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This study aimed to examine factors, healthcare utilization, and medical costs associated with potentially inappropriate use of benzodiazepines in persons living with HIV (PLWH). We used big data from Medicare claims in 2017. Potentially inappropriate use of benzodiazepines was defined as having any benzodiazepine claims in individuals 65+ years or having benzodiazepine claims for more than four weeks in individuals 18–64 years. Logistic regressions, zero-inflated negative binomial regressions, and generalized linear models were used. This study included 1,211 PLWH and 235 (19.41%) had potentially inappropriate use of benzodiazepines. PLWH who were 65+ years (OR: 0.56; 95% CI: 0.33, 0.96), non-Hispanic blacks (OR: 0.29; 95% CI: 0.20, 0.41), or Hispanics (OR: 0.55; 95% CI: 0.35, 0.88) were less likely to use benzodiazepines inappropriately. PLWH who had potentially inappropriate use of benzodiazepines had more inpatient (IRR: 1.46; 95% CI: 1.10, 1.94), outpatient (IRR: 1.14; 95% CI 1.02, 1.28), and emergency room (IRR: 1.32; 95% CI: 1.03, 1.68) visits. Potentially inappropriate use of benzodiazepines was associated with higher total (β: 0.16; 95% CI: 0.07, 0.25), Medicare (β: 0.18; 95% CI: 0.07, 0.28), and out-of-pocket (β: 0.21; 95% CI: 0.05, 0.36) costs. This study provides real-world evidence to support deprescribing benzodiazepines in PLWH. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains a global health challenge, necessitating innovative therapeutic approaches. Immunomodulation and immunotherapy have emerged as promising strategies for breast cancer treatment. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. Through suitable modifications, engineered exosomes exhibit the capability to overcome the limitations associated with traditional therapeutic approaches. This ability opens up novel avenues for the development of more effective, personalized, and minimally invasive interventions. Main body: In this comprehensive review, we explore the molecular insights and therapeutic potential of engineered exosomes in breast cancer. We discuss the strategies employed for exosome engineering and delve into their molecular mechanisms in reshaping the immune microenvironment of breast cancer. Conclusions: By elucidating the contribution of engineered exosomes to breast cancer immunomodulation, this review underscores the transformative potential of this emerging field for improving breast cancer therapy. Highlights: Surface modification of exosomes can improve the targeting specificity.The engineered exosome‐loaded immunomodulatory cargo regulates the tumour immune microenvironment.Engineered exosomes are involved in the immune regulation of breast cancer. [ABSTRACT FROM AUTHOR]

Despite significant advancements in deep learning-based video–text retrieval methods, three challenges persist: the alignment of fine-grained semantic information from text and video, ensuring that the obtained textual and video feature representations capture primary semantic information while maintaining good discriminability, and measuring the semantic similarity between different instances. To tackle these issues, we introduce an end-to-end video–text retrieval framework which exploit Multi-Modal Masked Transformer and Adaptive Attribute-Aware Graph Convolutional Network (M 3 Trans-A 3 GCN). Specifically, the features extracted from videos and texts are fed into M 3 Trans to jointly integrate the multi-modal content and mask irrelevant multi-modal context. Subsequently, a novel GCN with an adaptive correlation matrix (i.e., A 3 GCN) is constructed to obtain discriminative video representation for video–text retrieval. To better measure the semantic similarity between video–text pairs during training, we propose a novel Text-semantic-guided Multi-Modal Cross-Entropy (TMCE) loss function. Here, the similarity between different video–text pairs within a batch is computed based on the features of the corresponding text rather than their instance labels. Comprehensive experimental results on three benchmark datasets, MSR-VTT, MSVD and LSMDC, demonstrate the superiority of M 3 Trans-A 3 GCN, compared with the state-of-the-art methods in video–text retrieval. [ABSTRACT FROM AUTHOR]

This paper explores the task of visual grounding (VG), which aims to localize regions of an image through sentence queries. The development of VG has significantly advanced with Transformer-based frameworks, which can capture image and text contexts without proposals. However, previous research has rarely explored hierarchical semantics and cross-interactions between two uni-modal encoders. Therefore, this paper proposes a Hierarchical Cross-modal Contextual Attention Network (HCCAN) for the VG task. The HCCAN model utilizes a visual-guided text contextual attention module, a text-guided visual contextual attention module, and a Transformer-based multi-modal feature fusion module. This approach not only captures intra-modality and inter-modality relationships through self-attention mechanisms but also captures the hierarchical semantics of textual and visual content in a common space. Experiments conducted on four standard benchmarks, including Flickr30K Entities and RefCOCO, RefCOCO+, RefCOCOg, demonstrate the effectiveness of the proposed method. The code is publicly available at https://www.github.com/cutexin66/HCCAN. [ABSTRACT FROM AUTHOR]

This paper attacks the two challenging problems of image-based crowd counting, that is, scale variation and complex background. To that end, we present a novel crowd counting method, called the Scale and Background aware Asymmetric Bilateral Network (SBAB-Net), which is able to handle scale variation and background noise in a unified framework. Specifically, the proposed SBAB-Net contains three main components, a pre-trained backbone convolutional neural network (CNN) as the feature extractor and two asymmetric branches to generate a density map. These two asymmetric branches have different structures and use features from different semantic layers. One branch is densely connected stacked dilated convolution (DCSDC) sub-network with different dilation rates, which relies on one deep feature layer and can handle scale variation. The other branch is parameter-free densely connected stacked pooling (DCSP) sub-network with various pooling kernels and strides, which relies on shallow feature and can fuse features with several receptive fields to reduce the impact of background noise. Two sub-networks are fused by the attention mechanism to generate the final density map. Extensive experimental results on three widely-used benchmark datasets have demonstrated the effectiveness and superiority of our proposed method: (1) We achieve competitive counting performance compared to state-of-the-art methods; (2) Compared with baseline, the MAE and MSE are decreased by at least 6.3 % and 11.3 % , respectively. [ABSTRACT FROM AUTHOR]

The purpose is to apply deep learning to facial expression recognition and improve the efficiency of facial expression recognition in real scenes: first, convolutional neural network (CNN) theoretical model is proposed. On this basis, a new CNN model is proposed, which has six learning layers, including three convolutional layers and three fully connected layers. Then, based on the shortcomings of the model, weight decay and dropout optimization methods are proposed. Moreover, the attention module is designed based on the theory of attention mechanism. After each convolutional layer, a hybrid attention module (channel domain attention and spatial domain attention) is added. Finally, the frame error rate (FER) 2013 dataset and Cohn–Kanade (CK)+ dataset are used to test and compare the performance of the model. The results show that after 50Epoch, the accuracy rate of the original model fluctuates greatly in the process of convergence; however, after attention mechanism is added, the fluctuation of the accuracy of the model is obviously reduced. In the CK+ dataset, the accuracy of each model is maintained at about 95%, while the accuracy of FER2013 dataset is about 71%. After attention mechanism is added, the recognition rate of dynamic nonlinear expression is higher than that of basic model. The recognition rate of the original model and the optimized model with attention mechanism for the dynamic nonlinear expression with occlusion decreases in varying degrees, but the reduction of the recognition rate of the latter is alleviated. [ABSTRACT FROM AUTHOR]

