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RNA interference (RNAi) in plants can move from cell to cell, allowing for systemic spread of an antiviral immune response. How this cell-to-cell spread of silencing is regulated is currently unknown. Here, we describe that the C4 protein from Tomato yellow leaf curl virus can inhibit the intercellular spread of RNAi. Using this viral protein as a probe, we have identified the receptor-like kinase (RLK) BARELY ANY MERISTEM 1 (BAM1) as a positive regulator of the cell-to-cell movement of RNAi, and determined that BAM1 and its closest homolog, BAM2, play a redundant role in this process. C4 interacts with the intracellular domain of BAM1 and BAM2 at the plasma membrane and plasmodesmata, the cytoplasmic connections between plant cells, interfering with the function of these RLKs in the cell-to-cell spread of RNAi. Our results identify BAM1 as an element required for the cell-to-cell spread of RNAi and highlight that signaling components have been coopted to play multiple functions in plants.

Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling. Acute myocardial infarction (AMI) was induced by ligating left anterior descending (LAD) coronary artery. Autophagy was found to be induced sharply 12-24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day) or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day) one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation in vitro. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. In vitro, inhibition of NFκB restored autophagy in a negative reflex. Sustained myocardial ischemia impairs cardiomyocyte autophagy, which is an essential mechanism that protects against adverse cardiac remodeling. Augmenting autophagy could be a therapeutic strategy for acute myocardial infarction.

Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis . The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 ( AGO5 ). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing. Histone 3 Lys 27 trimethylation (H3K27me3) mediates epigenetic silencing of gene expression. Here, Zhang et al. show that in Arabidopsis, the BAH-domain H3K27me3-reader protein AIPP3 forms a complex with PHD proteins and CPL2, a plant-specific Pol II phosphatase, to inhibit Pol II activity by dephosphorylation.

In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the antiviral methylation of the Tomato yellow leaf curl virus (TYLCV) genome requires the Cajal body in Nicotiana benthamiana cells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is necessary for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and antiviral DNA methylation, paving the way for a deeper understanding of DNA methylation and antiviral defences in plants.

Background: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus, eventually leads to heart failure. Carvacrol is a food additive with diverse bioactivities. We aimed to study the protective effects and mechanisms of carvacrol in DCM.Methods: We used a streptozotocin-induced and db/db mouse model of types 1 and 2 diabetes mellitus (T1DM and T2DM), respectively. Both study groups received daily intraperitoneal injections of carvacrol for 6 weeks. Cardiac remodeling was evaluated by histological analysis. We determined gene expression of cardiac remodeling markers ( Nppa and Myh7 ) by quantitative real-time PCR and cardiac function by echocardiography. Changes of PI3K/AKT signaling were determined with Western blotting. GLUT4 translocation was evaluated by Western blotting and immunofluorescence staining.Results: Compared with control mice, both T1DM and T2DM mice showed cardiac remodeling and left ventricular dysfunction. Carvacrol significantly reduced blood glucose levels and suppressed cardiac remodeling in mice with T1DM and T2DM. At the end of the treatment period, both T1DM and T2DM mice showed lesser cardiac hypertrophy, Nppa and Myh7 mRNA expressions, and cardiac fibrosis, compared to mice administered only the vehicle. Moreover, carvacrol significantly restored PI3K/AKT signaling, which was impaired in mice with T1DM and T2DM. Carvacrol increased levels of phosphorylated PI3K, PDK1, AKT, and AS160 and inhibited PTEN phosphorylation in mice with T1DM and T2DM. Carvacrol treatment promoted GLUT4 membrane translocation in mice with T1DM and T2DM. Metformin was used as the positive drug control in T2DM mice, and carvacrol showed comparable effects to that of metformin on cardiac remodeling and modulation of signaling pathways.Conclusion: Carvacrol protected against DCM in mice with T1DM and T2DM by restoring PI3K/AKT signaling-mediated GLUT4 membrane translocation and is a potential treatment of DCM.

Carotid intima-media thickness (CIMT) is considered a marker of subclinical atherosclerosis; however, its reliability in predicting cardiovascular risk across different populations remains controversial. This study aimed to evaluate the correlation between B-mode ultrasound-measured CIMT and traditional cardiovascular risk scoring systems, and to investigate its value as a marker of cardiovascular risk. This cross-sectional study included 328 asymptomatic adults (excluding those with established cardiovascular disease). High-resolution B-mode ultrasound was used to measure CIMT bilaterally in the common carotid artery (CCA), carotid bulb, and internal carotid artery (ICA), and to calculate mean and maximum CIMT values. The Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) were computed, and data on traditional cardiovascular risk factors were collected. Pearson or Spearman correlation analyses, ROC curve analysis, and multivariate regression analysis were used to assess the relationship between CIMT and cardiovascular risk. The mean age of the 328 participants was 59.3 ± 10.2 years, with males comprising 48.2% of the cohort. The mean CIMT was 0.74 ± 0.09 mm, and the maximum CIMT was 0.95 ± 0.11 mm. CIMT showed significant positive correlations with both FRS (  = 0.68,  < 0.001) and PCE (  = 0.64,  < 0.001).Multivariate analysis demonstrated that mean CIMT (OR = 1.46, 95% CI: 1.23-1.72) and maximum CIMT (OR = 1.58, 95% CI: 1.31-1.91) were independently associated with high cardiovascular risk categories as defined by FRS and PCE after adjusting for traditional risk factors. ROC curve analysis revealed that maximum CIMT had an AUC of 0.79 (95% CI: 0.73-0.85) for identifying high FRS risk (>20%) and an AUC of 0.76 (95% CI: 0.70-0.82) for identifying high PCE risk (>7.5%). B-mode ultrasound-measured CIMT significantly correlates with traditional cardiovascular risk scores and is independently associated with high cardiovascular risk categories after adjustment for traditional risk factors. CIMT measurements of the carotid bulb appear to show stronger correlation with risk scores than common carotid artery measurements. CIMT demonstrates correlation with established risk scoring systems and shows the most significant risk reclassification effect in intermediate-risk populations, supporting its potential utility as a complementary assessment tool.

