Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis

Senescence, a stable state of growth arrest, affects many physiological and pathophysiological processes, especially aging. Previous work has indicated that transcription factors (TFs) play a role in regulating senescence. However, a systematic study of regulatory TFs during replicative senescence (RS) using multi-omics analysis is still lacking. Here, we generated time-resolved RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets during RS of mouse skin fibroblasts, which demonstrated that an enhanced inflammatory response and reduced proliferative capacity were the main characteristics of RS in both the transcriptome and epigenome. Through integrative analysis and genetic manipulations, we found that transcription factors E2F4, TEAD1 and AP-1 are key regulators of RS. Overexpression of E2f4 improved cellular proliferative capacity, attenuated SA-β-Gal activity and changed RS-associated differentially methylated sites (DMSs). Moreover, knockdown of Tead1 attenuated SA-β-Gal activity and partially altered the RS-associated transcriptome. In addition, knockdown of Atf3, one member of AP-1 superfamily TFs, reduced Cdkn2a (p16) expression in pre-senescent fibroblasts. Taken together, the results of this study identified transcription factors regulating the senescence program through multi-omics analysis, providing potential therapeutic targets for anti-aging.

Molecular Dynamics Simulation of Nanoscale Elastic Properties of Hydrated Na-, Cs-, and Ca-Montmorillonite

The knowledge of nanoscale mechanical properties of montmorillonite (MMT) with various compensation cations upon hydration is essential for many environmental engineering-related applications. This paper uses a Molecular Dynamics (MD) method to simulate nanoscale elastic properties of hydrated Na-, Cs-, and Ca-MMT with unconstrained system atoms. The variation of basal spacing of MMT shows step characteristics in the initial crystalline swelling stage followed by an approximately linear change in the subsequent osmotic swelling stage as the increasing of interlayer water content. The water content of MMT in the thermodynamic stable-state conditions during hydration is determined by comparing the immersion energy and hydration energy. Under this stable hydration state, the nanoscale elastic properties are further simulated by the constant strain method. Since the non-bonding strength between MMT lamellae is much lower than the boning strength within the mineral structure, the in-plane and out-of-plane strength of MMT has strong anisotropy. Simulated results including the stiffness tensor and linear elastic constants based on the assumption of orthotropic symmetry are all in good agreement with results from the literature. Furthermore, the out-of-plane stiffness tensor components of C33, C44, and C55 all fluctuate with the increase of interlayer water content, which is related to the formation of interlayer H-bonds and atom-free volume ratio. The in-plane stiffness tensor components C11, C22, and C12 decrease nonlinearly with the increase of water content, and these components are mainly controlled by the bonding strength of mineral atoms and the geometry of the hydrated MMT system. Young’s modulus in all three directions exhibits a nonlinear decrease with increasing water content.

The skyrmion annihilations induced by local reversal of background field in skyrmion lattice

The understanding of the creation and annihilation dynamics of a magnetic skyrmion is significant due to its potential applications in information storage and spintronics. Although there have been extensive investigations on the annihilation of isolated skyrmion, topological annihilation in periodic skyrmion lattice is a more complex process. We report a micromagnetic simulation study about the annihilation process of a two-dimensional skyrmion triangular lattice triggered by a uniform field HREV of comparable size to the skyrmion, which is opposite to the direction of the background field, revealing two annihilation modes. When the HREV center is within the range of a skyrmion, the neighboring skyrmions annihilate in situ, while the center is between adjacent skyrmions, anti-skyrmion is induced in the interstitial region. Both mechanisms tend to experience the intermediate topological vortex or antivortex structure, and the spin system undergoes a long period of relaxation to reach a stable state after the topological charge is stabilized. Our results present a local annihilation scheme that is easy to achieve in a 2D skyrmion lattice and highlight the role of interaction between skyrmions in the transformation between different kinds of topological defects.

Evolutionary Game Analysis of Responding to the EU’s Carbon Border Adjustment Mechanism

The European Union (EU) views the carbon border adjustment mechanism (CBAM) as a measure to tackle carbon leakage, which will have a profound impact on non-EU countries’ exports. Policymakers are faced with the question of how to deal with the CBAM. In contrast to previous studies, we explore the effects of the CBAM on non-EU countries from a dynamic game perspective. This study analyzed the potential effects of the CBAM on China and found that the government and export companies are the two main stakeholders. We found that they can both choose whether to respond actively or passively. Based on their interactive relationship, we adopted an evolutionary game to model the nexus between the government and export companies. We analyzed the evolutionary stable state of each stakeholder and the whole game with the replicator dynamic equation system. To make the system evolve to the optimal state where the government reacts actively and export companies implement low-carbon production, we provide a policy mechanism for how to set key parameters’ values. We used numerical simulation to verify the policy design and to conduct sensitivity analyses of the key parameters. Our results show that, when two stakeholders positively react to the CBAM, it is necessary to increase their profits and to reduce their costs. Therefore, some suggestions are proposed, including optimizing the trade structure, strengthening cooperation with the EU, improving the current carbon market, and adopting carbon tax.

