Temperature-dependent action of pepper mildew resistance locus O 1 in inducing pathogen immunity and thermotolerance.

Plant diseases tend to be more serious under conditions of high-temperature/high-humidity (HTHH) than under moderate conditions, and hence disease resistance under HTHH is an important determinant for plant survival. However, how plants cope with diseases under HTHH remains poorly understood. In this study, we used the pathosystem consisting of pepper (Capsicum annuum) and Ralstonia solanacearum (bacterial wilt) as a model to examine the functions of the protein mildew resistance locus O 1 (CaMLO1) and U-box domain-containing protein 21 (CaPUB21) under conditions of 80% humidity and either 28 °C or 37 °C. Expression profiling, loss- and gain-of-function assays involving virus-induced gene-silencing and overexpression in pepper plants, and protein-protein interaction assays were conducted, and the results showed that CaMLO1 acted negatively in pepper immunity against R. solanacearum at 28 °C but positively at 37 °C. In contrast, CaPUB21 acted positively in immunity at 28 °C but negatively at 37 °C. Importantly, CaPUB21 interacted with CaMLO1 under all of the tested conditions, but only the interaction in response to R. solanacearum at 37 °C or to exposure to 37 °C alone led to CaMLO1 degradation, thereby turning off defence responses against R. solanacearum at 37 °C and under high-temperature stress to conserve resources. Thus, we show that CaMLO1 and CaPUB21 interact with each other and function distinctly in pepper immunity against R. solanacearum in an environment-dependent manner.

Molecular characterization and ontogenetic expression profiles of LPXRFa and its receptor in Japanese flounder (Paralichthys olivaceus).

Investigations concerning the LPXRFa system are rarely conducted in flatfish species. Here, we first identified and characterized lpxrfa and its cognate receptor lpxrfa-r genes in the Japanese flounder (Paralichthys olivaceus). The coding DNA sequence of lpxrfa was 579 bp in length, wich encoded a 192-aa preprohormone that can produce three mature LPXRFa peptides. The open reading frame (ORF) of lpxrfa-r was 1446 bp in size, and encoded a 481-aa LPXRFa-R protein that encompassed seven hydrophobic transmembrane domains. Subsequently, tissue distribution expression profiles of lpxrfa and lpxrfa-r transcripts were assayed by quantitative real-time PCR. The results indicated that expressions of lpxrfa transcripts were detected at the highest levels in the brain of both females and males, however, lpxrfa-r transcripts were remarkablely expressed in the brain tissue of female fish and in the testis tissue of male fish. Furthermore, transcript levels of lpxrfa and lpxrfa-r genes were investigated during early ontogenetic development, with the maximum expression levels at 30 days post-hatching. Overall, these data contribute to providing preliminary proof for the existence and structure of the LPXRFa system in Japanese flounder, and the study is just the foundation for researching physiological function of LPXRFa system in this species.

Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Integrated network pharmacology to investigate the mechanism of Salvia miltiorrhiza Bunge in the treatment of myocardial infarction.

Salvia miltiorrhiza Bunge is a natural drug for treating myocardial infarction (MI). However, the targets and mechanisms of S. miltiorrhiza Bunge in the treatment of MI are yet to be elucidated. Traditional Chinese medicine systems pharmacology (TCMSP) data were used to screen out chemical constituents, and UniProt was used to predict relevant targets. Disease targets were obtained from the Online Mendelian Inheritance in Man and GeneCards databases. We used the STRING platform to build a protein-protein interaction network and used Cytoscape_v3.8.1 software to make a Drug-Ingredients-Gene Symbols-Disease network map. The Metascape database was used to perform gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses for drug-disease overlapping gene symbols. The targets identified by network pharmacology were further verified by in vitro and in vivo experiments. Seventy-five active components of S. miltiorrhiza Bunge were obtained from the TCMSP database, while 370 disease targets and 29 cross-targets were obtained from the Genecards database. The KEGG pathway enrichment results suggested that the mechanism of S. miltiorrhiza Bunge in the treatment of MI was significantly related to the VEGF signalling pathway. In vitro and in vivo experiments were used to evaluate the reliability of some important active ingredients and targets. S. miltiorrhiza Bunge alleviated the damage to cardiac function, attenuated myocardial fibrosis and protected endothelial cell function by increasing the expression of TGF-ß and VEGFA. S. miltiorrhiza Bunge showed the therapeutic effect of MI by promoting the expression of VEGFA signalling pathway, providing a reliable basis for exploring herbal treatment of MI.

