Search

Enterovirus consists of a variety of viruses that could cause a wide range of illness in human. The pathogenesis of these viruses remains incompletely understood and no specific treatment is available. Better methods to study enterovirus infection in live cells will help us better understand the pathogenesis of these viruses and might contribute to antiviral development. Here in this study, we developed fluorescent cell-based reporter systems that allow sensitive distinction of individual cells infected with enterovirus 71 (EV71). More importantly, these systems could be easily used for live-cell imaging by monitoring viral-induced fluorescence translocation after EV71 infection. We further demonstrated that these reporter systems could be used to study other enterovirus-mediated MAVS cleavage and they are sensitive for antiviral activity testing. Therefore, integration of these reporters with modern image-based analysis has the potential to generate new insights into enterovirus infection and facilitate antiviral development. [ABSTRACT FROM AUTHOR]

Under DFT calculations, a systematic investigation is carried out to explore the structures and oxygen evolution reaction (OER) catalytic activities of a series of 2D single-atom catalyst (SAC) systems, which are constructed by doping the transition metal (TM) atoms in group VIII into the cavities of rigid phthalocyanine carbide (pc-C3N2). We can find that when Co, Rh, Ir and Ru atoms are doped in the small or large cavities of a pc-C3N2 monolayer, they can be used as high-activity centers of OER. All these four new TM@C3N2 nanostructures can exhibit very low overpotential values in the range of 0.33~0.48 V, even smaller than the state-of-the-art IrO2 (0.56 V), which indicates considerably high OER catalytic activity. In particular, the Rh@C3N2 system can show the best OER performance, given that doped Rh atoms can uniformly serve as high-OER-active centers, regardless of the size of cavity. In addition, a detailed mechanism analysis was carried out. It is found that in these doped pc-C3N2 systems, the number of outer electrons, the periodic number of doped TM atoms and the size of the embedded cavity can be considered the key factors affecting the OER catalytic activity, and excellent OER catalytic performance can be achieved through their effective cooperation. These fascinating findings can be advantageous for realizing low-cost and high-performance SAC catalysts for OER in the near future. [ABSTRACT FROM AUTHOR]

Background: Health disparities between people who are African American (AA) versus their White counterparts have been well established, but disparities among AA people have not. The current study introduces a systematic method to determine subgroups within a sample of AA people based on their social determinants of health., Methods: Health screening data collected in the West Side of Chicago, an underserved predominantly AA area, in 2018 were used. Exploratory latent class analysis was used to determine subgroups of participants based on their responses to 16 variables, each pertaining to a specific social determinant of health., Results: Four unique clusters of participants were found, corresponding to those with "many unmet needs", "basic unmet needs", "unmet healthcare needs", and "few unmet needs"., Conclusion: The findings support the utility of analytically determining meaningful subgroups among a sample of AA people and their social determinants of health. Understanding the differences within an underserved population may contribute to future interventions to eliminate health disparities.

This study delineates the pivotal role of imaging within the field of neurology, emphasizing its significance in the diagnosis, prognostication, and evaluation of treatment responses for central nervous system (CNS) tumors. A comprehensive understanding of both the capabilities and limitations inherent in emerging imaging technologies is imperative for delivering a heightened level of personalized care to individuals with neuro-oncological conditions. Ongoing research in neuro-oncological imaging endeavors to rectify some limitations of radiological modalities, aiming to augment accuracy and efficacy in the management of brain tumors. This review is dedicated to the comparison and critical examination of the latest advancements in diverse imaging modalities employed in neuro-oncology. The objective is to investigate their respective impacts on diagnosis, cancer staging, prognosis, and post-treatment monitoring. By providing a comprehensive analysis of these modalities, this review aims to contribute to the collective knowledge in the field, fostering an informed approach to neuro-oncological care. In conclusion, the outlook for neuro-oncological imaging appears promising, and sustained exploration in this domain is anticipated to yield further breakthroughs, ultimately enhancing outcomes for individuals grappling with CNS tumors.

The molecular dynamics simulation was used to simulate the influence of the composite wall stacking effect on shale oil occurrence. The kerogen-illite heterogeneous wall pore model was established to study the effects of temperature, pore size, and wall component ratio on the adsorption ratio and diffusion capacity of shale oil. The calculation results show that the fluid density distribution in the hybrid nanopore is not uniform. When the pore size increases, the proportion of the first adsorption layer to the total adsorption amount decreases rapidly, and the phenomenon of the "solid-like layer" of shale oil in small pores is more obvious. In addition, increases in temperature have little effect on the density peak of the first adsorption layer. With increases in organic matter content in the shale pore model, the diffusion coefficient of fluid decreases gradually, along with adsorption capacity. The influence of the irregular arrangement of kerogen molecules on the adsorption of shale oil is greater than the influence of surface roughness caused by illite on the adsorption.

