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More than 40% of infertile men are diagnosed with oligoasthenozoospermia and the incidence is still rising, but the effective treatments are not been found until now. Astragalin, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. This study investigated the pharmacological effects of astragalin for treatment of oligoasthenozoospermia in male mice, induced by cyclophosphamide (CTX). Male mice were intraperitoneally injected by CTX (50 mg/kg), and astragalin (30 mg/kg) was given via oral gavage once daily. RNA-seq analysis highlighted astragalin upregulated gene expression of anti-apoptosis (AKT1and BCL2-XL), cell proliferation (ETV1, MAPKAPK2, and RPS6KA5) and synthesis of testosterone (STAR, CYP11A1, and PRKACB), but downregulated gene expression of cell apoptosis (BAD, BCL-2, CASPASE9, and CASPASE3) in mouse testis. Astragalin also significantly reversed the reduction in body weight, reproductive organs index, and sperm parameters (sperm concentration, viability, and motility) induced by CTX, and restored testicular abnormal histopathologic morphology induced by CTX. Furthermore, astragalin dramatically rescued the gene expression related to spermatogenesis (AKT1, BCL-2, CASPASE9, CASPASE3, MAPKAPK2, RPS6KA5, STAR, and PRKACB), and increased the level of testosterone by improving related proteins (STAR, CYP11A1, PRKACB) for oligoasthenozoospermia induced by CTX. In conclusion, astragalin may be a potential beneficial agent for oligoasthenozoospermia by increasing the testosterone levels in testis.

Considering static radial eccentricity, a Jeffcott rotor model is established for the rotor system of the permanent magnet synchronous motors in electric vehicles. The system conservative force, including unbalanced magnetic pull, which results in nonlinearity is analyzed, and center manifold theorem and Lyapunov method are used to determine the stabilities of multiple equilibrium points. This analysis shows that static eccentricity spoils the symmetry of the equilibrium points, although they are distributed in the line along the direction of the static eccentricity. This asymmetry leads to the pitchfork bifurcation of equilibrium points to a generic bifurcation with a defect. This analysis provides two stability conditions for the rotor system. Furthermore, the effect of the asymmetry on the dynamic characteristics that can induce backward whirling motion coupled with forward whirling motion is quite different from the case without static eccentricity. These characteristics are investigated by multi-scale method. As a result, the analytical solution of the system at steady state is obtained. The frequency characteristics of the main resonance are analyzed, and the stability of the solution is determined using Routh–Hurwitz criterion and the geometric constraint of the rotor whirling motion. The characteristics reveal that a globally unstable frequency band appears due to the geometric constraint. However, this frequency band narrows and even vanishes with increases in damping and electromagnetic stiffness and decreases in mass imbalance, mechanical stiffness and static eccentricity. The analysis by multi-scale method is based on the assumption of the time invariance of the forward and backward whirling amplitudes, which is validated by the numerical method. The results of the two methods agree well, which indicates that this assumption and the analysis are reasonable.

This paper investigates the application of adaptive tuned vibration absorbers (ATVAs) to lightly damped automotive powertrains. To achieve this, a vibration characteristic analysis of a dual lay-shaft dual clutch transmission (DCT)-equipped powertrain system was performed, including a natural frequency evaluation and sensitivity studies. Transient responses due to gear changes and variations of both the gear ratio and engine speed were also evaluated. The results demonstrate that the impact of ATVAs on transient responses during gear changes is minimal, suggesting that these short-duration transients are outside the scope of application for ATVAs. However, as excitation forces originate from the engine, speed has a significant impact on excitation frequency. Furthermore, the gear ratios significantly influence the engine operating range and natural frequency in any particular gear. Therefore, variations of engine speeds and gear ratios are the main influencing factors affecting the dominant excitation frequency. Consequently, the relationships among the system natural frequencies, the dominant external excitation frequency and the inherent frequency of the ATVA are comprehensively studied. By investigating the relationships among the dominant external excitation frequency and system natural frequencies and the system sensitivity analysis results, the installation position, stiffness range and optimal frequency tuning scheme of the ATVA can be determined. The results were applied to a DCT powertrain with continuously changing engine speeds and an ATVA with corresponding variable stiffness, and a frequency tuning scheme is installed on the powertrain. By comparing the simulation results, the effectiveness and reliability of the presented method can be verified.

