Dynamic Hybrid Models With Active Sampling and Adaptive Selection of Double-Domain Features for the Tuning of Microwave Cavity Filters.

Microwave cavity filters are essential electromechanical coupling devices in communication systems. Structural-parameter tuning by experienced operators improves the filter performance but is demanding and time-consuming. The automatic tuning method has received extensive research attentions using data-driven modeling approaches. However, two main issues affect the accuracy and efficiency of the model construction: 1) features of tuning processes, as model inputs, have limited adaptability and extraction accuracy to different resonant states and 2) models require plentiful training data and the training process is time-consuming. Thus, dynamic hybrid models are developed in this study with self-selected inputs, self-organized samples, and a self-learning structure. First, spatial features are extracted to flexibly depict the tuning characteristic, and double-domain (spatial or circuital) features are selected adaptively to accommodate distinct resonance states. Second, a trustworthiness-curiosity-driven active sampling method is exploited to attain fewer and better-training data. Third, an improved glsms broad learning system acrlong BLS is developed using new modules of incremental node calculation and weight pruning, characterized by more lightweight and flexible structures. The proposed method is effective and flexible demonstrated by simulations and experiments, and the tuning task of microwave cavity filters is fulfilled in a more accurate and efficient manner.

A Study on the Application Performance of High-Aspect-Ratio Nano-Ettringite in Photocurable Resin Composites.

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored. The nano-ettringite samples were modified using γ-Aminopropyltriethoxysilane (KH-550) and γ-methacryloxypropyl trimethoxy silane (KH-570). Then, 3 wt% or 6 wt% KH-550-modified, KH-570-modified, and unmodified nano-ettringite samples were dispersed into resin via ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-550 or KH-570 were analyzed through scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric (TG) analysis. The results demonstrate that KH-550 and KH-570 have been successfully grafted onto the surface of nano-ettringite. In addition, this study also focuses on the variations of composite materials in the viscosity, shrinkage, tensile strength, and elongation at break. The results indicate that increased dosages of unmodified, KH-550-modified, and KH-570-modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin containing KH-570-modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. From the analysis of tensile fracture surfaces, it was observed that compared to the KH-550 modified and unmodified variants, the KH-570 modified nano-ettringite exhibits superior dispersibility in photocurable epoxy acrylate resin. Notably, when the amount of KH-570-modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, representing a 72.57% increase compared to the blank sample. Furthermore, the incorporation of KH-570-modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Association between epigenetic age and type 2 diabetes mellitus or glycemic traits: A longitudinal twin study.

Epigenetic clocks based on DNA methylation have been known as biomarkers of aging, including principal component (PC) clocks representing the degree of aging and DunedinPACE representing the pace of aging. Prior studies have shown the associations between epigenetic aging and T2DM, but the results vary by epigenetic age metrics and people. This study explored the associations between epigenetic age metrics and T2DM or glycemic traits, based on 1070 twins (535 twin pairs) from the Chinese National Twin Registry. It also explored the temporal relationships of epigenetic age metrics and glycemic traits in 314 twins (157 twin pairs) who participated in baseline and follow-up visits after a mean of 4.6 years. DNA methylation data were used to calculate epigenetic age metrics, including PCGrimAge acceleration (PCGrimAA), PCPhenoAge acceleration (PCPhenoAA), DunedinPACE, and the longitudinal change rate of PCGrimAge/PCPhenoAge. Mixed-effects and cross-lagged modelling assessed the cross-sectional and temporal relationships between epigenetic age metrics and T2DM or glycemic traits, respectively. In the cross-sectional analysis, positive associations were identified between DunedinPACE and glycemic traits, as well as between PCPhenoAA and fasting plasma glucose, which may be not confounded by shared genetic factors. Cross-lagged models revealed that glycemic traits (fasting plasma glucose, HbA1c, and TyG index) preceded DunedinPACE increases, and TyG index preceded PCGrimAA increases. Glycemic traits are positively associated with epigenetic age metrics, especially DunedinPACE. Glycemic traits preceded the increases in DunedinPACE and PCGrimAA. Lowering the levels of glycemic traits may reduce DunedinPACE and PCGrimAA, thereby mitigating age-related comorbidities.

A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection.

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.

TRANSPARENT TESTA GLABRA2 defines trichome cell shape by modulating actin cytoskeleton in Arabidopsis thaliana.

The Arabidopsis (Arabidopsis thaliana) TRANSPARENT TESTA GLABRA2 (TTG2) gene encodes a WRKY transcription factor that regulates a range of development events like trichome, seed coat, and atrichoblast formation. Loss-of-function of TTG2 was previously shown to reduce or eliminate trichome specification and branching. Here, we report the identification of an allele of TTG2, ttg2-6. In contrast to the ttg2 mutants described before, ttg2-6 displayed unique trichome phenotypes. Some ttg2-6 mutant trichomes were hyper-branched, whereas others were hypo-branched, distorted, or clustered. Further, we found that in addition to specifically activating R3 MYB transcription factor TRIPTYCHON (TRY) to modulate trichome specification, TTG2 also integrated cytoskeletal signaling to regulate trichome morphogenesis. The ttg2-6 trichomes displayed aberrant cortical microtubules (cMTs) and actin filaments (F-actin) configurations. Moreover, genetic and biochemical analyses showed that TTG2 could directly bind to the promoter and regulate the expression of BRICK1 (BRK1), which encodes a subunit of the actin nucleation promoting complex suppressor of cyclic AMP repressor (SCAR)/Wiskott-Aldrich syndrome protein family verprolin homologous protein (WAVE). Collectively, taking advantage of ttg2-6, we uncovered a function for TTG2 in facilitating cMTs and F-actin cytoskeleton-dependent trichome development, providing insight into cellular signaling events downstream of the core transcriptional regulation during trichome development in Arabidopsis.