A quasi-three-dimensional (3-D) analytic method is presented for calculating the performance of single-sided linear induction motor with the ladder secondary. To simplify the analytic model, the ladder aluminum plate is equivalent to the flat-solid one, and the equivalent conductivity is derived and given. In the direction of the motion, the finite primary length and end effect are considered by the method of the Fourier transform and Residue theorem. In the transverse direction, considering finite width of the primary core and the region between the overhang of the primary windings and the secondary, the equivalent integral length is given. Finally, the thrust, vertical force and secondary efficiency are calculated and compared with the results of the 3-D finite-element method and experiment, it is shown that the method presented in the paper is much simpler and the accuracy of the analytic method is verified. [ABSTRACT FROM AUTHOR]

Mechanically robust optical homogeneous polyimide (PI) films with desirable atomic oxygen (AO) erosion duration were fabricated by initially synthesizing amine-functionalized hyperbranched polysiloxane (NH2-HBPSi), then reinforcing the pristine polyimide skeleton with it via copolycondensation reactions. NH2-HBPSi macromolecule imparts desirable AO survivability to the resulting hybrids. The mass loss per unit area of hybrid films had a downward trend with rising NH2-HBPSi content and AO dose before the complete silica protective layer was formed. It has been proven by the experiments in an underground simulated AO environment. It decreased to 1% of that of pristine polyimide when NH2-HBPSi accounted for 30% of the solid content after 24 h AO attack. The stable thickness uniformity that can meet the Rayleigh criterion was achieved in a 30 wt% HBPSi PI film, mainly due to the selection of the best process parameters. Meanwhile, 30 wt% HBPSi PI demonstrates satisfactory mechanical properties, with a tensile strength of 228.9 MPa and elongation at break of 7.3%. The characterization of scanning electron microscopy confirmed that pristine polyimide was substantially eroded after AO exposure while the surface morphology of 30 wt% HBPSi polyimide showed no evident change. The low AO erosion yield and prominent film thickness uniformity may find extensive usage in ultra-lightweight space diffractive optical elements (DOE) working in low earth orbit (LEO). [ABSTRACT FROM AUTHOR]

Since the linear induction motor commonly work with a laterally asymmetric secondary as it is applied to pull rail vehicles, this paper presents a complete equivalent circuit model considering the asymmetry to predict thrust, vertical and transversal forces. First, six correction factors are presented to quantify the variations in the air-gap magnetic flux and secondary induced current as the linear induction motor operating with a laterally asymmetric secondary. Second, it develops a circuit model based on the existing T-model for the rotary induction motor and two correction factors for the magnetizing branch, which is used to indicate the electromagnetic variations in the air-gap flux and secondary plate due to the asymmetry. Third, the mathematical expressions for the thrust, vertical and transversal forces are derived by applying the equivalent circuit model. Then, the six correction factors are calculated with a prototype motor, and the results of them are comprehensively analyzed. Finally, the characteristics in the prototype motor are calculated with the mathematical expressions in a range of rated speed, and validated by the experimental measurements carried out on a test rig and line for linear motors. [ABSTRACT FROM AUTHOR]

This study mainly investigates the key secondary parameter effecting on transverse force and the changing trend of its components, which include the repulsive and restoring components. Firstly, considering the transverse displacements, skin effect and end effects, the full 3D finite element models of the single‐sided linear induction motor (SLIM) are built. Secondly, when the width of the secondary varies, the transverse force and its two components are presented and analysed. At the same time, the air‐gap flux densities and the eddy currents along the transverse directions are calculated. Then when the topological transform of aluminium plate (e.g. Al‐cap type) and back‐iron plate (e.g. laminated type) are applied, the transverse force and its components are given. Finally, the transverse force, thrust and efficiencies are compared in the SLIMs with different secondaries as well as some experiments are given. It is shown that the width of the secondary is the main factor influencing the transverse force. [ABSTRACT FROM AUTHOR]

Metastasis and recurrence severely impact the treatment effect of hepatocellular carcinoma (HCC). HCC complicated with cholestasis is more prone to recurrence and metastasis. Previous studies have implicated pathogenesis of HCC by bile acid; however, the underlying mechanism is unknown yet. Glycochenodeoxycholate (GCDC) is one of most important component of bile acid (BA). In the present study, the role of GCDC in HCC cells invasion was detected by in vitro and in vivo assays. GCDC was found to significantly enhance the invasive potential of HCC cells; Further studies showed that GCDC could induce autophagy activation and higher invasive capability in HCC cells. Interestingly, inhibition of autophagy by chloroquine (CQ) reversed this phenomenon. Subsequently, the correlation between TBA expression level and clinicopathological characteristics was analyzed in HCC patients. Clinically, high TBA level in HCC tissue was found to be associated with more invasive and poor survival in HCC patients. Mechanistic study showed that bile acid induced autophagy by targeting the AMPK/mTOR pathway in HCC cells. Therefore, our results suggest that bile acid may promote HCC invasion via activation of autophagy and the level of bile acid may serve as a potential useful indicator for prognosis of HCC patients. • GCDC enhanced the metastasis of HCC which was mediated by autophagy. • AMPK/mTOR pathway contributed to the metastatic potential of HCC cells mediated by autophagy. • TBA level was correlated to autophagy activation and HCC prognosis in clinically specimens. [ABSTRACT FROM AUTHOR]

In this paper, the influence of the flat and cap secondary, which are usually applied in the linear metro system on transverse forces of linear induction motors, is calculated and analyzed. First, the cap-aluminum plate and lamination back iron of the cap secondary caused relative difficulty in the analytical calculation. Then, the equivalent of the cap-aluminum plate and lamination back iron is presented, and two equivalent coefficients are obtained. The two types of the asymmetry are discussed and the different magnetic motive forces are presented. Second, the analytical model and the method of the linear induction motor are presented. Third, for a cap secondary in practice, the two equivalent coefficients are calculated and discussed. Then, the flat and cap secondary are applied, and the different transverse forces are calculated and analyzed. For two types of the secondaries, the different eddy currents and air-gap flux densities are compared. Finally, the test workbench is built and the analytical result of the transverse force is experimentally validated. It shows that cap secondary has less influence on the railcar when the transverse displacement occurs. [ABSTRACT FROM AUTHOR]

Owing to the larger total harmonic distortion (HD) of the air‐gap magnetic field in the linear induction motors with the flat‐solid and direct‐slit secondary, the construction of V‐type secondary is proposed and investigated, to reduce the harmonic components. First, a skew factor is presented to indicate the influence of the tooth harmonic on the air‐gap magnetic field. The skew distance is a key point for the design of the V‐type secondary, and the influence of the different skew distances on the thrusts, HD, and efficiencies are analysed by the three‐dimensional finite‐element method. Finally, the eddy currents, the air‐gap flux densities, and electromagnetic forces are calculated in the linear induction motors with the V‐type secondary. It shows that the V‐type secondary can reduce the harmonic components and improve the performance. [ABSTRACT FROM AUTHOR]

