermal conductivity is increased by nearly twice and the degree of supercooling was lowered from ~64 °C to ~48 °C at the loading of 1.0 wt% GO nanosheets (the maximum loading tested). The addition of GO nanosheets also leads to an increase of the retrievable latent heat during crystallization, from ~187 kJ/kg to ~225 kJ/kg at the same loading, by increasing the crystallinity. However, the introduction of GO nanosheets can also lead to a rise in the dynamic viscosity of erythritol. As a result, the crystallization rate is slowed down and accordingly, the duration of crystallization becomes 62% longer when the loading reaches 1.0 wt%. In addition, favorable dispersion stability of the erythritol composites is observed, and their melting point (~117 °C) remains almost unchanged during 50 melting-crystallization cycles. Functionalized GO nanosheets have been shown to be an efficient additive for improving the performance of erythritol, but a trade-off analysis on the loading would be required to achieve the best overall performance., QC 20200722, KTH-ZheJiang University Collaboration

The genus Xanthomonas comprises several cosmopolitan plant-pathogenic bacteria that affect more than 400 plant species, most of which are of economic interest. Citrus canker is a bacterial disease that affects citrus species, reducing fruit yield and quality, and is caused by the bacterium Xanthomonas citri subsp. citri (Xac). The Xac3819 gene, which has previously been reported to be important for citrus canker infection, encodes an uncharacterized glutathione S-transferase (GST) of 207 amino-acid residues in length (XacGST). Bacterial GSTs are implicated in a variety of metabolic processes such as protection against chemical and oxidative stresses. XacGST shares high sequence identity (45%) with the GstB dehalogenase from Escherichia coli O6:H1 strain CFT073 (EcGstB). Here, XacGST is reported to be able to conjugate glutathione (GSH) with bromoacetate with a Km of 6.67 ± 0.77 mM, a kcat of 42.69 ± 0.32 s-1 and a kcat/Km of 6.40 ± 0.72 mM-1 s-1 under a saturated GSH concentration (3.6 mM). These values are comparable to those previously reported for EcGstB. In addition, crystal structures of XacGST were determined in the apo form (PDB entry 6nxv) and in a GSH-bound complex (PDB entry 6nv6). XacGST has a canonical GST-like fold with a conserved serine residue (Ser12) at the GSH-binding site near the N-terminus, indicating XacGST to be a serine-type GST that probably belongs to the theta-class GSTs. GSH binding stabilizes a loop of about 20 residues containing a helix that is disordered in the apo XacGST structure.

Nucleotide excision repair (NER) is a major DNA repair pathway for a variety of DNA lesions. XPB plays a key role in DNA opening at damage sites and coordinating damage incision by nucleases. XPB is conserved from archaea to human. In archaea, XPB is associated with a nuclease Bax1. Here we report crystal structures of XPB in complex with Bax1 from Archaeoglobus fulgidus (Af) and Sulfolobus tokodaii (St). These structures reveal for the first time four domains in Bax1, which interacts with XPB mainly through its N-terminal domain. A Cas2-like domain likely helps to position Bax1 at the forked DNA allowing the nuclease domain to incise one arm of the fork. Bax1 exists in monomer or homodimer but forms a heterodimer exclusively with XPB. StBax1 keeps StXPB in a closed conformation and stimulates ATP hydrolysis by XPB while AfBax1 maintains AfXPB in the open conformation and reduces its ATPase activity. Bax1 contains two distinguished nuclease active sites to presumably incise DNA damage. Our results demonstrate that protein-protein interactions regulate the activities of XPB ATPase and Bax1 nuclease. These structures provide a platform to understand the XPB-nuclease interactions important for the coordination of DNA unwinding and damage incision in eukaryotic NER.

Nucleotide excision repair (NER) removes various DNA lesions caused by UV light and chemical carcinogens. The DNA helicase XPB plays a key role in DNA opening and coordinating damage incision by nucleases during NER, but the underlying mechanisms remain unclear. Here, we report crystal structures of XPB from Sulfurisphaera tokodaii (St) bound to the nuclease Bax1 and their complex with a bubble DNA having one arm unwound in the crystal. StXPB and Bax1 together spirally encircle 10 base pairs of duplex DNA at the double-/single-stranded (ds-ss) junction. Furthermore, StXPB has its ThM motif intruding between the two DNA strands and gripping the 3'-overhang while Bax1 interacts with the 5'-overhang. This ternary complex likely reflects the state of repair bubble extension by the XPB and nuclease machine. ATP binding and hydrolysis by StXPB could lead to a spiral translocation along dsDNA and DNA strand separation by the ThM motif, revealing an unconventional DNA unwinding mechanism. Interestingly, the DNA is kept away from the nuclease domain of Bax1, potentially preventing DNA incision by Bax1 during repair bubble extension.