Leaf rust, caused by Puccinia triticina (Pt), is one of the most important wheat diseases of common wheat (Triticum aestivum L.). Using resistant cultivars is the most economical and efficient way to control the disease. A total of 86 wheat cultivars from Sichuan province in China were inoculated with 14 Pt races for postulating seedling leaf rust resistance (Lr) gene(s) in the greenhouse. Meanwhile, these cultivars were also planted in Baoding and Zhoukou trial fields for identifying slow leaf rusting genes during the 2014–2015 and 2015–2016 cropping seasons. Twelve specific markers for ten known Lr genes (Lr1, Lr9, Lr10, Lr19, Lr20, Lr24, Lr26, Lr34, Lr37 and Lr46) were also used for molecular marker detection. Based on the results from the gene postulation and molecular marker detection, nine Lr genes (Lr1, Lr2a, Lr26, Lr3ka, Lr30, Lr36, Lr15, Lr37, and Lr46) were identified in 45 cultivars either singly or in combination. Most frequently identified Lr genes were Lr26 in 25 cultivars and Lr37 in 21 cultivars. Less frequently detected genes were Lr1 and Lr46 each in nine cultivars, Lr3ka in five cultivars, Lr30 in three cultivars and Lr36 in two cultivars. Lr2a and Lr15 were found in Chuannong 16 and Chuanmai 1, respectively. Twenty-nine cultivars were found to have slow rusting resistance during the two growing seasons. The results should be useful for selecting cultivars with combinations of genes for effective resistance to grow and in breeding new cultivars with improved resistance to leaf rust.

In recent years, there has been significant interest in the study of spandex in high-elasticity sensors. As a new kind of special spandex, dyeable spandex shows strong adsorption capacity for anions. In this study, neutral red G was used as an anion adsorption simulator to study the adsorption mechanism of dyeable spandex on anionic materials. The structure of dyeable spandex was characterized by the modern instrumental analysis method, and the adsorption kinetics and thermodynamics of neutral red G on dyeable spandex were discussed. The results show that the use of mixed amines as chain extenders for dyeable spandex reduced the regularity of molecules and the crystallinity of spandex, which was beneficial to the diffusion adsorption of anions. On the other hand, the number of secondary amino groups increased, providing more adsorption sites under acidic conditions. The adsorption of neutral red G on dyeable spandex satisfied the quasi-second-order kinetics and the Langmuir adsorption model, indicating that dye adsorption on spandex was mainly electrostatic. The diffusion coefficient and equilibrium adsorption capacity of neutral red G on dyeable spandex increased significantly, whereas enthalpy and entropy decreased.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used solely for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLN. A low dose of I-R-F induces not only high titer long-lasting neutralizing antibodies but also comprehensive T cell responses than RBD, and even provides comprehensive protection in one dose without adjuvant. This study shows that the I-R-F vaccine provides rapid and complete protection throughout upper and lower respiratory tracts against high dose SARS-CoV-2 challenge in rhesus macaques. Due to its potency and safety, this engineered vaccine may become one of the next-generation vaccine candidates in the global race to defeat COVID-19.

Summary DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity.

Objective. To explore the mechanism of modified Huanglian Maidong decoction (Maidong-Sanqi-Huanglian Compounds, MSHCs) intervention in type 2 diabetes mellitus (T2DM). Method. This study used PubChem and SciFinder to collect the molecular structure of MSHCs, used PharmMapper to predict the potential targets of MSHC, and combined them with the T2DM gene to construct MSHC-T2DM protein-protein interaction (PPI) network. The plugin MCODE in Cytoscape 3.7.1 was then used to perform cluster analysis on the MSHC-T2DM PPI network. The genes and targets were input into DAVID for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the therapeutic effect of MSHC on T2DM. Results. Several T2DM-related targets, clusters, signaling pathways, and biological processes are found. The experimental results showed that compared with the blank group, the content of fasting blood glucose (FBG) in the model group was higher ( P < 0.01 ). Compared with the model group, the content of FBG decreased and the insulin level increased in the MSHC medium-dose (0.15 g/kg) and high-dose (0.45 g/kg) groups and metformin group after 4 weeks of drug administration ( P < 0.05 ). MSHC can also improve blood liquid levels and inflammatory factor levels ( P < 0.05 ). Conclusion. MSHC may achieve therapeutic effects through regulating the T2DM-related targets, biological processes, and pathways, such as insulin resistance, energy metabolism, oxidative stress, and inflammation, found in this research.

