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Copper, permalloy, cobalt, and silicon are the materials that have been widely utilised in magnetic devices. When the size of interest is down to the nanoscale, the inter-diffusion between certain materials becomes influential. This paper studies the nanoscale friction characteristics between frictional pairs with and without inter-diffusion properties through the atomic force microscope. The distinct evolution features of nanoscale friction force when inter-diffusion is involved are discovered experimentally, which is also confirmed through theoretical analysis. Firstly, through the thin film deposition method, four pairs of contact materials (Cu–Ni81Fe19, Si–Ni81Fe19, Cu–Co, Cu–Si) are designed for friction tests, in which diffusion occurs at the interface of Cu–Ni81Fe19 pair. Then, the effects of sliding velocity and loading force on the nano friction of each pair are measured. It is found that regardless of the diffusion phenomenon: (1) the adhesion force values exhibit a notable correlation to the values of the friction force; (2) the friction force in all four material pairs consistently increases with the growth of the normal loading force, although the growth rate may differ. In terms of the sliding velocity effect, the friction forces of immiscible materials (Si–Ni81Fe19, Cu–Co, and Cu–Si) are found to increase with the increasing sliding velocity. However, the friction force of Cu–Ni81Fe19, decreases with the increasing sliding velocity. Furthermore, a compositive friction model considering both the velocity and the normal force effect was proposed, which shows good agreement with the experimental results and explains the nano friction behaviour of both miscible and immiscible metals. [ABSTRACT FROM AUTHOR]

Due to the broadband response and high sensitivity to low excitation levels, bistable energy harvesters (BEHs) have been viewed as an efficient method to overcome the shortcomings of linear energy harvesters only performing well near the resonant frequency. Previously, most strategies for performance enhancement of BEHs have been extensively discussed for systems with perfectly symmetric potentials. However, it is difficult to achieve a BEH with a perfectly symmetric potential due to practical constraints and previous investigations indicated that asymmetric potentials have a negative effect on the performance of BEH. Therefore, an adjustable unilateral stopper is introduced and positioned at the side with deeper potential well to broaden the response frequency band. Numerical simulations of bifurcation diagrams and maps of 0–1 test and output power indicate that the introduction of the stopper could enable the asymmetric BEH to realize interwell oscillation in a wider frequency range, and the performance are closely related to the collision gap, collision position, excitation frequency, as well as excitation levels. Regarding the basins of attraction, it is demonstrated that the stopper leads the system to achieve interwell oscillation with a high probability under certain excited conditions. Overall, this study provides a possible strategy for improving the performance of the asymmetric BEHs. [ABSTRACT FROM AUTHOR]

Friction-induced vibration is very common in engineering areas, such as aerospace, high-speed railways, robotics, and human/artificial joints. Analysing the dynamic behaviour of systems containing a multiple-contact point frictional interface is an important topic. However, accurately simulating nonsmooth/discontinuous dynamic behaviour due to friction is challenging. This paper presents a new physics-informed neural network approach for solving nonsmooth dynamic problems involved in the friction-induced vibration or friction-involved vibration. Compared with schemes of the conventional time-stepping methodology, this novel computational framework integrates the theoretical formulations of nonsmooth multibody dynamics into the training process of the neural network. We found that this new framework can not only more accurately simulate nonsmooth dynamic behaviours, but also could be a promising method to improve the efficiency as it eliminates the need for extremely small time steps typically associated with the conventional time-stepping methodology for multibody systems. Specifically, four kinds of high-accuracy Physics-informed-neural network (PINN) strategies were proposed: (1) single PINN; (2) dual PINN; (3) advanced single PINN; and (4) advanced dual PINN. Two typical dynamics problems with nonsmooth contact were simulated, including a 1-dimensional contact problem with stick–slip and a 2-dimensional contact problem considering separation–reattachment and stick–slip. Both single and dual PINN methods showed their advantages in dealing with the 1-dimensional stick–slip problem, which outperformed conventional methods across friction models that are difficult to simulate with the conventional time-stepping method. In contrast, the advanced single and advanced dual PINN methods provided better accuracy in simulating the 2-dimensional problem, even in the cases where conventional methods failed to simulate. [ABSTRACT FROM AUTHOR]

