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Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance. [ABSTRACT FROM AUTHOR]

Carbonyl soft magnetic composites (SMCs) have garnered significant attention due to their excellent high-frequency adaptability and outstanding properties, aligning perfectly with the development trend of electronic components. In this work, carbonyl FeNi50 powders were chosen as the research subject, and phosphating treatment was utilized to generate a phosphate coating layer on the surface of the powders. The influences of phosphoric acid concentrations on the compositions and structures of the phosphate coating layer on the powders' surface were systematically investigated by combining various characterization techniques. The presence of phosphates was successfully characterized, and the reactions between phosphoric acid and the FeNi50 powder were inferred. Subsequently, the magnetic properties of the SMCs were measured, and the influences of phosphoric acid concentrations on the magnetic properties of the SMCs were investigated. The comprehensive magnetic properties of SMCs were found to be optimal at a phosphoric acid concentration of 0.15 wt%. In particular, the DC bias performance of up to 91.0% and the permeability stability of up to 20 MHz could meet the requirements of high-frequency and large DC bias applications, indicating extensive application prospects. [ABSTRACT FROM AUTHOR]

The accurate short-term point and probabilistic load forecasts are critically important for efficient operation of power systems and electricity bargain in the market. Fuzzy systems achieved limited success in electric load forecasting. On the other hand, support vector regression models have seldom been part of a winning solution of the electric load forecasting competitions during the last decade. In this paper, we propose a methodology to integrate the fuzzy memberships with support vector regression (SVR) and support vector quantile regression (SVQR) models for short-term point and probabilistic load forecasting, respectively. One fuzzy membership function is proposed to efficiently calculate the relative importance of the observations in the load history. Three SVR and one SVQR models, including L1-norm based SVR, L2-norm based SVR, kernel-free quadratic surface SVR and SVQR models, are utilized to demonstrate the effectiveness of the proposed methodology. For point load forecasting, we compare the proposed fuzzy SVR models with a multiple linear regression, a feed-forward neural network, a fuzzy interaction regression, and four SVR models. For probabilistic load forecasting, the proposed fuzzy SVQR model is compared with a quantile regression model, a quantile regression neural network, and a SVQR model. The results on the data of global energy forecasting competition 2012, demonstrate that the proposed fuzzy component can improve the underlying SVR and SVQR models to outperform their counterparts and commonly-used models for point and probabilistic load forecasting, respectively. [ABSTRACT FROM AUTHOR]

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness. [ABSTRACT FROM AUTHOR]

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group (P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244. [ABSTRACT FROM AUTHOR]

In cloud-edge-end scenarios, how to achieve rational resource allocation, implement effective service deployment, and ensure high service quality has become a hot research topic in academic domains. Service providers usually deploy services by considering the characteristics of different geographical regions, which helps to meet the diverse needs of users in different regions and optimize resource allocation and utilization. However, due to the widespread distribution of users and limited server resources, providing all types of services to users in every geographical region is not feasible. In addition, edge servers are prone to operational failures caused by software anomalies, hardware malfunctions, and malicious attacks, which will decrease service reliability. To address the problems above, this paper proposes a metric for service priorities based on user demands and regional characteristics for different geographical regions. Building upon this foundation, a Multi-Service Geographic region Deployment based on Priority (MS-GD-P) is proposed. This method takes user coverage and service reliability into consideration, which facilitates users' needs for multiple services in different geographical regions. Experimental results on real datasets demonstrate that MS-GD-P outperforms baseline methods in user coverage and service reliability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control. [ABSTRACT FROM AUTHOR]

The two-dimensional GTAW arc model is insufficient to fully explain the effects of the external longitudinal magnetic field on the arc. Therefore, a three-dimensional GTAW arc model was established to elucidate the recirculation flow and negative pressure arc characteristic of magnetic-controlled arc. The external magnetic field controls the surface temperature, pressure, and current density distribution of the workpiece by controlling the flow of arc plasma. When the magnetic flux density is 0.04T, the surface temperature, pressure, and current density of the workpiece exhibit a bimodal distribution. Under the negative pressure of the GTAW arc, the arc plasma on both sides flowed counterclockwise around the center in the spiral upward direction and then counterclockwise downward from 0.9 mm below the tungsten electrode. By controlling the welding current and magnetic flux density, the occurrence of negative surface pressure on the workpiece can be effectively controlled. [ABSTRACT FROM AUTHOR]

The development of novel soft magnetic composites (SMCs) is driven by the demand for lightweight and highly stable electronic components. In this work, the influence of fine powder content on the properties of high-flux SMCs was systematically investigated by the particle size distribution of FeNi50 powders across a broad range from 0 to 100 wt%. Furthermore, the differences between the two powders were compared, and the effects on the properties of the SMCs were analyzed. The density of SMCs reached a maximum at a fine powder content of 20 wt% and increased gradually as the fine powder content exceeded 40 wt%. The effective permeability of SMCs was found to be strongly dependent on density and changed accordingly. The quality factor of SMCs increased gradually as the fine powder content rose, indicating a progressive enhancement of high-frequency magnetic performance. The decrease in power loss with the increase in fine powder content can be attributed to the lower hysteresis loss and intraparticle eddy current loss. The DC-bias performance gradually increased as the fine powder content increased. These parameters varied with the fine powder content, showing that reducing the average powder particle size could improve the high-frequency magnetic performance of SMCs. The current work introduces a convenient approach to producing high-performance SMCs that can meet the requirements of electronic components in the future. [ABSTRACT FROM AUTHOR]

Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL. [ABSTRACT FROM AUTHOR]

