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Abstract Background Activator protein-1 (AP-1) represents a transcription factor family that has garnered growing attention for its extensive involvement in tumor biology. However, the roles of the AP-1 family in the evolution of lung cancer remain poorly characterized. FBJ Murine Osteosarcoma Viral Oncogene Homolog B (FOSB), a classic AP-1 family member, was previously reported to play bewilderingly two-polarized roles in non-small cell lung cancer (NSCLC) as an enigmatic double-edged sword, for which the reasons and significance warrant further elucidation. Methods and Results Based on the bioinformatics analysis of a large NSCLC cohort from the TCGA database, our current work found the well-known tumor suppressor gene TP53 served as a key code to decipher the two sides of FOSB – its expression indicated a positive prognosis in NSCLC patients harboring wild-type TP53 while a negative one in those harboring mutant TP53. By constructing a panel of syngeneically derived NSCLC cells expressing p53 in different statuses, the radically opposite prognostic effects of FOSB expression in NSCLC population were validated, with the TP53-R248Q mutation site emerging as particularly meaningful. Transcriptome sequencing showed that FOSB overexpression elicited diversifying transcriptomic landscapes across NSCLC cells with varying genetic backgrounds of TP53 and, combined with the validation by RT-qPCR, PREX1 (TP53-Null), IGFBP5 (TP53-WT), AKR1C3, and ALDH3A1 (TP53-R248Q) were respectively identified as p53-dependent transcriptional targets of FOSB. Subsequently, the heterogenous impacts of FOSB on the tumor biology in NSCLC cells via the above selective transcriptional targets were confirmed in vitro and in vivo. Mechanistic investigations revealed that wild-type or mutant p53 might guide FOSB to recognize and bind to distinct promoter sequences via protein-protein interactions to transcriptionally activate specific target genes, thereby creating disparate influences on the progression and prognosis in NSCLC. Conclusions FOSB expression holds promise as a novel prognostic biomarker for NSCLC in combination with a given genetic background of TP53, and the unique interactions between FOSB and p53 may serve as underlying intervention targets for NSCLC.

Bisphenol S (BPS) is widely presented and affects aging with unclear mechanisms. Here, we applied C. elegans to evaluate the effects of BPS on lifespan and healthspan and to investigate the underlying mechanisms. Both early-life and whole-life exposure to BPS at environmentally relevant doses (0.6, 6, 60 μg/L) significantly decreased lifespan, and healthspan (body bend, pharyngeal pumping, and lipofuscin accumulation). BPS exposure impaired mitochondrial structure and function, which promoted ROS production to induce oxidative stress. Furthermore, BPS increased expressions of the insulin/IGF-like signaling (IIS). Also, BPS inhibited expression of the IIS transcription factor daf-16 and its downstream anti-oxidative genes. Quercetin effectively improved BPS-induced oxidative stress byreversing BPS-regulated IIS/daf-16 pathway and anti-oxidative gene expressions. In daf-2 and daf-16 mutants, the effects of BPS and quercetin on lifespan, healthspan, oxidative stress, and anti-oxidative genes expressions were reversed, demonstrating the requirement of IIS/daf-16 for aging regulation. Molecular docking and molecular dynamics simulations confirmed the stable interaction between DAF-2 and BPS mainly via three residues (VAL1260, GLU1329, and MET1395), which was attenuated by quercetin. Our results highlighted that adverse effects of BPS on impairing lifespan and healthspan by affecting IIS/daf-16 function against mitochondrial stress, which could be inhibited by quercetin treatment. Thus, we first revealed the underlying mechanisms of BPS-induced aging and the potential treatment.

During the multi-layer forming process of laser-based directed energy deposition (L-DED) with coaxial powder feeding, the cladding layer is prone to defects, such as the rough surface, pores, and cracks. Moreover, more potential defects, e.g. humps and depressions on the surface of the cladding track, can occur in special processing attitudes such as tilted substrate. Investigating the mechanisms of defect formations is a prerequisite for realising defect suppression. Exploring the factors influencing the defect formations, e.g. the temperature characteristics and flow characteristics of the melt pool, is a must to realise the defect suppression. Moreover, the characteristics of the influencing factors during the multi-layer cladding process are not invariable. To provide a reference for the study of effective defect suppression under different processing scenarios, based on the main defects in the cladding layer when the substrate is in the horizontal processing attitude, the formation mechanisms of potential defects in special processing attitudes are supplemented and analyzed in depth in this paper. Then, the characteristics of the influencing factors and their changes with the progress of the multi-layer cladding process are further discussed based on a summary of the influential relationship between several influencing factors and defect formation.

Laser Charging means high energy laser beam to irradiate the solar cell to gain electricity power through photovoltaic generation. This kind of wireless energy transform way fits the IoT and other low energy satiation with the benefit of long-distance transmission. In this paper, we present a new way of information transferring while energy is gained which is called Simultaneous Wireless Information and Power Transfer. The main idea is to switch the laser device output power to generate the different PV current values, the dual level of laser power decides two ranges of the value. We imitate the On-Off Keying (OOK) named Low-High Keying(LHK) which turns the information into the energy code with a high or low current value. The issue of information coding is also presented with an example. And the application also provided the realization presented. The new method provides a brand way to Simultaneous Wireless Information and Power transfer without any extra equipment by contrast with others. It's suited for the long-distance, low power and limited information-connected occasions.

This is an article in the field of earth sciences. Jiulong area is the most concentrated area of Yanshanian granite found in western Sichuan, including Tiechanghe, Qiaopengzi-Landiao and Xinhuoshangranite. In this paper, LA-ICP-MS zircon U-Pb dating were carried out to determine the formation age of the granite， and its temporal-spatial relationship with the surrounding granites, providing a basis for the comparative study of Liwu copper deposit in the southern margin of Songpan-Ganzi block. The results show thatthe diagenetic age of Huajiaoping granite is (163.1±1.4) Ma, andit underwent magmatic or tectonic thermal events at (146±3) Ma, which is consistent withthe geological events ofTiechanghe, Xinhuoshan and Luomogranite. The magma temperature of Huajiaoping granite is 592～727 ℃ (average temperature 648 ℃), which is significantly lower than that of Qiaopengzi granite (766～804 ℃). Combined with the regional geological background, about 170 ～ 140 Ma, the lithosphere in the southern margin of Songpan Ganzi block is in the extension stage. The granite magma activity dominated in the early stage (163 Ma) by Huajiaoping granite, and in the late stage (146 Ma) by magmatism or tectonic thermal events. This discovery enriched the Yanshannian granitic magmatic thermal events in Jiulong area.