Carbonate rock chemical weathering carbon sinks reduce the rate of increase of the atmospheric CO2 concentration and global warming. However, uncertainty still exists in the estimation results of carbonate rock chemical weathering carbon sink fluxes (CCSF), and the contributions of climate change and ecological restoration to the CCSF are not clear. To this end, we compiled published site data on ion concentrations in different watersheds in China and used a classical thermodynamic dissolution model to reassess the potential and spatial and temporal patterns of the CCSF in China from 1991 to 2020. We quantified the contributions of temperature (MAT), precipitation (MAP), evapotranspiration (ET), soil water (SM), and the normalized difference vegetation index (NDVI) to the CCSF. The results revealed that (1) China's CCSF was 22.76 t CO2 km−2 yr−1, which was higher than the global average (15.771CO2 km−2 yr−1). The total carbonate rock chemical weathering carbon sink (CCS) was 4772.67×104 t CO2, contributing 14.91% of the global CCS through a carbonate rock area of 252.98×104 km−2. (2) China's CCSF decreased gradually from southeast to northwest, with values of 33.14, 12.93, and 7.27 t CO2 km−2 yr−1 in the southern karst, Qinghai-Tibetan karst, and northern karst regions, respectively. (3) The overall CCSF in China exhibited an increasing trend from 1991 to 2020, with a rate of increase of 0.16 t CO2 km−2 yr−1. (4) The contributions of the MAP, MAT, ET, SM, and NDVI to the CCSF were 63.3%, 3.02%, 27.5%, 3.1%, and 3.05%, respectively. Among them, the increase in precipitation was the main contributor to the increase in the CCSF in China over the last 30 years, while the enhancement of ET offset part of the positive contribution of the increase in precipitation to the CCSF. In conclusion, the results of this study provide a systematic quantification of the magnitude, the patterns, and the influencing factors of CCS over a long time series in China. The results are of great significance and provide a reference for the diagnosis and gap analysis of the national and global carbon neutrality capacities. [ABSTRACT FROM AUTHOR]

Modelling and simulating of the friction-induced vibration of a multi-point contact system are widely encountered and challenging problems. Non-smooth transitions between stick and slip and between contact and separation (during vibration) at each contact point can happen simultaneously in practice, which should be considered together in a theoretical model. This work is innovative in that it addresses the comprehensive dynamic analysis of a multi-point contact system considering the two types of complex non-smooth behaviour at the interface as well as mode-coupling instability, which has not been studied in previous research on multi-point contact dynamics, to the authors' best knowledge. To deal with this complex situation, a new mix-level time iteration scheme for the simulations of the non-smooth/discontinuous system with elastic contact and friction is formulated. This is an essential step as it provides a generic and effective approach that can be used for different systems with the same contact features regardless of the internal structural configurations of the systems. Interesting results and discoveries through a detailed dynamic analysis of a 10-DoF system with two sliders are reported: (1) the mass and mass ratio between the components linked with the contact interface are the essential factors of mode-coupling instability and mode-veering phenomenon through the stability analysis. These findings serve to guide the subsequent transient analysis, which is much more time-consuming and would otherwise be costly to use for revealing the roles of these masses; (2) the individual contributions of non-smoothness and mode-coupling instability, and the critical influences of the contact states, the normal compression force, and the belt speed on the vibration frequency and non-stationary vibration range of the components in the system are clarified from the complex dynamic behaviour. [ABSTRACT FROM AUTHOR]

Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease. Here, the authors perform a whole-genome sequencing association analysis of genetic variants in ≤11,840 multi-ethnic participants with ≤1666 circulating metabolites, discovering 1985 novel variant-metabolite associations and insights into human disease. [ABSTRACT FROM AUTHOR]