The rapid development of the Internet technology along with the emergence of intelligent applications has put forward higher requirements for task offloading. In Cloud-Edge-End (CEE) environments, offloading computing tasks of terminal devices to edge and cloud servers can effectively reduce system delay and alleviate network congestion. Designing a reliable task offloading strategy in CEE environments to meet users' requirements is a challenging issue. To design an effective offloading strategy, a Service Reliability Analysis and Elite-Artificial Bee Colony Offloading model (SRA-E-ABCO) is presented for cloud-edge-end environments. Specifically, a Service Reliability Analysis (SRA) method is proposed to assist in predicting the offloading necessity of terminal tasks and analyzing the attributes of terminal devices and edge nodes. An Elite Artificial Bee Colony Offloading (E-ABCO) method is also proposed, which optimizes the offloading strategy by combining elite populations with improved fitness formulas, position update formulas, and population initialization methods. Simulation results on real datasets validate the efficient performance of the proposed scheme that not only reduces task offloading delay but also optimize system overhead in comparison to baseline schemes. [ABSTRACT FROM AUTHOR]

Background and aim: A novel study found interferon enhanced antitumor activity of anti-PD-1-based immunotherapy and played a crucial role in improving efficacy on HCC, but the opposite results about the efficacy of interferon on HBV-related HCC were obtained from previous clinical studies and meta-analyses. Thus, this meta-analysis aimed to re-evaluate whether interferon could improve survival and reduce recurrence of patients with HBV-related HCC after curative surgery. Methods: MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science and CNKI were searched for eligible studies from inception to November 2022 and a meta-analysis was done. Results: 10 trials with a total of 2062 subjects were screened. Interferon significantly improved 1-, 2-, 3- and 5-year OS and 1-, 2- and 3-year DFS, and reduced 2-, 3- and 5-year recurrence rates of patients with HBV-related HCC after curative surgery. However, interferon did not improve 8-year OS and 5-year DFS, did not reduce 1-year recurrence rate. Conclusions: Interferon may significantly reduce recurrence and improve DFS of patients with HBV-related HCC after curative surgery, and finally improve the OS. However, the efficacy advantage may gradually weaken as time goes on. The clinical application of interferon combined with NAs recommended in this meta-analysis is needed to be further studied. [ABSTRACT FROM AUTHOR]

Homeobox A13 (HOXA13) has been verified as an oncogen in some malignancies. However, its role in nasopharyngeal carcinoma (NPC) is still unclear. This study aims to explore the role of HOXA13 in NPC and its underlying mechanism. The mRNA expression of HOXA13 in NPC was obtained from the GSE53819 and GSE64634 datasets in the Gene Expression Omnibus (GEO) database. MTT, colony formation and transwell assays and xenograft tumour models were used to investigate the effects of HOXA13 on NPC HNE1 cells in vitro and in vivo. The expression of HOXA13, epithelial-mesenchymal transition-transcription factor (EMT-TF) Snail and matrix metalloproteinase 2 (MMP-2) was detected by immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The results showed that HOXA13 was upregulated in NPC. Silencing HOXA13 suppressed the proliferation, migration, and invasion of HNE1 cells, which inhibited tumour growth, while overexpression of HOXA13 induced the opposite effects. In addition, the expression of Snail and MMP-2 at the transcriptional and protein levels was associated with the expression of HOXA13. In summary, our results suggest that HOXA13 plays a role as a cancer-promoting gene in NPC. The underlying mechanism may be related to the upregulation of Snail and MMP-2. [ABSTRACT FROM AUTHOR]

A facile and cost-efficient multiple fully printed method to fabricate p-type carbon nanotube field-effect transistor (CNTFET) on the flexible paper substrate is proposed in this paper. Through the selective separation of polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-(benzo [2,1,3] thiadiazol-4,7-diyl)] (PFO-BT) and stable dispersion of sodium dodecylbenzene sulfonate (SDBS) surfactant, the obtained CNTs individually dispersed ink (denoted as mono-dispersion ink) is applied in standard inkjet printers. The multiple system of Roll-to-Roll (R2R) flexo printing (to print silver-based catalyst ink for the subsequent electroless copper plating process) and inkjet printing (to print semiconductor channel material) is adopted in p-type metal-oxide-semiconductor field-effect transistor (MOSFET) fabrication with good printing line accuracy and high-throughput. The transistors obtained by this fabrication process can maintain an on-off ratio (Ion/Ioff ≈ 2806), with approximately 70% of the devices’ on-off ratio is concentrated in 103–104 with a threshold voltage of about + 3 V. The flexible and fully printed strategy presented in this paper has a strong migration ability, which can be applied to a variety of semiconductor channel materials with diverse flexible substrates (e.g., polyimide, polyethylene terephthalate, etc.) and provide an effective and facile route for large-scale preparation of flexible integrated electronic devices. [ABSTRACT FROM AUTHOR]

Background: The long non-coding RNA HOXA transcript at the distal tip (HOTTIP) and homeobox A13 (HOXA13) have been identified as oncogenes that play a pivotal role in tumorigenesis. However, their specific mechanisms of action in nasopharyngeal carcinoma (NPC) progression remain unclear. Methods and results: In the present study, RT-qPCR was employed to quantify RNA expression in NPC cells and tissues. Flow cytometry, MTT, CCK8 and colony formation assays were utilized to assess cell apoptosis and proliferation. Transwell assay was conducted to evaluate migration and invasion while Western blotting was performed for protein expression analysis. Our findings revealed that the expression of HOTTIP was significantly upregulated in NPC cell lines. Inhibition of HOTTIP could induce apoptosis and suppress proliferation, clonogenicity, invasion and metastasis in NPC cells. Knockdown of HOTTIP led to downregulation of HOXA13 expression, which subsequently inhibited the proliferation and metastasis in NPC cells. The inhibitory effects on cell proliferation and metastasis caused by HOTTIP silencing were rescued by HOXA13 overexpression. Additionally, there was a significant positive correlation between HOTTIP and HOXA13, which were found to be elevated in NPC tissues compared to normal tissues. Conclusions: We have determined that LncRNA HOTTIP facilitates tumorigenesis by modulating the expression of HOXA13 in NPC cells. Targeting HOTTIP/HOXA13 may be a promising therapeutic strategy for NPC. [ABSTRACT FROM AUTHOR]