This is an article in the field of earth sciences. Taka dome and Jianglang dome are located in the southern margin of Songpan-Ganzi block, and their geological characteristics indicate similar composition and metamorphic-deformation characteristics. Liwu, Heiniudong and Zhongsui deposits have been found in Jianglang Dome, while no similar deposits have been found in the same horizon of Taka Dome. To investigate the medium-deep part structure characteristics and mineralization of the Taka Dome, the geophysical electrical parameters and audio magnetotelluric sounding profiles of different strata of different ages were measured to obtain the electrical characteristics of the middle and deep subsurface. The results show that the overall characteristics of the dome are low and medium resistance on both sides, and high resistance in the core is mainly mixed with low resistance. The overall electrical characteristics are consistent with the spatiotemporal law of the dome structure. There are three main low-resistivity anomaly zones in the deep electrical profile, which are inferred to reflect the low-resistivity lithology, fault or structural fracture zone. The three main high-resistivity anomaly belts are inferred to be reflected by the upper member of the Mesoproterozoic Liwu Group (Pt2l3) with complete medium-high resistivity characteristics in the Taka dome. The above understanding provides geophysical evidence for exploring the medium-deep geological spatial structure of the Taka Dome.

Abstract Background Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. Methods To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition. In molecular level, the synaptic injury and autophagic defects were evaluated. To address the Meth induced neuronal damage, the epidermal growth factor receptor (EGFR) degradation assay was performed to evaluate the degradability of the “cargos” mediated by Meth, and mechanistically, the maturation of the vesicles, including autophagosomes and endosomes, were validated by the Co-IP and the GTP-agarose affinity isolation assays. Results Overexpression of Stx17 in the hippocampus markedly rescued the Meth-induced cognitive impairment and synaptic loss. For endosomes, Meth exposure upregulated Rab5 expression and its guanine-nucleotide exchange factor (GEF) (immature endosome), with a commensurate decreased active form of Rab7 (Rab7-GTP) and impeded the binding of Rab7 to CCZ1 (mature endosome); for autophagosomes, Meth treatment elicited a dramatic reduction in the overlap between Stx17 and autophagosomes but increased the colocalization of ATG5 and autophagosomes (immature autophagosomes). After Stx17 overexpression, the Rab7-GTP levels in purified late endosomes were substantially increased in parallel with the elevated mature autophagosomes, facilitating cargo (Aβ42, p-tau, and EGFR) degradation in the vesicles, which finally ameliorated Meth-induced synaptic loss and memory deficits in mice. Conclusion Stx17 decrease mediated by Meth contributes to vesicle fusion defects which may ascribe to the immature autophagosomes and endosomes, leading to autophagic dysfunction and finalizes neuronal damage and cognitive impairments. Therefore, targeting Stx17 may be a novel therapeutic strategy for Meth-induced neuronal injury.

The traditional dynamic window approach (DWA) adopts the constant intervals for the sampling window, which limits the trajectory exploration possibility. This paper employs the twin delayed deep deterministic policy gradient (TD3) approach to generate a reinforcement-learning-based auxiliary candidate trajectory with variable sampling mechanism in the prediction domain for the automated guided vehicle (AGV). Subsequently, this auxiliary trajectory would compete with the traditional DWA sampling trajectories in the optimal evaluation. The proposed method significantly reduces computational costs while expanding the search space of the DWA scheme, which improving sampling utilization efficiency and planning effectiveness. In contrast to completed data-driven methods that directly generate planning solutions through the policy networks, the proposed method overall ensures planning effectiveness by the DWA mechanism unit and demonstrates superior generalization capabilities. Simulation results reveal that the proposed reinforcement-learning-based DWA generates the improvement with 11.97% in planning reward and 17.46% in calculation efficiency towards the traditional DWA approach, which demonstrating a significant performance improvement over the traditional DWA method in AGV local planning mission.

As a preventive maintenance treatment, the ultra-thin porous friction course (UPFC) has been widely recognized and used in road maintenance because of its excellent performance and cost effectiveness. The Marshall compaction method (MCM) has been adopted to design UPFC mixtures worldwide, particularly in China. However, there are few studies concerning the field compaction properties of MCM-designed UPFCs. The laboratory test results of this study from simulating on-site compaction showed that all UPFC specimens with thicknesses of less than 20 mm barely achieved the target compaction thickness, and all UPFC specimens with different thicknesses failed to meet the air void (AV) requirements of UPFC mixes designed using the MCM. According to the results of a virtual compaction test, and using the discrete element method, the strong force chains were strengthened as the UPFC thickness decreased inside the specimen, making it difficult to evenly diffuse and transfer inside the specimen and resulting in insufficient compaction of the UPFC. Furthermore, it was demonstrated that the MCM-designed UPFC specimens showed significant differences in the AV distributions along the vertical and lateral directions from those of the UPFC specimens that simulated field compaction. The UPFCs designed using the MCM had a poor correlation with field compaction.