Due to the influence of the switch and rail equipment, the secondary cannot be laid continuously in the linear metro. An equivalent circuit of the single‐sided linear induction motor (SLIM) is presented to consider the discontinuity of the secondary plate, and the electromagnetic characteristics of the motor with the discontinuous secondary are obtained. First, the analysis model of the SLIM considering the missing part of the secondary plate is proposed. Second, the variation of the length of the coupled region between the primary and secondary are considered by the method of approximate linearisation to correct the parameters including the primary leakage inductance, magnetising inductance, secondary resistance and secondary leakage inductance. Third, three typical cases of the relative position between the primary and discontinuous secondary are analysed, and the equivalent circuit in each case is deduced according to the distribution of the secondary magnetic motive force and air gap flux density. Then, two coefficients considering the longitudinal end effect, on the basis of the corrected secondary time constant, are proposed to correct the magnetising inductance and secondary resistance. Finally, the analytical results are verified by the results measured on the test rig of an SLIM. [ABSTRACT FROM AUTHOR]

Since single-sided linear induction motors working with a lateral asymmetric cap secondary is a frequent operating condition, this paper develops an equivalent circuit model considering the asymmetric condition. First, an analysis model, which takes the longitudinal end effect and skin effect into consideration, is proposed. Second, a transversal analysis model considering the laterally asymmetric cap secondary is developed to derive its correction factors. Then, the influence of lamination eddy current on the effective air gap to transversely directed flux is contrastively analyzed. Third, the traction characteristics of a prototype motor with symmetric and asymmetric cap secondary are calculated by the equivalent circuit. Finally, these calculated results are verified by measurements carried out by a test rig of the linear motor. [ABSTRACT FROM AUTHOR]

Abstract Aim Spinal cord injury (SCI) causes increased apoptosis of neurons, leading to irreversible dysfunction of the spinal cord. In this study, we investigated the effects of the progression of SCI and potential regulation of apoptosis after the Pleckstrin homology (PH) domain and leucine rich repeat protein phosphatase 1 ( PHLPP1 ) gene was silenced. Main methods Spinal cord injection, and neuronal transfection with a recombinant adenovirus vector encoding small interfering RNA (siRNA) against PHLPP1 (AdsiPHLPP1) successfully silenced PHLPP1. These created in vivo and in vitro PHLPP1-silenced models, respectively, resulting in stable expression of the transgene in neurons. Key findings The results showed that silencing of PHLPP1 evidently reduced levels of the nuclear factor erythroid 2-related factor 2 (Nrf2) after SCI. Western blot analysis revealed that the mice injected with AdsiPHLPP1 showed increased the expression of pro-apoptotic factors (Bax and cleaved-caspase 3), and reduced levels of neurotrophic (BDNF) and anti-apoptotic (Bcl-2) factors, both in vivo and in vitro. The motor function of AdsiPHLPP1-injected mice was restored more slowly than that of wild type (WT) mice. In addition, the number of motor neurons surviving in the anterior horn of the spinal cord was also reduced after SCI. Significance Our results confirm that silencing of PHLPP1 promotes neuronal apoptosis and inhibits functional recovery after injury in vivo and in vitro. Consequently, PHLPP1 represents a potential therapeutic target gene for the clinical treatment of SCI. [ABSTRACT FROM AUTHOR]

Text image captioning aims to understand the scene text in images for generating image captions. The key challenge of this task is to accurately and comprehensively understand the OCR tokens of scene text. Due to the dual modal of visual and textual features of scene text, expressing the multimodal semantic features of OCR tokens accurately is a challenging task. Additionally, since scene text cannot exist independently of specific objects and is always associated with its surroundings, establishing a scene graph centered around OCR tokens is also an important approach to understand its relationship with other objects in the image. In this paper, we propose a novel model named C lip- O CR and M aster Obj E ct (dubbed as COME) for text image captioning. First, we introduce a CLIP-OCR module to enhance the multimodal representation of OCR tokens. We separate the OCR representation into visual and textual items and narrow the similarity by contrastive learning. With the assistance of the CLIP-OCR module, we realize correlation alignment between different modes. Next, we propose the concept of master object for each OCR text and purify the OCR-oriented scene graph with it. The master object is defined as the object to which the OCR is attached, which bridges the semantic relationship between the OCR tokens and the image. We consider the master object as a proxy that connects OCR tokens and other regions in the image. By exploring the master object for each OCR token, we build a purified scene graph based on the master object and then enrich the visual embedding by the Graph Convolution Network (GCN). Furthermore, we cluster the OCR tokens and append the hierarchical information on the input embedding to provide a complete representation. Experiments on the TextCaps validation set and test set demonstrate the effectiveness of the proposed framework. • A new framework COME for text image captioning that understands OCR tokens of scene text. • A CLIP-OCR module to enhance the multimodal representation of OCR tokens. • The concept of master object to purified the relationships of OCR token. [ABSTRACT FROM AUTHOR]

GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. The preproglucagon neurons located in the brainstem can also produce GLP-1. GLP-1 analogs have a long-acting effect and are able to pass the blood-brain barrier, which probably extends the therapeutic efficacy of GLP-1R activation. Neurodegenerative or traumatic conditions can damage the spinal cord and result in motor and sensory dysfunction. Evidence supports that GLP-1R activation in the spinal cord possesses beneficial effects and significant therapeutic potential. Herein, we review studies that have focused on GLP-1 and the spinal cord, and summarize the expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as well as the potential therapeutic benefits of GLP-1R activation. [ABSTRACT FROM AUTHOR]

In order to improve the performance of linear induction motors for urban rail transit, the ladder-slit secondary is designed, and the performance of linear induction motors with the ladder-slit and flat-solid secondary is calculated and compared. First, for the ladder-slit secondary, the slot combination, widths of the secondary conductor, and side bar are designed. Second, the finite-element model of the linear induction motor with the ladder-slit secondary is developed, and the influence of vertical forces on widths of secondary conductors is presented. Third, the eddy current and the transversal air-gap flux density are compared when the ladder-slit and flat-solid secondaries are applied, respectively. Finally, experiments are carried out by test lines to validate the calculated results of the force and efficiency. It shows that the ladder-slit secondary can reduce the edge effect and improve the performance. [ABSTRACT FROM PUBLISHER]

This study investigates the influence of the composite secondary with the solid and laminated back iron on the thrust, vertical force, secondary losses and efficiency in the prototype single-sided linear induction motor for metro by space harmonic method. First, a 3-D space harmonic analytical model, which can consider the skin effects, secondary constructions as well as end and edge effects, is proposed. Second, the air-gap flux and secondary eddy current density distributions along longitudinal and transverse directions are presented. Then, variations of secondary losses and efficiency with a specific number of secondary back iron laminations are comprehensively compared in the full slip, and the optimal number of laminations is obtained. Third, the propulsive and vertical forces are analytically calculated under full slip, and the efficiency in a range of rated speed is presented. Finally, these results are verified by measurements on an experimental rig of the linear motor. [ABSTRACT FROM AUTHOR]