In the beyond visual range (BVR) air combat, the low hit rate of air-to-air missile (AAM) caused by evasive maneuvers of targets has long been a question of great interest. This paper attempts to address this problem by sending a corrected relay guidance command based on the missile dynamic attack zone (DAZ) to adjust the trajectory of the missile in real time. First, the physical model of the attack zone (AZ) is built and analyzed with the conditions of maneuvering target. Second, considering the increasing complexity of the environment, large battlefield range and the high mobility of targets, the traditional AZ can not meet the needs of current BVR air combat very well. Thus, to adapt the changes of air combat better, the probabilistic dependencies between multiple kinematic parameters and DAZ is modelled by Bayesian Networks (BN). The conditional probability tables (CPT) of BN is learnt from datasets derived from the physical model. Finally, through the inference and analysis of BN, we get an additional relay guidance command to adjust the trajectory of the missile in real time. The proposed method is exemplified by simulation, and results show that this method is effective and has a higher hitting accuracy.

Given a graphical degree sequence ${\bf d}=(d_1,\ldots, d_n)$, let $G(n, {\bf d})$ denote a uniformly random graph on vertex set $[n]$ where vertex $ i$ has degree $d_i$ for every $1\le i\le n$. We give upper and lower bounds on the joint probability of an arbitrary set of edges in $G(n,{\bf d})$. These upper and lower bounds are approximately what one would get in the configuration model, and thus the analysis in the configuration model can be translated directly to $G(n,{\bf d})$, without conditioning on that the configuration model produces a simple graph. Many existing results of $G(n,{\bf d})$ in the literature can be significantly improved with simpler proofs, by applying this new probabilistic tool. One example we give is about the chromatic number of $G(n,{\bf d})$. In another application, we use these joint probabilities to study the connectivity of $G(n,{\bf d})$. When $\Delta^2=o(M)$ where $\Delta$ is the maximum component of ${\bf d}$, we fully characterise the connectivity phase transition of $G(n,{\bf d})$. We also give sufficient conditions for $G(n,{\bf d})$ being connected when $\Delta$ is unrestricted.

The thermal deformation of gears will affect the vibration of the planetary system; this research mainly studied the effect of thermal conditions on planetary systems nonlinear vibration under the thermal equilibrium state. To study the influence of gear temperature on the planetary gear system, a nonlinear dynamic model considering thermal deformation was established. The mathematical expression of the thermal time-varying mesh stiffness (TTVMS) varied with temperature, and the backlash caused by the temperature change was also computed. The influence of temperature on the TTVMS was investigated. The calculation results indicated that the methods used to determine the TTVMS and backlash of gear pairs were effective, and the trends of the change in the nonlinear dynamic characteristics with temperature were obtained. According to the fast Fourier transform (FFT) spectrums and root-mean-square (RMS) analysis, the influence of temperature change on the nonlinear dynamic characteristics of the system was analyzed. When the temperature was lower than 80 °C, the vibration displacement and the supporting shaft load remained unchanged or decreased. Once the temperature was higher than 80 °C, the vibration displacement and load of the system were strengthened.

Aiming at the problems of uneven image illumination, strong noise, and blurred edges caused by the acquisition environment or point light sources of downhole images, a spatial fusion enhancement algorithm for downhole images is proposed. First, HSV transforms the source image to obtain the luminance component, and uses a smoothing guided filter to denoise it, perform edge feature extraction on the image, and then perform non-downsampling shear wave on the extracted edge feature image, NSST transform and decompose the luminance component after noise reduction. The high-frequency sub-band uses the PCNN model to fuse the maximum value of the total ignition amplitude to fuse the high-frequency features of the image. The low-frequency sub-band is fused using an improved energy maximum method, which is obtained by inverse NSST and HSV inverse transformation. Finally, the image is enhanced. Experiments show that the improved algorithm enriches the local detail information of the downhole image and achieves good results in objective evaluation indicators.

We give sufficient conditions under which a random graph with a specified degree sequence is symmetric or asymmetric. In the case of bounded degree sequences, our characterisation captures the phase transition of the symmetry of the random graphs. This phase transition coincides with that of the graph connectivity. However, when the maximum degree is a growing function as the number of vertices tends to infinity, our results suggest that these two thresholds do not coincide any more, 22 pages

