Induction of type I IFN (IFN-I) is essential for host antiviral immune responses. However, IFN-I also plays divergent roles in antibacterial immunity, persistent viral infections, autoimmune ...diseases, and tumorigenesis. IFN regulatory factor 3 (IRF3) is the master transcription factor that controls IFN-I production via phosphorylation-dependent dimerization in most cell types in response to viral infections and various innate stimuli by pathogen-associated molecular patterns (PAMPs). To monitor the dynamic process of IRF3 activation, we developed a novel IRF3 dimerization reporter based on bimolecular luminescence complementation (BiLC) techniques, termed the IRF3-BiLC reporter. Robust induction of luciferase activity of the IRF3-BiLC reporter was observed upon viral infection and PAMP stimulation with a broad dynamic range. Knockout of TANK-binding kinase 1, the critical upstream kinase of IRF3, as well as the mutation of serine 386, the essential phosphorylation site of IRF3, completely abolished the luciferase activity of IRF3-BiLC reporter, confirming the authenticity of IRF3 activation. Taken together, these results demonstrated that the IRF3-BiLC reporter is a highly specific, reliable, and sensitive system to measure IRF3 activity. Using this reporter system, we further observed that the temporal pattern and magnitude of IRF3 activation induced by various PAMPs are highly complex with distinct cell type-specific characteristics, and IRF3 dimerization is a direct regulatory node for IFN-α/β receptor-mediated feed-forward regulation and crosstalk with other pathways. Therefore, the IRF3-BiLC reporter has multiple potential applications, including mechanistic studies as well as the identification of novel compounds that can modulate IRF3 activation.
IntroductionPharmacist-participated medication reconciliation proved an effective strategy to decrease the risk of medication discrepancy-related errors. However, it is still under pilot in China and ...its effectiveness in the Chinese healthcare system remains unclear. This study aims to conduct a pharmacist-participated medication reconciliation intervention for elderly patients in county hospitals in China and to evaluate its effect.Methods and analysisThis is a multicentre, prospective, open-label, assessor-blinded, cluster, non-randomised, controlled study for elderly patients. The study will be conducted in seven county hospitals, and the clusters will be hospital wards. In each hospital, two internal medicine wards will be randomly allocated into either intervention group or control group. Patients in the intervention group will receive pharmacist-participated medication reconciliation, and those in the control group will receive standard care. The primary outcome is the incidence of medication discrepancy, and the secondary outcomes are patients’ medication adherence, healthcare utilisation and medical costs within 30 days after discharge.Ethics and disseminationEthics committee approval of this study was obtained from Peking University Institution Review Board (IRB00001052-21016). We have also obtained ethical approvals from all the participating centres. The findings will be published in scientific and conference presentations.Trail registration numberChiCTR2100045668.
The normal and lateral (in the sliding direction) vibration can achieve 'dynamic superlubricity' at the atomic scale which has been studied and proved by other researchers. In this study, we have ...found that the lateral excitation (perpendicular to the sliding direction) which has rarely been studied before can also reduce the average friction force greatly. By utilizing the tip path on the interaction potential energy surface and plotting the interaction potential energy as a function of support position, we elucidated the reason of dynamic superlubricity caused by lateral excitation. The details of the lateral excitation at the atomic scale friction have been demonstrated by molecular dynamics simulations and numerical computation based on the Prandtl-Tomlinson model. This study can increase the understanding of the ultrasonic vibration excitation at atomic scale friction.
Base on the accurate inverse of a system, the feedforward compensation method can compensate the tracking error of a linear system dramatically. However, many control systems have complex dynamics ...and their accurate inverses are difficult to obtain. In the paper, a variable parameter model is proposed to describe a system and a multi-step adaptive seeking approach is used to obtain its parameters in real time. Based on the proposed model, a variable-parameter-model-based feedforward compensation method is proposed, and a disturbance observer is used to overcome the influence of the model uncertainty. Theoretical analysis and simulation results show that the variable-parameter-model-based feedforward compensation method can obtain better performance than the traditional feedforward compensation.
This study aims to determine hub genes related to the incidence and prognosis of EGFR-mutant (MT) lung adenocarcinoma (LUAD) with weighted gene coexpression network analysis (WGCNA). From The Cancer ...Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we used 253 EGFR-MT LUAD samples and 38 normal lung tissue samples. At the same time, GSE19188 was additionally included to verify the accuracy of the predicted gene. To discover differentially expressed genes (DEGs), the R package “limma” was used. The R packages “WGCNA” and “survival” were used to perform WGCNA and survival analyses, respectively. The functional analysis was carried out with the R package “clusterProfiler.” In total, 1450 EGFR-MT–specific DEGs were found, and 7 tumor-related modules were marked with WGCNA. We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (
p
< 0.05). Functional analysis of the hub genes showed the metabolism and protein synthesis–related terms added value. In conclusion, we used WGCNA to identify hub genes in the development of EGFR-MT LUAD. The established prognostic factors could be used as clinical biomarkers. To confirm the mechanism of those genes in EGFR-MT LUAD, further molecular research is required.
