Coxsackievirus A10 (CV-A10) is responsible for an escalating number of severe infections in children, but no prophylactics or therapeutics are currently available. KREMEN1 (KRM1) is the entry ...receptor for the largest receptor-group of hand-foot-and-mouth disease causing viruses, which includes CV-A10. We report here structures of CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle. The receptor spans the viral canyon with a large footprint on the virus surface. The footprint has some overlap with that seen for the neonatal Fc receptor complexed with enterovirus E6 but is larger and distinct from that of another enterovirus receptor SCARB2. Reduced occupancy of a particle-stabilising pocket factor in the complexed virus and the presence of both unbound and expanded virus particles suggests receptor binding initiates a cascade of conformational changes that produces expanded particles primed for viral uncoating.
Oxidative stress and inflammation are implicated in the development of sepsis-related acute lung injury (ALI). MicroRNA-1224-5p (miR-1224-5p) plays critical roles in regulating inflammatory response ...and reactive oxygen species (ROS) production. The present study is aimed at investigating the role and underlying mechanisms of miR-1224-5p in sepsis-related ALI. Mice were intratracheally injected with lipopolysaccharide (LPS, 5 mg/kg) for 12 h to induce sepsis-related ALI. To manipulate miR-1224-5p level, mice were intravenously injected with the agomir, antagomir, or matched controls for 3 consecutive days. Murine peritoneal macrophages were stimulated with LPS (100 ng/mL) for 6 h to further validate the role of miR-1224-5p in vitro. To inhibit adenosine 5′-monophosphate-activated protein kinase alpha (AMPKα) or peroxisome proliferator activated receptor-gamma (PPAR-γ), compound C or GW9662 was used in vivo and in vitro. We found that miR-1224-5p levels in lungs were elevated by LPS injection, and that the miR-1224-5p antagomir significantly alleviated LPS-induced inflammation, oxidative stress, and ALI in mice. Conversely, the miR-1224-5p agomir aggravated inflammatory response, ROS generation, and pulmonary dysfunction in LPS-treated mice. In addition, the miR-1224-5p antagomir reduced, while the miR-1224-5p agomir aggravated LPS-induced inflammation and oxidative stress in murine peritoneal macrophages. Further findings revealed that miR-1224-5p is directly bound to the 3′-untranslated regions of PPAR-γ and subsequently suppressed PPAR-γ/AMPKα axis, thereby aggravating LPS-induced ALI in vivo and in vitro. We demonstrate for the first time that endogenous miR-1224-5p is a critical pathogenic factor for inflammation and oxidative damage during LPS-induced ALI through inactivating PPAR-γ/AMPKα axis. Targeting miR-1224-5p may help to develop novel approaches to treat sepsis-related ALI.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Autonomous vehicles can achieve accurate localization and real-time road information perception using sensors such as global navigation satellite systems (GNSSs), light detection and ranging (LiDAR), ...and inertial measurement units (IMUs). With road information, vehicles can navigate autonomously to a given position without traffic accidents. However, most of the research on autonomous vehicles has paid little attention to road profile information, which is a significant reference for vehicles driving on uneven terrain. Most vehicles experience violent vibrations when driving on uneven terrain, which reduce the accuracy and stability of data obtained by LiDAR and IMUs. Vehicles with an active suspension system, on the other hand, can maintain stability on uneven roads, which further guarantees sensor accuracy. In this paper, we propose a novel method for road profile estimation using LiDAR and vehicles with an active suspension system. In the former, 3D laser scanners, IMU, and GPS were used to obtain accurate pose information and real-time cloud data points, which were added to an elevation map. In the latter, the elevation map was further processed by a Kalman filter algorithm to fuse multiple cloud data points at the same cell of the map. The model predictive control (MPC) method is proposed to control the active suspension system to maintain vehicle stability, thus further reducing drifts of LiDAR and IMU data. The proposed method was carried out in outdoor environments, and the experiment results demonstrated its accuracy and effectiveness.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The mature retrovirus capsid consists of a variably curved lattice of capsid protein (CA) hexamers and pentamers. High-resolution structures of the curved assembly, or in complex with host factors, ...have not been available. By devising cryo-EM methodologies for exceedingly flexible and pleomorphic assemblies, we have determined cryo-EM structures of apo-CA hexamers and in complex with cyclophilin A (CypA) at near-atomic resolutions. The CA hexamers are intrinsically curved, flexible and asymmetric, revealing the capsomere and not the previously touted dimer or trimer interfaces as the key contributor to capsid curvature. CypA recognizes specific geometries of the curved lattice, simultaneously interacting with three CA protomers from adjacent hexamers via two noncanonical interfaces, thus stabilizing the capsid. By determining multiple structures from various helical symmetries, we further revealed the essential plasticity of the CA molecule, which allows formation of continuously curved conical capsids and the mechanism of capsid pattern sensing by CypA.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study investigated the association between a healthy lifestyle with all-cause, cause-specific mortality, and cancer incidence among individuals with metabolic syndrome (MetS). Healthy lifestyle ...scores were created based on MetS management guidelines, including never/quitting smoking, moderate drinking, good sleep, healthy diet, sufficient exercise, social support, and less sedentary behaviour. Weighted healthy lifestyle scores were further constructed and classified into three groups: unfavourable (lowest quintile), intermediate (quintiles 2−4), and favourable (highest quintile) lifestyles. We included 87,342 MetS participants from the UK Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted Cox proportional hazards regression. During a median follow-up of 12.54 years, 6739 deaths were reported; during a median follow-up of 10.69 years, 10,802 new cancer cases were documented. We found a favourable lifestyle was inversely associated with all-cause mortality (HR: 0.57; 95%CI: 0.53−0.62), cause-specific mortality from respiratory disease, cancer, digestive disease, cardiovascular disease (HR < 1; p-trend < 0.001), and overall cancer incidence (HR: 0.84; 95% CI: 0.79−0.90). Our results indicate that adherence to healthy lifestyles is associated with lower overall cancer incidence and all-cause mortality risk among MetS individuals. However, causality cannot be made due to the nature of observational studies.