Quantitative susceptibility mapping in rats with minimal hepatic encephalopathy: Does iron overload aggravate cognitive impairment by promoting neuroinflammation?

BACKGROUND AND AIMS: Minimal hepatic encephalopathy (MHE) is a mild form of hepatic encephalopathy that lacks observable signs and symptoms. Nevertheless, MHE can cause neurocognitive dysfunction, although the neurobiological mechanisms are not fully understood. Here, the effects of hippocampal iron deposition on cognitive function and its role in MHE were investigated. MATERIALS AND METHODS: Eighteen rats were assigned to experimental and control groups. MHE was induced by thioacetamide. Spatial memory and exploratory behavior were assessed by the Morris water and elevated plus mazes. Hippocampal susceptibility was measured by quantitative susceptibility mapping, iron deposition in the hippocampus and liver by Prussian blue staining, and inflammatory cytokine and ferritin levels in the hippocampus were measured by ELISA. RESULTS: MHE rats showed impaired spatial memory and exploratory behavior (P < 0.05 for all parameters). The bilateral hippocampal susceptibility values were significantly raised in MHE rats, together with evidence of neuroinflammation (increased pro-inflammatory and reduced anti-inflammatory cytokine levels (all P < 0.05). Further analysis indicated good correlations between hippocampal susceptibility values with latency time and inflammatory cytokine levels in MHE but not in control rats. CONCLUSION: MHE induced by thioacetamide was associated with hippocampal iron deposition and inflammation, suggesting that iron overload may be an important driver of neuroinflammatory responses.

MADS-box protein AGL8 interacts with chromatin-remodelling component SWC4 to activate thermotolerance and environment-dependent immunity in pepper.

Pepper (Capsicum annuum) employs distinct defence responses against Ralstonia solanacearum infection (RSI); however, the mechanisms by which pepper activates these defence responses in a context-dependent manner is unclear. Here we study pepper plants defence response to RSI under room temperature-high humidity (RSRT, 28 °C / 90%) and high temperature-high humidity (RSHT, 37 °C / 90%) conditions, and non-infected plants under high temperature-high humidity (HTHH, 42 °C / 90%) stress. Herein, we found that the MADS-box transcription factor CaAGL8 was up-regulated by HTHH stress and RSRT or RSHT, and its silencing significantly reduced pepper thermotolerance and susceptibility to infection under both room and high temperature-high humidity (RSRT and RSHT). This was coupled with down-regulation of CaSTH2 and CaDEF1 upon RSRT, down-regulation of CaMgst3 and CaPRP1 upon RSHT, and down-regulation of CaHSP24 upon HTHH. In contrast, the ectopic overexpression of CaAGL8 significantly increased the resistance of Nicotiana benthamiana plants to RSRT, RSHT, and HTHH. In addition, CaAGL8 was found to interact with CaSWC4, which acted as a positive regulator of the pepper response to RSRT, RSHT, and HTHH. Silencing of either CaAGL8 or CaSWC4 blocked the hypersensitive response (HR) cell death and context-dependent up-regulation of defence-related genes triggered by the other. Importantly, enrichment of H4K5Ac, H3K9Ac, H3K4me3, and H3K9me2 on the tested defence-related genes was context- and gene-specifically regulated through synergistic interaction between CaSWC4 and CaAGL8. Our results indicate that pepper employs CaAGL8 to modulate chromatin remodelling by interacting with CaSWC4, thereby activating defence responses to RSRT, RSHT, and HTHH.

