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Selenoneine, an ergothioneine analog, is important for antioxidation and detoxification. SenB and SenA are two crucial enzymes that form carbon–selenium bonds in the selenoneine biosynthetic pathway. To investigate their underlying catalytic mechanisms, we obtained complex structures of SenB with its substrate UDP-N-acetylglucosamine (UDP-GlcNAc) and SenA with N-α-trimethyl histidine (TMH). SenB adopts a type-B glycosyltransferase fold. Structural and functional analysis of the interaction network at the active center provide key information on substrate recognition and suggest a metal-ion-independent, inverting mechanism is utilized for SenB-mediated selenoglycoside formation. Moreover, the complex structure of SenA with TMH and enzymatic activity assays highlight vital residues that control substrate binding and specificity. Based on the conserved structure and substrate-binding pocket of the type I sulfoxide synthase EgtB in the ergothioneine biosynthetic pathway, a similar reaction mechanism was proposed for the formation of C–Se bonds by SenA. The structures provide knowledge on selenoneine synthesis and lay groundwork for further applications of this pathway.

Abstract Since 2019, SARS-CoV-2 has evolved rapidly and gained resistance to multiple therapeutics targeting the virus. Development of host-directed antivirals offers broad-spectrum intervention against different variants of concern. Host proteases, TMPRSS2 and CTSL/CTSB cleave the SARS-CoV-2 spike to play a crucial role in the two alternative pathways of viral entry and are characterized as promising pharmacological targets. Here, we identify compounds that show potent inhibition of these proteases and determine their complex structures with their respective targets. Furthermore, we show that applying inhibitors simultaneously that block both entry pathways has a synergistic antiviral effect. Notably, we devise a bispecific compound, 212-148, exhibiting the dual-inhibition ability of both TMPRSS2 and CTSL/CTSB, and demonstrate antiviral activity against various SARS-CoV-2 variants with different viral entry profiles. Our findings offer an alternative approach for the discovery of SARS-CoV-2 antivirals, as well as application for broad-spectrum treatment of viral pathogenic infections with similar entry pathways.

ObjectiveBreast cancer is one of the most common causes of death among women. Statins, typically used for cholesterol management, have been hypothesized to reduce recurrence and mortality rates in breast cancer. However, this association remains a subject of debate. This study evaluates the potential impact of statins on breast cancer recurrence and mortality.MethodsA comprehensive search was conducted in the PubMed, EMBASE, and Cochrane databases for articles published up to June 2023. These articles examined the effect of statins on breast cancer recurrence and mortality both before and after diagnosis. The analysis was performed using random-effects models, calculating pooled hazard ratios (HR) and their 95% confidence intervals (CI).ResultsA total of 31 cohort studies, involving 261,834 female breast cancer patients, were included in this analysis. It was found that statin use prior to diagnosis was associated with a decrease in overall mortality (HR, 0.8; 95% CI, 0.69–0.93; I2 = 77.6%; P = 0.001) and breast cancer-specific mortality (HR, 0.76; 95% CI, 0.67–0.87; I2 = 72.7%; P = 0.005). Additionally, statin use after diagnosis was observed to reduce the recurrence of breast cancer (HR, 0.71; 95% CI, 0.61–0.82; I2 = 60%; P = 0.003), overall mortality (HR, 0.81; 95% CI, 0.70–0.92; I2 = 80.7%; P < 0.001), and breast cancer-specific mortality (HR, 0.76; 95% CI, 0.67–0.86; I2 = 74.5%; P < 0.001).ConclusionsThe findings of this study indicate that statin usage, both before and after breast cancer diagnosis, may be associated with reduced risks of overall and breast cancer-specific mortality, as well as lower recurrence rates.