A growing body of evidence shows that cigarette smoking impairs cognitive performance. The 'Calcium Hypothesis' theory of neuronopathies reveals a critical role of aberrant calcium signaling in compromised cognitive functions. However, the underlying implications of abnormalities in calcium signaling in the neurotoxicity induced by cigarette smoke (CS) have not yet been identified. CACNA2D1, an important auxiliary subunit involved in the composition of voltage-gated calcium channels (VGCCs), was reported to affect the calcium signaling in neurons by facilitating VGCCs-mediated Ca2+ influx. ΔFOSB, an alternatively-spliced product of the Fosb gene, is an activity-dependent transcription factor induced robustly in the brain in response to environmental stimuli such as CS. Interestingly, our preliminary bioinformatics analysis revealed a significant co-expression between ΔFOSB and CACNA2D1 in brain tissues of patients with neurodegenerative diseases characterized by progressive cognitive decline. Therefore, we hypothesized that the activation of the ΔFOSB-CACNA2D1 axis in response to CS exposure might cause dysregulation of calcium homeostasis in hippocampal neurons via VGCCs-mediated Ca2+ influx, thereby contributing to cognitive deficits. To this end, the present study established a CS-induced mouse model of hippocampus-dependent cognitive impairment, in which the activation of the ΔFOSB-CACNA2D1 axis accompanied by severe calcium overload was observed in the mouse hippocampal tissues. More importantly, ΔFOSB knockdown-/overexpression-mediated inactivation/activation of the ΔFOSB-CACNA2D1 axis interdicted/mimicked CS-induced dysregulation of calcium homeostasis followed by severe cellular damage in HT22 mouse hippocampal neurons. Mechanistically speaking, a further ChIP-qPCR assay confirmed the physical interaction between transcription factor ΔFOSB and the Cacna2d1 gene promoter, suggesting a direct transcriptional regulation of the Cacna2d1 gene by ΔFOSB. Overall, our current work aims to deliver a unique insight into the neurotoxic mechanisms induced by CS to explore potential targets for intervention.

In the course of asphalt pavement usage, exposure to fuel infiltration accelerates particle detachment, leading to the occurrence of problems such as looseness and peeling. The aim of this study was to comprehensively evaluate the impact of a fuel-resistant modifier (FRM; 1%, 3%, 5%, 7%) on the performance of asphalt and asphalt mixture. Conventional physical tests and high–low temperature rheological tests were conducted on the fuel-resistant modified asphalt (FRMA). The results indicate that, with increased FRM content, the penetration and ductility of FRMA decreased, while the softening point increased. The high-temperature performance improved, but the low-temperature ductility declined. High–low temperature rheological test results demonstrate that the addition of FRM significantly enhanced the asphalt’s shear deformation resistance. A moderate amount of FRM modification improved the asphalt’s low-temperature crack resistance, but excessive FRM resulted in reduced flexibility. In addition, fuel-resistant modified asphalt mixture (FRMAM) specimens were prepared and evaluated for performance. In comparison to the base asphalt, FRM modification enhanced the resistance to oil erosion and peeling as well as the Marshall stability of asphalt mixtures. It reduced the scattering loss caused by fuel dissolution and improved both low-temperature indirect tensile (IDT) strength and high-temperature shear strength. A low content of FRM effectively reduced the sensitivity of asphalt mixtures to fuel infiltration, thus enhancing their road performance.

Because of its uneven and large slope, unstructured pavement presents a great challenge to obtaining the adhesion coefficient of pavement. An estimation method of the peak adhesion coefficient of unstructured pavement on the basis of the extended Kalman filter is proposed in this paper. The identification accuracy of road adhesion coefficients under unstructured pavement is improved by introducing the equivalent suspension model to optimize the calculation of vertical wheel load and modifying vehicle acceleration combined with vehicle posture data. Finally, the multi-condition simulation experiments with Carsim are conducted, the estimation accuracy of the adhesion coefficient is at least improved by 3.6%, and then the precision and effectiveness of the designed algorithm in the article are verified.

Unmanned transportation in construction scenarios presents a significant challenge due to the presence of complex dynamic on-ground obstacles and potential airborne falling objects. Consequently, the typical methodology for composite air–ground risk avoidance in construction scenarios holds enormous importance. In this paper, an integrated potential-field-based risk assessment approach is proposed to evaluate the threat severity of the environmental obstacles. Meanwhile, the self-adaptive dynamic window approach is suggested to manage the real-time motion planning solution for air–ground risks. By designing the multi-objective velocity sample window, we constrain the vehicle’s speed planning instructions within reasonable limits. Combined with a hierarchical decision-making mechanism, this approach achieves effective obstacle avoidance with multiple drive modes. Simulation results demonstrate that, in comparison with the traditional dynamic window approach, the proposed method offers enhanced stability and efficiency in risk avoidance, underlining its notable safety and effectiveness.

The optimal preventive maintenance timing of traditional asphalt pavement is based on the maximum benefit-cost ratio. For cost evaluation indicators, mainly agency cost and user cost, use life cycle cost analysis (LCCA) to determine. The environmental impact of pavement preventive maintenance activities is often overlooked. For the benefit evaluation index, only the new area under the performance curve is used to express the maintenance benefit, and the benefit evaluation index is single. This study proposes an integrated approach combining life cycle assessment (LCA) and LCCA to model preventive maintenance timing decisions considering economic, social, and environmental factors. In this paper, LCA is used to quantitatively analyze the energy consumption and emissions in the pavement operation and maintenance process, and the environmental costs are also included in the accounting scope of the costs. The costs that constitute pavement use are analyzed from three aspects: the agency cost, the user cost, and the environmental cost. At the same time, in the process of constructing the cost model, the costs caused by the maintenance construction process to users and the environment are also taken into consideration. Aiming at the benefit index and comprehensively considering the economic benefits, social benefits, and environmental benefits brought by maintenance, a comprehensive evaluation model of maintenance benefits was constructed based on the analytic hierarchy process (AHP). On the basis of accurately calculating the cost and benefit of maintenance in the life cycle, the model of the optimal preventive maintenance timing of asphalt pavement is constructed so as to calculate the optimal timing of preventive maintenance and provide certain information for the formulation of expressway pavement preventive maintenance programs. For reference. Taking a highway project in China as an example to verify the applicability of the model