This paper develops a novel magnetomotive forces (mmfs) distribution model along the transverse direction for the 3-D analysis of linear induction motor, and it investigates the influence of a laterally asymmetric cap-secondary on the thrust, vertical force, lateral force, and efficiency in a prototype single-sided linear induction motor for linear metro. First, the mmf distribution model and its working conditions are defined, and the model is transferred into a mathematical model. Second, the air-gap flux and secondary eddy current in a prototype linear motor with a cap-secondary are obtained by a 3-D space harmonic analytical method. Third, the thrust, vertical force, lateral force, and efficiency of the test motor are analyzed with various lateral deflection, and the power factor in secondary is also presented. Finally, these results are experimentally verified by measurements on the test rig of the linear motor, and the comprehensive effect on the operating performance can be accurately calculated by the mmf model. [ABSTRACT FROM PUBLISHER]

Vitamin D plays a major role primarily in bone mineral homeostasis; however, the action of vitamin D on male reproduction of boars remains unknown. This study was conducted to evaluate the effects of dietary vitamin D 3 supplementation on reproductive performance of boars. Twenty-four Yorkshire boars with eighteen months were randomly allocated to one of three vitamin D 3 levels diets: 200 IU/kg (C), 2000 IU/kg (T1) and 4000 IU/kg (T2) of vitamin D 3 for a 16-week period. Results showed that sperm motility, effective sperm number per ejaculate, acrosome intactness ratio, and membrane intactness ratio in T1 group were significantly higher than those in C group. The sperm membrane intactness ratio was higher in T1 group than in T2 group, whereas the deformity ratio was significantly lower in T1 than in C and T2 groups. Dietary supplementation with vitamin D 3 significantly increased 25-OHD 3 concentration in the blood and seminal plasma, but there was no significant difference in its concentration in the seminal plasma between T1 and T2 groups. The concentrations of blood testosterone and aromatase activity increased following vitamin D supplementation. Seminal plasma Ca 2+ , fructose concentration, and acid phosphatase activity were higher in T1 group than in C group, but not significantly different from the corresponding values in T2 group. Furthermore, expression of CYP19, CYP24A1, and VDR mRNAs in sperm was up-regulated in T1 group compared to that in C group. In conclusion, supplementation of boar diets with 2000 IU/kg vitamin D 3 increased the sperm motility and effective sperm number, which was in line with the elevated concentrations of vitamin D, hormone secretion and gene expression. [ABSTRACT FROM AUTHOR]

The secondary is an important design factor of single‐sided linear induction motors (SLIMs), as well as has influence on the cost and performance of SLIMs. In this study, the cap‐lamination secondary is designed and relations of the secondary parameter and performance of SLIMs are calculated. First, the aluminium (Al) cap and lamination back iron of the cap‐lamination secondary are designed and discussed. Then, improvements in performance caused by two potentially significant effects of the cap‐lamination secondary, i.e. the thick cap edge and lamination, are identified. Second, a flat‐solid secondary is applied and two SLIMs, which are the same primary and two different secondaries, are calculated by three‐dimensional finite‐element method. Eddy current densities in the Al and back iron plate, which are two parts of the secondary, are analysed. Owing to different transverse edge effects, variations of the air‐gap flux density are calculated with different secondaries. Finally, the numerical results of the thrust, power factor, and efficiency are experimentally validated by measurements on test rig of SLIMs. It shows that the SLIM with cap‐lamination secondary, which has higher performance, is affected greatly by the conductor structure of the secondary and the lamination of the iron back plate. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mechanism-informed phenotypic screening guides lead optimization. • The structural simplification approach identifies a 4-phenoxy-quinoline-based hit. • Lead compound disables AURKB by disrupting its mitotic localization. • Lead compound elicits cytotoxicity in diverse cancer cell lines at low nM concentrations. We combined a mechanism-informed phenotypic screening (MIPS) assay with a structural simplification strategy to guide the discovery of compounds that disrupt the localization of the mitotic regulator, Aurora kinase B (AURKB), rather than inhibiting its catalytic activity. An initial hit 4-(4-methylthiophen-2-yl)-N-(4-(quinolin-4-yloxy)phenyl)phthalazin-1-amine was identified after screening an in-house library of small molecules and phenocopied the loss of function mutations in AURKB without inhibiting its catalytic activity. We isolated this hit compound activity to its 4-phenoxy-quinoline moiety. The fragment was further optimized into a class of new chemical entities that potently disrupt the mitotic localization of AURKB at low nanomolar concentrations and consequently elicit severe growth inhibition in diverse human cancer cell lines. A lead compound, N-(3-methoxy-5-(6-methoxyquinolin-4-yl)oxy)phenyl)acetamide possessed desirable pharmacokinetic properties such as AUC 0-∞ : 227.15 [ng∙h/mL/(mg/kg)]; C max : 3378.52 ng/mL T 1/2 : 3.52 h; and F%: 42 % and produced the AURKB-inhibitory phenotypes in a mouse xenograft model. A lead compound is a powerful tool for interrogating the regulation of AURKB and has the potential to be further developed as a first-in-class oncology therapeutic. [ABSTRACT FROM AUTHOR]

Activity-based drug screens have successfully led to the development of various inhibitors of the catalytic activity of aurora kinases (AURKs), major regulatory kinases of cell division. Disrupting the localization of AURKB, rather than its catalytic activity, represents a largely unexplored alternative approach to disabling AURKB-dependent processes. Localization disruptors could be just as specific as direct inhibitors of AURKB activity, may bypass their off-target and select on-target toxicities, and are likely less susceptible to drug resistance resulting from mutations of the AURKB catalytic site. In this study, we demonstrate that the pan-AURK inhibitor AMG900 works at a low concentration not by inhibiting the phosphorylation of H3 at Ser10, an AURKB substrate, but by disrupting the mitotic localization of AURKB. Structural deletion studies pinpoint this undescribed activity to the 2-phenoxy-3,4′-bipyridine moiety of AMG900. Guided by a mechanism-informed phenotypic screening (MIPS) assay, the drug fragment is optimized into a novel class of inhibitors that, at low nanomolar concentrations, can disable AURKB through disruption of its mitotic localization and have desirable oral PK properties. Hierarchical clustering of cell fitness profiles reveals that these compounds cluster with each other, rather than with known AURK inhibitors such as AMG900 and VX-680. Validation studies in mice demonstrate that compound 15a elicits mitotic arrest and apoptosis in NCI–H23 human lung adenocarcinoma xenografts, resulting in a pronounced suppression of tumor growth. The discovery and optimization of compounds that disrupt AURKB localization are successfully facilitated by MIPS. Our findings suggest that 2-phenoxy-3, 4′-bipyridine derivatives have the potential to be further developed as effective therapeutics for the treatment of malignancy by delocalizing AURKB. [Display omitted] • Mechanism-informed phenotype approach to guide lead optimization. • Structural simplification to identify 2-phenoxy-3,4′-bipyridine moiety of AMG900. • Lead compound 15a disables AURKB by disrupting its mitotic localization. • 15a elicits broad spectrum cytotoxicity at low nM concentrations. [ABSTRACT FROM AUTHOR]