Empagliflozin (EMPA) is an SGLT-2 inhibitor that can control hyperglycemia. Clinical trials have indicated its cardio-protective effects against cardiac remodeling in diabetes or non-diabetes patients. However, the underlying molecular mechanisms of EMPA's cardio-protective effects remain elusive. We evaluated whether the EMPA attenuated the pressure-overload-induced cardiac hypertrophy by inhibiting the Wnt/β-catenin pathway. Furthermore, the effects of the EMPA on a mouse model of transverse aortic constriction (TAC) induced cardiac hypertrophy was also evaluated. Mice were administrated with 0.5% CMC-Na as a vehicle or EMPA (10 mg/kg/day, daily, throughout the study) by intragastric gavage. The echocardiography and histologic morphological analyses revealed that EMPA attenuated TAC-induced cardiac hypertrophy. Moreover, it also ameliorated TAC-induced cardiac fibrosis and decreased the cell size of the cardiomyocytes in isolated adult cardiomyocytes. Molecular mechanism analysis revealed that the EMPA reduced the TAC-induced enhanced expression of the Wnt/β-catenin pathway . For assessments, isolated neonatal rat cardiomyocytes (NRCMs) were treated with Angiotensin II (AngII) and EMPA; the results showed that in the absence of EMPA, the expression of the Wnt/β-catenin pathway was enhanced. In the trans-genetic heterozygous β-catenin deletion mice, EMPA attenuated TAC-induced cardiac remodeling by reducing the Wnt/β-catenin pathway. In addition, molecular docking analysis indicated that EMPA interacts with FZD4 to inhibit the TAC and AngII induced Wnt/β-catenin pathway in cardiomyocytes. Our study illustrated that EMPA might directly interact with FZD4 to inhibit the TAC and AngII-induced activation of the Wnt/β-catenin pathway to attenuate the adverse cardiac remodeling.

Accurate core loss evaluation is essential in the design of magnetic components. Core loss is critically influenced by excitation waveform, temperature, and magnetic material; therefore, we develop a waveform equivalence coefficient, a temperature polynomial, and an electrical conductivity term to revise the Steinmetz Equation and propose a physics–data dual-driven core loss model across materials and operating conditions. The waveform equivalence coefficient achieved 100% waveform classification, and temperature polynomial modification reduced the mean square error by an order of magnitude. Using three-way analysis of variance (ANOVA), we measured the individual and synergistic impacts of the three key factors on core loss. The waveform exerts the greatest individual influence while waveform and material, as a combination, exerts the greatest synergistic influence. Given the discovery that Material 1 demonstrates a property transition point under triangular waveform, the dual-objective optimization result indicates that using Material 1 under operating conditions of 90 °C, 501,180 Hz frequency, 0.0047 T peak flux density, and a triangular excitation waveform enables the magnetic component to achieve minimum core loss with maximum transmitted magnetic energy.

To characterize volume reduction in benign solid and predominantly solid thyroid nodules during long-term ultrasound surveillance, and to describe distinct absorption patterns over time. This retrospective study included 34 solid or predominantly solid thyroid nodules from 32 patients (median age, 46 years; 78.1% female), who underwent longitudinal ultrasound surveillance for a median of 28 months (interquartile range, 47-120 months). Volumetric measurements were obtained at multiple time points. Generalized additive mixed models (GAMMs) were employed to model nonlinear trends in volume over time. Unsupervised clustering was applied to identify representative regression trajectories based on individual volume curves. Clinical and ultrasound features were compared between trajectory-defined groups. All nodules exhibited measurable volume decrease over time (median reduction: 85.6%). Two representative volume change patterns were identified: a rapid-absorption group with early shrinkage and a slow-absorption group with gradual decline. Nodules in the latter were more frequently located in the lower pole and lacked Doppler flow at baseline ( < 0.05). Some nodules developed hypoechoic or stiff appearances over time, leading to higher TIRADS categories despite continuous shrinkage and no clinical signs of malignancy. Solid and predominantly solid thyroid nodules can undergo significant volume reduction during long-term surveillance, resembling the well-documented absorption phenomenon of cystic nodules. This phenomenon may be underrecognized in clinical practice. Describing the diversity of volume change patterns may improve the understanding and interpretation of nodule evolution during follow-up.

The prediction of chemical oxygen demand (COD) by ultraviolet–visible absorption spectrum is a common method. Many researchers use the absorbance at the characteristic wavelength to establish COD prediction models. However, selecting the characteristic wavelength is a problem. In this paper, the extreme values of absorption spectrum change rate, was proposed as a new characteristic parameter to determine the characteristic wavelengths. On this basis, a novel hybrid strategy for detecting COD in surface water was proposed. We first proposed to combine the first derivative method with the permutation entropy method (FDPE) to determine the characteristic wavelengths. Then we used partial least square (PLS) to establish a COD prediction model. Experimental results demonstrated the linear correlation coefficient (R2) of the FDPE_PLS was above 0.99 without turbidity interference. Secondly, a dual-wavelength method (DWM) was proposed to determine the turbidity values. The DWM used slopes of absorbance values at 400 nm and 600 nm to predict the turbidity values. Compared with the single-wavelength method, the DWM improves the measurement accuracy of turbidity. Finally, a new turbidity compensation method was proposed to compensate for the interference in the first derivative spectrum. After compensation, FDPE_PLS can predict COD concentrations accurately, whose R2 was 0.99.