Background: Electrocardiogram (ECG) provides a straightforward and non-invasive approach for various applications, such as disease classification, biometric identification, emotion recognition, and so on. In recent years, artificial intelligence (AI) shows excellent performance and plays an increasingly important role in electrocardiogram research as well.Objective: This study mainly adopts the literature on the applications of artificial intelligence in electrocardiogram research to focus on the development process through bibliometric and visual knowledge graph methods.Methods: The 2,229 publications collected from the Web of Science Core Collection (WoSCC) database until 2021 are employed as the research objects, and a comprehensive metrology and visualization analysis based on CiteSpace (version 6.1. R3) and VOSviewer (version 1.6.18) platform, which were conducted to explore the co-authorship, co-occurrence and co-citation of countries/regions, institutions, authors, journals, categories, references and keywords regarding artificial intelligence applied in electrocardiogram.Results: In the recent 4 years, both the annual publications and citations of artificial intelligence in electrocardiogram sharply increased. China published the most articles while Singapore had the highest ACP (average citations per article). The most productive institution and authors were Ngee Ann Polytech from Singapore and Acharya U. Rajendra from the University of Technology Sydney. The journal Computers in Biology and Medicine published the most influential publications, and the subject with the most published articles are distributed in Engineering Electrical Electronic. The evolution of research hotspots was analyzed by co-citation references’ cluster knowledge visualization domain map. In addition, deep learning, attention mechanism, data augmentation, and so on were the focuses of recent research through the co-occurrence of keywords.

As an infrastructure project, the cost and benefits of road maintenance should be measured through social costs. In order to fully consider user interests and make road maintenance decisions more reasonable, two types of user costs that may affect road maintenance benefits have been quantified through analysis of existing literature. At the same time, environmental issues have gradually become the focus of various industries, and in optimizing road maintenance decisions, the impact of environmental issues on decision making should also be considered. This article first analyzes and quantifies the user costs that affect the effectiveness of road maintenance. Secondly, based on the concept of sustainable development of roads, the optimization of road maintenance decisions is divided into two steps: the first step is to determine the minimum maintenance budget funds, and the second step is to determine the optimal plan. The specific optimization method is to use the 0-1 mathematical programming method to establish a network-level pavement maintenance decision optimization model based on a quantitative model. The most reasonable maintenance optimization plan is determined from four aspects: maintenance funds, maintenance performance improvement value, user benefit improvement, and reducing environmental impact. Finally, a provincial road network for a case study is selected. The applicability of the new model is verified through a case study. This study can help decision makers deal with asphalt pavement maintenance arrangements at the network level with four decision objectives: maintenance funds, pavement performance, road users, and environmental impacts.

Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by the calcification and ossification of ligaments and tendons. Progressive dysphagia caused by DISH-related anterior cervical osteophytes and deteriorating dysphagia caused by DISH combined with neurological dysfunction resulting from the posterior longitudinal ligament is rare. The initial diagnosis is misleading and patients often consult several specialists before spine surgeons. This study aims to provide a comprehensive review of the literature on this challenging pathological association. We also present a case illustration where a 53-year-old man presented with progressive dysphagia and foreign body sensation in the pharynx, accompanied by a neurological numbness defect in the right upper limb. Radiography and computed tomography confirmed the existence of osteophytes at the anterior edge of the C4–C7 pyramid and ossification of the posterior longitudinal ligament, in which the giant coracoid osteophyte could be seen at the anterior edge of the C4–C5 pyramid. The anterior cervical osteophyte was removed, and decompression and fusion were performed. The symptoms were relieved postoperatively. No recurrence of symptoms was found during the six-month follow-up. Spine surgeons should consider progressive dysphagia caused by DISH-related osteophytes at the anterior edge of the cervical spine as it is easily misdiagnosed and often missed on the first evaluation. When combined with ossification of the posterior longitudinal ligament, following cervical osteophyte resection it is necessary to consider stabilizing the corresponding segments via fusion.

Coal accounted for around 80 percent of power production in Poland in 2018. Facing the serious climate problem and pressure from all sides, Poland has laid out a long-term energy strategy: reducing the proportion of coal in electricity production to about 60% by 2030. However, considering the history of Poland’s dependence on coal and blank in the field of forecasting Polish coal consumption, many researchers and politicians have shown worry about this commitment. Therefore, we proposed a novel time series prediction method ‘ASR’ which combined Adaptive Boosting, Simulated Annealing and Relevance Vector Machine. ASR inherited the advantages of the three algorithms and was applied to predict carbon consumption in Poland. To confirm the effectiveness of ASR, we compared ASR with several previous methods by two experiments using the Polish coal consumption data from 1965 to 2018. The experimental results showed that the mean absolute error of ASR was 1.2% in executing single point prediction and 5.8% in long-term prediction, which were much lower than previous methods. After verifying ASR, finally, we trained a final ASR model to predict the coal consumption of Poland with 95% confidence interval from 2019 to 2030. Results showed Poland is likely to fulfill its promises under current policy.

Polar codes have been applied for physical downlink control channel in the 5th generation wireless communication system. Although successive cancellation flip (SCF) decoding algorithm can improve decoding performance of polar codes, it has also led to the increasing in decoding latency and calculation complexity. Candidate flipping positions set (CFPS) of traditional SCF decoding is consisted of indexes of all information bits. However, some subchannels are reliable enough so that it is almost impossible to cause decoding errors for these subchannels. In order to reduce decoding latency and calculation complexity of SCF decoding algorithm, a new method of constructing the CFPS based on genetic algorithm (GA) is proposed in this paper. What's more, the paper fills a gap of applying GA for decoding of polar codes. In our proposed method, indexes of all information bits are used as individuals of GA. Then through some genetic operations, a vector that can indicate the reliability of all information bits is obtained. Based on the obtained vector, a new CFPS is constructed. Simulation results show that SCF decoding algorithm based on CFPS constructed by GA can achieve competitive decoding performance, while keeping lower calculation complexity and decoding latency. Compared with SCF decoding algorithm based on critical set, the normalized decoding latency of proposed SCF decoding algorithm can be reduced by 39% at 1.5dB when code length and code rate are equal to 1024 and 0.5, respectively.