Aging is a major risk factor for Alzheimer's disease (AD). AD mouse models are frequently used to assess pathology, behavior, and memory in AD research. While the pathological characteristics of AD are well established, our understanding of the changes in the metabolic phenotypes with age and pathology is limited. In this work, we used the Promethion cage systems ® to monitor changes in physiological metabolic and behavioral parameters with age and pathology in wild-type and 5xFAD mouse models. Then, we assessed whether these parameters could be altered by treatment with oleocanthal, a phenolic compound with neuroprotective properties. Findings demonstrated metabolic parameters such as body weight, food and water intake, energy expenditure, dehydration, and respiratory exchange rate, and the behavioral parameters of sleep patterns and anxiety-like behavior are altered by age and pathology. However, the effect of pathology on these parameters was significantly greater than normal aging, which could be linked to amyloid-β deposition and blood-brain barrier (BBB) disruption. In addition, and for the first time, our findings suggest an inverse correlation between sleep hours and BBB breakdown. Treatment with oleocanthal improved the assessed parameters and reduced anxiety-like behavior symptoms and sleep disturbances. In conclusion, aging and AD are associated with metabolism and behavior changes, with the changes being greater with the latter, which were rectified by oleocanthal. In addition, our findings suggest that monitoring changes in metabolic and behavioral phenotypes could provide a valuable tool to assess disease severity and treatment efficacy in AD mouse models.

Whole-genome sequencing provides a robust platform for investigating the epidemiology and transmission of emerging viruses. Oxford Nanopore Technologies allows for real-time viral sequencing on a local laptop system for point-of-care testing. Seoul orthohantavirus (Seoul virus, SEOV), harbored by Rattus norvegicus and R. rattus , causes mild hemorrhagic fever with renal syndrome and poses an important threat to public health worldwide. We evaluated the deployable MinION system to obtain high-fidelity entire-length sequences of SEOV for the genome identification of accurate infectious sources and their genetic diversity. One-step amplicon-based nanopore sequencing was performed from SEOV 80-39 specimens with different viral copy numbers and SEOV-positive wild rats. The KU-ONT-SEOV-consensus module was developed to analyze SEOV genomic sequences generated from the nanopore system. Using amplicon-based nanopore sequencing and the KU-ONT-consensus pipeline, we demonstrated novel molecular diagnostics for acquiring full-length SEOV genome sequences, with sufficient read depth in less than 6 h. The consensus sequence accuracy of the SEOV small, medium, and large genomes showed 99.75-100% (for SEOV 80-39 isolate) and 99.62-99.89% (for SEOV-positive rats) identities. This study provides useful insights into on-site diagnostics based on nanopore technology and the genome epidemiology of orthohantaviruses for a quicker response to hantaviral outbreaks.

The successful implementation of Human-Robot Collaboration (HRC) has become a prominent feature of smart manufacturing environments. Key industrial requirements, such as flexibility, efficiency, collaboration, consistency, and sustainability, present pressing HRC needs in the manufacturing sector. This paper provides a systemic review and an in-depth discussion of the key technologies currently being employed in smart manufacturing with HRC systems. The work presented here focuses on the design of HRC systems, with particular attention given to the various levels of Human-Robot Interaction (HRI) observed in the industry. The paper also examines the key technologies being implemented in smart manufacturing, including Artificial Intelligence (AI), Collaborative Robots (Cobots), Augmented Reality (AR), and Digital Twin (DT), and discusses their applications in HRC systems. The benefits and practical instances of deploying these technologies are showcased, emphasizing the substantial prospects for growth and improvement in sectors such as automotive and food. However, the paper also addresses the limitations of HRC utilization and implementation and provides some insights into how the design of these systems should be approached in future work and research. Overall, this paper provides new insights into the current state of HRC in smart manufacturing and serves as a useful resource for those interested in the ongoing development of HRC systems in the industry.

The vehicle particle model was built to compare and analyze the effectiveness of three different collision avoidance methods. The results show that during vehicle high-speed emergency collision avoidance, lane change collision avoidance requires a smaller longitudinal distance than braking collision avoidance and is closer to that with a combination of lane change and braking collision avoidance. Based on the above, a double-layer control strategy is proposed to avoid collision when vehicles change lanes at high speed. The quintic polynomial is chosen as the reference path after comparing and analyzing three polynomial reference trajectories. The multiobjective optimized model predictive control is used to track the lateral displacement, and the optimization objective is to minimize the lateral position deviation, yaw rate tracking deviation, and control increment. The lower longitudinal speed tracking control strategy is to control the vehicle drive system and brake system to track the expected speed. Finally, the lane changing conditions and other speed conditions of the vehicle at 120 km/h are verified. The results show that the control strategy can track the longitudinal and lateral trajectories well and achieve effective lane change and collision avoidance.

Exposure-response (E-R) is a key aspect of pharmacometrics analysis that supports drug dose selection. Currently, there is a lack of understanding of the technical considerations necessary for drawing unbiased estimates from data. Due to recent advances in machine learning (ML) explainability methods, ML has garnered significant interest for causal inference. To this end, we used simulated datasets with known E-R "ground truth" to generate a set of good practices for the development of ML models required to avoid introducing biases when performing causal inference. These practices include the use of causal diagrams to enable the careful consideration of model variables by which to obtain desired E-R relationship insights, keeping a strict separation of data for model-training and for inference generation to avoid biases, hyperparameter tuning to improve the reliability of models, and estimating proper confidence intervals around inferences using a bootstrap sampling with replacement strategy. We computationally confirm the benefits of the proposed ML workflow by using a simulated dataset with nonlinear and non-monotonic exposure-response relationships.