Nanocrystalline alloys (nanoalloys) are prone to grain growth. It is known that grain boundary segregation and precipitation can stabilize nanoalloys, but the stabilization becomes less effective at high temperatures and adding grain growth inhibitors often reduces sinterability. Herein, we have simultaneously achieved exceptional high-temperature stability and improved sinterability for a class of TiNbMoTaW-based refractory high-entropy nanoalloys (RHENs). Bulk pellets of RHENs were fabricated through ball milling and spark plasma sintering, achieving 93–96% relative densities with 50–100 nm grain sizes for three compositions. For example, Ti17.8Nb17.8Mo17.8Ta17.8W17.8Ni6Zr5 sintered at 1300 °C attained ~ 96% relative density with ~ 55 nm mean grain size. Moreover, these RHENs exhibited exceptional stability at 1300 °C. Both Ti17.8Nb17.8Mo17.8Ta17.8W17.8Ni6Zr5 and Ti18.8Nb18.8Mo18.8Ta18.8W18.8Ni6 retained < 150 nm grain sizes after five hours annealing at 1300 °C. Notably, the addition of Ni, a well-known sintering aid for activated sintering of refractory metals such as W and Mo, in high-entropy TiNbMoTaW can promote sintering while maintaining high-temperature stability against rapid grain growth. This may be explained by hypothesized high-entropy grain boundary (HEGB) effects, while we recognize the possible (additional) effects of compositional inhomogeneity and secondary phase (Zener) pinning. These RHENs possess some of the highest temperature stability achieved for nanoalloys and ultrafine-grained metals. [ABSTRACT FROM AUTHOR]

The enhancement of separation processes and electrochemical technologies such as water electrolysers1,2, fuel cells3,4, redox flow batteries5,6 and ion-capture electrodialysis7 depends on the development of low-resistance and high-selectivity ion-transport membranes. The transport of ions through these membranes depends on the overall energy barriers imposed by the collective interplay of pore architecture and pore–analyte interaction8,9. However, it remains challenging to design efficient, scaleable and low-cost selective ion-transport membranes that provide ion channels for low-energy-barrier transport. Here we pursue a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels. The near-frictionless ion flow is synergistically fulfilled by robust micropore confinement and multi-interaction between ion and membrane, which afford, for instance, a Na+ diffusion coefficient of 1.18 × 10−9 m2 s–1, close to the value in pure water at infinite dilution, and an area-specific membrane resistance as low as 0.17 Ω cm2. We demonstrate highly efficient membranes in rapidly charging aqueous organic redox flow batteries that deliver both high energy efficiency and high-capacity utilization at extremely high current densities (up to 500 mA cm–2), and also that avoid crossover-induced capacity decay. This membrane design concept may be broadly applicable to membranes for a wide range of electrochemical devices and for precise molecular separation.The authors develop a strategy that allows the diffusion limit of ions in water to be approached for large-area, free-standing, synthetic membranes using covalently bonded polymer frameworks with rigidity-confined ion channels. [ABSTRACT FROM AUTHOR]

Oxide solid electrolytes (OSEs) have the potential to achieve improved safety and energy density for lithium-ion batteries, but their high grain-boundary (GB) resistance generally is a bottleneck. In the well-studied perovskite oxide solid electrolyte, Li3xLa2/3-xTiO3 (LLTO), the ionic conductivity of grain boundaries is about three orders of magnitude lower than that of the bulk. In contrast, the related Li0.375Sr0.4375Ta0.75Zr0.25O3 (LSTZ0.75) perovskite exhibits low grain boundary resistance for reasons yet unknown. Here, we use aberration-corrected scanning transmission electron microscopy and spectroscopy, along with an active learning moment tensor potential, to reveal the atomic scale structure and composition of LSTZ0.75 grain boundaries. Vibrational electron energy loss spectroscopy is applied for the first time to reveal atomically resolved vibrations at grain boundaries of LSTZ0.75 and to characterize the otherwise unmeasurable Li distribution therein. We find that Li depletion, which is a major reason for the low grain boundary ionic conductivity of LLTO, is absent for the grain boundaries of LSTZ0.75. Instead, the low grain boundary resistivity of LSTZ0.75 is attributed to the formation of a nanoscale defective cubic perovskite interfacial structure that contained abundant vacancies. Our study provides new insights into the atomic scale mechanisms of low grain boundary resistivity. Oxide solid electrolytes generally suffer from high grain boundary resistance. Here, the authors use advanced electron microscopy, along with an active learning moment tensor potential, to reveal the atomic-scale origin of low grain-boundary resistance in Li0.375Sr0.4375Ta0.75Zr0.25O3. [ABSTRACT FROM AUTHOR]

Oxide solid electrolytes (OSEs) have the potential to achieve improved safety and energy density for lithium-ion batteries, but their high grain-boundary (GB) resistance generally is a bottleneck. In the well-studied perovskite oxide solid electrolyte, Li3xLa2/3-xTiO3 (LLTO), the ionic conductivity of grain boundaries is about three orders of magnitude lower than that of the bulk. In contrast, the related Li0.375Sr0.4375Ta0.75Zr0.25O3 (LSTZ0.75) perovskite exhibits low grain boundary resistance for reasons yet unknown. Here, we use aberration-corrected scanning transmission electron microscopy and spectroscopy, along with an active learning moment tensor potential, to reveal the atomic scale structure and composition of LSTZ0.75 grain boundaries. Vibrational electron energy loss spectroscopy is applied for the first time to reveal atomically resolved vibrations at grain boundaries of LSTZ0.75 and to characterize the otherwise unmeasurable Li distribution therein. We find that Li depletion, which is a major reason for the low grain boundary ionic conductivity of LLTO, is absent for the grain boundaries of LSTZ0.75. Instead, the low grain boundary resistivity of LSTZ0.75 is attributed to the formation of a nanoscale defective cubic perovskite interfacial structure that contained abundant vacancies. Our study provides new insights into the atomic scale mechanisms of low grain boundary resistivity. Oxide solid electrolytes generally suffer from high grain boundary resistance. Here, the authors use advanced electron microscopy, along with an active learning moment tensor potential, to reveal the atomic-scale origin of low grain-boundary resistance in Li0.375Sr0.4375Ta0.75Zr0.25O3. [ABSTRACT FROM AUTHOR]