Pancreatic cancer (PC) is one of the most aggressive malignancies. A combination of targeted therapies could increase the therapeutic efficacy in tumors with heterogeneous target expression. Overexpression of the human epidermal growth factor receptor type 3 (HER3) and the epithelial cell adhesion molecule (EpCAM) in up to 40% and 30% of PCs, respectively, is associated with poor prognosis and highlights the relevance of these targets. Designed ankyrin repeat protein (DARPin) Ec1 fused with the low immunogenic bacterial toxin LoPE provides specific and potent cytotoxicity against EpCAM-expressing cancer cells. Here, we investigated whether the co-targeting of HER3 using the monoclonal antibody seribantumab (MM-121) and of EpCAM using Ec1–LoPE would improve the therapeutic efficacy in comparison to the individual agents. Radiolabeled 99mTc(CO)3-Ec1–LoPE showed specific binding with rapid internalization in EpCAM-expressing PC cells. MM-121 did not interfere with the binding of Ec1–LoPE to EpCAM. Evaluation of cytotoxicity indicated synergism between Ec1–LoPE and MM-121 in vitro. An experimental therapy study using Ec1–LoPE and MM-121 in mice bearing EpCAM- and HER3-expressing BxPC3 xenografts demonstrated the feasibility of the therapy. Further development of the co-targeting approach using HER3 and EpCAM could therefore be justified.

Shock reflected by a spherical interface is involved in shock-droplet interaction. Here, we investigate the pressure dynamics of an internal spherical shock wave and the potential cavitation inside a spherical water droplet. We conduct hydrodynamic simulation and employ the linear geometrical acoustics approximation to analyze the negative pressure and the wavefront at different intervals d between the source point of the shock and the droplet surface. Studies indicate that the negative pressure at a very large d is primarily attributed to the focusing effect of the droplet surface, whereas the collision of the reflected waves contributes to negative pressure at a small d . The caustic, which is the locus of the cusps (singular points) on the shock wavefront is determined by the parametric equations. Notably, the caustic also has singular points owing to the off-axis reflection. Finally, we evaluate the cavitation inside the droplet. Cavitation occurs on the opposite side of the droplet and moves away from the surface with d increasing, which agrees with previous experimental results. Additionally, we demonstrate that cavitation can occur with less damage to the droplet compared to a planar shock impact on a water droplet.

Extracellular vesicles are commonly found in human body fluids and can reflect current physiological conditions of human body and act as biomarkers of disease. The quality of isolated extracellular vesicles facilitates the early diagnosis of various diseases accompanied by hyperlipidemia. Nonetheless, there are no reports on which special methods are suitable for isolating extracellular vesicles from the plasma of patients with hyperlipidemia. Thus, this study compared three different research-based extracellular vesicle isolation approaches, namely ultracentrifugation (UC), polyethylene glycol (PEG) precipitation, and size exclusion chromatography (SEC), and determined which of them was the most effective method. We selected blood samples from 12 patients with clinically diagnosed hyperlipidemia and isolated plasma-derived extracellular vesicles using three methods. The morphology of the isolated extracellular vesicles was observed using transmission electron microscopy, while the concentration was detected by asymmetric flow field-flow fractionation and multi-angle light scattering. Marker proteins were identified by Western blotting, and protein composition was evaluated by silver staining. Both determined the contaminations in the extracellular vesicle samples. The results showed that the three methods can be successfully used for the isolation of extracellular vesicles. The extracellular vesicles isolated by UC were larger in size, and the yield was much lower. Although the yield of extracellular vesicles isolated by PEG precipitation was greatly improved, the contamination was increased. Of the three methods, only the SEC-isolated extracellular vesicles were characterized by high yield and low contamination. Therefore, our data suggested that the SEC was a more ideal method for isolating extracellular vesicles from the plasma of patients with hyperlipidemia.

In this paper, we study a proposal put forward recently by Bodendorfer, Mele and Münch and García-Quismondo and Marugán, in which the two polymerization parameters of spherically symmetric black hole spacetimes are the Dirac observables of the four-dimensional Ashtekar’s variables. In this model, black and white hole horizons in general exist and naturally divide the spacetime into the external and internal regions. In the external region, the spacetime can be made asymptotically flat by properly choosing the dependence of the two polymerization parameters on the Ashtekar variables. Then, we find that the asymptotical behavior of the spacetime is universal, and, to the leading order, the curvature invariants are independent of the mass parameter m. For example, the Kretschmann scalar approaches zero as K≃A0r−4 asymptotically, where A0 is generally a non-zero constant and independent of m, and r the geometric radius of the two-spheres. In the internal region, all the physical quantities are finite, and the Schwarzschild black hole singularity is replaced by a transition surface whose radius is always finite and non-zero. The quantum gravitational effects are negligible near the black hole horizon for very massive black holes. However, the behavior of the spacetime across the transition surface is significantly different from all loop quantum black holes studied so far. In particular, the location of the maximum amplitude of the curvature scalars is displaced from the transition surface and depends on m; so does the maximum amplitude. In addition, the radius of the white hole is much smaller than that of the black hole, and its exact value sensitively depends on m, too.

60NiTi alloys have a tremendous potential to be used in aerospace, marine and automotive industries. There is still a need to further improve the deformability due to the high brittleness of the previously prepared 60NiTi. In this work, 200 °C hot silicone oil was selected as the quenching medium for 60NiTi for the first time to overcome its high brittleness. It is found that the unique microstructure of 60NiTi quenched by hot oil has a lamellar structure composed of a channel-like NiTi matrix and lenticular Ni4Ti3 phase containing a nano-lath NiTi phase. The 60NiTi exhibits a high compression fracture strain of 10% and large reversible strain of 7.5%; which originates from the superelastic behavior of the NiTi SMA constituent. Upon loading, the R phase reorientation releases the stress concentration at the initial stage; while the stress-induced martensitic transformation accommodates the large elastic deformation of the Ni4Ti3 phase at the later stage. This synergistic effect of the two promotes the compressive deformability.