Venous thromboembolism occurs in up to one-third of patients with COVID-19. Venous thromboembolism and COVID-19 may share a common genetic architecture, which has not been clarified. To fill this gap, we leverage summary-level genetic data from the latest COVID‐19 host genetics consortium and UK Biobank and examine the shared genetic etiology and causal relationship between COVID-19 and venous thromboembolism. The cross-trait and co-localization analyses identify 2, 3, and 4 shared loci between venous thromboembolism and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, which are mapped to ABO, ADAMTS13, FUT2 genes involved in coagulation functions. Enrichment analysis supports shared biological processes between COVID-19 and venous thromboembolism related to coagulation and immunity. Bi-directional Mendelian randomization suggests that venous thromboembolism was associated with higher risk of three COVID-19 traits, and SARS-CoV-2 infection was associated with a higher risk of venous thromboembolism. Our study provides timely evidence for the genetic etiology between COVID-19 and venous thromboembolism (VTE). Our findings contribute to the understanding of COVID-19 and VTE etiology and provide insights into the prevention and comorbidity management of COVID-19. Joint analysis of existing summary statistics data using genome-wide crosstrait analysis and bi-directional Mendelian randomization provides further evidence for a shared genetic etiology between COVID-19 and venous thromboembolism. [ABSTRACT FROM AUTHOR]

Ample evidence suggests that estrogen replacement therapy is associated with beneficial effects with regard to cardiovascular diseases when the therapy is initiated temporally close to menopause but not when it is initiated later. Little is known about the complex interactions between hormone receptors after menopause. Coronary artery function and cardiac function were measured in rats that had either received no treatment or had been pretreated with an androgen receptor (AR) antagonist and/or a GPER agonist G-1. ICI 182,780 was used to block the classical estrogen receptors (ERs) to investigate their complex interactions with GPER. The beneficial effects of GPER were only observed by blocking ARs and classical ERs in aged female rats. The results demonstrate that GPER activation is a potential therapeutic target for the inhibition of age-dependent coronary artery dysfunction and cardiac dysfunction under the condition of blocking ARs and classical ERs after menopause. Clinical Relevance: The risk of cardiovascular disease in postmenopausal women significantly increased. The role of sex hormones and their receptors during this process is still complicated. Our present study demonstrated that the imbalance of androgen and estrogen may contribute to the impairment of vascular reactivity and subsequent cardiac function. Treatment with GPER agonist G1 combined with the inhibition of ERα and ERβ could improve vascular function and reduce the myocardial ischemia reperfusion injury. These findings may provide the novel and effective strategy for the treatment of cardiovascular diseases in postmenopausal women. [ABSTRACT FROM AUTHOR]

Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids. Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data. [ABSTRACT FROM AUTHOR]