BackgroundAn increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this systematic review and meta-analysis to resolve the discrepancies in reported results concerning the efficacy of VC in septic patients.MethodsWe comprehensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled trials for randomized controlled trials (RCTs) evaluating the efficacy of intravenous VC (IVVC) on adult septic patients published from inception to November 28, 2022. The quality of outcomes for eligible studies was assessed using the Recommendations Assessment, Development, and Evaluation methodology. The results were analyzed using the pooled mean difference (MD) or risk ratio (RR) and 95% confidence intervals (CIs).ResultsTwenty-two studies (3,570 adult septic patients) were included. IVVC treatment did not improve 28-day mortality compared to the control group (RR, 0.92; 95% CI, 0.81–1.04; I2 = 26%; evidence risk, moderate). IVVC monotherapy decreased mortality (RR, 0.69; 95% CI, 0.52–0.93; I2 = 57%), whereas combination therapy did not affect mortality (RR, 1.03; 95% CI, 0.90–1.17; I2 =0%). IVVC had a trend to decrease the mortality of septic patients (RR, 0.83; 95% CI, 0.69–1.00; I2 = 33%) but did not affect septic shock patients (RR, 1.01; 95% CI, 0.85–1.21; I2 = 18%). IVVC reduced the duration of vasopressor use (MD, −8.45; 95% CI, −15.43 to −1.47; evidence risk, very low) but did not influence the incidence of AKI, ICU length of stay, duration of mechanical ventilation.ConclusionsIVVC treatment did not improve the 28-day mortality in septic patients. Subgroup analysis indicated that VC had a trend to decrease the 28-day mortality in patients with sepsis but not septic shock. IVVC monotherapy, rather than combination therapy, decreased the 28-day mortality in septic patients. The findings imply that Hydrocortisone, Ascorbic acid, Thiamine (HAT) combination therapy is not superior to IVVC monotherapy for septic patients. These findings warrant further confirmation in future studies, which should also investigate the mechanisms underlying the enhanced efficacy of IVVC monotherapy in septic patients.Systematic review registrationhttps://inplasy.com/.

In the paper, nonlinear vibration characteristics of a rotor system are investigated. Such a nonlinear rotor system is subjected to brush seal forces, which are obtained by integrating the bristle force along the entire ring. The nonlinear brush seal rotor system is constructed by merging a flexible rotor with nonlinear seal forces. The research is aimed at studying the nonlinear vibration characteristics and bifurcations of the motions under a variety of eccentricity circumstances. Different kinds of bifurcations are successfully obtained by mathematical discretization and mapping manipulation. Such a discrete mapping method successfully predicts the stable and unstable motions accurately. The period-doubling bifurcations and saddle node bifurcations of the rotor system are obtained. The sole unstable solutions are obtained, which are special, and a normal numerical integration method cannot solve this problem, which provides advantages in rotor design and motion control. According to the results, nonlinear resonances are found between the stable and unstable motions. The greater the eccentricity of the rotor, the greater the number of bifurcation points that occur during the rotor’s nonlinear motions, as well as the larger the ranges of speeds where the motions are unstable. Saddle node bifurcations generate unstable nonlinear motions and non-smooth motions, which may bring damage to the mechanical rotors. The period-doubling bifurcations produce the route from period-1 to period-2 motions in the nonlinear rotor system. The research provides a new perspective to study the bifurcations and stability of the nonlinear rotor systems.

Understanding phase transformation behaviors and microstructural evolutions during optimized post-heat treatments is essential for tuning the mechanical performances of additively manufactured titanium alloys. In this work, distinctive dual-stage heat treatments were proposed for improving the microstructure and properties of the laser powder bed fusion processed Ti-6Al-4V alloy. The effects of the heat treatments on phase transformation behaviors, microstructural characteristics, mechanical and tribological properties of the alloy were investigated systematically. The dual-stage heat treatments combined with salt bath quenching proved to be an effective approach for obtaining fine lamellar α/β microstructures through the introduction of martensitic and massive phase transformations, as well as achieving optimized strength and ductility. The grain boundary populations of the alloy were strongly influenced by the phase transformation behaviors. Moreover, high-density dislocations were introduced during the dual-stage heat treatments, and the type dislocations were dominant. The nonadditive strengthening mixture rule between obstacles and dislocations was substantiated in this alloy. Different wear mechanisms were found in the dual-stage heat-treated alloys depending on their microstructural characteristics. Furthermore, the underlying mechanisms of phase transformation, strengthening and toughening are also discussed.

Abstract In the past few decades, radar reflectivity data have been widely used in thunderstorm identification research. Many thunderstorm identification algorithms for ground-based weather radar have been developed. But for airborne weather radar, due to the relative scarcity of data, the thunderstorm identification research is insufficient and there are still few effective identification methods. Airborne weather radar has the realization capability of close-range detection, but most existing airborne weather radars do not have scanning capability. This paper proposes an airborne weather radar volume scan mode, under which there is a total of 31 sector scans at 31 elevations in a volume scan. And a reflectivity data simulation model of the airborne weather radar is established based on this scan strategy, then the ground-based X-band radar reflectivity data are used as input to obtain the simulated X-band airborne radar reflectivity data. Moreover, this paper studies a thunderstorm identification algorithm for the X-band airborne radar with the proposed scan mode. An improved SCI (storm cell identification) algorithm is proposed on the basis of the traditional SCI algorithm which is applicable to S-band ground-based weather radar. The results of thunderstorm identification carried out on the simulated airborne radar data show that the algorithm can effectively identify the thunderstorm cells in the mature stage and the developing stage.