The bacterial effector MavC catalyzes non-canonical ubiquitination of host E2 enzyme UBE2N without engaging any of the conventional ubiquitination machinery, thereby abolishing UBE2N’s function in forming K63-linked ubiquitin (Ub) chains and dampening NF-кB signaling. We now report the structures of MavC in complex with conjugated UBE2N~Ub and an inhibitor protein Lpg2149, as well as the structure of its ortholog, MvcA, bound to Lpg2149. Recognition of UBE2N and Ub depends on several unique features of MavC, which explains the inability of MvcA to catalyze ubiquitination. Unexpectedly, MavC and MvcA also possess deubiquitinase activity against MavC-mediated ubiquitination, highlighting MavC as a unique enzyme possessing deamidation, ubiquitination, and deubiquitination activities. Further, Lpg2149 directly binds and inhibits both MavC and MvcA by disrupting the interactions between enzymes and Ub. These results provide detailed insights into catalysis and regulation of MavC-type enzymes and the molecular mechanisms of this non-canonical ubiquitination machinery., The bacterial effector MavC can ubiquitinate the host E2 enzyme UBE2N to dampen the host immune response. Here, the authors provide mechanistic insight into this non-canonical ubiquitination machinery and reveal the structural basis for the functional differences between MavC and its close homolog MvcA.

Kim and Vu made the following conjecture (Advances in Mathematics, 2004): if d G log n, then the random d-regular graph G(n, d) can asymptotically almost surely be "sandwiched" between G(n, p1) and G(n, p2) where p1 and p2 are both (1 + o(1))d/n. They proved this conjecture for log n L d L n1/3−o(1), with a defect in the sandwiching: G(n, d) contains G(n, p1) perfectly, but is not completely contained in G(n, p2). Recently, the embedding G(n, p1) ⊆ G(n, d) was improved by Dudek, Frieze, Rucinski and Sileikis to d = o(n). In this paper, we prove Kim-Vu's sandwich conjecture, with perfect containment on both sides, for all [MATH HERE]. For [MATH HERE], we prove a weaker version of the sandwich conjecture with p2 approximately equal to (d/n) log n, without any defect. In addition to sandwiching regular graphs, our results cover graphs whose degrees are asymptotically equal. The proofs rely on estimates for the probability that a random factor of a pseudorandom graph contains a given edge, which is of independent interest. As applications, we obtain new results on the properties of random graphs with given near-regular degree sequences, including Hamiltonicity and universality in subgraph containment. We also determine several graph parameters in these random graphs, such as the chromatic number, small subgraph counts, the diameter, and the independence number. We are also able to characterise many phase transitions in edge percolation on these random graphs, such as the threshold for the appearance of a giant component.

The semi-random graph process is a single player game in which the player is initially presented an empty graph on n vertices. In each round, a vertex u is presented to the player independently and uniformly at random. The player then adaptively selects a vertex v , and adds the edge u v to the graph. For a fixed monotone graph property, the objective of the player is to force the graph to satisfy this property with high probability in as few rounds as possible. We focus on the problem of constructing a Hamilton cycle in as few rounds as possible. In particular, we present a novel strategy for the player which achieves a Hamiltonian cycle in c ∗ n rounds, where the value of c ∗ is the result of a high dimensional optimization problem. Numerical computations indicate that c ∗ 2 . 61135 . This improves upon the previously best known upper bound of 3 n rounds. We also show that the previously best lower bound of ( ln 2 + ln ( 1 + ln 2 ) + o ( 1 ) ) n is not tight.

Based on the principle of vibration absorber, an adaptive tunable vibration absorber with the magnetorheological elastomer as the core intelligent component was designed to eliminate variable frequency vibration of the powertrain system. The simulation of the magnetic circuit of the adaptive tunable vibration absorber was carried out to ensure the magnetic field generated by the design with a closed magnetic circuit could meet the requirement. The transient dynamic simulation analysis of the adaptive tunable vibration absorber shows that the natural frequency of the vibration absorber could well follow the external excitation signal. The natural vibration sensitivity analysis of the 4-degree-of-freedom dynamic system of the powertrain system was performed to obtain the key moment of inertia that affects the natural frequencies of each stage and then the installation position of the adaptive tunable vibration absorber corresponding to external excitation near the resonant frequency band could be determined. Subsequently, taking the third natural vibration as an example, an adaptive tunable vibration absorber with corresponding variable-stiffness range was installed on the key moment of inertia affecting the vibration of this order. The transient changes of each natural vibration frequency of the powertrain system with the adaptive tunable vibration absorber were studied and then the best starting and stopping frequencies were determined. According to the optimal frequency tuning scheme, the variation range of the storage modulus required for the magnetorheological elastomer material in the limited magnetic field range was obtained. The relationship between the controllable current and the torsional stiffness of the vibration absorber is established. Aiming at the vibration problem near the third-order natural vibration, the best vibration reduction performance parameters were matched to the adaptive tunable vibration absorber. Finally, a time-frequency analysis was applied to the powertrain system with adaptive tunable vibration absorber, and the result shows that the best performance parameter matching for the adaptive tunable vibration absorber could effectively improve its vibration reduction performance.