The microstructure and mechanical properties of semi-continuous casting Mg-Gd-Y-Zr magnesium alloys with different Zn contents were studied in this paper. The results showed that an increase in Zn content resulted in gradual refinement of the grains and a gradual increase in the volume fraction of the second phase. At a Zn content of 0.7 wt%, the microstructure was mainly composed of the α-Mg matrix and the Mg5(GdY) and long-period stacking order (LPSO) phases. An increase in the Zn content lowered the volume fraction of the Mg5(GdY) phase and increased the volume fraction of the LPSO phase. At a Zn content of 3.3 wt%, the microstructure was mainly composed of the α-Mg matrix and the LPSO phase. Among these alloys, the alloy without Zn addition showed an optimal ultimate tensile strength and yield strength of 229 MPa and 185 MPa, respectively, while the alloy with 3.3 wt% Zn showed an excellent elongation after fracture of 4.5%. The tensile fracture analysis indicated that the cracks of the alloy without Zn mainly originated at the trigeminal junction of the grain boundary, the cracks of the 0.7 wt% Zn and 1.5 wt% Zn alloy mainly originated at the interface of the Mg/lamellar LPSO phase, and the cracks of the 3.3 wt% Zn alloy mainly originated at the bulk LPSO phase of the grain boundary and then propagated along the bulk LPSO phase.

Certain re-emerging alphaviruses, such as chikungunya virus (CHIKV), cause serious disease and widespread epidemics. To develop virus-specific therapies, it is critical to understand the determinants of alphavirus pathogenesis and virulence. One major determinant is viral evasion of the host interferon response, which upregulates antiviral effectors, including zinc finger antiviral protein (ZAP). Here, we demonstrated that Old World alphaviruses show differential sensitivity to endogenous ZAP in 293T cells: Ross River virus (RRV) and Sindbis virus (SINV) are more sensitive to ZAP than o'nyong'nyong virus (ONNV) and CHIKV. We hypothesized that the more ZAP-resistant alphaviruses evade ZAP binding to their RNA. However, we did not find a correlation between ZAP sensitivity and binding to alphavirus genomic RNA. Using a chimeric virus, we found the ZAP sensitivity determinant lies mainly within the alphavirus non-structural protein (nsP) gene region. Surprisingly, we also did not find a correlation between alphavirus ZAP sensitivity and binding to nsP RNA, suggesting ZAP targeting of specific regions in the nsP RNA. Since ZAP can preferentially bind CpG dinucleotides in viral RNA, we identified three 500-bp sequences in the nsP region where CpG content correlates with ZAP sensitivity. Interestingly, ZAP binding to one of these sequences in the nsP2 gene correlated to sensitivity, and we confirmed that this binding is CpG-dependent. Our results demonstrate a potential strategy of alphavirus virulence by localized CpG suppression to evade ZAP recognition.

Enavogliflozin is a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor approved for clinical use in South Korea. As SGLT2 inhibitors are a treatment option for patients with diabetes, enavogliflozin is expected to be prescribed in various populations. Physiologically based pharmacokinetic (PBPK) modelling can rationally predict the concentration-time profiles under altered physiological conditions. In previous studies, one of the metabolites (M1) appeared to have a metabolic ratio between 0.20 and 0.25. In this study, PBPK models for enavogliflozin and M1 were developed using published clinical trial data. The PBPK model for enavogliflozin incorporated a non-linear urinary excretion in a mechanistically arranged kidney model and a non-linear formation of M1 in the liver. The PBPK model was evaluated, and the simulated pharmacokinetic characteristics were in a two-fold range from those of the observations. The pharmacokinetic parameters of enavogliflozin were predicted using the PBPK model under pathophysiological conditions. PBPK models for enavogliflozin and M1 were developed and validated, and they seemed useful for logical prediction.

To decrease energy consumption and improve the performance of micro-arc oxidation (MAO) films on 6063 Al alloy, a policy of K 2 TiF 6 additive and electrolyte temperature control was adapted. The specific energy consumption relied on the K 2 TiF 6 additive and more particularly on the electrolyte temperatures. Scanning electron microscopy demonstrates that electrolytes with 5 g/L K 2 TiF 6 can effectively seal the surface pores and increase the thickness of the compact inner layer. Spectral analysis shows that the surface oxide coating consists of γ-Al 2 O 3 phase. Following 336 h of the total immersion process, the impedance modulus of the oxidation film, prepared at 25 °C (Ti5-25), remained 1.08 × 10 6 Ω·cm 2 . Moreover, Ti5-25 has the best performance/energy-consumption ratio with a compact inner layer (2.5 ± 0.3 μm). This research found that the time of the big arc stage increased with the temperature, resulting in producing more internal defects in the film. In this work, we employ a dual-track strategy of additive and temperature providing an avenue to reduce the energy consumption of MAO on alloys.

Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure-response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin.