Secular trend in disease burden of leukemia and its subtypes in China from 1990 to 2019 and its projection in 25 years.

Leukemia and its subtypes impose a major public health challenge in China. Identifying the secular trend of leukemia burden is critical to facilitate optimal healthcare planning and improve the management of leukemia. The incidence rates of leukemia from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database according to the following: subtype (acute lymphocytic leukemia [ALL], acute myeloid leukemia [AML], chronic lymphocytic leukemia [CLL], chronic myelogenous leukemia [CML], and other leukemia subtypes), sex, and age group. The average annual percentage changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. The Bayesian age-period-cohort model was also applied to predict the future trend of the incidence of leukemia and its subtypes in the next 25 years. From 1990 to 2019, the age-standardized incidence rates (ASIRs) of leukemia slightly declined in males and females, which is similar to the trend of other leukemia subtypes. However, the four major leukemia subtypes, namely, ALL, AML, CLL, and CML, have been on the rise over the past three decades. The incidence rates of leukemia in children and the elderly were considerably higher than those in other age groups in males and females. Age effects were the most influential risk factor for leukemia incidence. Period effects showed that the risks of leukemia and its subtypes incidence increased with time. For cohort effects, the risks of leukemia and its subtypes were higher among the early-born cohorts compared with the late-born cohorts. The ASIRs of leukemia and its subtypes will continue to increase in the next 25 years. The burden of leukemia and its subtypes is expected to continue to increase in the next 25 years in males and females. A comprehensive understanding of the risk characteristics and disease pattern of leukemia and its subtypes is needed to formulate timely and effective intervention measures to reduce the leukemia burden in China.

GPR97 deficiency ameliorates renal interstitial fibrosis in mouse hypertensive nephropathy.

Hypertensive nephropathy (HTN) ranks as the second-leading cause of end-stage renal disease (ESRD). Accumulating evidence suggests that persistent hypertension injures tubular cells, leading to tubulointerstitial fibrosis (TIF), which is involved in the pathogenesis of HTN. G protein-coupled receptors (GPCRs) are implicated in many important pathological and physiological processes and act as important drug targets. In this study, we explored the intrarenal mechanisms underlying hypertension-associated TIF, and particularly, the potential role of GPR97, a member of the adhesion GPCR subfamily, in TIF. A deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mouse model was used. We revealed a significantly upregulated expression of GPR97 in the kidneys, especially in renal tubules, of the hypertensive mice and 10 patients with biopsy-proven hypertensive kidney injury. GPR97-/- mice showed markedly elevated blood pressure, which was comparable to that of wild-type mice following DOCA/salt treatment, but dramatically ameliorated renal injury and TIF. In NRK-52E cells, we demonstrated that knockdown of GPR97 suppressed the activation of TGF-ß signaling by disturbing small GTPase RhoA-mediated cytoskeletal reorganization, thus inhibiting clathrin-mediated endocytosis of TGF-ß receptors and subsequent Smad activation. Collectively, this study demonstrates that GPR97 contributes to hypertension-associated TIF at least in part by facilitating TGF-ß signaling, suggesting that GPR97 is a pivotal intrarenal factor for TIF progression under hypertensive conditions, and therapeutic strategies targeting GPR97 may improve the outcomes of patients with HTN.

CTHRC1 expressed in periodontitis and human periodontal fibroblasts exposed to inflammatory stimuli.