A high-static-low-dynamic-stiffness (HSLDS) isolator has good application prospects in low-frequency vibration and micro-vibration isolation. The nonlinear stiffness of the vibration isolation system strongly influences its dynamic responses and vibration isolation performance. In this paper, for a HSLDS isolator model, a stiffness range parameter d and a static equilibrium position stiffness Ksep are introduced to indicate the different stiffnesses of the nonlinear isolator. The averaging method is employed to solve the nonlinear dynamic equation of the proposed system at steady state for each excitation frequency. The effects of the parameters d and Ksep on the dynamic responses and isolation effectiveness of the HSLDS isolator are clearly analysed. The results show that an increase in d and a reduction in Ksep improve the isolation performance of the system. Considering the application of the HSLDS isolator in micro-vibration environments, the beneficial stiffness design under various excitation amplitudes and damping conditions is discussed on the basis of the limited maximum response amplitude. Several useful guidelines for the stiffness design of the HSLDS isolator are developed, which help to improve the vibration isolation performance of the system. The results provide useful insight for the design, analysis and application of HSLDS vibration isolators.

Based on a multiple degrees of freedom dynamic model of a vehicle powertrain system, natural vibration analyses and sensitivity analyses of the eigenvalues are performed to determine the key inertia for each natural vibration of a powertrain system. Then, the results are used to optimize the installation position of each adaptive tuned vibration absorber. According to the relationship between the variable frequency torque excitation and the natural vibration of a powertrain system, the entire vibration frequency band is divided into segments, and the auxiliary vibration absorber and dominant vibration absorber are determined for each sensitive frequency band. The optimum parameters of the auxiliary vibration absorber are calculated based on the optimal frequency ratio and the optimal damping ratio of the passive vibration absorber. The instantaneous change state of the natural vibrations of a powertrain system with adaptive tuned vibration absorbers is studied, and the optimized start and stop tuning frequencies of the adaptive tuned vibration absorber are obtained. These frequencies can be translated into the optimum parameters of the dominant vibration absorber. Finally, the optimal tuning scheme for the adaptive tuned vibration absorber group, which can be used to reduce the variable frequency vibrations of a powertrain system, is proposed, and corresponding numerical simulations are performed. The simulation time history signals are transformed into three-dimensional information related to time, frequency and vibration energy via the Hilbert-Huang transform (HHT). A comprehensive time-frequency analysis is then conducted to verify that the optimal tuning scheme for the adaptive tuned vibration absorber group can significantly reduce the variable frequency vibrations of a powertrain system.

The magnetorheological properties of a series of magnetorheological elastomers with ferromagnetic particles of different mass fractions and different diameters are investigated. The aim is to provide a basis for the preparation of high-performance material. The shear behavior of the magnetorheological elastomers is also investigated as a function of temperature. The results essentially reveal the temperature-dependent nature of the variable stiffness of the magnetorheological elastomers. A modified Gauss distribution columnar model of ferromagnetic particles (with a temperature-dependent magnetic permeability) and a modified super-elastic rubber matrix (with a linear thermal expansion coefficient) is developed and used to explore the nature of the temperature-dependent variable stiffness. The results suggest that the interaction between the rubber matrix and ferromagnetic particles is the most critical factor responsible for the temperature dependence and not the features of the two components themselves. On the basis of System Identification Theory, a fitting polynomial is added to modify the constitutive model, which can represent the interaction between the rubber matrix and ferromagnetic particles. Polynomial data fitting and a theoretical model were used to derive an expression for the temperature dependence. As a result, the magnetic field-induced shear modulus was obtained as a semi-empirical model. This was then used to draw maps of the temperature-induced and magnetic field-induced shear modulus. The calculated results were compared with the experimental data and the errors found to be acceptable, which verifies the effectiveness and reliability of the semi-empirical model. Finally, the temperature dependence of the shear modulus is converted into the temperature dependence of the shear stiffness.

Vibration absorbers can absorb vibration energy and reduce the vibration amplitude of the primary system. With adaptive tuning, an adaptively tuned vibration absorber (ATVA) can track the dominant frequency of the external excitation, and reduce the vibration response amplitude of the primary system under variable-frequency external excitation. To realize the optimal vibration reduction performance, the 100% frequency tracking scheme of the adaptively tuned absorber must be optimized. In this regard, a dynamic model of an undamped primary system and a vibration absorber is established based on vibration absorption theory, and alternative tuning schemes for these absorbers are investigated in this paper. Using ATVA with the 100% frequency tracking scheme as a reference, a frequency tracking scheme is optimized by the segmented intercept optimization method. This optimization method continuously tunes the ratio of the absorber natural frequency and external excitation frequency to minimize the response in the variable-frequency vibration regions. Hilbert-Huang transform (HHT) time-frequency analysis is performed on the vibration response to reveal the vibration reduction mechanism of the improved vibration absorber. The vibration reduction effects are verified by comprehensive analysis results and experimental results.