Abstract Metallic Sn has provoked tremendous progress as an anode material for sodium-ion batteries (SIBs). However, Sn anodes suffer from a dramatic capacity fading, owing to pulverization induced by drastic volume expansion during cycling. Herein, a flexible three-dimensional (3D) hierarchical conductive network electrode is designed by constructing Sn quantum dots (QDs) encapsulated in one-dimensional N,S co-doped carbon nanofibers (NS-CNFs) sheathed within two-dimensional (2D) reduced graphene oxide (rGO) scrolls. In this ingenious strategy, 1D NS-CNFs are regarded as building blocks to prevent the aggregation and pulverization of Sn QDs during sodiation/desodiation, 2D rGO acts as electrical roads and “bridges” among NS-CNFs to improve the conductivity of the electrode and enlarge the contact area with electrolyte. Because of the unique structural merits, the flexible 3D hierarchical conductive network was directly used as binder- and current collector-free anode for SIBs, exhibiting ultra-long cycling life (373 mAh g−1 after 5000 cycles at 1 A g−1), and excellent high-rate capability (189 mAh g−1 at 10 A g−1). This work provides a facile and efficient engineering method to construct 3D hierarchical conductive electrodes for other flexible energy storage devices.

Abstract The remaining useful life (RUL) prediction of mechanical products has been widely studied for online system performance reliability, device remanufacturing, and product safety (safety awareness and safety improvement). These studies incorporated many different models, algorithms, and techniques for modeling and assessment. In this paper, methods of RUL assessment are summarized and expounded upon using two major methods: physics model based and data driven based methods. The advantages and disadvantages of each of these methods are deliberated and compared as well. Due to the intricacy of failure mechanism in system, and difficulty in physics degradation observation, RUL assessment based on observations of performance variables turns into a science in evaluating the degradation. A modeling method from control systems, the state space model (SSM), as a first order hidden Markov, is presented. In the context of non-linear and non-Gaussian systems, the SSM methodology is capable of performing remaining life assessment by using Bayesian estimation (sequential Monte Carlo). Being effective for non-linear and non-Gaussian dynamics, the methodology can perform the assessment recursively online for applications in CBM (condition based maintenance), PHM (prognostics and health management), remanufacturing, and system performance reliability. Finally, the discussion raises concerns regarding online sensing data for SSM modeling and assessment of RUL.

Herein, we investigated experimentally the dynamics of three laser-induced, same-sized, symmetrically aligned, and synchronized bubbles. Three synchronized laser beams split from the same beam using a Diffractive Optical Element splitter were focused on water, and then we obtained three bubbles. Another nanosecond laser pulse was used to probe the bubbles to obtain shadowgraphs. The exact delay of the excited and detected light was controlled using a delay generator. The results revealed that the maximum volumes of bubbles in arrays decrease as the normalized distance falls, while the lifetimes and translation increase. It was explained by the interaction between the acoustic radiation of bubbles and the surrounding bubbles. The shrinkage of linear bubble arrays exists an anomaly. The center bubbles were stretched, to ellipsoid, stick, even fractured, by the peripheral bubbles. The closer they are, the more distinct is the above phenomenon. However, when the normalized distance was sufficiently small, instead of being stretched, the center bubbles were compressed to disk shape and thus shrank with the whole array. Finally, the dependence of the distance on the energy transfer of the bubble system is also discussed.

In IoT applications, energy supply, especially wireless power transfer (WPT), has attracted the most attention in the relevant literature. In this paper, we present a new approach to laser irradiance solar cell panels and predicting energy transfer efficiency. From the previous experimental datasets, it has been discovered that in the laser charging (LC) process, temperature has a great impact on the efficiency, which is highly correlated with the laser intensity. Then, based on artificial neural network (ANN), we set the above temperature and laser intensity as inputs, and the efficiency as output through back propagation (BP) algorithm, and use neural network and BP to train and modify the network parameters to approach the real efficiency value. We also propose the genetic algorithm (GA) to optimize the learning rate of the BP, which achieved slightly superior results. The results of the experiment indicate that the prediction method reaches a high accuracy of about 99.4%. The research results in this paper provide an improved solution for the LC application, particularly the energy supply of IoT devices or small electronic devices through WPT.

This paper analyses the mechanical and mathematical models in Yanbin Wang et al.‘s six papers on mechanical analysis of marine riser: “Wang, Yanbin, Gao, Deli, Fang, Jun 2014. Static analysis of deep-water marine riser subjected to both axial and lateral forces in its installation. J. Nat. Gas Sci. Eng. 19, 84–90”, “Wang, Yanbin, Gao, Deli, Fang, Jun 2014. Axial dynamic analysis of marine riser in installation. J. Nat. Gas Sci. Eng. 21, 112–117”, “Wang, Yanbin, Gao, Deli, Fang, Jun 2015. Coupled dynamic analysis of deepwater drilling riser under combined forcing and parametric excitation. J. Nat. Gas Sci. Eng. 27, 1739–1747”, “Wang, Yanbin, Gao, Deli, Fang, Jun 2015. Study on lateral vibration analysis of marine riser in installation-via variational approach. J. Nat. Gas Sci. Eng. 22, 523–529”, “Wang, Yanbin, Gao, Deli, Fang, Jun 2015. Mechanical behavior analysis for the determination of riser installation window in offshore drilling. J. Nat. Gas Sci. Eng. 24, 317–323”, and “Wang, Yanbin, Gao, Deli, Fang, Jun 2015. Finite element analysis of deepwater conductor bearing capacity to analyze the subsea wellhead stability with consideration of contact interface models between pile and soil. J. Pet. Sci. Eng. 126, 48–54”; and finds that the mechanical and mathematical models described in these papers are clearly incorrect. Therefore, new mechanical and mathematical models have been suggested in this study. Keywords: Marine riser, Mechanical analysis, Mechanical model, Mathematical model

