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For equine-assisted therapy, a bionic horse configuration is presented. A bionic horse’s single leg system has two degrees of freedom (DOFs), which is driven by a cam-linkage mechanism and can adjust the leg’s endpoint trajectory. Based on analyzing the motion law of the bionic horse and the foot trajectory’s requirements of the leg system, a multi-objective optimization model is established based on the foot trajectory performance index. To determine the objective function, the errors between the ideal foot trajectory and the mechanism motion model’s foot trajectory, and the errors between the actual adjustable values and the target values for the motion range are taken as the optimization objective. In terms of the constraint conditions, the structural constraints, kinematic feasible region conditions, pressure angle requirements, et al., are considered. The ideal mechanism parameters are obtained by the intelligent optimization method. The results are verified by simulation modeling and experimental prototype, and the relevant ideas can provide a reference for the research of similar problems.

We present a new technique to self-mitigate the RF power variations in microwave photonic phase shifters (MPPS) based on microring resonators by exploiting the root problem of varying optical intensities at different optical phase shifts to harness a varying and opposing optical equalization gain. Whilst optical gain mediums are commonly present in microwave photonic systems to overcome optical loss, choosing an appropriate equalization gain point to strike a balance between the optical gain transformation of weak and preservation of strong signals allows the proposed system to effectively achieve minimal radio frequency (RF) power variation across all signals without interfering with the RF phase shifting operation. Simulation results show an inline MPPS based on the phase and amplitude of conventional resonant structures with a capability to successfully minimize the RF power variations by 80% for up to 25 dB of phase-dependent power variations throughout the full 360° phase tuning range. Experimental results verify the MPPS operation based on a single microring resonator by significantly reducing the large RF power variations from 9 dB to less than ±1.25 dB, while maintaining the same RF phase shifting operation. We then verify the use of the proposed inline MPPS to adaptively minimize the self-interference by optimizing the phase compensation in a self-interference cancellation system. We demonstrate a cancellation bandwidth of 100 MHz with peak in-band cancellation of up to 40 dB while exhibiting the capability to recover weak signals of interest at operating center frequencies ranging from 5-20 GHz.

The nonstructural proteins (Nsps) of porcine reproductive and respiratory syndrome virus (PRRSV) play essential roles in virus replication—a multistep process that requires the participation of host factors. It is of great significance for the development of antiviral drugs to characterize the host proteins that interact with PRRSV Nsps and their functions in PRRSV replication. Here, we determined that proteasome subunit β type 1 (PSMB1) interacted with viral Nsp12 to inhibit PRRSV replication in target and permissive cells. PSMB1 could be downregulated by PRRSV infection through interaction with the transcription factor EBF1. Proteasome and autophagy inhibitor assays showed that PSMB1 was regulated by the autophagic pathway to degrade Nsp12. Cotransfection of PSMB1 and Nsp12 increased the level of intracellular autophagy; both molecules were colocated in lysosomes. We also found that the selective autophagy cargo receptor protein NBR1 and E3 ubiquitin ligase STUB1 interacted with PSMB1 and Nsp12, respectively, in the autophagic degradation of Nsp12. Furthermore, the degradation of Nsp12 by PSMB1 was mainly dependent on the ubiquitination of Nsp12 at lysine site 130. Our results indicate for the first time that PSMB1 is an anti-PRRSV host protein that inhibits the replication of PRRSV by degradation of Nsp12 through the selective autophagy pathway. IMPORTANCE PRRS is a major threat to the global pig industry and urgently requires an effective and sustainable control strategy. PRRSV Nsps have important roles in viral RNA synthesis, proteinase activity, induction of replication-associated membrane rearrangements, replicative endoribonuclease activity, determination of virulence, and regulation of host immune response. Research associated with PRRSV Nsps can provide vital guidance to modify the PRRSV genome through reverse genetics in the development of vaccines and diagnostics. The function of Nsp12, which generally plays essential roles in virus replication, remains unclear. We demonstrated that PSMB1 interacted with and degraded Nsp12 through an autophagic pathway to inhibit PRRSV replication. Our data confirmed a novel antiviral function of PSMB1 and allowed us to elaborate on the roles of Nsp12 in PRRSV pathogenesis. These findings suggest a valid and highly conserved candidate target for the development of novel therapies and more effective vaccines and demonstrate the complex cross talk between selective autophagy and PRRSV infection.