Travel Reduction Control of Distributed Drive Electric Agricultural Vehicles Based on Multi-Information Fusion

In agricultural vehicles with internal combustion engines, owing to the use of rear-wheel drive or four-wheel drive, it is difficult to obtain information regarding the slip of the driving wheels. Excessive wheel slip, an inevitable phenomenon occurring during agricultural activities, can easily damage the original soil surface and result in excessive energy consumption. To solve these problems, a distributed drive agricultural vehicle (DDAV) based on multi-information fusion was proposed. The actual travel reduction of each wheel was calculated by determining the vehicle parameters in order to deliver the required torque to the four drive wheels via sliding mode control (SMC) and incremental proportional-integral (PI) control. Through this process, the vehicle always operates in a straight line. Test results show that, on a uniform surface, the travel reduction of each wheel can be maintained at the target value by using the incremental PI control strategy, with only minor fluctuations, to make the vehicle run in a straight line (R2 = 0.9999). Furthermore, on a separated surface, the travel reduction of each wheel can be maintained at the target value, and using the SMC strategy enables more identical coefficient of gross tractions for each wheel to make the vehicle run in a straight line (R2 = 0.9902). Unlike the non-control strategy, the vehicle reaches a stable state within 1 s, owing to the use of a controller that can effectively reduce the impact of road changes on vehicle velocity. This study can provide a reference for the drive control of DDAVs.

Modeling Cell Biological Features of Meiotic Chromosome Pairing

During meiosis, homologous chromosomes become associated side by side in a process known as homologous chromosome pairing. Pairing requires long range chromosome motion through a nucleus that is full of other chromosomes. It remains unclear how the cell manages to align each pair of chromosomes quickly while mitigating and resolving interlocks. Here, we use a coarse-grained molecular dynamics model to investigate how specific features of meiosis, including motor-driven telomere motion, nuclear envelope interactions, and increased nuclear size, affect the rate of pairing and the mitigation/resolution of interlocks. By creating in silico versions of three yeast strains and comparing the results of our model to experimental data, we find that a more distributed placement of pairing sites along the chromosome is necessary to replicate experimental findings. Active motion of the telomeric ends speeds up pairing only if binding sites are spread along the chromosome length. Adding a meiotic bouquet significantly speeds up pairing but does not significantly change the number of interlocks. An increase in nuclear size slows down pairing while greatly reducing the number of interlocks. Interestingly, active forces increase the number of interlocks, which raises the question: How do these interlocks resolve? Our model gives us detailed movies of interlock resolution events which we then analyze to build a step-by-step recipe for interlock resolution. In our model, interlocks must first translocate to the ends, where they are held in a quasi-stable state by a large number of paired sites on one side. To completely resolve an interlock, the telomeres of the involved chromosomes must come in close proximity so that the cooperativity of pairing coupled with random motion causes the telomeres to unwind. Together our results indicate that computational modeling of homolog pairing provides insight into the specific cell biological changes that occur during meiosis.

Research on seismic performance of traditional Chinese hall-style timber buildings in the Song and Yuan dynasties (960–1368 AD): a case study of the main hall of Baoguo Temple

The hall-style timber frame built in the Song and Yuan dynasties (960–1368 AD) is one of the most important structural prototypes of the traditional timber architecture in East Asia. The current research, through a typical case of the main hall of Baoguo Temple in Ningbo, China, aims to present an accurate and effective seismic performance evaluation method applicable to hall-style timber structures without time–cost expenditure. To obtain more realistic seismic response of hall-style timber frame, a simplified numerical model of the main hall of Baoguo Temple is established based on in situ measurements and low-cycle reversed loading tests results of mortise–tenon joints, moreover, nonlinear static pushover analysis has been performed to quantify the seismic performance levels under five loading conditions. The generalized force–deformation relationship of the timber plastic hinges is modified regarding to the moment–rotation curves of four special mortise–tenon joints. The seismic behaviour of global hall-style timber frame is evaluated through capacity spectrum method and verified by time history analysis, local failure mechanisms are evaluated by the occurrence sequence of plastic hinges. Finally, a performance-based assessment method adequate for the traditional hall-style timber architectures has been proposed with comparison to the current codes. The results have shown that the structural stiffness of the width-direction is less than that of the depth direction due to the asymmetrical configuration of the timber frame, and the building can maintain a stable state under large lateral displacement before collapsing. The inter-storey drift angles of the building under peak ground accelerations of 0.1 g, 0.2 g, and 0.3 g are less than the suggested ultimate values in the current local codes, however, the main hall represents to be more vulnerable to damage when suffer seismic action along the width-direction. This research can provide a reference for seismic performance evaluation and preventive conservation of ancient hall-style timber architectural heritage.