Under DFT calculations, a systematic investigation is carried out to explore the structures and oxygen evolution reaction (OER) catalytic activities of a series of 2D single-atom catalyst (SAC) systems, which are constructed by doping the transition metal (TM) atoms in group VIII into the cavities of rigid phthalocyanine carbide (pc-C 3 N 2 ). We can find that when Co, Rh, Ir and Ru atoms are doped in the small or large cavities of a pc-C 3 N 2 monolayer, they can be used as high-activity centers of OER. All these four new TM@C 3 N 2 nanostructures can exhibit very low overpotential values in the range of 0.33~0.48 V, even smaller than the state-of-the-art IrO 2 (0.56 V), which indicates considerably high OER catalytic activity. In particular, the Rh@C 3 N 2 system can show the best OER performance, given that doped Rh atoms can uniformly serve as high-OER-active centers, regardless of the size of cavity. In addition, a detailed mechanism analysis was carried out. It is found that in these doped pc-C 3 N 2 systems, the number of outer electrons, the periodic number of doped TM atoms and the size of the embedded cavity can be considered the key factors affecting the OER catalytic activity, and excellent OER catalytic performance can be achieved through their effective cooperation. These fascinating findings can be advantageous for realizing low-cost and high-performance SAC catalysts for OER in the near future.

Auxin plays a critical role in organogenesis in plants. The classical auxin signaling pathway holds that auxin initiates downstream signal transduction by degrading Aux/IAA transcription repressors that interact with ARF transcription factors. In this study, 23 MoIAA genes were identified in the drumstick tree genome. All MoIAA genes were located within five subfamilies based on phylogenetic evolution analysis; the gene characteristics and promoter cis-elements were also analyzed. The protein interaction network between the MoIAAs with MoARFs was complex. The MoIAA gene family responded positively to NAA treatment, exhibiting different patterns and degrees, notably for MoIAA1 , MoIAA7 and MoIAA13 . The three genes expressed and functioned in the nucleus; only the intact encoding protein of MoIAA13 exhibited transcriptional activation activity. The shoot regeneration capacity in the 35S::MoIAA13-OE transgenic line was considerably lower than in the wild type. These results establish a foundation for further research on MoIAA gene function and provide useful information for improved tissue culture efficiency and molecular breeding of M. oleifera .

The timing, amount, and quality of sleep are critical for an individual's health and quality of life. This paper provides a focused narrative review of the existing literature around multidimensional environments and sleep health for aging adults. Five electronic databases, Scopus, Web of Science, PubMed/Medline; EBSCOhost, PsycINFO (ProQuest), and Google Scholar yielded 54,502 total records. After removing duplicates, non-peer reviewed academic articles, and nonrelevant articles, 70 were included for review. We were able to categorize environmental factors into housing security, home environment, and neighborhood environment, and, within each environmental category, specific elements/aspects are discussed. This paper provides a comprehensive map connecting identified levels of influence (individual, home/house, and neighborhood-level) in which subfactors are listed under each level of influence/category with the related literature list. Our review highlights that multidimensional environmental factors can affect aging adults' sleep health and eventually their physical, mental, and cognitive health and that sleep disparities exist in racial minorities in socioeconomically disadvantaged communities in which cumulative environmental stressors coexist. Based on this focused narrative review on the multidimensional sleep environments for aging adults, knowledge gaps are identified, and future research directions are suggested.

B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients' blood could enable early disease profiling and therapy response monitoring. Here, we report the development and validation of a slide-based immunofluorescence assay (i.e., CD138, BCMA, CD45, DAPI) for enrichment-free detection, quantification, and morphogenomic characterization of BCMA-expressing cells in patients (N = 9) with plasma cell neoplasms. Varying morphological subtypes of circulating BCMA-expressing cells were detected across the CD138(+/-) and CD45(+/-) compartments, representing candidate clonotypic post-germinal center B cells, plasmablasts, and both normal and malignant plasma cells. Genomic analysis by single-cell sequencing and correlation to clinical FISH cytogenetics provides validation, with data showing that patients across the different neoplastic states carry both normal and altered BCMA-expressing cells. Furthermore, altered cells harbor cytogenetic events detected by clinical FISH. The reported enrichment-free liquid biopsy approach has potential applications as a single-cell methodology for the early detection of BCMA+ B-lymphoid malignancies and in monitoring therapy response for patients undergoing anti-BCMA treatments.

Background: Glioma is the most common primary tumor of the central nervous system with a high lethality rate. This study aims to mine fibroblast-related genes with prognostic value and construct a corresponding prognostic model., Methods: A glioma-related TCGA (The Cancer Genome Atlas) cohort and a CGGA (Chinese Glioma Genome Atlas) cohort were incorporated into this study. Variance expression profiling was executed via the "limma" R package. The "clusterProfiler" R package was applied to perform a GO (Gene Ontology) analysis. The Kaplan-Meier (K-M) curve, LASSO regression analysis, and Cox analyses were implemented to determine the prognostic genes. A fibroblast-related risk model was created and affirmed by independent cohorts. We derived enriched pathways between the fibroblast-related high- and low-risk subgroups using gene set variation analysis (GSEA). The immune infiltration cell and the stromal cell were calculated using the microenvironment cell populations-counter (MCP-counter) method, and the immunotherapy response was assessed with the SubMap algorithm. The chemotherapy sensitivity was estimated using the "pRRophetic" R package., Results: A total of 93 differentially expressed fibroblast-related genes (DEFRGs) were uncovered in glioma. Seven prognostic genes were filtered out to create a fibroblast-related gene signature in the TCGA-glioma cohort training set. We then affirmed the fibroblast-related risk model via TCGA-glioma cohort and CGGA-glioma cohort testing sets. The Cox regression analysis proved that the fibroblast-related risk score was an independent prognostic predictor in prediction of the overall survival of glioma patients. The fibroblast-related gene signature revealed by the GSEA was applicable to the immune-relevant pathways. The MCP-counter algorithm results pointed to significant distinctions in the tumor microenvironment between fibroblast-related high- and low-risk subgroups. The SubMap analysis proved that the fibroblast-related risk score could predict the clinical sensitivity of immunotherapy. The chemotherapy sensitivity analysis indicated that low-risk patients were more sensitive to multiple chemotherapeutic drugs., Conclusion: Our study identified prognostic fibroblast-related genes and generated a novel risk signature that could evaluate the prognosis of glioma and offer a theoretical basis for clinical glioma therapy.