A thermoelectric generation (TEG) system has the weakness of relatively low thermoelectric conversion efficiency caused by heterogeneous temperature distribution (HgTD). Dynamic reconfiguration is an effective technique to improve its overall energy efficiency under HgTD. Nevertheless, numerous combinations of electrical switches make dynamic reconfiguration a complex combinatorial optimization problem. This paper aims to design a novel adaptive coordinated seeker (ACS) based on an optimal configuration strategy for large-scale TEG systems with series–parallel connected modules under HgTDs. To properly balance global exploration and local exploitation, ACS is based on 'divide-and-conquer' parallel computing, which synthetically coordinates the local searching capability of tabu search (TS) and the global searching capability of a pelican optimization algorithm (POA) during iterations. In addition, an equivalent re-optimization strategy for a reconfiguration solution obtained by meta-heuristic algorithms (MhAs) is proposed to reduce redundant switching actions caused by the randomness of MhAs. Two case studies are carried out to assess the feasibility and superiority of ACS in comparison with the artificial bee colony algorithm, ant colony optimization, genetic algorithm, particle swarm optimization, simulated annealing algorithm, TS, and POA. Simulation results indicate that ACS can realize fast and stable dynamic reconfiguration of a TEG system under HgTDs. In addition, RTLAB platform-based hardware-in-the-loop experiments are carried out to further validate the hardware implementation feasibility. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumours (NETs) are rare cancers with positive somatostatin receptor 2 (SSTR2) expression, and treatment strategies for NETs are not satisfactory. Nanomaterial-mediated therapy targeting SSTR2 in NETs is very promising. This study firstly combined mesoporous silica-coated gold nanorods (AuNRs@mSiO2) and targeting-SSTR2 dodecane tetraacetic acid-tyrosine3-octreotate (DOTA-TATE) into AuNRs@mSiO2@DOTA-TATE to investigate NETs inhibition under near-infrared light. AuNRs@mSiO2@DOTA-TATE showed good photothermal conversion efficiency. In vitro, under light irradiation, the cell viability significantly decreased with increasing AuNR@mSiO2@DOTA-TATE concentration; in two successfully established neuroendocrine tumour organoids with SSTR2 expression, AuNRs@mSiO2@DOTA-TATE with light inhibited tumours significantly better than AuNRs@mSiO2 with light. In vivo, the SSTR2-targeting ability and biodistribution of AuNRs@mSiO2@DOTA-TATE were confirmed with AuNRs@mSiO2@64Cu-DOTA-TATE under micro-positron emission tomography/computed tomography (micro-PET/CT); in the AuNRs@mSiO2@DOTA-TATE with laser group, the tumour surface temperature increased rapidly, with tumour volumes similar to those in the octreotide group and significantly lower than those in other groups. There was no significant difference in mice body weight between the AuNRs@mSiO2@DOTA-TATE with laser group and other groups. No significant inflammatory lesions or cell necrosis was found in the main organs. In summary, we presented a feasible strategy to construct AuNRs@mSiO2@DOTA-TATE with good photothermal conversion efficiency, targeting-SSTR2 ability, significant antitumour effects, and good biocompatibility, warranting further explorations of AuNRs@mSiO2@DOTA-TATE for NETs therapy applications. [ABSTRACT FROM AUTHOR]

Mouse caspase-11 and human caspase-4 and caspase-5 recognize cytosolic lipopolysaccharide (LPS) to induce pyroptosis by cleaving the pore-forming protein GSDMD1–5. This non-canonical inflammasome defends against Gram-negative bacteria6,7. Shigella flexneri, which causes bacillary dysentery, lives freely within the host cytosol where these caspases reside. However, the role of caspase-11-mediated pyroptosis in S. flexneri infection is unknown. Here we show that caspase-11 did not protect mice from S. flexneri infection, in contrast to infection with another cytosolic bacterium, Burkholderia thailandensis8. S. flexneri evaded pyroptosis mediated by caspase-11 or caspase 4 (hereafter referred to as caspase-11/4) using a type III secretion system (T3SS) effector, OspC3. OspC3, but not its paralogues OspC1 and 2, covalently modified caspase-11/4; although it used the NAD+ donor, this modification was not ADP-ribosylation. Biochemical dissections uncovered an ADP-riboxanation modification on Arg314 and Arg310 in caspase-4 and caspase-11, respectively. The enzymatic activity was shared by OspC1 and 2, whose ankyrin-repeat domains, unlike that of OspC3, could not recognize caspase-11/4. ADP-riboxanation of the arginine blocked autoprocessing of caspase-4/11 as well as their recognition and cleavage of GSDMD. ADP-riboxanation of caspase-11 paralysed pyroptosis-mediated defence in Shigella-infected mice and mutation of ospC3 stimulated caspase-11- and GSDMD-dependent anti-Shigella humoral immunity, generating a vaccine-like protective effect. Our study establishes ADP-riboxanation of arginine as a bacterial virulence mechanism that prevents LPS-induced pyroptosis.This study reports the identification of a new post-translational modification, termed ADP riboxanation, which is mediated by the Shigella effector OspC3 and inactivates the cytosolic LPS sensing pathway of caspase-4 and caspase-11. [ABSTRACT FROM AUTHOR]