NAMPT is an attractive target in cancer therapy and numerous NAMPT inhibitors have been developed. However, the clinical activities of NAMPT inhibitors have displayed disappointing results in clinical trials for their dose-limiting toxicities. In this study, reactive oxygen species (ROS)-responsive prodrugs of a NAMPT inhibitor FK866 were designed and synthesized. A short synthesis method was developed to shield the activity of FK866 through a quaternary ammonium connection. Two prodrugs, with boronic acid as a responsive group to ROS, were prepared and one of the prodrugs 122-066 also contained a fluorescence carrier. Both of the prodrugs released the active compound by the treatment of H2O2,, and the biological evaluation showed that they exhibited a higher potency in cells with high levels of ROS. Moreover, prodrug 122-066 had the ability to release FK866 and simultaneously induce the fluorescence activation under the stimulation of H2O2. This method has the potential to improve the therapeutic window of NAMPT inhibitors.

Abstract Multiple weather radars’ joint detection can enlarge the radar detection range and can improve the detection accuracy, which has become an important method to monitor large-scale weather effectively. In this paper, the methods of interpolating reflectivity volume scan data onto the grids in the Cartesian coordinate system and three-dimensional mosaic for gridded reflectivity data of several radars are studied. In order to retain the physical characteristics of the raw data, the smoothing parameters of adaptive Barnes interpolation are improved which based on the space structure of the raw reflectivity data. Through comparison of constant altitude plan position indication (CAPPI) images obtained by the commonly used interpolation schemes and the improved Adaptive Barnes interpolation, it was found that the latter can provide consecutive reflectivity fields and retain high-resolution structure comparable to the raw data. The mean deviation filter filtering erroneous grid data and the data are fused by various fusion methods. Result shows that Exponential Weighting is an excellent method which can provide continuous three-dimensional reflectivity mosaic data.

In order to study the effect of the dry friction damping structure on the localized vibration of mistuned bladed disk, the forced vibration response of a mistuned bladed disk with dry friction damping structure is investigated by using three-dimension microslip friction contact model which could reproduce the characteristics of local micro-motion slip and anti-aliasing hybrid frequency-time domain method. The variation of blade vibration response and the change of localization factor are compared with considering dry friction damping at the blade shroud and not considering dry friction damping. And the influence of the dry friction damping parameters on the vibration control of mistuned bladed disk system is discussed. The results show that the dry friction damping structure can reduce the degree of localization of the vibration response of the mistuned bladed disk system, the friction force between the blades is completely different, and the optimal initial normal pressure and the optimal friction coefficient for each blade are different. Therefore, the effect of the dry friction damping structure to each blade of the mistuned bladed disk is different, and the vibration reduction design of the mistuned bladed disk needs to consider the matching relationship between control parameters and mistuned blade.

Doppler weather radar can detect the changes in precipitation clouds for short-term forecasting. In the process of development of Doppler weather radar and weather identification algorithms, some typical Doppler weather radar base data corresponding to different weather phenomena are necessary for signal processing unit test and algorithm verification. However, the existing real weather radar base data with high quality can't meet the requirement in amount. In this paper, an algorithm based on Deep Convolutional Generative Adversarial Networks (DCGAN) to generate typical weather radar base data is proposed. And in the test signal simulation step, the power spectrum algorithm is improved. The results show that the data produced by the DCGAN have the same characteristics with the real weather radar base data without obvious non-meteorological noise. Moreover, the improved power spectrum algorithm performs better in terms of accuracy rate of the simulation echo signal.

Using the skeletal structure and muscle distribution of the hind limbs of a jumping kangaroo as inspiration, a bionic jumping leg was designed with pneumatic artificial muscles (PAMs) as actuators. Referring to the position of biarticular muscles in kangaroos, we constructed a bionic joint using biarticular and monoarticular muscle arrangements. At the same time, the problem of the joint rotation angle limitations caused by PAM shrinkage was solved, and the range of motion of the bionic joint was improved. Based on the output force model of the PAM, we established a dynamic model of the bionic leg using the Lagrange method. In view of the coupling problem caused by the arrangement of the biarticular muscle, an extended state observer was used for decoupling. The system was decoupled into two single-input and single-output systems, and angle tracking control was carried out using active disturbance rejection control (ADRC). The simulation and experimental results showed that the ADRC algorithm had a better decoupling effect and shorter adjustment time than PID control. The jumping experiments showed that the bionic leg could jump with a horizontal displacement of 320 mm and a vertical displacement of 150 mm.