Polycythemia vera (PV) is a malignant clonal hematological disease of hematopoietic stem cells characterized by the proliferation of peripheral blood cells, and JAK2 mutation is one of the main causes of PV peripheral blood cell proliferation. Abnormal cell metabolism is a new feature of malignant proliferation of tumor cells, but the role of metabolism in the pathogenesis and prognosis of PV remains unclear. We analyzed metabolic differences of peripheral blood sera between 32 PV patients and 20 healthy controls (HCs) by liquid chromatography-mass spectrometry (LC-MS) to investigate their relationship with cell proliferation and to screen for prognosis-related metabolic biomarkers. Compared to HC, 33 endogenous metabolites were significantly changed in PV and were involved in fatty acid metabolism, glucose metabolism, sphingolipid metabolism, and amino acid metabolism pathways. Among them, seven metabolites were closely associated with JAK2 mutations, 2 of which may contribute to the proliferation of peripheral blood cells in PV patients. A set of potential prognostic metabolic biomarkers containing four metabolites was identified by a receiver operating characteristic (ROC) curve according to the risk stratification of the PV patients and their combined AUC value of 0.952, with a sensitivity of 90.905% and specificity of 90.909% at the optimal cutoff point. Metabonomics is an important tool for the study of the pathogenesis of PV and the relationship between JAK2 gene mutation. Furthermore, the potential biomarkers of this study may provide a reference for the prognosis of PV.

Closed-cell metal syntactic foam is a new material consisting of hollow spheres embedded in metal matrix syntactic foams. These foams have good physical and mechanical properties and are increasingly used worldwide in industrial and high-tech fields. Magnesium matrix syntactic foams containing hollow Al 2 O 3 spheres ((Al 2 O 3hs )/AZ91D) were successfully fabricated by hot press sintering at different temperatures. The fabrication of Al 2 O 3hs /AZ91D and the effect of sintering temperature on the microstructure and properties are reported in this paper. Additionally, sandwiched magnesium matrix syntactic foams were prepared by placing magnesium plates on both sides of the syntactic foam. Some Al 2 O 3hs particles became filled with matrix particles during preparation. Thus, the actual density was greater than the theoretically calculated value and increases with increasing sintering temperature. Above 723 K, a brittle phase MgAl 2 O 4 formed in Al 2 O 3hs /AZ91D. The quasistatic and dynamic compressive strengths of Al 2 O 3hs /AZ91D first increased and then decreased with increasing sintering temperature, and the maximums were 162 MPa and 167.87 MPa, respectively. Thus, this paper reports a new strategy for the controlled preparation of metal matrix syntactic foams with predetermined porosity. The results show that this strategy improved the performance of lightweight and high-strength syntactic foam materials and shows potential for further research.

Isothermal-compression tests of B 4 C p /6063Al composites containing 20 vol.% B 4 C were performed using a Gleeble-3500 device, at strain rates ranging from 0.001 s -1 to 1 s -1 and deformation temperatures ranging from 723 K to 823 K. The results showed that the high-temperature flow stress of B 4 C p /6063Al composites increases with the decrease in deformation temperature or the increase in the strain rate. After friction correction, the friction corrected stress was less than the original experimental stress. At the initial stage of deformation, the difference between the rheological stress after friction correction and the measured rheological stress is small, but with the continuous increase in the strain, the difference between the rheological stress after friction correction and the measured rheological stress is grows. Under the same strain, the difference between the rheological stress before and after friction correction becomes more significant with the decrease in the deformation temperature and the increase in the strain rate. Next, the material constants (i.e., α, β, Q, A, n) of B 4 C p /6063Al composites were calibrated based on the experimental data, and a constitutive equation was established based on Arrhenius theory. The experimental values and predicted values of the stress-strain curves are in good agreement with the stress-strain curves of the finite element simulation, and the validity of the constitutive equation was verified.