Additional file 1: Supplementary figure 1. A diagram of the mechanism of the KS method, exhibiting a tumor tissue with a more mesenchymal phenotype. The lower ECDF curve represented the higher expression of mesenchymal gene signatures, thus the EMT score of the presented sample is positive. Supplementary figure 2. EMT scores were distributed unevenly when stratified by grade (A), histological subtype (B), MI (C) and molecular subtypes (D). LN: lymph node; MI: myometrial invasion; CNH: Copy-number high; CNL: copy-number low; MSI-H: microsatellite instability-high. Supplementary figure 3. Heatmap for ERGs between tumor samples from LN positive and negative cases (normalized for exhibition). ERG: EMT-related gene; LN: lymph node. Supplementary figure 4. A DAG displaying the relationship between BPs from GO analysis. DAG: directed acyclic graph. BP: biological process; GO: Gene Ontology. Supplementary figure 5. PPI network by Cytohubba, with top 5 hub genes highlighted by colors. PPI: protein–protein interaction. Supplementary figure 6. Calibration plot suggesting predicted probabilities of LNM corresponded closely to the actually observed proportions. LNM: lymph node metastasis. Supplementary figure 7. A significantly positive correlation between proteins and mRNA in members of the 7-gene signature based on CPTAC. X axis: mRNA, Y axis: protein. CPTAC: Clinical Proteomic Tumor Analysis Consortium.

We propose a new microwave photonic (MWP) sensor based on cascaded silicon-on-insulator microring resonators (MRRs) with the incorporation of a seamless auto-corrective MWP sideband processing scheme to achieve multi-parameter sensing with high sensitivity and high-resolution. By using two MRRs with different waveguide widths, we take advantage of the resulted dual resonances which are not only distinct, but also exhibit different sensitivities. A multi-parameter sensing model can thus be established by deriving the difference in the sensitivity slope of the resonance notch shifts. The technique enables dynamic MWP sideband processing to actively compensate for variations in the optical resonances where limited extinction ratios in the optical domain are mapped instantaneously into ultra-high rejection ratios in the RF spectrum. We then demonstrate the cascaded optical MRR based auto-correction assisted MWP sensor for the environmental sensing of both humidity and temperature variations. Besides negligible hysteresis effect, the humidity sensitivity of the sensor reached over 291 MHz/%RH for both MRRs, which is over 3.5 times that of the microdisk-based humidity sensor. With the aid of the seamless auto-correction mechanism, the dual RF notches with albeit different but very high sensitivities are well maintained over 50 dB of rejection ratio, thus preserving a consistently high resolution throughout the whole sensing range. Additionally, a complete sensing model for measuring both parameters is also established and verified experimentally. Results show the capability of the proposed high-resolution sensor scheme for independent measurand detection for multi-parameter sensing applications.

Catalytic steam reforming of propylene, benzene and toluene was investigated over Mn-Cr-O spinel oxides with different stoichiometry. The catalysts were structurally stable during reforming conditions except for Mn3O4, which reduced in situ to MnO. The Cr2O3 catalyst showed the highest initial rate for propylene reforming, whereas the Mn-rich Mn1.5Cr1.5O4 spinel was the most active and stable catalyst for aromatic reforming. Reforming rates of olefins and aromatics were comparable under 0.05 bar hydrocarbon and 0.40 bar steam at 873 K. The reforming rate of olefins and aromatics was first order in hydrocarbon and slightly inhibited by H2O, which is consistent with a Mars-van Krevelen type mechanism. Of the hydrocarbons investigated, only the rate of toluene reforming was negative first order in excess H2. Results from diffuse reflectance infrared Fourier transform spectroscopy of adsorbed toluene on a spinel catalyst suggest that H2 inhibits the rapid oxidation of the methyl group of toluene.