Purpose: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. Methods: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. Results: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. Conclusions: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains. [ABSTRACT FROM AUTHOR]

Mapping abandoned land is very important for accurate agricultural management. However, in karst mountainous areas, continuous high-resolution optical images are difficult to obtain in rainy weather, and the land is fragmented, which poses a great challenge for remote sensing monitoring of agriculture activities. In this study, a new method for identifying abandoned land is proposed: firstly, a few Google Earth images are used to transform arable land into accurate vectorized geo-parcels; secondly, a time-series data set was constructed using Sentinel-1A Alpha parameters for 2020 on each farmland geoparcel; thirdly, the semi-variation function (SVF) was used to analyze the spatial-temporal characteristics, then identify abandoned land. The results show: (1) On the basis of accurate spatial information and boundary of farmland land, the SAR time-series dataset reflects the structure and time-series response. The method eventually extracted abandoned land with an accuracy of 80.25%. The problem of remote sensing monitoring in rainy regions and complex surface areas is well-resolved. (2) The spatial heterogeneity of abandoned land is more obvious than that of cultivated land within geo-parcels. The step size for significant changes in the SVF of abandoned land is shorter than that of cultivated land. (3) The SVF time sequence curve presented a strong peak feature when farmland was abandoned. This reveals that the internal spatial structure of abandoned land is more disordered and complex. It showed that time-series variations of spatial structure within cultivated land have broader applications in remote sensing monitoring of agriculture in complex imaging environments. [ABSTRACT FROM AUTHOR]

Entropic stabilized ABO3 perovskite oxides promise many applications, including the two-step solar thermochemical hydrogen (STCH) production. Using binary and quaternary A-site mixed {A}FeO3 as a model system, we reveal that as more cation types, especially above four, are mixed on the A-site, the cell lattice becomes more cubic-like but the local Fe–O octahedrons are more distorted. By comparing four different Density Functional Theory-informed statistical models with experiments, we show that the oxygen vacancy formation energies ( E V f ) distribution and the vacancy interactions must be considered to predict the oxygen non-stoichiometry (δ) accurately. For STCH applications, the E V f distribution, including both the average and the spread, can be optimized jointly to improve Δδ (difference of δ between the two-step conditions) in some hydrogen production levels. This model can be used to predict the range of water splitting that can be thermodynamically improved by mixing cations in {A}FeO3 perovskites. [ABSTRACT FROM AUTHOR]

Fluorine-containing coatings play an essential role in waterproof paint, but the harm of fluoride to the environment does not meet the current environmental protection requirements. The present study reports an eco-friendly and fluoride-free waterproof hybrid coating prepared by a semi-continuous seed emulsion method employing vinyl tributbutoxy silane (VTBS) as the functional monomer and octyl triethoxysilane modified SiO2 (OTES@ SiO2) as the inorganic filler. In vinyl acetate/butyl acrylate hybrid coatings, the surface covering of OTES@SiO2 and the cross-linking structure produced by VTBS not only significantly improve the thermal stability, mechanical properties, and strong hydrophobicity but also reduce the water absorption. In addition, the gloss loss of the organic–inorganic hybrid layer is <30% after being exposed to UV-irradiation for 720 h. The obtained coating could be a lovely environmental-friendly protective coating for many functional areas, especially for outdoor applications. [ABSTRACT FROM AUTHOR]

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Authenticity identification is crucial for the legal control of meat fraud and adulteration. Authentication capability of a method in mixed meat is essential for authenticity identification. This study aimed to develop a triplex real-time PCR method with better authentication capability to identify ovine, porcine, bovine, and equine DNAs in meat. The target DNAs were identified using specific primers and probes in the developed triplex real-time PCR technique, and an endogenous control was simultaneously amplified to eliminate false-negative results. The method had limits of detection (LOD) of 0.01–0.001 ng, 0.01–0.0005 ng, 0.1–0.001 ng, and 0.001–0.00005 ng for ovine, porcine, bovine, and equine, respectively. Furthermore, increasing the primer specificity enhanced this method's authentication capability for complex meat from 10 to 0.1–1%. Overall, the results indicate that conservation for forward primer and specificity for reverse primer guarantee the compatibility and specificity of multiplex real-time PCR to detect minor adulteration. Therefore, this optimized method is an economical and efficient technique for authentication in food. [ABSTRACT FROM AUTHOR]

Support vector machine (SVM) is a popular and important machine learning technique based on the central idea of maximizing the minimummargin , i.e., the smallest distance from the training points to the classification boundary. However, recent theoretical studies revealed that maximizing the minimum is not crucial to the generalization performance, while the margindistribution is essential. Furthermore, kernel-free quadratic support vector machine becomes a new trend in the SVM area since it can avoid some difficulties such as finding appropriate kernel functions and tuning their hyper-parameters. This paper proposes two novel non-kernel quadratic surface optimal margin distribution machine (QSODM L and QSODM) models. Their basic idea is to optimize the margin distribution of training points by maximizing the margin mean, minimizing the margin variance and classifying data points by directly constructing a quadratic surface in the original space. These proposed models are convex so that they can be solved by some well-known solvers. Moreover, in order to improve the efficiencies of proposed models on large-scale data sets, a stochastic gradient descent with variance reduction (SVRG) algorithm is proposed to solve the proposed models. The numerical results on some artificial and benchmark data sets verify that QSODM L and QSODM are superior to some other well-known SVM models in classification accuracy and computational efficiency. [ABSTRACT FROM AUTHOR]