A density-functional and Car–Parrinello molecular dynamics methods were employed to study the adsorption of the methylguanidine or methylguanidinium on Ag(111) surface with Vanderbilt pseudopotentials and PBE functional. The geometry, interacting energy, vibrational frequency, Mayer bond order and electrostatic fit charges were calculated. The results show that the methylguanidine interacts with the Ag(111) surface mainly through the interaction between thesp2hybridisation imine nitrogen and its nearest silver atom on top site, assisted with the Ag∙∙∙H interaction, with the most stabilising interacting energy −78.83 kJ/mol. The Car–Parrinello molecular dynamics results at 293.15 or 300.00 K indicate that the Ag∙∙∙N interaction exists stably for more than 6 psand the Mayer bond order analysis shows that it is the main interaction in adsorption. For the methylguanidinium on Ag(111) surface, the weak interaction between N−H and its neighbour silver atoms, with the energy of −40.73–−42.68 kJ/mol and the interacting time of 0.2–0.3 ps at 300 K, could not keep it steady on Ag(111). The CP dynamics results show that only the methylguanidine could adsorb on Ag(111) at the room temperature. [ABSTRACT FROM AUTHOR]

Allied to the extensive use of online shopping, product recommendation on websites is vitally important for E-commerce. Consequently, collaborative filtering and content-based filtering have been widely used in recommendation systems on E-commerce websites. However, these filtering methods have many problems, such as cold start, prejudiced ratings and inaccurate suggestions. To generate valid and accurate suggestions, researchers have proposed integrating semantic features of the data in an ontology into the recommendation process. However, most existing studies only include the type and features of a product without considering the relational characteristics thereof. Given that the relational characteristics can provide much useful information during the recommendation process, we have designed an easily realizable recommendation system framework based on relational data by integrating the relational data in the domain ontology and applying a genetic algorithm to process the recommendation. Experimental results show that there are obvious improvements in the methods for dealing with sparsity and cold start problems as well as the accuracy and timeliness of recommendations. [ABSTRACT FROM AUTHOR]

Due to the magnetic distortion and nonuniform force density of the single-side linear induction motor (SLIM) caused by the lateral movement, edge, and end effects, three types of torques, i.e., the side, normal, and horizontal torques, are produced. This paper investigates these special torques of the SLIM for metro and the variations of these torques when the primary is displaced sideways from a symmetrical position. It is of prime importance to take longitudinal end effects, edge effects, overhang of the primary windings, and lateral displacement into consideration when the air-gap flux density distributions and special torques are calculated via a 3-D analytical method. The air-gap flux density distributions along longitudinal and transverse directions, as well as the force density and torques with the different lateral displacements, are comprehensively investigated when the motor works in the motoring operation. The analytical results are experimentally validated by measurements on a reciprocal power-fed test rig. It shows that the horizontal and side torques, which increase the instability of the suspension system and the antirolling bar of bogie, increase almost linearly with the increase of the lateral displacement. Normal torque decreases with the increasing lateral displacement. [ABSTRACT FROM PUBLISHER]

Electromagnetic variations of the single‐sided linear induction motor (SLIM) are calculated by three‐dimensional (3D) finite‐element method (FEM) when the primary is displaced sideways from a symmetrical position. For geometrical and electrical asymmetry, a full 3D model, which considering the longitudinal and transverse end effects, overhangs of the primary windings and secondary, as well as lateral displacement, is developed. Apart from the thrust and vertical force, lateral force is produced when the transverse asymmetry occurred. Hence, the calculation equation of thrust, vertical and lateral forces in each element of the 3D FEM model and boundary conditions are presented. Air‐gap flux densities along the longitudinal and transverse directions with different lateral displacements are obtained, as well as the distortion coefficients of the air‐gap flux density is proposed. Corresponding induced currents in the secondary are predicted. Finally, the variations of the thrust, vertical and lateral forces are experimentally validated by measurements on reciprocal power‐fed test rig. It shows that the flux in between overhangs of the primary winding and secondary has great effect on the lateral force, the thrust and vertical force decrease with the increase of the lateral displacement. [ABSTRACT FROM AUTHOR]

This study investigates the influence of lateral displacement of the primary on the thrust, vertical and lateral forces in a single‐side linear induction motor for linear metro. A three‐dimensional analytical model, which is able to consider the longitudinal and transversal end effects, overhang of the primary windings and lateral displacement, is developed to obtain the air‐gap flux density distributions along longitudinal and transverse directions as well as forces. Variations of the thrust, vertical and lateral forces with the lateral displacements are comprehensive investigated when the motor is torque motoring, negative sequence braking or regenerative braking operation. The analytically predicted results are experimentally validated by measurements on reciprocal power‐fed test rig. It shows that the thrust and vertical force of single‐side linear induction motor decrease almost linearly with the increase of the lateral displacement in all regions, and lateral force is restoring which helps centralising the railcar in the regenerative braking and most parts of motoring regions. [ABSTRACT FROM AUTHOR]

The CuCe/ZSM-5 catalysts with different cerium loadings (0, 0.5, 1.0, 1.5 and 2.0 wt.%) was investigated to evaluate the correlation between structural characteristics and catalytic performance for the selective catalytic reduction (SCR) of NO by NH 3 . It was found that the addition of cerium increased copper dispersion and prevented its crystallization. According to the results of X-ray photoelectron spectroscopy (XPS) and temperature-programmed reduction by hydrogen (H 2 -TPR), copper species were enriched on the ZSM-5 grain surfaces and part of copper ions was incorporated into the cerium lattice. Addition of cerium improved the redox properties of the CuCe/ZSM-5 catalysts, owing to the higher valence of copper and mobility of lattice oxygen than those of Cu/ZSM-5 catalyst. Hence the introduction of cerium in Cu/ZSM-5 improved significantly NO conversion. On the one hand, the cerium introduction into Cu-Z enhances their low-temperature activities. 95% NO conversion is reached around 197 °C for Cu-Z while the corresponding temperature value decreases to 148 °C for CuCe4-Z. On the other hand, the temperature range of efficient NO reduction (95%) also extends to higher temperature when the cerium are added to Cu/ZSM-5. Among the Cu-Ce/ZSM-5 catalysts tested, the CuCe4-Z sample exhibits the highest catalytic activity with the temperature range for 90% NO removal of 148–427 °C. [ABSTRACT FROM AUTHOR]