Vehicle emissions have become a significant source of air pollution in urban cities, especially in China. Mobile sources account for 45% of local fine particle emissions in the Chinese capital Beijing. The Beijing–Tianjin–Hebei (BTH) area, one of China’s most representative urban clusters, is suffering from severe air pollution. With the rapid growth of vehicle ownership in the past two decades, vehicle emissions in China have also undergone great changes under various management measures. The BTH region is also a place where mobile source emission management was carried out earlier. It is of important research value to understand the evolution trend of the vehicle ownerships in the BTH region and the actual effects of various management measures for the control of vehicle emissions. Due to the imperfect evaluation of the current vehicle emission limitation measures from 2000 to 2019, the vehicle emission inventory of the BTH region was established, and the major control measures in the BTH region were evaluated. Results showed that the vehicle ownership has been increasing year by year over the past 20 years, from 2.39 million in 2000 to 25.32 million in 2019, with an average annual growth rate of 13.24%. However, the pollutants discharged by motor vehicles showed a trend of first rising and then falling due to various measures except CO2. The unsynchronized control measures have resulted in huge differences in vehicle growth trends and emissions among Beijing, Tianjin and Hebei. The emissions of carbon monoxide (CO), volatile organic compounds (VOCs), nitrogen oxides (NOX), and particulate matter (PM10) in Beijing showed a trend of increasing first and then decreasing. The changes in these pollutants in Tianjin were similar to those in Beijing, but there was a secondary increase for NOX and PM10 in the later period. The discharge of all pollutants in Hebei Province showed a growing trend except sulfur dioxide (SO2). The major emission source of CO and VOCs in BTH was PCs, and the contribution rate of PCs to VOCs, reached 86.0–89.6% in 2019. Heavy-duty trucks (HDTs) and buses were the main sources of NOX emissions, contributing 78.2–85.4% of NOX in 2019. Eliminating high emission vehicles was the best control measure in the BTH Region, which had a good emission reduction effect on all pollutants. For sustainable development of the BTH region, it is suggested that Beijing, Tianjin and Hebei province implement vehicle control policies simultaneously and establish a joint management mechanism.

We present a novel workflow for forecasting production in unconventional reservoirs using reduced-order models and machine-learning. Our physics-informed machine-learning workflow addresses the challenges to real-time reservoir management in unconventionals, namely the lack of data (i.e., the time-frame for which the wells have been producing), and the significant computational expense of high-fidelity modeling. We do this by applying the machine-learning paradigm of transfer learning, where we combine fast, but less accurate reduced-order models with slow, but accurate high-fidelity models. We use the Patzek model (Proc Natl Acad Sci 11:19731–19736, https://doi.org/10.1073/pnas.1313380110, 2013) as the reduced-order model to generate synthetic production data and supplement this data with synthetic production data obtained from high-fidelity discrete fracture network simulations of the site of interest. Our results demonstrate that training with low-fidelity models is not sufficient for accurate forecasting, but transfer learning is able to augment the knowledge and perform well once trained with the small set of results from the high-fidelity model. Such a physics-informed machine-learning (PIML) workflow, grounded in physics, is a viable candidate for real-time history matching and production forecasting in a fractured shale gas reservoir.

Introduction The pseudorabies virus (PRV) gene encoding thymidine kinase (tk) is an important virulence-associated factor. Attenuation of PRV in susceptible animals is a frequent result of tk deletion. The aim of the study was to assess the pathogenicity of tk-deleted PRV in rats. Material and Methods Sprague Dawley rats were infected with the tk-deleted PRV strain SuHV-1 ΔTK:247via intranasal or intramuscular inoculation. PRV loads in ten tissues from dead and euthanised rats were determined using real-time PCR. Results Infection with SuHV-1 ΔTK:247 could cause death in rats. The 50% lethal dose (LD50) of SuHV-1 ΔTK:247 via intranasal inoculation was 103.16 TCID50 in rats. Intramuscular inoculation required a higher dose of SuHV-1 ΔTK:247 (105.0 TCID50). A high SuHV-1 ΔTK:247 titre was observed in the trigeminal ganglia or spinal cord of dead rats. Conclusion The results of this study show that rats are highly susceptible to PRV infection, and tk deletion did not completely diminish the pathogenicity of PRV in rats.