This paper presents a method to determine the optimal configuration for a dual-arm space robot grasping a tumbling target. In contrast to the existing studies that focus on static targets, this paper selects configurations based on task compatibility to achieve fast stabilization of tumbling targets. First, the kinematics and dynamics task compatibility is derived as metrics to evaluate the manipulability of the dual-arm space robot. Second, a cooperative workspace under a closed kinematic chain is generated to describe the reachability of the target manipulated by a dual-arm space robot. Then, the task compatibility along the target tumbling direction is calculated for all the configurations in the cooperative workspace, considering the field-of-view constraint of the camera to create constrained capability maps. Subsequently, the optimal configuration of the dual-arm space robot is selected from the constrained capability maps. In this way, the space robot is able to eliminate the tumbling motion of the target with its maximum manipulability and successfully complete the grasping task. Simulation and experiment are conducted to verify the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is a well known risk factor for Alzheimer's disease. Mitochondria are the center of intracellular energy metabolism and the main source of reactive oxygen species. Mitochondrial dysfunction has been identified as a key factor in diabetes-associated brain alterations contributing to neurodegenerative events. Defective insulin signaling may act in concert with neurodegenerative mechanisms leading to abnormalities in mitochondrial structure and function. Mitochondrial dysfunction triggers neuronal energy exhaustion and oxidative stress, leading to brain neuronal damage and cognitive impairment. The normality of mitochondrial function is basically maintained by mitochondrial quality control mechanisms. In T2DM, defects in the mitochondrial quality control pathway in the brain have been found to lead to mitochondrial dysfunction and cognitive impairment. Here, we discuss the association of mitochondrial dysfunction with T2DM and cognitive impairment. We also review the molecular mechanisms of mitochondrial quality control and impacts of mitochondrial quality control on the progression of cognitive impairment in T2DM. [ABSTRACT FROM AUTHOR]

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment. [ABSTRACT FROM AUTHOR]

Points of interest (POIs) are some focused geographic entities or specific locations that a considerable group of persons find useful or interesting. They are always the basis for supporting location-based applications such as navigation systems, recommendation systems and so on. And these applications always rely on the accurate POIs classification. In this paper, a novel classification method based on weighted quadratic surface support vector machine (WQSSVM) is proposed to classify Chinese POIs from different websites. We first utilize the large number of Chinese POIs to build sparse feature vectors. Then, a weight function is designed to calculate the relative importance of each sample, which is the input to the WQSSVM model. Finally, the proposed WQSSVM model is trained to obtain a suitable classifier supporting by a small proportion of the high-quality samples, and classify the rest large portion of POIs automatically. The WQSSVM model avoids the disadvantages induced by the kernel functions used in classic support vector machine models with kernels. The numerical results on thirteen real-life Chinese POIs datasets indicate that the WQSSVM model not only outperforms the QSSVM model due to the designed weight function but also outperforms other state-of-the-art text classification models in terms of classification accuracy. [ABSTRACT FROM AUTHOR]

Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1–3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.Fgf17 in young CSF boosts oligodendrocyte progenitor cell proliferation and differentiation in the aged hippocampus, improving memory function. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are crucial for the pathogenesis of human diseases, including osteoarthritis (OA). Here, we set to elucidate the biological action of circ-LRP1B in OA pathogenesis. Human C28/I2 chondrocytes were stimulated by lipopolysaccharide (LPS). Circ-LRP1B, nuclear factor, erythroid 2 like 1 (NRF1) and microRNA (miR)-34a-5p were quantified by quantitative real-time PCR (qRT-PCR) or immunoblotting. Cell viability, proliferation, and apoptosis abilities were gauged by MTT, 5-Ethynyl-2'-Deoxyuridine (EdU) staining, and flow cytometry assays, respectively. Direct relationship between miR-34a-5p and circ-LRP1B or NRF1 was validated by RNA pull-down and dual-luciferase reporter assays. Circ-LRP1B was found to be underexpressed in OA cartilage and LPS-stimulated C28/I2 chondrocytes. Enforced expression of circ-LRP1B promoted cell proliferation, and repressed apoptosis and oxidative stress, as well as impacted OA-specific hallmarks expression of LPS-stimulated C28/I2 cells. NRF1 was identified as a downstream effector of circ-LRP1B function. Moreover, NRF1 was identified as a miR-34a-5p target in LPS-stimulated C28/I2 cells. Circ-LRP1B acted as a competing endogenous RNA (ceRNA) for miR-34a-5p to involve the post-transcriptional regulation of NRF1 expression. Furthermore, the effects of circ-LRP1B overexpression partly depended on the reduction of available miR-34a-5p. These findings demonstrate that circ-LRP1B functions as a ceRNA to regulate the proliferation, apoptosis and oxidative stress of LPS-stimulated human C28/I2 chondrocytes by miR-34a-5p/NRF1 network. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that the continuous and intense nociceptive from inflamed tissue may increase the excitability of spinal dorsal horn neurons, which can signal back and modulate peripheral inflammation. Previous studies have demonstrated that spinal interleukin (IL)-33 contributes to the hyperexcitability of spinal dorsal horn neurons. This study was undertaken to investigate whether spinal IL-33 can also influence a peripheral inflammatory response in a rat model of arthritis. Lentivirus-delivered short hairpin RNA targeting IL-33 (LV-shIL-33) was constructed for gene silencing. Rats with adjuvant-induced arthritis (AIA) were injected intrathecally with LV-shIL-33 3 days before the complete Freund's adjuvant (CFA) injection. During an observation period of 21 days, pain-related behavior and inflammation were assessed. In addition, the expression of spinal proinflammatory cytokines and the activation of spinal extracellular signal–regulated kinase (ERK) and nuclear factor-κB (NF-κB) pathways were evaluated on 9 days after CFA treatment. The existence of tissue injury or inflammation in rats with AIA resulted in the upregulation of spinal IL-33, which is predominantly expressed in neurons, astrocytes, and oligodendrocytes. Intrathecal administration of LV-shIL-33 significantly alleviated hyperalgesia, paw swelling, and joint destruction, and attenuated the expression of proinflammatory cytokines [IL-6, IL-1β, and tumor necrosis factor-α (TNF-α)], as well as the activation of ERK and NF-κB/p65 in the spinal cord. Our data suggest that spinal IL-33 contributes to the development of both peripheral inflammation and hyperalgesia. Thus, interference with IL-33 at the spinal level might represent a novel therapeutic target for painful inflammatory disorders. [ABSTRACT FROM AUTHOR]