As the aviation industry has entered a critical period of development, the demand for Automatic Dependent Surveillance Broadcast (ADS-B) technology is becoming increasingly urgent. Real-time detection of aviation wind field information and the early warning of wind field shear by atmospheric sounding system are two important factors related to the safe operation of aviation and airport. According to the advantages of ADS-B and Mode S data, this paper uses the Meteo-Particle (MP) model proposed by Sun et al., in their previous research to retrieve high-altitude wind field. Comparing the precision and accuracy of wind field retrieved results, and the optimization parameters of MP model suitable for meteorological model are further studied. To solve the problem of incomplete wind field coverage obtained by retrieval, an extrapolation algorithm of wind field is proposed. The results show that: (1) a comprehensive evaluation index is introduced, which can more effectively evaluate the comprehensive difference of wind field retrieval results in wind speed and direction. (2) The adaptability results of MP model in different periods and altitudes provide some reference for the research of other scholars. (3) The new parameter setting can improve the accuracy of the retrieved results, and the appropriate extrapolation of wind field fills in the blank part of aviation and meteorology.

This study represents a self-consistent three-dimensional (3D) fluid plasma model coupled with Maxwell equations at an intermediate pressure between 1000 and 5000 Pa. The model was established using the finite element method to analyze the effects of time–space characteristics, which is the variation of plasma parameters with time and the 3D spatial distribution of plasma parameters in the plasma torch at various times. The numerical modeling was demonstrated in three different stages, where the growth of electron density is associated with time. From the distribution characteristics of molecular ions, it can be concluded that they are distributed mainly at the port of the quartz tube of the torch, which is larger than the center of the tube. The density ratio of molecular ion to electron is decreased because of the reduction of pressure and distance, which has been calculated from the port to the center of the quartz tube. The analysis of microwave plasma parameters indicated that intermediate pressure is useful for modeling and plasma source designing, especially for carbon dioxide conversion.

A new simplified analysis is carried out to predict the dynamic response of clamped metal sandwich plates with various lattice cores subjected to impulsive loading. Based on the yield condition for sandwich plate cross-section, the interaction of bending moment and axial force for the section is decoupled. The simplified analytical solutions of the maximum midspan deflection and structural response time are obtained. Moreover, neglecting the effect of bending moment, a simplified plastic-string model is developed. Comparisons of the present theoretical predictions with previous analytical and numerical results are conducted and good agreement is achieved for a wide range of sandwich core topologies.

Damage can be identified using generalized flexibility matrix based methods, by using the first natural frequency and the corresponding mode shape. However, the first mode is not always appropriate to be used in damage detection. The contact interface of rod-fastened-rotor may be partially separated under bending moment which decreases the flexural stiffness of the rotor. The bending moment on the interface varies as rotating speed changes, so that the first- and second-modal parameters obtained are corresponding to different damage scenarios. In this paper, a structural damage detection method requiring single nonfirst mode is proposed. Firstly, the system is updated via restricting the first few mode shapes. The mass matrix, stiffness matrix, and modal parameters of the updated system are derived. Then, the generalized flexibility matrix of the updated system is obtained, and its changes and sensitivity to damage are derived. The changes and sensitivity are used to calculate the location and severity of damage. Finally, this method is tested through numerical means on a cantilever beam and a rod-fastened-rotor with different damage scenarios when only the second mode is available. The results indicate that the proposed method can effectively identify single, double, and multiple damage using single nonfirst mode.

Central poststroke pain (CPSP) is a medical complication that arises poststroke and significantly impacts the quality of life and social functioning of affected individuals. Despite ongoing research, the exact pathomechanisms of CPSP remain unclear, and practical treatments are still unavailable. Our review aims to systematically analyse current clinical and preclinical studies on CPSP, which is critical for identifying gaps in knowledge and guiding the development of effective therapies. The review will clarify the clinical characteristics, evaluation scales and contemporary therapeutic approaches for CPSP based on clinical investigations. It will particularly emphasise the CPSP model initiated by stroke, shedding light on its underlying mechanisms and evaluating treatments validated in preclinical studies. Furthermore, the review will not only highlight methodological limitations in animal trials but also offer specific recommendations to researchers to improve the quality of future investigations and guide the development of effective therapies. This review is expected to provide valuable insights into the current knowledge regarding CPSP and can serve as a guide for future research and clinical practice. The review will contribute to the scientific understanding of CPSP and help develop effective clinical interventions.