Abstract Background Guang-Pheretima, which is originated from Pheretima aspergillum, has been documented in academic Chinese herbal studies for nearly 2000 years for its prominent treating effects of various inflammatory diseases such as asthma, cough and fever. However, the anti-inflammatory activity and mechanism of Guang-Pheretima has been rarely reported. Hence, we investigated the inhibitory effect and the underlying mechanism of Guang-Pheretima aqueous extracts on inflammatory response in RAW 264.7 cells. Method RAW 264.7 macrophages were pretreated with various concentrations of Guang-Pheretima decoction (GPD) or protein-free Guang-Pheretima decoction (PF-GPD) and subsequently stimulated with lipopolysaccharide (LPS) to trigger the inflammatory response. Productions of nitric oxide (NO) were determined by Griess reaction, and prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 were measured by enzyme-linked immunosorbent assays (ELISA). The protein expressions and messenger ribonucleic acid (mRNA) amounts of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were analyzed by Western Blot and Real-Time polymerase chain reaction (PCR), respectively. Finally, the translocation of nuclear factor (NF)-κB was observed by Western Blot. Results GPD of the experimental concentrations showed no anti-inflammatory activity. In contrast, PF-GPD at concentrations of 40–320 μg/mL significantly inhibited NF-κB activation and reduced the production of inflammatory mediators, such as NO, PGE2, TNF-α, as well as the related key synthases including iNOS and COX-2. Moreover, PF-GPD markedly suppressed the release of inflammatory cytokines, such as IL-1β and IL-6. Conclusion These results demonstrate the excellent anti-inflammatory properties of PF-GPD, and suggest that Guang-Pheretima may be used to treat and prevent certain inflammatory diseases.

The parameters of In0.3Ga0.7As PV cell applied in laser wireless power transmission (LWPT) system dependence on temperature was investigated at a temperature range of 5-90°C under 100mW/cm2 laser intensity with 1070nm wavelength. The pollination algorithm method was used to extract parameters, viz., photocurrent, series and shunt resistance, reverse saturation current, and ideality factor from the I-V curves at each temperature point. The results show that the short circuit current decrease exponentially with temperature increasing, which is obviously different from the condition with solar irradiation. As temperature increases, the conversion efficiency and the open circuit voltage decreases linearly at the rate of 0.095%/°C and 1.89mV/°C, respectively. In addition, the dependence of series and shunt resistance, ideality factor, and fill factor on temperature was also analyzed. This research gives us a new understanding of PV cells under laser irradiation condition, also provides a direction for manufacturing the cells used in LWPT system.

The alterations of wettability on metallic nickel surface by sub-nanosecond laser (1 ns, 1064 nm) induced surface modification was investigated. An approximate linear relation between surface contact angles (CAs) and accumulated fluence was established, which shows that with proper combinations of laser parameters, CA would reduce significantly from its initial value (∼96°) to approximately 3.1°. The microscopic inspection and roughness test reveal that the surface roughness on irradiated areas would increase remarkably due to the distribution of micro/nanoparticels and cracks that induced by laser ablation, which consequently improve the hydrophilic performance effectively. On the other hand, elemental analyses by use of XPS demonstrate that the nickel dioxides and nickel hydroxides were generated as the main components covering the self-organized structures. Such increasement in oxygen content, especially the growth of NiO and hydroxyl group provides a prerequisite in the transformation of nickel from initial hydrophobicity to hydrophilicity. And the integrated effects of surface morphology, roughness and chemistry ultimately led to the formation of super-wettability. The investigation indicates that, the sub-nanosecond laser is an effective tool to transform the metallic nickel into functional material with a highly hydrophilic surface by creating controllable topographical features and chemical properties on its surface.

The ultrasound-assisted preparation of a curcumin-loaded metal organic framework (MOF) UiO-66-NH2 stabilized Pickering emulsion system was carried out in this study. A 3-level-4-factor Box–Behnken design (BBD) and response surface methodology (RSM) analysis were employed to systematically evaluate the effect of different experimental parameters (i.e., ultrasonic power, ultrasonic time, oil content, and MOF content) on curcumin loading capacity (LC) and encapsulation efficiency (EE). The results indicated that ultrasonic power and MOF content significantly affected LC and EE, whereas ultrasonic time and oil content had little effect. A mathematical model for optimizing the preparation of emulsion systems was established. Based on the ridge max analysis, an optimal condition for the newly developed curcumin-loaded MOF-Pickering emulsion was identified, i.e., ultrasonic power 150 W, ultrasonic time 11.17 min, oil content 20.0%, and MOF content 1.10%. At this condition, the LC and EE of curcumin obtained from the experiment reached 7.33% ± 0.54% and 56.18% ± 3.03%, respectively, which were within the prediction range of LC (7.35% ± 0.29%) and EE (54.34% ± 2.45%). The emulsion systems created in this study may find new applications for the delivery of bioactive compounds in food and pharmaceutical areas.

The Ni-based coatings with different content of spherical tungsten carbide were deposited by plasma transfer arc welding (PTAW) method on 304 austenitic stainless steel sheets in this study. The microstructure and wear property of spherical tungsten carbide particle reinforced composite coatings were investigated by means of optical microscope, scanning electron microscope (SEM), X-ray diffraction (XRD), electron probe microanalysis (EPMA) and sliding wear test. It is shown that the fraction of spherical tungsten carbides has an important influence on microstructure of Ni-based overlay. The Ni40 overlay consists of γ-Ni dendrites with interdendritic Ni-based eutectics, borides and carbides improving the wear resistance. In the case of composite coatings with different content of tungsten carbide, many new phases are observed, such as Ni2W4C and NiW. In addition, there are a large number of irregular structures in composite coatings, such as acicular structure and irregular stripe organization. The results of sliding wear test indicate that the mass loss of coatings is influenced by the content of tungsten carbide. The mass loss decreases with the increase of tungsten carbide fraction. At high load, the abrasive resistance of composite coating with 60 wt. % tungsten carbide is improved about 50-fold compared to that of Ni40 overlay.