Summary NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here, we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with double-stranded RNA (dsRNA) in vitro and in cells, and an intrinsically disordered poly-lysine sequence (K350-354) of NLRP6 is important for multivalent interactions, phase separation, and inflammasome activation. Nlrp6-deficient or Nlrp6K350-354A mutant mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, implicating NLRP6 LLPS in anti-microbial immunity. Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. Lipoteichoic acid, a known NLRP6 ligand, also promotes NLRP6 LLPS, and DHX15, a helicase in NLRP6-induced interferon signaling, co-forms condensates with NLRP6 and dsRNA. Thus, LLPS of NLRP6 is a common response to ligand stimulation, which serves to direct NLRP6 to distinct functional outcomes depending on the cellular context.

In this paper, a method for the dynamic modification of tooth width is used to optimize the problem of uneven loading of helical gears. Considering the meshing error caused by gear manufacturing, installation, time-varying meshing stiffness, clearance, and shaft bending, the distributed meshing transverse-torsion-pendulum nonlinear dynamic model of a helical gear pair is established. A method to modify the tooth width of the helical gear pair is proposed to optimize the uniform load characteristics of the tooth surface. Through the research of dynamic tooth width modification, the optimal modification parameters are obtained so that the dynamic load distribution of the tooth surface is uniform and the load distribution centre is close to the centre of the tooth surface, which reduces the swing phenomenon. During experimental testing, the swing vibration response of the modified gear is reduced by a maximum of 26.15%, the dynamic load coefficient is reduced by a maximum of 20.84%, and the stress distribution on the tooth surface is uniform.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.

We study the arboricity A and the maximum number T of edge-disjoint spanning trees of the classical random graph G (n, p). For all p(n) ∈ [0, 1], we show that, with high probability, T is precisely the minimum between δ and bm/(n − 1)c, where δ is the smallest degree of the graph and m denotes the number of edges. Moreover, we explicitly determine a sharp threshold value for p such that: above this threshold, T equals bm/(n−1)c and A equals dm/(n−1)e; and below this threshold, T equals δ, and we give a two-value concentration result for the arboricity A in that range. Finally, we include a stronger version of these results in the context of the random graph process where the edges are sequentially added one by one. A direct application of our result gives a sharp threshold for the maximum load being at most k in the two-choice load balancing problem, where k →∞.

Objective: To explore the therapeutic effect of minimally invasive intracranial hematoma evacuation in the treatment of hypertensive cerebral hemorrhage and the value of dynamic TCD monitoring in predicting the neurological function recovery. Methods: A total of 70 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group and conservative group with 35 cases in each group according to different treatment protocols. The patients in the two groups were given drug conservative treatments. On this basis, the patients in the minimally invasive group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. TCD was performed before treatment, 1 d, 5 d, 10 d, and 21 d after treatment. The hematoma and edema volume was calculated. NIHSS was used to evaluate the neurological function recovery. Results: Vs, Vd, and Vm after treatment in the minimally invasive group were significantly elevated, while PI was significantly reduced. Vs, Vd, and Vm after treatment in the conservative group were reduced first and elevated later, while PI was elevated first and reduced later, and reached the lowest/peak 10d after treatment. Vs, Vd, and Vm 5 d, 10 d, and 21 d after treatment in the minimally invasive group were significantly higher than those in the conservative group, while PI was significantly lower than that in the conservative group. The hematoma and edema volume after treatment in the two groups was significantly reduced. The hematoma and edema volume at each timing point was significantly lower than that in the conservative group. NIHSS score after treatment in the minimally invasive group was significantly reduced. NIHSS score in the conservative group was elevated first and reduced later, reached the peak 10d after treatment, and at each timing point was higher than that in the minimally invasive group. Conclusions: The early minimally invasive operation can significantly improve the hematoma adjacent blood flow volume in patients with hypertensive cerebral hemorrhage, and contribute to the neurological function recovery. TCD not only can be applied in the dynamic monitoring of cerebral blood flow volume in patients with hypertensive cerebral hemorrhage, but also has a certain value in evaluating the prognosis of neurological function.