•The big five personality traits affect individuals’ disgust with eating insects.•The big five personality traits affect individuals’ interest in eating insects.•The effects of the big five ...personality traits differed between males and females.
Because of their comparatively high nutritious and various environmental advantages compared to other livestock, the academic and public interest in edible insects increased greatly. In previous studies, personality traits have been recognized as important factors in shaping consumers’ food choices and evaluations. However, the exploration of the connections between personality traits and entomophagy remains an area with limited research. With a valid sample size of 284 Japanese consumers, we investigated the relationships between the big five personality traits and attitudes towards entomophagy (i.e., disgust towards and interest in entomophagy). The analysis results indicate that the big five personality traits influence consumer attitudes towards entomophagy. More specifically, while conscientiousness and neuroticism present positive correlations with the disgust, openness presents a negative correlation with the disgust. Similarly, while openness presents a positive correlation with the interest, conscientiousness presents a negative correlation with the interest. Besides, agreeableness and extraversion show insignificant connections with both attitudes. We also examined gender differences and found that the correlations between the big five personality traits and the attitudes differ between males and females.
•Anthropomorphism can be a helpful tactic for promoting insect foods.•Psychological closeness mediates the anthropomorphic effect on purchase intention.•Food neophobia moderates the anthropomorphic ...effect on purchase intention.
There is growing academic and practical interest in entomophagy as a viable and sustainable solution to the environmental problems of conventional livestock production and future food crises. Although researchers are examining how to effectively increase consumer acceptance of insect food, the existing findings of relevant studies are limited. This study examined whether and how anthropomorphism, one of the most widely used marketing tactics for product promotions, affects consumers’ purchase intentions for insect foods. The results of these two studies demonstrate that anthropomorphic packaging can increase consumers’ purchase intentions for insect foods. Moreover, the effect of anthropomorphism on purchase intention was mediated by perceived psychological closeness to insect food. Our study demonstrates the moderating effect of food neophobia. Specifically, when an individual has a high food neophobia score, the effect of psychological closeness on purchase intention is weakened. This study is the first to demonstrate that anthropomorphic packaging can be a desirable tactic to increase consumers’ purchase intentions for insect foods, and reveals how and when the tactic is effective in promoting these foods.
A multi-objective optimization based robust beam-forming (BF) scheme is proposed to realize secure transmission in a cognitive satellite and unmanned aerial vehicle (UAV) net-work. Since the ...satellite network coexists with the UAV network, we first consider both achievable secrecy rate maximization and total transmit power minimization, and formulate a multi-object-ive optimization problem (MOOP) using the weighted Tchebycheff approach. Then, by supposing that only imperfect channel state information based on the angular information is available, we propose a method combining angular discretiza-tion with Taylor approximation to transform the non-convex ob-jective function and constraints to the convex ones. Next, we adopt semi-definite programming together with randomization technology to solve the original MOOP and obtain the BF weight vector. Finally, simulation results illustrate that the Pareto opti-mal trade-off can be achieved, and the superiority of our pro-posed scheme is confirmed by comparing with the existing BF schemes.
The collision between the Indian and Eurasian plates continues to drive significant deformation and uplift within the interior of the Tibetan Plateau, together with its outward expansion along the ...margins. In particular, the North Qilian Shan fold-thrust belt (NQLS) and the Hexi Corridor basins (HXBS) represent the northernmost region of the northeastern Tibetan Plateau. This area serves as a natural laboratory for deciphering mechanisms of crustal deformation and thickening along the plateau’s margins. Specifically, the northeastern Tibetan Plateau has been attributed to 1) southward underthrusting of the Asian lithosphere, 2) distributed shortening and crustal thickening, 3) vertical inflation of the Tibetan crust due to mid-lower crustal channel flow, and 4) intracontinental subduction facilitated by large-scale strike–slip faults. The exact mechanism underlying the most concentrated convergent stress in the western segment of NQLS–HXBS remains a subject of debate. To address this uncertainty, we gathered seismic data along a 130-km-long linear array that extends northward from NQLS, traversing the Jiuquan Basin and reaching the Huahai Basin. Our analysis, conducted through the receiver function method, reveals intriguing findings. The Moho depth deepens from 45–50 km beneath the Huahai Basin to 55–60 km beneath NQLS. Notably, a double Moho structure emerged, marked by a distinctive near-flat positive amplitude at a depth of 45–50 km beneath NQLS within a distance of 0–50 km. Our study presents a comprehensive analysis of the crust-scale deformation mechanism, shedding light on the following key aspects: 1) the development of a decollement at 12–20 km depth decoupling the upper and lower crust; 2) deformation of the upper crust occurring through south-dipping brittle thrust faults, while the lower crust features imbricate structures and duplexes; 3) evidence pointing to the underthrusting of the Beishan Block beneath NQLS, indicated by the double Moho beneath NQLS; and 4) the formation of a Moho ramp beneath the Jiuquan Basin, facilitating the transfer of shortening stress from beneath NQLS and HXBS to the north. In the context of the western segment of NQLS and HXBS, our speculation is that coupled distributed shortening and Beishan Block subduction beneath NQLS work in tandem to accommodate crustal deformation.
PDF