Platelet-derived growth factor (PDGF) plays an essential role in proliferation of vascular smooth muscle cells (VSMCs). The Rb/E2F and TSC/mTOR pathways contribute to the proliferation of VSMCs, but its exact roles in PDGF-induced proliferation are unclear. In this study, we demonstrated the roles of Rb/E2F and TSC/mTOR pathways in PDGF-induced proliferation in VSMCs. We found that PDGF stimulates the activity of E2F and mTOR pathways, and knockdown of either Rb or TSC2 increases PDGF-induced proliferation in VSMCs. More interestingly, we revealed that enhancing both E2F and mTOR activity leads to synergistic inhibition of PDGF-induced proliferation in VSMCs. We further identified that the synergistic inhibition effect is caused by the induced oxidative stress. Summarily, these data suggest the important regulations of Rb/E2F and TSC/mTOR pathways in PDGF-induced proliferation in VSMCs, and also present a promising way to limit deregulated proliferation by PDGF induction in VSMCs.

In the present study, a novel breeding strategy of atmospheric and room temperature plasma (ARTP) mutagenesis was used to improve the uridine production of engineered Bacillus subtilis TD12np. A high-throughput screening method was established using both resistant plates and 96-well microplates to select the ideal mutants with diverse phenotypes. Mutant F126 accumulated 5.7 and 30.3 g/L uridine after 30 h in shake-flask and 48 h in fed-batch fermentation, respectively, which represented a 4.4- and 8.7-fold increase over the parent strain. Sequence analysis of the pyrimidine nucleotide biosynthetic operon in the representative mutants showed that proline 1016 and glutamate 949 in the large subunit of B. subtilis carbamoyl phosphate synthetase were of importance for the allosteric regulation caused by uridine 5'-monophosphate. The proposed mutation method with efficient high-throughput screening assay was proved to be an appropriate strategy to obtain uridine-overproducing strain.

Previous data have proven that microvesicles derived from hypoxia-induced mesenchymal stem cells (MSC-MVs) can be internalized into endothelial cells, enhancing their proliferation and vessel structure formation and promoting in vivo angiogenesis. However, there is a paucity of information about how the MSC-MVs are up-taken by endothelial cells.MVs were prepared from the supernatants of human bone marrow MSCs that had been exposed to a hypoxic and/or serum-deprivation condition. The incorporation of hypoxia-induced MSC-MVs into human umbilical cord endothelial cells (HUVECs) was observed by flow cytometry and confocal microscopy in the presence or absence of recombinant human Annexin-V (Anx-V) and antibodies against human CD29 and CD44. Further, small interfering RNA (siRNA) targeted at Anx-V and PSR was delivered into HUVECs, or HUVECs were treated with a monoclonal antibody against phosphatidylserine receptor (PSR) and the cellular internalization of MVs was re-assessed.The addition of exogenous Anx-V could inhibit the uptake of MVs isolated from hypoxia-induced stem cells by HUVECs in a dose- and time-dependent manner, while the anti-CD29 and CD44 antibodies had no effect on the internalization process. The suppression was neither observed in Anx-V siRNA-transfected HUVECs, however, addition of anti-PSR antibody and PSR siRNA-transfected HUVECs greatly blocked the incorporation of MVs isolated from hypoxia-induced stem cells into HUVECs.PS on the MVs isolated from hypoxia-induced stem cells is the critical molecule in the uptake by HUVECs.

Although Si nanowires (NWs) arrays are superior candidates for visible light photocatalysis, reports about the photodegradation activity of various crystal-orientated Si NWs are still insufficient. Here, light-doped hydrogen-terminated Si NWs arrays with different crystal orientations were prepared via a metal-assisted chemical etching method (MACE), which simply modulated the concentration of the oxidizer, H2O2. Their dye photodegradation activities were systematically and comprehensively investigated. When compared with Si NWs arrays with crystal orientations of (110) and (111), Si NWs arrays with (100) crystal orientation exhibit a superior photodegradation activity and stability due to the anisotropy of optical and physical properties. The n-type Si NWs arrays exhibit better photodegradation activity than the p-type Si NWs arrays of the same crystal orientation and similar length. The results provide a further understanding of the synthesis of Si NWs arrays with various orientations, and the relationships between photodegradation activity/stability and crystal orientations.

A flexible acoustic pressure sensor was developed based on the change in electrical resistance of three-dimensional (3D) graphene change under the acoustic waves action. The sensor was constructed by 3D graphene foam (GF) wrapped in flexible polydimethylsiloxane (PDMS). Tuning forks and human physiological tests indicated that the acoustic pressure sensor can sensitively detect the deformation and the acoustic pressure in real time. The results are of significance to the development of graphene-based applications in the field of health monitoring, in vitro diagnostics, advanced therapies, and transient pressure detection.

With the increasing awareness of environmental protection and sustainable manufacturing, the environmental impact of laser additive manufacturing (LAM) technology has been attracting more and more attention. Aiming to quantitatively analyze the energy consumption and extract possible ways to save energy during the LAM process, this investigation studies the effects of input variables including laser power, scanning speed, and powder feed rate on the overall energy consumption during the laser deposition processes. Considering microhardness as a standard quality, the energy consumption of unit deposition volume (ECUDV, in J/mm3) is proposed as a measure for the average applied energy of the fabricated metal part. The potential energy-saving benefits of the ultrasonic vibration–assisted laser engineering net shaping (LENS) process are also examined in this paper. The experimental results suggest that the theoretical and actual values of the energy consumption present different trends along with the same input variables. It is possible to reduce the energy consumption and, at the same time, maintain a good part quality and the optimal combination of the parameters referring to Inconel 718 as a material is laser power of 300 W, scanning speed of 8.47 mm/s and powder feed rate of 4 rpm. When the geometry shaping and microhardness are selected as evaluating criterions, American Iron and Steel Institute (AISI) 4140 powder will cause the largest energy consumption per unit volume. The ultrasonic vibration–assisted LENS process cannot only improve the clad quality, but can also decrease the energy consumption to a considerable extent.