Effect of salicylic acid (SA) on chilling injury (Cl) of sponge gourd during storage (9 days, 9°C) plus shelf life (2 days, 20°C) was evaluated in this study. SA treatment at the concentration of 1.5 mmol L−1 significantly reduced postharvest Cl of sponge gourds. Besides, the application of SA could effectively decrease the electrolyte leakage, reduce the accumulation of malondialdehyde (MDA) and total phenolics, enhance the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX), and inhibit the activities of phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). The beneficial effects of SA could be attributed to preserved membrane integrity, inhibited membrane peroxidation, enhanced antioxidant system and suppressed activities of browning related enzymes. In a sense, SA as a postharvest tool may be commercially used in alleviating Cl of sponge gourd.

Aiming at improving regenerative braking ability in electric vehicles without compromising any safety, two different regenerative braking strategies are proposed in this study. The impact of continuously varying braking force distributions between front/rear wheel and electric/friction corresponding in two different strategies on braking noise are investigated. Based on the closed-loop coupling disk brake model, the relationship between the contact coupling stiffness and the braking force is established by considering the stationary modal test, the nonlinear optimization, and the relationship between brake-line pressure and braking force. The continuously varying braking force is initially transformed to continuously varying contact coupling stiffness, then, the brake noise tendency at each frequency band is calculated in closed-loop coupled model. The predicted result shows good consistency with the result recorded in bench test, verifying the reliability and effectivity of the presented method. The comparison of the two different electric braking strategies shows that the second braking strategy is superior to the first braking strategy in terms of suppressing the brake noise tendency.

Let $H_n$ be a graph on $n$ vertices and let $\overline{H_n}$ denote the complement of $H_n$. Suppose that $\Delta = \Delta(n)$ is the maximum degree of $\overline{H_n}$. We analyse three algorithms for sampling $d$-regular subgraphs ($d$-factors) of $H_n$. This is equivalent to uniformly sampling $d$-regular graphs which avoid a set $E(\overline{H_n})$ of forbidden edges. Here $d=d(n)$ is a positive integer which may depend on $n$. Two of these algorithms produce a uniformly random $d$-factor of $H_n$ in expected runtime which is linear in $n$ and low-degree polynomial in $d$ and $\Delta$. The first algorithm applies when $(d+\Delta)d\Delta = o(n)$. This improves on an earlier algorithm by the first author, which required constant $d$ and at most a linear number of edges in $\overline{H_n}$. The second algorithm applies when $H_n$ is regular and $d^2+\Delta^2 = o(n)$, adapting an approach developed by the first author together with Wormald. The third algorithm is a simplification of the second, and produces an approximately uniform $d$-factor of $H_n$ in time $O(dn)$. Here the output distribution differs from uniform by $o(1)$ in total variation distance, provided that $d^2+\Delta^2 = o(n)$.

Summary: Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically restricts a wide range of viruses. ZAP selectively binds to CG-dinucleotide-enriched RNA sequences and recruits multiple RNA degradation machines to degrade target viral RNA. However, the molecular mechanism and structural basis for ZAP recognition of specific RNA are not clear. Here, we report the crystal structure of the ZAP N-terminal domain bound to a CG-rich single-stranded RNA, providing the molecular basis for its specific recognition of a CG dinucleotide and additional guanine and cytosine. The four zinc fingers of ZAP adopt a unique architecture and form extensive interactions with RNA. Mutations of both protein and RNA at the RNA-ZAP interacting surface reduce the in vitro binding affinity and cellular antiviral activity. This work reveals the molecular mechanism of ZAP recognition of specific target RNA and also provides insights into the mechanism by which ZAP coordinates downstream RNA degradation processes. : ZAP is a host antiviral factor that specifically restricts a wide range of viruses. Luo et al. determine the structural and molecular basis for the specific recognition of a CG dinucleotide and additional guanine and cytosine by ZAP. Keywords: ▪▪▪

© 2019 Elsevier Ltd Vibration absorbers have the capacity to significantly reduce local and global system vibrations under both resonant and forced vibration conditions. The subset absorbers known as semi-active vibration absorbers are characterized by the ability to reduce vibrations across a range of resonance and forced vibration conditions. Achieving an optimal tuning scheme for these vibration absorbers under a variable frequency external excitation is critical for realising maximum performance of the system. In this paper according to the dynamic tuned vibration absorption principle, an innovative magnetorheological elastomer torsional vibration absorber is proposed and installed in the torsional vibration system. Through the proposed absorber tuning process, the change in each order of natural vibration of the torsional vibration system is thoroughly analysed. The analysis results are used to optimize the frequency tuning scheme and modify the structural design scheme of the torsional vibration absorber. The effectiveness and reliability of the improved frequency tuning scheme and the structural design scheme are verified by simulation results.