Protease-activated receptor 2 (PAR2) is a G-protein-coupled receptor (GPCR) activated by proteolytic cleavage of its N-terminal domain. Once activated, PAR2 is rapidly desensitized and internalized by phosphorylation and β-arrestin recruitment. Due to its irreversible activation mechanism, some agonists that rapidly desensitized PAR2 have been misconceived as antagonists, and this has impeded a better understanding of the pathophysiological role of PAR2. In the present study, we found that GB83, initially identified as a PAR2 antagonist, is a bona fide agonist of PAR2 that induces unique cellular signaling, distinct from trypsin and PAR2-activating peptide (AP). Activation of PAR2 by GB83 markedly elicited an increase in intracellular calcium levels and phosphorylation of MAPKs, but in a delayed and sustained manner compared to the rapid and transient signals induced by trypsin and PAR2-AP. Interestingly, unlike PAR2-AP, GB83 and trypsin induced sustained receptor endocytosis and PAR2 colocalization with β-arrestin. Moreover, the recovery of the localization and function of PAR2 was significantly delayed after stimulation by GB83, which may be the reason why GB83 is recognized as an antagonist of PAR2. Our results revealed that GB83 is a bona fide agonist of PAR2 that uniquely modulates PAR2-mediated cellular signaling and is a useful pharmacological tool for studying the pathophysiological role of PAR2.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it is the most common cause of dementia and has no treatment. It is characterized by two pathological hallmarks, the extracellular deposits of amyloid beta (Aβ) and the intraneuronal deposits of Neurofibrillary tangles (NFTs). Yet, those two hallmarks do not explain the full pathology seen with AD, suggesting the involvement of other mechanisms. Neuroinflammation could offer another explanation for the progression of the disease. This review provides an overview of recent advances on the role of the immune cells' microglia and astrocytes in neuroinflammation. In AD, microglia and astrocytes become reactive by several mechanisms leading to the release of proinflammatory cytokines that cause further neuronal damage. We then provide updates on neuroinflammation diagnostic markers and investigational therapeutics currently in clinical trials to target neuroinflammation.

In fault diagnosis research, compound faults are often regarded as an isolated fault mode, while the association between compound faults and single faults is ignored, resulting in the inability to make accurate and effective diagnoses of compound faults in the absence of compound fault training data. In an examination of the rotate vector (RV) reducer, a core component of industrial robots, this paper proposes a compound fault identification method that is based on an improved convolutional capsule network for compound fault diagnosis of RV reducers. First, one-dimensional convolutional neural networks are used as feature learners to deeply mine the feature information of a single fault from a one-dimensional time-domain signal. Then, a capsule network with a two-layer stack structure is designed and a dynamic routing algorithm is used to decouple and identify the single fault characteristics for compound faults to undertake the diagnosis of compound faults of RV reducers. The proposed method is verified on the RV reducer fault simulation experimental bench, the experimental results show that the method can not only diagnose a single fault, but it is also possible to diagnose the compound fault that is composed of two types of single faults through the learning of two types of single faults of the RV reducer when the training data of the compound faults of the RV reducer are missing. At the same time, the proposed method is used for compound fault diagnosis of bearings, and the experimental results confirm its applicability.

Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.

In the current investigation, micro-arc oxidation (MAO) ceramic coatings on aluminum are galvanostatically synthesized at various processing stages in an alkaline silicate system. The resultant coatings are systematically investigated in terms of the following respects: The working voltage and surface sparking evolution over the studied course of MAO are recorded by the signal acquisition system and the real-time imaging, respectively; the phase composition, the surface morphology, and the polished cross-section of the coatings are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) assisted with an energy-dispersive X-ray spectrometer (EDS), respectively. In particular, with the help of a low-rate increase in working voltage, the evolution of the sparks, the energy consumption, and the microstructure development of aluminum in alkaline silicate electrolyte by pre-anodizing are systematically investigated. The results show that the pre-anodized film can accelerate the evolution process of MAO spark and shorten the reaction process in the early stage of MAO reaction, reducing energy consumption and improving the corrosion resistance of the MAO coating. The γ-Al2O3 phase content after pre-anodized is significantly increased in MAO coatings. In particular, the thicker the pre-anodized film (beyond 8 μm) was broken down and fragmentation thinning in the early stage of the MAO process with the presence of micro discharges. This is due to the fact that the electron transition will be released by the emission of radiative recombination and reveals obvious galvanoluminescence (GL) behavior on the surface of the pre-anodized film. Further, based on the present MAO coating microstructure, a model of coating growth after pre-anodized that evolves over time is proposed.

Relative permeability of polymer flooding plays a very important role in oil field development. This paper aimed to measure and calculate the relative permeability curves of polymer flooding more accurately. First, viscosity variation law of polymer in porous media was studied. Rock particles of different diameters and cementing agent were used to make artificial cores and hydrophobically associating polymer solutions were prepared for experiments. Polymer solutions were injected into the cores filled with crude oil and irreducible water. In the process of polymer flooding, produced fluid was collected at different water saturations and locations of the core. Polymer solutions were separated and their viscosities were measured. With the experimental data, the viscosity variation rule of polymer transporting in porous media was explored. The result indicates that the viscosity retention rate of polymer solutions transporting in porous media has power function relationship with the water saturation and the dimensionless distance from the core inlet. Finally, the relative permeability curves of polymer flooding were measured by unsteady state method and the viscosity variation rule was applied to the calculation of the relative permeability curves.