Organic chemosensors with excited‐state intramolecular proton transfer (ESIPT) behavior have attracted much attention because it has great potential in a wide range of applications. Considering the paramount behavior of excited‐state relaxation, in this work, we mainly focus on deciphering photo‐induced hydrogen bonding effects and ESIPT mechanism for the novel 2‐(benzo[d]thiazol‐2‐yl)‐4‐(9H‐carbazol‐9‐yl)phenol (mCzOH) dye. Considering the effects of different solvents on excited‐state dynamics of mCzOH flurophore, we adopt four solvents with different polarities. Analyses of fundamental structural changes, infrared (IR) vibrational spectra, and core valence partition index between S0 and S1 state, we confirm hydrogen bond OH···N of mCzOH should be enhanced via photoexcitation. Especially, the increase of solvent polarity could promote hydrogen bonding strengthening degree. Intramolecular charge transfer (ICT) resulting from photoexcitation qualitatively facilitates the ESIPT occurrence to a large extent. For further checking and probing into ESIPT mechanism, via constructing potential energy curves (PECs) in four solvents, we clarify the ESIPT behavior for mCzOH. Most worthy of mention is that polar solvent plays critical roles in lowering potential barrier of ESIPT reaction and in facilitating ESIPT process. We not only clarify the detailed excited‐state process, but also present the solvent‐polarity‐dependent ESIPT mechanism for mCzOH fluorophore. [ABSTRACT FROM AUTHOR]

Cystatin plays a crucial role in immune evasion by parasites. It regulates diverse immune response processes, such as antigen presentation, cytokine and NO production, and phagocytosis. In recent years, an increasing number of parasite cystatins have been identified and studied for the treatment of inflammatory diseases. In contrast, cystatin from Spirometra erinaceieuropaei has received limited research attention. The objective of this study was to utilize bioinformatics tools and molecular biology techniques to predict the biological properties and obtain a recombinant cystatin analogue from Spirometra erinaceieuropaei (SeCystatin). The SeCystatin gene consists of 417 bp and encodes a putative 100-amino acid protein. The predicted molecular weight and isoelectric point of SeCystatin were 10.89 kDa and 6.82, respectively; SeCystatin possesses 12 phosphorylation sites and five post-translational modification sites but has no signal peptide and transmembrane region. The secondary structure of SeCystatin consists of one α-helix, four β-folds and six coils. It also possesses a cystatin-specific conserved domain, QxVxG, which is positioned at the boundary between the first and second β-folds, thereby demonstrating the characteristic features of type I cystatin. In the context of molecular evolution, SeCystatin demonstrates the highest level of evolutionary similarity to Schistocephalus solidus. The SeCystatin gene was fully synthesized, and the recombinant plasmid pET-30a (+)-SeCystatin was constructed to express the target protein in Escherichia coli BL 21. Recombinant SeCystatin was successfully induced for expression by IPTG and subsequently purified using affinity chromatography (Ni-IDA). Our study provides a solid foundation for further studies on the biological functions of SeCystatin. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: We investigate the feasibility, safety, and clinical therapeutic effect of laparoscopic sigmoid vaginoplasty in women with Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome. Methods: We performed a retrospective case review cohort study of 56 patients with MRKHs undergoing laparoscopic sigmoid vaginoplasty in Wuhan Union Hospital between 2000 and 2020, and all patients were followed up. Results: The median operating time was 165 min (120–420 min). The median hospital stay was 10 days (rang 7–15 days). A functional neovagina was created 11–15 cm in length and two fingers in breadth in all patients. No introitus stenosis was observed. No intra- or post-operative complications occurred. Two patients were lost to follow-up after 3 months of outpatient visits. Six patients had no intercourse and were required to wear a vaginal mold occasionally. None of the patients had complained of local irritation or dyspareunia. Patients who had post-surgery sexual intercourse were satisfied with their sexual life and the mean total Female Sexual Function Index (FSFI) score was 25.17 ± 0.63. The cosmetic results were excellent. Conclusions: The laparoscopic sigmoid vaginoplasty can achieve the goal of making a functional neovagina. The main advantage of this surgical technique is that it is minimally invasive and that there are fewer complications post-operation. It is an acceptable procedure for patients with MRKH syndrome. [ABSTRACT FROM AUTHOR]

• The oscillation frequencies of an edge skyrmion in circular nano-pillars are analytically derived. • The size of the sample to produce isolated edge skyrmion oscillation is relatively small. • The oscillation frequencies strongly depend on the eccentricity and the perimeter of the elliptical nanopillar. The magnetic skyrmions have received a lot of attention because they have potential applications in spin torque nano-oscillators. In this paper, we numerically and analytically study the dynamics of edge skyrmions in circular nano-pillar oscillators with perpendicular magnetic anisotropy (PMA) free layer and spin polarizer. Numerical simulations demonstrate that a steady edge skyrmion oscillation mode with GHz frequency can be driven by spin currents and magnetic fields. The oscillation frequencies in circular nano-pillars with different radius are analytically derived, which agrees well with the numerical results. In addition, the steady oscillations of edge skyrmions are also observed in elliptical nano-pillars, in which the oscillation frequencies strongly depend on the eccentricity and perimeter of the elliptical nanopillar. It is found that the oscillation frequency of this edge skyrmion can range from 1 GHz to 6.7 GHz. The line width is about 55 MHz. [ABSTRACT FROM AUTHOR]

In this study, cable-stiffened steel columns (CSSCs), which primarily aim to enhance compression behaviour, were experimentally investigated. In contrast to other stiffened column types, the cable-stiffened steel columns investigated in this work were equipped with a three-branch crossarm system. A series of tests were performed on 2.4 m CSSCs with two different crossarm–main column connection types (i.e., rigid and scissor types). In addition to the connection types, the effects of crossarm length and initial pretension on the load carrying capacities of CSSCs were also studied experimentally. The experimental results indicate that the three-branch crossarm system is effective in improving the buckling load of ordinary compression columns. The findings prove that the scissor-type connections between the crossarms and the main column could also be used in practical applications. Moreover, a unique, asymmetric post-buckling mode for a CSSC with a three-branch crossarm system was observed. The effects of crossarm length and pretension in cables are also demonstrated. This results presented in this work could be of assistance in the further design of CSSCs. The buckling modes of cable-stiffened steel columns with three branch crossarm system could be symmetric, anti-symmetric, and asymmetric. [Display omitted] • A cable-stiffened column with three branch crossarm system was firstly experimentally studied. • A unique asymmetric buckling mode was experimentally demonstrated. • The effects of different parameters on the buckling behaviour of CSSCs were examined. [ABSTRACT FROM AUTHOR]

Presents corrections to funding information from the above named paper. [ABSTRACT FROM AUTHOR]

• The semi-skyrmions-based oscillation mode with GHz frequencies is observed. • The mode frequencies strongly depend on the in-plane dimension. • The mode frequency is affected by the material parameters. • The shape of the ellipse influences the velocity of the semiskyrmion. Magnetic skyrmions have been proved to be applicable to spin torque nano-oscillator. In this paper, we show dynamics of magnetic skyrmions in elliptical spin-valve nanopillar with perpendicular magnetic anisotropy (PMA) free layer and spin polarizer by using micromagnetic simulation. A novel semi-skyrmions-based oscillation mode with GHz frequencies appears in this geometry. We find that the mode frequencies strongly depend on the in-plane dimension of the elliptical nanopillar. The fitting function between the mode frequency and the perimeter of the ellipse is obtained. Simulation results also show that the exchange constant and the temperature effect have great influence on the mode frequency. [ABSTRACT FROM AUTHOR]