Background: Depressive disorders are common in children and adolescents. Antidepressants, psychotherapies, and their combination are often used in routine clinical practice; however, available evidence on the comparative efficacy and safety of these interventions is inconclusive. Therefore, we sought to compare and rank all available treatment interventions for the acute treatment of depressive disorders in children and adolescents. Methods: We did a systematic review and network meta-analysis. We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, PsycINFO, ProQuest, CINAHL, LiLACS, international trial registries, and the websites of regulatory agencies for published and unpublished randomised controlled trials from database inception until Jan 1, 2019. We included placebo-controlled and head-to-head trials of 16 antidepressants, seven psychotherapies, and five combinations of antidepressant and psychotherapy that are used for the acute treatment of children and adolescents (≤18 years old and of both sexes) with depressive disorder diagnosed according to standard operationalised criteria. Trials recruiting participants with treatment-resistant depression, bipolar disorder, psychotic depression, treatment duration of less than 4 weeks, or an overall sample size of fewer than ten patients were excluded. We extracted data following a predefined hierarchy of outcome measures, and assessed risk of bias and certainty of evidence using validated methods. Primary outcomes were efficacy (change in depressive symptoms) and acceptability (treatment discontinuation due to any cause). We estimated summary standardised mean differences (SMDs) or odds ratios (ORs) with credible intervals (CrIs) using network meta-analysis with random effects. This study was registered with PROSPERO, number CRD42015020841. Findings: From 20 366 publications, we included 71 trials (9510 participants). Depressive disorders in most studies were moderate to sev

Based on the non-isothermal phase change behaviors of twenty-one pure and mixture sugar alcohols presented in our previous study (Part 1), the isothermal melting and crystallization behaviors were further tested in this supplemental work for five selected pure sugar alcohols (xylitol, erythritol, dmannitol, d-dulcitol and inositol) and their five binary eutectic mixtures to make an advanced screening of these candidates for low-to-medium temperature latent heat storage. The isothermal melting and crystallization behaviors of these ten candidates were tested at a constant degree of superheat (10 degrees C) and various degrees of subcooling up to 210 degrees C. The phase change temperatures, degrees of supercooling and durations of phase change were determined by the recorded temperature-history curves. It was found that the incrystallizable xylitol and its eutectic mixture of xylitol (75 mol%) + erythritol with low melting points under 100 degrees C are also unable to crystallize during isothermal cool-down at any degrees of subcooling (30-90 degrees C) due to the unavailability to nucleation. The rest eight crystallizable candidates all suffer from severe supercooling and are unable to crystallize at low degrees of subcooling (<20 degrees C). They undergo both one-phase supercooling due to poor nucleation performance and two-phase supercooling, which was unable to be obtained previously by non-isothermal cooling, due to slow crystallization kinetics. However, it seems difficult to find a correlation between the observed degrees of supercooling in both the liquid and solid phases and the prescribed degrees of subcooling by only three consecutive isothermal melting and crystallization cycles, as a result of the randomness of nucleation and large size of samples. The duration of crystallization was shown to decrease with increasing the degree of subcooling for both pure and mixture sugar alcohols due to the enhanced driving force for crystallization. The durations o, QC 20190805

Dysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in the microtubule-binding domain, but how these mutations alter neuronal excitability is largely unknown. Here, using CRISPR/Cas9-based gene editing in human pluripotent stem cell (iPSC)-derived neurons and isogenic controls, we show that the FTD-causing V337M tau mutation impairs activity-dependent plasticity of the cytoskeleton in the axon initial segment (AIS). Extracellular recordings by multi-electrode arrays (MEAs) revealed that the V337M tau mutation in human neurons leads to an abnormal increase in neuronal activity in response to chronic depolarization. Stochastic optical reconstruction microscopy of human neurons with this mutation showed that AIS plasticity is impaired by the abnormal accumulation of end-binding protein 3 (EB3) in the AIS submembrane region. These findings expand our understanding of how FTD-causing tau mutations dysregulate components of the neuronal cytoskeleton, leading to network dysfunction.

One challenge for FDD massive MIMO communication system is how to obtain the downlink channel state information (CSI) at the base station. Except for traditional codebook feedback through uplink pilot transmission, some channel reciprocity properties can be utilized through uplink channel estimation and channel parameter estimation algorithms. In this paper, the uplink and downlink channel reciprocity properties are analyzed. It is theoretically proved that not all multipath parameters for FDD downlink and uplink channels are equivalent. Therefore, the so called full reciprocity property does not hold while the partial reciprocity property holds. Moreover, the channel measurement campaign is conducted to verify our theoretical analysis. Finally, in order to support the partial reciprocity property, the revision for the standardization 5G channel model is proposed as well. With the contribution of this paper, the FDD massive MIMO system transmission scheme design could be led to the right direction.