In this paper, the rice husk ash and crumb rubber powder were used as a combined modifier for asphalt. The impact of the aging on the physical and rheological properties of crumb rubber powder, rice husk ash, and the combined modified asphalt was studied through the rolling thin film oven (RTFO) simulations. A Fourier-transform infrared Spectroscopy (FTIR) test was used to study the aging mechanisms of the combined crumb-rubber-powder- and rice-husk-ash-modified asphalt before and after aging through the changes in functional groups. Impacts of the combined, crumb rubber powder, and rice husk ash modifiers on the anti-aging characteristic of the asphalt binder were analyzed through different aging indices and the variations in intensity of the absorption peaks. According to the combined results, the addition of the combined crumb rubber powder, and rice husk ash could enhance the thermal oxidative aging resistance binder. Moreover, the optimal content of composite modified asphalt was (7% rice husk ash + 10% crumb rubber powder). In addition, the combined modified asphalt binder had all the peaks of neat asphalt, rice-husk-ash-modified asphalt, and crumb-rubber-powder-modified asphalt and no appearance of new peaks. A scanning electron microscope (SEM) test was carried out to observe the microstructure of the combined crumb-rubber-powder- and rice-husk-ash-modified asphalt binders. The obtained result demonstrated that different SEM images showed that the combined crumb rubber powder, and rice husk ash modifiers were uniformly dispersed inside the asphalt binder and consequently leading to format a homogeneous blended binder.

Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial fibrillation (VAF), and thrombosis. The process of transforming mechanical signals into biological signals has been revealed, which offers new insights into the study of VAF. Methods: Computational fluid dynamics simulations use numeric analysis and algorithms to compute flow parameters, including turbulent shear stress (TSS) and wall pressure in the left atrium (LA). Real-time PCR and western blotting were used to detect the mRNA and protein expression of IKCa2.3/3.1, ATK1, and P300 in the left atrial tissue of 90 patients. Results: In the valvular disease group, the TSS and wall ressure in the LA increased, the wall pressure increased in turn in all disease groups, mainly near the mitral valve and the posterior portion of the LA, the increase in TSS was the most significant in each group near the mitral valve, and the middle and lower part of the back of the LA and the mRNA expression and protein expression levels of IKCa2.3/3.1, AKT1, and P300 increased (p < 0.05) (n = 15). The present study was preliminarily conducted to elucidate whether there might be a certain correlation between IKCa2.3 and LA hemodynamic changes. Conclusions: The TSS and wall pressure changes in the LA are correlated with the upregulation of mRNA and protein expression of IKCa2.3/3.1, AKT1, and P300.

Amanita poisoning is one of the most deadly types of mushroom poisoning. α-Amanitin is the main lethal toxin in amanita, and the human-lethal dose is about 0.1 mg/kg. Most of the commonly used detection techniques for α-amanitin require expensive instruments. In this study, the α-amanitin aptamer was selected as the research object, and the stem-loop structure of the original aptamer was not damaged by truncating the redundant bases, in order to improve the affinity and specificity of the aptamer. The specificity and affinity of the truncated aptamers were determined using isothermal titration calorimetry (ITC) and gold nanoparticles (AuNPs), and the affinity and specificity of the aptamers decreased after truncation. Therefore, the original aptamer was selected to establish a simple and specific magnetic bead-based enzyme linked immunoassay (MELISA) method for α-amanitin. The detection limit was 0.369 μg/mL, while, in mushroom it was 0.372 μg/mL and in urine 0.337 μg/mL. Recovery studies were performed by spiking urine and mushroom samples with α-amanitin, and these confirmed the desirable accuracy and practical applicability of our method. The α-amanitin and aptamer recognition sites and binding pockets were investigated in an in vitro molecular docking environment, and the main binding bases of both were T3, G4, C5, T6, T7, C67, and A68. This study truncated the α-amanitin aptamer and proposes a method of detecting α-amanitin.

Postprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose, but how berberine lowers postprandial blood glucose is still elusive. Here, we investigated the effect of berberine on intestinal glucose transporter 2 (GLUT2) translocation and intestinal glucose absorption in type 2 diabetes mouse model. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin and diabetic mice were treated with berberine for 6 weeks. The effects of berberine on intestinal glucose transport and GLUT2 translocation were accessed in isolated intestines and intestinal epithelial cells (IEC-6), respectively. We found that berberine treatment improved glucose tolerance and systemic insulin sensitivity in diabetic mice. Furthermore, berberine decreased intestinal glucose transport and inhibited GLUT2 translocation from cytoplasm to brush border membrane in intestinal epithelial cells. Mechanistically, berberine inhibited intestinal insulin-like growth factor 1 (IGF-1R) phosphorylation and thus reduced localization of PLC-β2 in the membrane, leading to decreased GLUT2 translocation. These results suggest that berberine reduces intestinal glucose absorption through inhibiting IGF-1R-PLC-β2-GLUT2 signal pathway.