EVOLUTIONARY GAME ANALYSIS FOR RENT-SEEKING BEHAVIOR SUPERVISION OF MAJOR INFRASTRUCTURE PROJECTS BASED ON PROSPECT THEORY

Major infrastructure projects (MIPs) possess significant strategic positions in the national economy and social development. However, recently, the rent-seeking behavior between supervision units and project contractors has intensified in project construction. This paper aims to study the behavior decision-making of stakeholders in rent-seeking behavior supervision system of MIPs. In the complex and uncertain environment of MIPs, game players have cognitive bias and value perception preference. Therefore, this study introduced prospect theory and constructed the perceived return matrix and evolutionary game model of MIP rent-seeking behavior supervision among project owners, supervision units, and project contractors. From the perspective of risk perception theory, the reasons for the behavioral tendencies of game participants and the conditions for the steady state of strategy selection were explored through system dynamics simulations. The results showed that the stable state of the optimal strategy in the rent-seeking behavior supervision system of MIPs is related to the cognitive bias of the game players and is influenced by the level of regulation cost, the intensity of punishment and the size of accident losses. The contribution of this study lies in providing theoretical basis and decision support for constructing a long-term preventive mechanism for rent-seeking activities in MIPs.

A Systematic Review and Meta-Analysis of the Prevalence and Impact of Pulmonary Bacterial Colonisation in Stable State Chronic Obstructive Pulmonary Disease (COPD)

Background: Half of acute exacerbations of COPD are due to bacterial infection, and the other half are likely influenced by microbial colonisation. The same organisms commonly cultured during acute exacerbations are often found in the sputum of patients during stability. A robust assessment of the prevalence of potentially pathogenic microorganisms (PPMs) in the sputum of stable COPD patients may help to inform the targeted prevention of exacerbation by these organisms. Methods: A systematic review and meta-analysis was carried out to determine the prevalence of PPMs in patients with COPD in the stable state. Meta-analysis of prevalence was carried out using the Freeman–Tukey double arcsine transformation random effects model, and sub-group analysis was performed for sputum modality. Prevalence of total and individual PPMs was calculated from patient-level data from individual studies. Results: Pooled prevalence of PPMs identified by sputum culture was found to be 41% (95% CI 36–47%). Significant heterogeneity was found across all studies, which can likely be attributed to inconsistent measuring and reporting of PPMs. The most commonly reported organisms were H. influenzae, M catarrhalis, S. pneumoniae, S. aureus, and P. aeruginosa. Declining lung function was weakly correlated with prevalence of PPMs. Conclusion: The airways of patients with COPD are colonised with PPMs during the stable state in almost half of patients. A complex relationship likely exists between the microbiome in the stable state and the phenotype of COPD patients. Targeted microbial therapy for preventing exacerbations of COPD should carefully consider the stable microbiome as well as the exacerbated.

STUDY ON ACTIVE ANTI ROLLOVER CONTROL AND MODEL TEST OF TRACTOR MOMENTUM FLYWHEEL

The tractor working environment is complex and changeable, and the dynamic variation range of the center of gravity position of the tractor body is large. In order to avoid rollover accident, an active anti rollover control method of tractor momentum flywheel and its model test are proposed in this paper. The tractor dynamic system model and control strategy are verified by a 1:16 scale tractor model. The research results show that when the model tractor crosses the trapezoidal obstacle B, the roll angle of the whole machine is temporarily stable near 35 °, indicating that at this time, the tires on one side of the whole machine are in actual contact with the obstacle, showing a short stable state of the whole machine. When the pavement roughness reaches F-H level, without any active anti rollover control, the evaluation index EP shows a divergence trend when it is greater than 1, and the simulation calculation is terminated due to the occurrence of rollover of the whole machine. The test data and simulation results under two different driving speeds are in good agreement, which verifies the effectiveness and reliability of the tractor rollover dynamic system model and the momentum flywheel active stabilization system.