Two-dimensional molybdenum disulfide (2D MoS2) has great application prospects in the field of optoelectronic devices. Defect engineering is an effective way to regulate the electronic and optical properties of 2D MoS2. However, defect controlling on 2D materials remains a major challenge. Fluorine, as the most electronegative element, may cause many interesting phenomena after doping in 2D materials. So far, there have been no reports on the effect of fluoride ion (F− ion) irradiation on 2D material properties. In this paper, the monolayer MoS2 (ML-MoS2) synthesized by the chemical vapor deposition method was taken as the research object, and defects with controllable densities were produced by 30 keV F− ion irradiation, in which the defects were dominated by S vacancies. Based on Raman, photoluminescence, and x-ray photoelectron spectroscopy, it is shown that the ion irradiation-induced defects significantly affect the optoelectronic properties of MoS2. We also observed the p-doping of ML-MoS2, which is attributed to the introduction of F− ions and the electron transfer from MoS2 to O2 at defect adsorption sites. This study reveals that 2D materials could be effectively doped or compensated using irradiation technology, potentially fabricating novel 2D electrical devices through defect engineering. [ABSTRACT FROM AUTHOR]

The research on stochastic resonance (SR) which is used to extract weak signals from noisy backgrounds is of great theoretical significance and promising application. To address the shortcomings of the classical tristable SR model, this article proposes a novel compound multistable stochastic resonance (NCMSR) model by combining the Woods–Saxon (WS) and tristable models. The influence of the parameters of the NCMSR systems on the output response performance is studied under different α stable noises. Meanwhile, the adaptive synchronization optimization algorithm based on the proposed model is employed to achieve periodic and non-periodic signal identifications in α stable noise environments. The results show that the proposed system model outperforms the tristable system in terms of detection performance. Finally, the NCMSR model is applied to 2D image processing, which achieves great noise reduction and image recovery effects. [ABSTRACT FROM AUTHOR]

In this article, an electrodynamic suspension (EDS) maglev scheme with a novel coil topology named traveling magnetic electromagnetic Halbach array (TMEHA) is proposed and investigated in which thrust and lift forces are simultaneously created above a conductive flat guideway. First, the topological structure and principle of the TMEHA-EDS is introduced. Then the effectiveness of the TMEHA is analyzed qualitatively according to the analytic model based on harmonic analytical theory. Third, the 2-D analytical model of the TMEHA-EDS is proposed, and the thrust, lift force, efficiency, and the lift-to-weight ratio of the TMEHA-EDS are analyzed. Finally, a TMEHA-EDS prototype is manufactured, and experiments are carried out to verify the predicted results. [ABSTRACT FROM AUTHOR]

• A new approach to the CFETR divertor RH compatible structures is put forward based on the DOF and the stability theories. • DOF and stability for the divertor are analyzed to prove that the newly-design scheme is feasible. • CFETR divertor RH maintenance simulation process is carried on in Delmia to validate RH feasibility. The divertor area of China Fusion Engineering Test Reactor (CFETR) vacuum vessel (VV) consists of 48 modular cassettes which must be replaced during operation of the CFETR. Considering the working environment for the divertor in Tokamak, the process for replacing is conducted by remote handling (RH) ways. In this paper, the work mainly focuses on the development of a new approach to the conceptual design of CFETR Divertor RH compatible structures. The approach is based on two theories: degree of freedom (DOF) and the stability.DOF theory requires the divertor should be constraint completely, and then its DOF is equal to zero. Besides that, the stability theory requires the divertor cannot be shaken due to the projection of the centre of mass and cannot be rotated due to the larger tilting moment. Then a new design scheme for the compatible structures is put forward based on theories to fulfill the working requirements. Finally, the simulation process in Delmia is carried on in order to validate the RH feasibility. [ABSTRACT FROM AUTHOR]

This paper focuses on the correlation between the oxidative reactivity and electrical properties of soot particles. Soot particles were produced from an n -heptane inverse diffusion flame and were sampled at different heights above the burner (HAB) using a thermophoretic and probe sampling techniques. The electrical properties were characterized by the electrical conductivity and work function, which were evaluated by an atomic force microscopy. The soot reactivity was assessed in terms of activation energy (E a) and characteristic oxidation temperatures, including peak temperature (T P) and burnout temperature (T b), using thermogravimetric analysis. As the soot particles gradually age, they have various electrical conductivity distributions. The average electrical conductivity presents an increase by three orders of magnitude when increasing the HAB from 10 to 60 mm. The work function of bulk soot particles shows an increase with the soot maturation. The soot reactivity gradually reduces during the soot maturation process because the values of E a , T P , and T b show increases with the increase in HAB. For the soot particles, the E a and T p have strongly positive correlations with the work function and with the logarithm of the electrical conductivity. Thus, electrical properties can serve as an indicator of soot reactivity. [Display omitted] • The electrical properties and reactivity of soot particles were assessed. • The electrical conductivity and work function increase as soot particles mature. • Soot reactivity decreases with the increase in logarithm of electrical conductivity. • Soot reactivity decreases with the increase in work function. • Soot electrical properties can serve as an indicator of soot reactivity. [ABSTRACT FROM AUTHOR]

To explore the role of hydrogen in radiation degradation of AlGaN/GaN high-electron-mobility transistors (HEMTs), the performance degradation of the hydrogen untreated and pretreated devices is compared under the exposure of carbon ions. The energy of carbon ions is chosen as 7.6 MeV, and the maximum fluence reaches 4 × 1012 cm−2. By electrical character measuring, it is found that the positive shift of the threshold voltage and the decrease of the transconductance occur after to the irradiation. Hydrogen pretreatment accelerates the shift of threshold voltage and the decrease of the transconductance. The threshold voltage of the device is almost unchanged under 1-MeV electron irradiations. This means that the displacement damage leads to the shift of the threshold voltage. The height of Schottky barrier hardly changes in the hydrogen pretreated devices, showing that the ionization defects such as the formation of interface states under the gate are not the main cause of device degradation. Deep level transient spectrum (DLTS) results show that the irradiations cause the increase of gallium vacancies, and the hydrogen pretreatment inhibits its formation. According to the first principle calculation, the existence of hydrogen in GaN layer can reduce the formation energy of and the number of charges of the defects. It is speculated that hydrogen atoms participate in the evolution of radiation defects, which changes the types and number of defects in the devices. [ABSTRACT FROM AUTHOR]