Cyclic GMP-AMP synthase (cGAS) is the primary sensor for aberrant intracellular dsDNA producing the cyclic dinucleotide cGAMP, a second messenger initiating cytokine production in subsets of myeloid lineage cell types. Therefore, inhibition of the enzyme cGAS may act anti-inflammatory. Here we report the discovery of human-cGAS-specific small-molecule inhibitors by high-throughput screening and the targeted medicinal chemistry optimization for two molecular scaffolds. Lead compounds from one scaffold co-crystallize with human cGAS and occupy the ATP- and GTP-binding active site. The specificity and potency of these drug candidates is further documented in human myeloid cells including primary macrophages. These novel cGAS inhibitors with cell-based activity will serve as probes into cGAS-dependent innate immune pathways and warrant future pharmacological studies for treatment of cGAS-dependent inflammatory diseases., Cyclic GMP-AMP synthase (cGAS) is involved in the modulation of inflammatory responses. Here, the authors present small-molecule inhibitors of human cGAS, characterize their interaction with the protein, and show that the compounds are active in interferon-producing cells including primary human macrophages.

We investigate the circle surrounding control problem of multiple targets, in which communication topology is undirected and connected. First of all, an estimator is given for each agent to obtain the geometric center of multiple targets in a finite time. Combined with such an estimator, a distributed controller is presented such that all agents can achieve a circular formation and rotate around the geometric center of multiple targets. Meanwhile, agents enclose all targets. Especially, the position of each agent in circular formation can be arbitrary arranged by adjusting the time-varying coefficients. Simulations demonstrate the correctness of the estimator and the surrounding control protocol.

Puccinia triticina Eriks. (Pt), the causal agent of wheat (Triticum aestivum L.) leaf rust, is the most widespread disease of common wheat worldwide. In the present study, 83 wheat cultivars from three provinces of China and 36 tester lines with known leaf rust resistance (Lr) genes were inoculated in the greenhouse with 18 Pt pathotypes to identify seedling effective Lr genes. Field tests were also performed to characterize slow leaf rusting responses at the adult plant growth stage in Baoding and Zhoukou in the 2014–15 and 2015–16 cropping seasons. Twelve Lr genes, viz. Lr1, Lr26, Lr3ka, Lr11, Lr10, Lr2b, Lr13, Lr21, Lr34, Lr37, Lr44, and Lr46 either singly or in combination were identified in 41 cultivars. Known Lr genes were not detected in the remaining 42 cultivars. The most commonly identified resistance genes were Lr26 (20 cultivars), Lr46 (18 cultivars), and Lr1 (eight cultivars). Less frequently detected genes included Lr13, Lr34, and Lr37 (each present in four cultivars), Lr10 (three cultivars), and Lr3ka and Lr44 (each in two cultivars). Evidence for the presence of genes Lr11, Lr2b, and Lr21 (each in one cultivar) was also obtained. Seventeen cultivars were found to have slow rusting resistance in both field growing seasons.

We determine the rank of a random matrix over an arbitrary field with prescribed numbers of non-zero entries in each row and column. As an application we obtain a formula for the rate of low-density parity check codes. This formula vindicates a conjecture of Lelarge (2013). The proofs are based on coupling arguments and a novel random perturbation, applicable to any matrix, that diminishes the number of short linear relations., Comment: This article supersedes arXiv:1810.07390

As one of the most popular nutrient supplements, creatine has been highly used to increase muscle mass and improve exercise performance. Here, we report an adverse effect of creatine using orthotopic mouse models, showing that creatine promotes colorectal and breast cancer metastasis and shortens mouse survival. We show that glycine amidinotransferase (GATM), the rate-limiting enzyme for creatine synthesis, is upregulated in liver metastases. Dietary uptake, or GATM-mediated de novo synthesis of creatine, enhances cancer metastasis and shortens mouse survival by upregulation of Snail and Slug expression via monopolar spindle 1 (MPS1)-activated Smad2 and Smad3 phosphorylation. GATM knockdown or MPS1 inhibition suppresses cancer metastasis and benefits mouse survival by downregulating Snail and Slug. Our findings call for using caution when considering dietary creatine to improve muscle mass or treat diseases and suggest that targeting GATM or MPS1 prevents cancer metastasis, especially metastasis of transforming growth factor beta receptor mutant colorectal cancers.