The radical cascade reaction is considered as one of the most powerful methods to build molecular complexity. However, highly stereoselective intermolecular radical cascade reactions that can produce complex cyclic compounds bearing multiple stereocenters via visible-light-induced photocatalysis have been challenging yet desirable. Herein we report a facile and efficient synthesis of multi-substituted trans-fused hexahydrocarbazoles via a stereoselective intermolecular radical cascade reaction of readily available tryptophans and acrylamides enabled by visible-light-induced photoredox catalysis. The trans-fused hexahydrocarbazoles with up to five stereocenters including two quaternary ones can be accessed in up to 82% yield, >20/1 diastereoselectivity, and 96% ee. Interestingly, the tetrahydrocarbazoles are favorably formed when the reaction is performed under air. Moreover, by simply switching the starting material from tryptophans to ɤ-alkenyl substituted α-amino acids, this protocol can be further applied to the stereoselective syntheses of 1,3,5-trisubstituted cyclohexanes which are otherwise challenging to access. Preliminary mechanistic studies suggest that the reaction goes through radical addition cascade and radical-polar crossover processes. Photocatalytic radical cascade reactions enable the facile construction of diverse cyclic compounds, though they rely on templated precursors. In this paper, the authors report on stereoselective intermolecular radical cascade reaction between tryptophan or ɤ-alkenyl substituted amino acids and acrylamides to synthesise multi-substituted trans-fused hexahydrocarbazoles or 1,3,5-trisubstituted cyclohexanes. [ABSTRACT FROM AUTHOR]

The human brain vasculature is of great medical importance: its dysfunction causes disability and death1, and the specialized structure it forms—the blood–brain barrier—impedes the treatment of nearly all brain disorders2,3. Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer’s disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer’s disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer’s disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer’s disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy.A method called vessel isolation and nuclei extraction for sequencing (VINE-seq) produces a molecular map of vascular and perivascular cell types in the human brain and reveals their contributions to Alzheimer’s disease risk. [ABSTRACT FROM AUTHOR]

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, is highly secreted by the osteoblast lineage in the subchondral bone tissue of osteoarthritis (OA) patients. However, NSAIDs, including COX-2 inhibitors, have severe side effects during OA treatment. Therefore, the identification of novel drug targets of PGE2 signaling in OA progression is urgently needed. Osteoclasts play a critical role in subchondral bone homeostasis and OA-related pain. However, the mechanisms by which PGE2 regulates osteoclast function and subsequently subchondral bone homeostasis are largely unknown. Here, we show that PGE2 acts via EP4 receptors on osteoclasts during the progression of OA and OA-related pain. Our data show that while PGE2 mediates migration and osteoclastogenesis via its EP2 and EP4 receptors, tissue-specific knockout of only the EP4 receptor in osteoclasts (EP4LysM) reduced disease progression and osteophyte formation in a murine model of OA. Furthermore, OA-related pain was alleviated in the EP4LysM mice, with reduced Netrin-1 secretion and CGRP-positive sensory innervation of the subchondral bone. The expression of platelet-derived growth factor-BB (PDGF-BB) was also lower in the EP4LysM mice, which resulted in reduced type H blood vessel formation in subchondral bone. Importantly, we identified a novel potent EP4 antagonist, HL-43, which showed in vitro and in vivo effects consistent with those observed in the EP4LysM mice. Finally, we showed that the Gαs/PI3K/AKT/MAPK signaling pathway is downstream of EP4 activation via PGE2 in osteoclasts. Together, our data demonstrate that PGE2/EP4 signaling in osteoclasts mediates angiogenesis and sensory neuron innervation in subchondral bone, promoting OA progression and pain, and that inhibition of EP4 with HL-43 has therapeutic potential in OA. [ABSTRACT FROM AUTHOR]

Articular cartilage repair and regeneration is an unmet clinical need because of the poor self-regeneration capacity of the tissue. In this study, we found that the expression of prostaglandin E receptor 4 (PTGER4 or EP4) was largely increased in the injured articular cartilage in both humans and mice. In microfracture (MF) surgery-induced cartilage defect (CD) and destabilization of the medial meniscus (DMM) surgery-induced CD mouse models, cartilage-specific deletion of EP4 remarkably promoted tissue regeneration by enhancing chondrogenesis and cartilage anabolism, and suppressing cartilage catabolism and hypertrophy. Importantly, knocking out EP4 in cartilage enhanced stable mature articular cartilage formation instead of fibrocartilage, and reduced joint pain. In addition, we identified a novel selective EP4 antagonist HL-43 for promoting chondrocyte differentiation and anabolism with low toxicity and desirable bioavailability. HL-43 enhanced cartilage anabolism, suppressed catabolism, prevented fibrocartilage formation, and reduced joint pain in multiple pre-clinical animal models including the MF surgery-induced CD rat model, the DMM surgery-induced CD mouse model, and an aging-induced CD mouse model. Furthermore, HL-43 promoted chondrocyte differentiation and extracellular matrix (ECM) generation, and inhibited matrix degradation in human articular cartilage explants. At the molecular level, we found that HL-43/EP4 regulated cartilage anabolism through the cAMP/PKA/CREB/Sox9 signaling. Together, our findings demonstrate that EP4 can act as a promising therapeutic target for cartilage regeneration and the novel EP4 antagonist HL-43 has the clinical potential to be used for cartilage repair and regeneration. [ABSTRACT FROM AUTHOR]