As a standard digital signature may be verified by anybody, it is unsuitable for personal or economically sensitive applications. The chameleon signature system was presented by Krawczyk and Rabin as a solution to this problem. It is based on a hash then sign model. The chameleon hash function enables the trapdoor information holder to compute a message digest collision. The holder of a chameleon signature is the recipient of a chameleon signature. He could compute collision on the hash value using the trapdoor information. This keeps the recipient from disclosing his conviction to a third party and ensures the privacy of the signature. The majority of the extant chameleon signature methods are built on the computationally infeasible number theory problems, like integer factorization and discrete log. Unfortunately, the construction of quantum computers would be rendered insecure to those schemes. This creates a solid requirement for construct chameleon signatures for the quantum world. Hence, this paper proposes a novel quantum secure chameleon signature scheme based on hash functions. As a hash-based cryptosystem is an essential candidate of a post-quantum cryptosystem, the proposed hash-based chameleon signature scheme would be a promising alternative to the number of theoretic-based methods. Furthermore, the proposed method is key exposure-free and satisfies the security requirements such as semantic security, non-transferability, and unforgeability.

The acrylamide (AM)/methacryloyl ethyl sulfobetaine (SPE)/behenyl polyoxyethylene ether methacrylate (BEM) terpolymer (PASB) was synthesized by soap-free emulsion polymerization. Four types of PASBs were synthesized by adjusting the moles of AM and BEM with constant total moles of monomers. The synthesized copolymers were characterized by Fourier-transform infrared spectroscopy, thermogravimetry, molecular weight, and viscosity. By measuring the microscopic morphology and backscattered light intensity of the emulsions, the instability process of the emulsions prepared by PASBs was investigated in detail. The main instability processes of the emulsions prepared from PASBs within 45 min were flocculation and coalescence. The intermolecular association of copolymer PASBs was dominated by the behenyl functional groups on the molecular chains. The stability of the emulsions, which were prepared from isoviscosity aqueous solutions controlled by the concentration of the associative copolymers, was increased with the degree of association of copolymers. The hydrophobic association between the copolymer molecules can further slow down the flocculation and coalescence of the emulsion droplets on the basis of the same aqueous solution viscosity, which is one of the reasons for improving the stability of the emulsion.

The plant embryogenic callus (EC) is an irregular embryogenic cell mass with strong regenerative ability that can be used for propagation and genetic transformation. However, difficulties with EC induction have hindered the breeding of drumstick, a tree with diverse potential commercial uses. In this study, three drumstick EC cDNA libraries were sequenced using an Illumina NovaSeq 6000 system. A total of 7191 differentially expressed genes (DEGs) for embryogenic callus development were identified, of which 2325 were mapped to the KEGG database, with the categories of plant hormone signal transduction and Plant-pathogen interaction being well-represented. The results obtained suggest that auxin and cytokinin metabolism and several embryogenesis-labeled genes are involved in embryogenic callus induction. Additionally, 589 transcription factors from 20 different families were differentially expressed during EC formation. The differential expression of 16 unigenes related to auxin signaling pathways was validated experimentally by quantitative real time PCR (qRT-PCR) using samples representing three sequential developmental stages of drumstick EC, supporting their apparent involvement in drumstick EC formation. Our study provides valuable information about the molecular mechanism of EC formation and has revealed new genes involved in this process.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including oral squamous cell carcinoma (OSCC). OSCC is a highly aggressive cancer and the most common oral malignancy. ANO1 has been proposed as a potential candidate for targeted anticancer therapy. In this study, we performed a cell-based screening to identify novel regulators leading to the downregulation of ANO1, and discovered cinobufagin, which downregulated ANO1 expression in oral squamous cell carcinoma CAL-27 cells. ANO1 protein levels were significantly reduced by cinobufagin in a dose-dependent manner with an IC 50 value of ~26 nM. Unlike previous ANO1 inhibitors, short-term (≤10 min) exposure to cinobufagin did not alter ANO1 chloride channel activity and ANO1-dependent intestinal smooth muscle contraction, whereas long-term (24 h) exposure to cinobufagin significantly reduced phosphorylation of STAT3 and mRNA expression of ANO1 in CAL-27 cells. Notably, cinobufagin inhibited cell proliferation of CAL-27 cells expressing high levels of ANO1 more potently than that of ANO1 knockout CAL-27 cells. In addition, cinobufagin significantly reduced cell migration and induced caspase-3 activation and PARP cleavage in CAL-27 cells. These results suggest that downregulation of ANO1 by cinobufagin is a potential mechanism for the anticancer effect of cinobufagin in OSCC.

Identifying the biological change from hormone-naïve prostate cancer to castration-resistant prostate cancer (CRPC) is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully completely understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Androgen deprivation therapy (ADT) is used as a primary treatment for preventing the progression of prostate cancer (PCa). Here we investigated PCa tissues at each stage of progression, from benign prostatic hyperplasia (BPH) to CRPC, based on quantitative proteomic technology, including tissues after ADT. In total, 4768 proteins were identified in this study, of which 4069 were quantified in the combined PCa tissues. Among the quantified proteins, 865 were differentially expressed proteins (21.2%). Based on the quantitative protein results, we performed systematic bioinformatics analysis and found that the levels of 15 proteins, including FOXA1 and HMGN1-3, increased among T3G3, T3GX, and CRPC, despite the ADT. Among all targets, we verified the increased levels of FOXA1 and HMGN1-3 in CRPC by immunoblotting and indirect enzyme-linked immunosorbent assay. In summary, we discuss the changes in intracellular factors involved in the progression of CRPC PCa despite ADT. Moreover, we suggest that FOXA1 and HMGN1-3 proteins could be used as potential CRPC-related factors in clinical therapeutic agents.