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration. METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment C, DOR 100 mg + 3TC 300 mg + TDF 300 mg; ≥7-day washout between periods. RESULTS: Study 1: geometric mean ratios (GMRs) (90% confidence interval [CI]) of DOR AUC0–∞ and C24h (DOR + TDF / DOR) were 0.95 (0.80, 1.12) and 0.94 (0.78, 1.12), respectively. Study 2: GMRs (90% CI) of DOR AUC0–∞ and C24h (DOR + 3TC + TDF / DOR) were 0.96 (0.87, 1.06) and 0.94 (0.83, 1.06), respectively. GMRs (90% CI) of 3TC and tenofovir AUC0–∞ (DOR + 3TC + TDF / 3TC + TDF) were 0.94 (0.88, 1.00) and 1.11 (0.97, 1.28), respectively. Study drugs were generally well tolerated. CONCLUSIONS: Multiple doses of TDF did not have a clinically meaningful effect on DOR PK. The PK of DOR were similar when administered alone or in combination with 3TC and TDF. DOR had no meaningful effect on the PK of 3TC and tenofovir.

Jiagui Mu,1 Li Fan,1 Duo Liu,1 Dongsheng Zhu2 1Department of Urology, The Second People’s Hospital of Lianyungang, Lianyungang Tumor Hospital, Lianyungang Hospital Affiliated to Bengbu Medical University, Haizhou District, Lianyungang 22200, China; 2Department of Graduate School Urology, Tianjin Medical University, Heping District, Tianjin 300000, China Objective: The aim of the study was to investigate the role of shugoshinl (SGO1) in human prostate cancer (PCa).Materials and methods: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of SGO1 in PCa tissues and cell lines. The correlation between SGO1 expression and clinicopathological characteristics of PCa patients was analyzed using Kaplan–Meier analysis. SGO1 siRNA was successfully constructed and transfected into PCa cell lines (LNCaP and PC3). The knockdown efficacy was assessed by qRT-PCR. MTT assay and Transwell assay were conducted to observe the effect of SGO1 on the proliferation and invasion of PCa cell lines.Results: SGO1-expression levels were found to be higher in the PCa tissues and cell lines. Correlation was identified between the expression of SGO1 and preoperative prostate-specific antigen (P=0.017), lymph-node metastasis (P=0.044), and Gleason score (P=0.041). Patients with higher SGO1 expression displayed more advanced clinicopathological characteristics in addition to a shorter biochemical recurrence-free survival time. Additionally, SGO1 knockdown resulted in the inhibition of PCa cell proliferation, migration, and invasion.Conclusion: Taken together, the findings of the current study present evidence suggesting that SGO1 could inhibit the growth and invasion of PCa cells, highlighting its potential as a novel therapeutic target for the treatment of PCa. Keywords: shugoshinl, prostate cancer, RNAi &nbsp

Membrane-bound transcription factors (MTFs) are transcription factors (TFs) that are anchored in membranes in a dormant state. Activated by external or internal stimuli, MTFs are released from parent membranes and are transported to the nucleus. Existing research indicates that some plasma membrane (PM)-bound proteins and some endoplasmic reticulum (ER) membrane-bound proteins have the ability to enter the nucleus. Upon specific signal recognition cues, some PM-bound TFs undergo proteolytic cleavage to liberate the intracellular fragments that enter the nucleus to control gene transcription. However, lipid-anchored PM-bound proteins enter the nucleus in their full length for depalmitoylation. In addition, some PM-bound TFs exist as full-length proteins in cell nucleus via trafficking to the Golgi and the ER, where membrane-releasing mechanisms rely on endocytosis. In contrast, the ER membrane-bound TFs relocate to the nucleus directly or by trafficking to the Golgi. In both of these pathways, only the fragments of the ER membrane-bound TFs transit to the nucleus. Several different nuclear trafficking modes of MTFs are summarized in this review, providing an effective supplement to the mechanisms of signal transduction and gene regulation. Moreover, targeting intracellular movement pathways of disease-associated MTFs may significantly improve the survival of patients.

Non-coding RNAs (ncRNAs) can be divided into circular non-coding RNAs (circRNAs) and linear ncRNAs. ncRNAs exist in different cell types, including normal cells, tumor cells and immunocytes. Linear ncRNAs, such as long ncRNAs and microRNAs, have been found to play important roles in the regulation of tumor immunity and immunotherapy; however, the functions of circRNAs in tumor immunity and immunotherapy are less known. Here, we review the current status of ncRNAs in the regulation of tumor immunity and immunotherapy and emphatically discuss the potential roles of circRNAs as tumor antigens in the regulation of tumor immunity and immunotherapy.