As essential information acquisition tools in our lives, mobile social networks have brought us great convenience for communication. However, misleading information such as spam emails, clickbait links, and false health information appears everywhere in mobile social networks. Prior studies have adopted various approaches to detecting this information but ignored global semantic features of the corpus and lacked interpretability. In this paper, we propose a novel end-to-end model called Topic-Aware BiLSTM (TA-BiLSTM) to handle the problems above. We firstly design a neural topic model for mining global semantic patterns, which encodes word relatedness into topic embeddings. Simultaneously, a detection model extracts local hidden states from text content with LSTM layers. Then, the model fuses those global and local representations with the Topic-Aware attention mechanism and performs misleading information detection. Experiments on three real datasets prove that the TA-BiLSTM could generate more coherent topics and improve the detecting performance jointly. Furthermore, case study and visualization demonstrate that the proposed TA-BiLSTM could discover latent topics and help in enhancing interpretability. [ABSTRACT FROM AUTHOR]

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73–55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application. [ABSTRACT FROM AUTHOR]

First-principles computational studies under density functional theory (DFT) framework were used to investigate the structural stability, conductivity and voltage profile of LiFe1−nNnP1−mMmO4 (N, M = Si or S) electrode materials. It is found that the LiFeP7/8Si1/8O4 system has the most stable structure. After doping, the band gap values of the systems decrease gradually, and LiFe7/8S1/8PO4 system has a minimum band gap of 1.553 eV, attributed to the hybridization of the Fe-d and S-p orbital electrons. The LiFeP7/8S1/8O4 system demonstrates the characteristic of n-type semiconductor, and other doping systems have the feature of p-type semiconductor. Charge density difference maps show that the covalent property of Si–O bond is enhanced in the LiFeP7/8Si1/8O4 system. The average distance of Li and O atoms in the S doping systems increases from 0.21026 to 0.21486 and 0.21129 nm, respectively, indicating that doping broadens significantly the channel of Li ion de-intercalation in LiFe7/8S1/8PO4 and LiFeP7/8S1/8O4. Additionally, the results of lithium intercalation potential imply that the voltages of the doping systems fall into the range of 2.23–2.86 V. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to compare the safety and efficacy of transhepatic puncture tract embolization with n-butyl cyanoacrylate (n-BCA) versus coils after percutaneous transhepatic portal vein interventions in patients with hepatocellular carcinoma (HCC). It was also the aim of the study to evaluate the extent of artifacts in CT exams during FU. Methods: Single-center retrospective study from 2017–2019 in 190 patients who underwent percutaneous transhepatic portal vein interventions. The transhepatic puncture tracts were embolized with n-BCA in 88 patients (Group A) and with coils in 102 patients (Group B). Procedure-related complications and image noise around coils and n-BCA were compared between the groups. No significant differences were noted at baseline between both groups (platelets, coagulation, liver disease, types of procedures, liver function, liver tumors). Results: All patients underwent transhepatic puncture tract embolization. Procedure-related complications were only observed in patients from Group B: subcapsular hemorrhage (n = 2; 1.96%), hepatic artery hemorrhage (n = 1; 0.98%), and pseudoaneurysms combined with hemobilia occurred (n = 1; 0.98%). In Group A, the distal part of the punctured portal vein branch was embolized with n-BCA in 1 patient (1.14%). Four major complications in Group B Vs 0 in Group A were observed, respectively (p < 0.0001). The image noise around n-BCA was significantly lower than that around coils (10.7 ± 1.7 HU vs. 54.3 ± 15.0 HU, p <.001). Conclusions: n-BCA tract embolization is more effective than using coils, with fewer bleeding events, at the cost of a higher potential for unintended embolization of portal vein branches. [ABSTRACT FROM AUTHOR]

Semi-supervised classification methods are widely-used and attractive for dealing with both labeled and unlabeled data in real-world problems. In this paper, a novel kernel-free Laplacian twin support vector machine method is proposed for semi-supervised classification. Its main idea is to classify data points into two classes by constructing two nonparallel quadratic surfaces so that each surface is close to one class of points and far away from the other class of points. The proposed method not only saves much computational time by avoiding choosing a kernel function and its related parameters in the classical support vector machine, but also addresses the issue of computational complexity by adopting manifold regularization technique. Moreover, two small-sized convex quadratic programming problems need to be solved to implement the proposed method, which is much easier than solving the non-convex problem of mixed integer programming to implement the well-known semi-supervised support vector machine. Finally, the numerical results on some artificial and benchmark data sets validate the competitive performance of proposed method in terms of efficiency, classification accuracy and generalization ability, by comparing to well-known semi-supervised methods. In particular, the proposed method handles five benchmarking disease diagnosis problems well and efficiently, which indicates the potential of proposed method in diagnosing and forecasting the diseases. [ABSTRACT FROM AUTHOR]

Computing the grain boundary (GB) counterparts to bulk phase diagrams represents an emerging research direction. Using a classical embrittlement model system Ga-doped Al alloy, this study demonstrates the feasibility of computing temperature- and composition-dependent GB diagrams to represent not only equilibrium thermodynamic and structural characters, but also mechanical properties. Specifically, hybrid Monte Carlo and molecular dynamics (MC/MD) simulations are used to obtain the equilibrium GB structure as a function of temperature and composition. Simulated GB structures are validated by aberration-corrected scanning transmission electron microscopy. Subsequently, MD tensile tests are performed on the simulated equilibrium GB structures. GB diagrams are computed for not only GB adsorption and structural disorder, but also interfacial structural and chemical widths, MD ultimate tensile strength, and MD tensile toughness. This study suggests a research direction to investigate GB composition–structure–property relationships via computing GB diagrams of thermodynamic, structural, and mechanical (or potentially other) properties. [ABSTRACT FROM AUTHOR]