Alzheimer's disease (AD) has become a major public health problem affecting the elderly population, and there is currently no effective treatment. Although the pathogenesis of AD is unclear, neurotoxicity induced by oxidative stress plays an important role in the progression of AD. Ginseng, the root and rhizome of Panax ginseng C. A. Meyer, is used not only as an herbal medicine but also as a functional food to support bodily functions. Ginsenoside Rk3 (Rk3), the main bioactive component in ginseng, has a strong antioxidant effect and has not been reported in AD. In this study, we showed that Rk3 improved neuronal apoptosis, decreased intracellular reactive oxygen species (ROS) production and restored mitochondrial membrane potential in PC12 and primary neuronal cells. In vivo, we found that Rk3 improved spatial learning and memory deficit in precursor protein (APP)/presenilin 1 (PS1) double transgenic mouse model of AD. Additionally, Rk3 increases glutathione reductase (GSH) and superoxide dismutase (SOD) levels while inhibits malondialdehyde (MDA) production, apoptosis and activation of glial cells in APP/PS1 mice. Mechanistically, we found that the protective effect of Rk3 is in correlation with the activation of AMPK/Nrf2 signaling pathway. In conclusion, the findings of this study provide support for Rk3 as a new strategy for the treatment of AD.

Infrared small-target detection under heterogeneous background, as a challenging task, plays an important role in many applications. In practice, there are not only bright targets but also dim targets, e.g., rescue aircraft and vehicles in the forest fire scene. Considering that most existing infrared small-target detection methods are merely aimed at bright targets, a novel method using multiple morphological profiles (MMP) is proposed, which can detect various types of targets whose brightness varies greatly. In the designed morphological feature extraction, different attributes, i.e., area attribute and height attribute, are applied to extract spatial size and contrast information of small-target in the max-tree and min-tree, respectively. Furthermore, discontinuous pruning values are further utilized for different attributes, and a designed fusion strategy of different pruning values results in more robust detection performance. Experimental results validated on two synthetic data and six real data sets demonstrate that the proposed MMP can not only detect a variety of brightness of targets and different types of targets and kinds of spatial sizes of targets but also further improve the contrast between targets and background, and the background clutter is significantly suppressed.

Background Endometrial cancer (EC) identified in pelvic/para-aortic lymph nodes suggests a poorer prognosis. Literature focusing on the role of epithelial-mesenchymal transition (EMT) in lymph node metastasis (LNM) remains few. Methods Transcriptional data were acquired from TCGA database. Patients with stage IA-IIIC2 EC were included, constituting the LN positive and negative groups. To evaluate the extent of EMT, an EMT signature composed of 315 genes was adopted. EMT-related genes (ERGs) were obtained from dbEMT2 database, differentially expressed ERGs (DEERGs) of which between the two groups were screened out. On the basis of DEERGs, pathway analysis was carried out. We finally used the logistic regression model to build an ERG-based gene signature with diagnostic value for LNM in EC. Results A total of 498 patients were included, with 75 in the LN positive group. Median EMT score of tumor tissues from LN negative group was − 0.369, while that from LN positive group was − 0.296 (P CIRBP, DDR1, F2RL2, HOXA10, PPARGC1A, SEMA3E and TGFB1. A logistic regression model including the 7-genes based risk score, age, grade, myometrial invasion and histological subtype was built, with an AUC of 0.850 and a good calibration (P = 0.074). In a validation dataset composed of 83 EC patients, the model exhibited a promising diagnostic value and was well calibrated (P = 0.42). Conclusion The EMT status and expression of ERGs varied in EC tissues from LN positive and negative cases, involving multiple EMT-related signalling pathways, and the distribution of DEGs differed among molecular subtypes. An ERG-based gene signature including 7 DEERGs exhibited a potential application value.

Mn–Cr–O spinel catalysts (MnCr2O4 and Mn1.5Cr1.5O4) and single oxides of Mn and Cr are coked under ethylene and ethylene–steam mixtures to simulate reaction conditions occurring in steam cracker fu...

In order to determine the main parameters affecting the kinematic performance of the quadrupedal bionic horse robot, this paper investigates the sensitivity analysis of structural parameters on performance changes. Based on the introduction of the structure of the bionic horse robot used for equine-assisted therapy, the establishment of a kinematic model, and the kinematic analysis by the closed-loop vector method, the kinematic relationship between the trajectory of the foot end of the bionic horse and the structural parameters is calculated by full differential calculations, and the influence laws of the changes of the structural parameters on the change of the trajectory of the foot end of the bionic horse are analyzed, and the indexes for evaluating the sensitivity of the structural parameters are introduced, so that the key structural parameters with high sensitivity to the robot performance are obtained. The results are verified by simulation. This research lays the foundation for further optimization of the structural parameters of the robot.