This work aimed to optimize the washcoat slurry for hydrotalcite-based lean NOx trap (LNT) catalyst. The effects of the slurry properties including pH, solid content, binder and additive on the hydrotalcite-based slurry viscosity were investigated. The particle size distribution of the optimal hydrotalcite-based slurry was measured. A cordierite material was used to coat the optimal slurry, and the washcoat was characterized by X-ray diffraction, scanning electron microscopy and N2 adsorption. The optimal slurry containing Pt and Ba was coated on the cordierite for the preparation of hydrotalcite-based LNT catalyst, and the performances of this catalyst were evaluated by NOx storage test, temperature programmed desorption and NOx reduction. For comparison, the performance of the commercial LNT catalyst with Pt/BaO/Al2O3 was analyzed. After coating, the hydrotalcite-based washcoat was closely contacted with the support, being the main phase MgO and presenting a specific surface area of 86.3 m2/g. The hydrotalcite-based LNT catalyst had better NOx storage and desorption ability, selectivity to N2 and LNT efficiency than the Pt/BaO/Al2O3 catalyst. [ABSTRACT FROM AUTHOR]

Metastasis and recurrence severely impact the treatment effect of hepatocellular carcinoma (HCC). HCC complicated with cholestasis is more prone to recurrence and metastasis. Previous studies have implicated pathogenesis of HCC by bile acid; however, the underlying mechanism is unknown yet. Glycochenodeoxycholate (GCDC) is one of most important component of bile acid (BA). In the present study, the role of GCDC in HCC cells invasion was detected by in vitro and in vivo assays. GCDC was found to significantly enhance the invasive potential of HCC cells; Further studies showed that GCDC could induce autophagy activation and higher invasive capability in HCC cells. Interestingly, inhibition of autophagy by chloroquine (CQ) reversed this phenomenon. Subsequently, the correlation between TBA expression level and clinicopathological characteristics was analyzed in HCC patients. Clinically, high TBA level in HCC tissue was found to be associated with more invasive and poor survival in HCC patients. Mechanistic study showed that bile acid induced autophagy by targeting the AMPK/mTOR pathway in HCC cells. Therefore, our results suggest that bile acid may promote HCC invasion via activation of autophagy and the level of bile acid may serve as a potential useful indicator for prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Accumulating studies authenticate that circular RNAs (circRNAs) are involved in the progression of cancers. However, their role in breast cancer (BC) remains largely unknown. In this study, real‐time polymerase chain reaction was employed to detect the circ_0000291 and miR‐326 expressions in BC tissues and cells. The correlation between the expression level of circ_0000291 and clinicopathological parameters of BC patients was analyzed. Western blot was used to detect the expression of E26 transformation‐specific sequence‐1 (ETS1), E‐cadherin, N‐cadherin and Vimentin in BC cells. Cell proliferation was measured using the cell counting kit‐8 assay and the bromodeoxyuridine assay. Cell migration and invasion were detected by Transwell assay. The interactions between circ_0000291 and miR‐326, miR‐326 and ETS1 were verified using bioinformatics prediction, the dual‐luciferase reporter gene assay or/and RNA binding protein immunoprecipitation assay. We demonstrated that circ_0000291 was significantly upregulated in BC, and its high expression was positively correlated with T stage and local lymph node metastasis. Functional assays validated that circ_0000291 promoted BC cell proliferation, migration and invasion. The mechanism studies indicated that circ_0000291 could decoy miR‐326 and in turn upregulate the expression of ETS1. In conclusion, circ_0000291 is the novel oncogenic circRNA and promotes BC progression via modulating the miR‐326/ETS1 axis. [ABSTRACT FROM AUTHOR]

Background: Long noncoding RNAs (lncRNAs) have been reported to have potential diagnostic and prognostic values for numerous cancers. However, the plasma expression of lncRNA BLACAT1 and its clinical value in patients with papillary thyroid cancer (PTC) remain unknown. Methods: The expression profile of BLACAT1 in 87 PTC patients (case group) and 36 patients with nodular goiter (control group) were investigated by qRT-PCR. The Kaplan–Meier method was used for RFS curves, and the univariate survival differences were analyzed by the log-rank test. Results: BLACAT1 expression was downregulated in the plasma of case group compared with control group (P = 0.003). We also found that low plasma BLACAT1 expression was correlated with lymph node metastasis (LNM) (P < 0.001). Multivariate analysis showed that BLACAT1 was an independent risk factor for lymph node metastasis and gender (P < 0.05). The area under the ROC curve for BLACAT1 was 0.825 in LNM prediction (P < 0.001). Conclusion: The present study demonstrated that BLACAT1 could act as a possible suppressor gene in PTC and may serve as a potential biomarker for prognosis prediction of PTC. [ABSTRACT FROM AUTHOR]

• As of March 10, 2020, Italy had reported 9172 COVID-19 cases with 463 deaths. • We report the real-time reproductive numbers (R (t)) and case fatality rates for selected European countries (Italy, France, Germany, and Spain) by March 9, 2020. • The R (t) was greater than 2 in the selected European countries, indicating that the outbreak will continue. As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective of this study was to report the real-time effective reproduction numbers (R (t)) and case fatality rates (CFR) in Europe. Data for this study were obtained mainly from the World Health Organization website, up to March 9, 2020. R (t) were estimated by exponential growth rate (EG) and time-dependent (TD) methods. 'R0' package in R was employed to estimate R (t) by fitting the existing epidemic curve. Both the naïve CFR (nCFR) and adjusted CFR (aCFR) were estimated. With the EG method, R (t) was 3.27 (95% confidence interval (CI) 3.17–3.38) for Italy, 6.32 (95% CI 5.72–6.99) for France, 6.07 (95% CI 5.51–6.69) for Germany, and 5.08 (95% CI 4.51–5.74) for Spain. With the TD method, the R value for March 9 was 3.10 (95% CI 2.21–4.11) for Italy, 6.56 (95% CI 2.04–12.26) for France, 4.43 (95% CI 1.83–7.92) for Germany, and 3.95 (95% CI 0–10.19) for Spain. This study provides important findings on the early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority. [ABSTRACT FROM AUTHOR]

The stable isotope technique provides the possibility to trace ancient textiles because the technique is associated with advantages such as trace indication, fast detection, and accurate results. Since different cocooning conditions may impact cocoons even under identical habitats, it is important to investigate the effects of different cocooning temperatures and humidity on the isotope incorporation values in the cocoons. In this study, silk fibers were reeled under different conditions of temperature and humidity, followed by analysis of the secondary structure of cocoon proteins and isotope incorporation patterns. We found that the deviations in carbon isotope values of silk under different cocooning conditions could reach up to 0.76‰, while the deviation in carbon isotope values at different locations of a single silk was 2.75‰. Further, during the cocooning process, depletion of the 13C-isotope at different locations of the silk fibers was observed, reducing the δ13C values. We proposed that the changes in carbon isotopes in silk were related to the content of sericin and silk fibroin in silk. Finally, we did not observe a significant difference in isotope ratios in degummed cocoons. In summary, the 13C isotope was enriched in sericin, whereas 15N was enriched in fibroin, and these findings provide basic information for tracing the provenance of silks. [ABSTRACT FROM AUTHOR]