Oxidized low-density lipoprotein (ox-LDL) accumulation in the vascular wall plays a pivotal role in the development of atherosclerosis and vascular calcification. However, few studies focus on the regulatory roles of microRNAs in ox-LDL stimulated vascular calcification. The aim of the present study was to investigate how miR-33a-5p regulated vascular calcification stimulated by ox-LDL. In the present study, miR-33a-5p was downregulated during vascular smooth muscle cells (VSMCs) calcification and upon ox-LDL treatment. ox-LDL significantly stimulated VSMCs calcification, while miR-33a-5p overexpression by its mimics transfection inhibited alkaline phosphatase (ALP) activity, mineralization and marker genes associated with VSMCs calcification even in the presence of ox-LDL. Methyltransferase like 3 (METTL3) was the target gene of miR-33a-5p. METTL3 was upregulated during VSMCs calcification and upon ox-LDL treatment. When VSMCs were transfected with miR-33a-5p mimics, METTL3 was downregulated. METTL3 downregulation by siRNA method decreased VSMCs calcification even in the presence of ox-LDL. Taken together, these results suggest miR-33a-5p suppresses VSMCs calcification stimulated by ox-LDL via targeting METTL3, highlighting the critical role of miR-33a-5p/METTL3 in vascular calcification. [ABSTRACT FROM AUTHOR]

Prostate cancer remains one of the most lethal cancers for men in the United States. The study aims to detect fusion transcripts in the blood samples of prostate cancer patients. We analyzed nine fusion transcripts including MAN2A1-FER, SLC45A2-AMACR, TRMT11-GRIK2, CCNH-C5orf30, mTOR-TP53BP1, KDM4-AC011523.2, TMEM135-CCDC67, LRRC59-FLJ60017 and Pten-NOLC1147 in the blood samples from 147 prostate cancer patients and 14 healthy individuals, using Taqman RT-PCR and Sanger's sequencing. Similar analyses were also performed on 25 matched prostate cancer samples for matched-sample evaluation. Eighty-two percent blood samples from the prostate cancer patients were positive for MAN2A1-FER transcript, while 41.5% and 38.8% blood samples from the prostate cancer patients were positive for SLC45A2-AMACR and Pten-NOLC1, respectively. CCNH-c5orf30 and mTOR-TP53BP1 had low detection rates, positive in only 5.4% and 4% of the blood samples from the prostate cancer patients. Only 2 blood samples were positive for KDM4B-AC011523.2 transcript. Overall, 89.8% patients were positive for at least one fusion transcript in their blood samples. The statistical analysis showed varied sensitivity of fusion transcript detection in the blood based on the types of fusions. In contrast, the blood samples from all healthy individuals were negative for the fusion transcripts. Detection of fusion transcripts in the blood samples of the prostate cancer patients may be a fast and cost-effective way to detect prostate cancer. [ABSTRACT FROM AUTHOR]

The bacteria, Serratia marcescens (SM1) was previously obtained from the black-winged termite, Odontotermes formosanus Shiraki. SM1 was highly toxic to O. formosanus, however, the mechanism of toxicity is unclear. In this study, toxicity test results showed that the main components that affected O. formosanus were in a supernatant and that the insecticidal protease in the supernatant resulted in the death of O. formosanus. In addition, zinc sulphate recovery experiments indicated that the metalloproteinases in the supernatant were more harmful. These results provide a theoretical foundation for the future biological control of termites, the basis for the development of pest control technology and the discovery of new pesticides. [ABSTRACT FROM AUTHOR]

Odontotermes formosanus (Shiraki), a black-winged subterranean termite, is a common forest pest. A red pigment-producing bacterial strain isolated from the termite was identified as Serratia marcescens and named SM1. A bioassay of SM1 on O. formosanus show that the LD50 ranged from 1.77 × 104 to 10.82 × 104 cells/termite over 21–39 h. Three biological control agents, Beauveria bassiana (2 × 1010 cells/mL), Metarhizium anisopliae (1 × 1010 cells/mL) and Bacillus thuringiensis (1.6 × 108 IU/mL), were used for an O. formosanus bioassay. The results show that the insecticidal effect of B. bassiana was stronger than that of M. anisopliae. In addition, two mixtures were obtained by combining B. bassiana (2 × 1010 cells/mL) with SM1 (1.5 × 1010 cells/mL), and M. anisopliae (1 × 1010 cells/mL) with S. marcescens (SM1) (1.5 × 1010 cells/mL) in equal volumes. The results show that B. bassiana and SM1 was less effective than SM1 alone. However, the insecticidal effect of M. anisopliae and SM1 was better than that of M. anisopliae or SM1 individually. These studies provide an important contribution for termite biocontrol. [ABSTRACT FROM AUTHOR]

The characterization of human gene expression is limited by short read lengths, high error rates and large input requirements. Here, we used a synthetic long read (SLR) sequencing approach, LoopSeq, to generate accurate sequencing reads that span full length transcripts using standard short read data. LoopSeq identified isoforms from control samples with 99.4% accuracy and a 0.01% per-base error rate, exceeding the accuracy reported for other long-read technologies. Applied to targeted transcriptome sequencing from colon cancers and their metastatic counterparts, LoopSeq revealed large scale isoform redistributions from benign colon mucosa to primary colon cancer and metastatic cancer and identified several previously unknown fusion isoforms. Strikingly, single nucleotide variants (SNVs) occurred dominantly in specific isoforms and some SNVs underwent isoform switching in cancer progression. The ability to use short reads to generate accurate long-read data as the raw unit of information holds promise as a widely accessible approach in transcriptome sequencing. Silvia Liu et al. present LoopSeq, a synthetic long-read sequencing method that generates accurate long-read transcriptome data from short Illumina reads. As an example of possible applications, they use LoopSeq to investigate differential isoform expression, isoform-specific single nucleotide variants, and potential fusion genes in multiple stages of colon cancer. Altogether, LoopSeq is a valuable method for analyzing complex transcriptomes and investigating gene expression at the isoform level. [ABSTRACT FROM AUTHOR]