A new class of metal-free, easy to synthesize redox catalysts based on a triarylimidazole framework is described. With those synthesized thus far, one can access a potential range of ca. 410 mV. They ...proved to be useful mediators for the activation of benzylic C–H bonds under mild conditions.
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IJS, KILJ, NUK, PNG, UL, UM
As a manipulation terminal for a teleoperated system, a joystick requires force sensors to accurately reproduce the haptic information, resulting in large and expensive haptic joysticks. Moreover, ...the actuator of the haptic joystick usually contains uncertain parameters related to its DC servo motor, making accurate haptic reproduction control a challenge. This study proposes an adaptive haptic control scheme based on the backstepping method for a haptic joystick system with unknown parameters and unmeasurable disturbances without using force sensors. In the scheme, the joystick end force is considered an unknown disturbance of the DC motor. A universal model of the joystick system actuator, i.e., a DC servo motor, and the dynamic model of the joystick are established. The control law is then derived on the basis of the established model. The stability of the closed-loop system is demonstrated analytically on the basis of the Lyapunov function. Furthermore, numerical simulation results verify the effectiveness of the proposed control scheme.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chang'E-4 (CE-4) was the first mission to accomplish the goal of a successful soft landing on the lunar farside. The landing trajectory and the location of the landing site can be effectively ...reconstructed and determined using series of images obtained during descent when there were no Earth-based radio tracking and the telemetry data. Here we reconstructed the powered descent trajectory of CE-4 using photogrammetrically processed images of the CE-4 landing camera, navigation camera, and terrain data of Chang'E-2. We confirmed that the precise location of the landing site is 177.5991°E, 45.4446°S with an elevation of -5935 m. The landing location was accurately identified with lunar imagery and terrain data with spatial resolutions of 7 m/p, 5 m/p, 1 m/p, 10 cm/p and 5 cm/p. These results will provide geodetic data for the study of lunar control points, high-precision lunar mapping, and subsequent lunar exploration, such as by the Yutu-2 rover.
In this study, we designed a new type of digital hydraulic transformer using four gear-pump/motor units with a displacement ratio of 2
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and two control valve groups that consist of four ...solenoid directional valves. The driving gear shafts of the four gear-pump/motor units are fixedly connected to achieve synchronous rotation. The two control valve groups are respectively installed through an integrated valve block on the inlet and outlet of each gear-pump/motor unit. With the objective of reducing the installed power and energy consumption of hydraulic traction systems, we propose a new energy-saving hydraulic system based on a digital hydraulic transformer. This hydraulic system uses a digital hydraulic transformer as a pressure/flow control element. By controlling the power on/off states of eight solenoid directional valves, the digital hydraulic transformer can realize a change in output flow and then a change in speed of the hydraulic cylinder piston rod. Through the theoretical derivation and simulation analysis of the hydraulic system pressure/flow change process, and the experimental verification of the built hydraulic traction system based on the experimental platform, a conclusion is drawn that the proposed digital hydraulic transformer can change the output pressure/flow of a hydraulic system through a binary digital control, verifying the feasibility of the pressure change principle of the designed digital hydraulic transformer and the rationality of the hydraulic traction system circuit.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background The relationship between tea and coffee consumption and mortality among patients with metabolic syndrome (MetS) remains barely explored. Herein, this study aimed to examine the association ...between tea and coffee consumption and the likelihood of all-cause and cause-specific mortality in patients with MetS. Methods A total of 118,872 participants with MetS at baseline from the UK Biobank cohort were included. Information on tea and coffee consumption was obtained during recruitment using a touchscreen questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were determined using Cox proportional hazards models. Results During a median follow-up of 13.87 years, 13,666 deaths were recorded, with 5913, 3362, and 994 deaths from cancer, cardiovascular diseases (CVD), and respiratory disease (RD), respectively. This research showed a significant inverse association between tea intake and the risk of all-cause and cancer mortality, the respective HRs (95% CI) for consuming tea 2 vs. 0 cup/day were 0.89 (0.84-0.95), and 0.91 (0.83-0.99), and tea intake greater than or equal to 4 cups/day could reduce CVD mortality by 11% (HR 0.89; 95% CI 0.81-0.98). The U-shaped nonlinear association between coffee intake and all-cause/CVD mortality was examined (all p-nonlinear < 0.001). The HRs (95% CI) for coffee consumption 1 vs. 0 cup/day were 0.93 (0.89-0.98) and 0.89 (0.80-0.99), and for greater than or equal to 4 vs. 0 cup/day were 1.05 (1.01-1.11) and 1.13 (1.03-1.25), respectively. Notably, the combined intake of tea and coffee presented a protective effect against all-cause mortality (HR < 1). Conclusions The importance of daily tea and moderate coffee consumption in individuals with MetS to optimise health benefits are highlighted. Keywords: Coffee, Tea, Metabolic syndrome, All-cause mortality, Cause-specific mortality
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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