OBJECTIVES: Collagen triple helix repeat containing-1 (CTHRC1) is a glycoprotein that can be secreted extracellularly and is involved in the regulation of collagen matrix in a variety of diseases. The expression level of CTHRC1 in periodontitis was detected in this study. MATERIALS AND METHODS: The gingival tissues from clinically healthy subjects (15 cases) and those with periodontitis (30 cases) were taken for immunohistochemical staining. Lipopolysaccharide of the Porphyromonas gingivalis was added in the periodontal ligament fibroblast culture in vitro. Cells were collected, and the mRNA levels of the intracellular CTHRC1 and protein expression of the extracellular CTHRC1 were detected. RESULTS: The protein expression of CTHRC1 in the periodontitis group was higher than that of the clinically healthy group. The in vitro cell experiments showed that 10 µg/ml of P.g LPS could induce a significant increase in protein secretion of CTHRC1, and 5 µg/ml P.g LPS had a significant effect on promoting the mRNA expression of CTHRC1. CONCLUSIONS: Collagen triple helix repeat containing-1 might be involved in the development of periodontitis, and the expression level might be significantly correlated with the stimulation of P.g LPS on fibroblasts. Different stimulation intensities of P.g LPS might result in different expression patterns of CTHRC1.

Efficacy of two opportunistic methods for screening osteoporosis in lumbar spine surgery patients.

PURPOSE: Hounsfield unit (HU) measurements and vertebral bone quality (VBQ) scores are opportunistic screening methods for evaluating bone quality. Since studies comparing the efficacies of the two methods are rare, this retrospective study aimed to examine the efficacy of VBQ scores compared with that of HU measurements for diagnosing osteoporosis in lumbar spine surgery patients. METHODS: We selected patients who had undergone spinal surgery between January 2020 and May 2022 from our database. The VBQ scores based on magnetic resonance imaging (MRI) and HU measurements based on computed tomography (CT) were calculated. Correlation analysis of the dual-energy X-ray absorptiometry (DEXA) T score and study parameters was performed. The Delong test and decision curve analysis (DCA) were used to compare the efficacies of the two methods. RESULTS: We included 118 consecutive patients who underwent selective spinal surgery. The VBQ score and HU measurement were significantly correlated with the DEXA T score. Based on the Delong test, HU measurement predicted osteoporosis more effectively than the VBQ score did. The DCA revealed that the VBQ score performed better than the HU measurement did. CONCLUSIONS: The calculation of VBQ scores is a novel opportunistic screening method for diagnosing osteoporosis; however, CT-based HU measurements outperform MRI-based VBQ scores. HU measurements can be used as a screening method when pre-operative CT scans are available.

Genomic and Transcriptomic Insights into the Evolution and Divergence of MIKC-Type MADS-Box Genes in Carica papaya.

MIKC-type MADS-box genes, also known as type II genes, play a crucial role in regulating the formation of floral organs and reproductive development in plants. However, the genome-wide identification and characterization of type II genes as well as a transcriptomic survey of their potential roles in Carica papaya remain unresolved. Here, we identified and characterized 24 type II genes in the C. papaya genome, and investigated their evolutional scenario and potential roles with a widespread expression profile. The type II genes were divided into thirteen subclades, and gene loss events likely occurred in papaya, as evidenced by the contracted member size of most subclades. Gene duplication mainly contributed to MIKC-type gene formation in papaya, and the duplicated gene pairs displayed prevalent expression divergence, implying the evolutionary significance of gene duplication in shaping the diversity of type II genes in papaya. A large-scale transcriptome analysis of 152 samples indicated that different subclasses of these genes showed distinct expression patterns in various tissues, biotic stress response, and abiotic stress response, reflecting their divergent functions. The hub-network of male and female flowers and qRT-PCR suggested that TT16-3 and AGL8 participated in male flower development and seed germination. Overall, this study provides valuable insights into the evolution and functions of MIKC-type genes in C. papaya.

Incorporation of cinnamaldehyde, carvacrol, and eugenol into zein films for active food packaging: enhanced mechanical properties, antimicrobial activity, and controlled release.

Active packaging with antimicrobial functions to improve the quality and extend the shelf life of food products has gained great interest. Because commercial plastic packaging materials are not biodegradable and cause great environmental problems, plant-derived natural materials have been widely studied for the application of biodegradable packaging materials. Herein, we reported a study of essential oils (EOs)-loaded zein film. Cinnamaldehyde (CIN), carvacrol, and eugenol were added to equip the films with antimicrobial effects, while polyethylene glycol (PEG) and oleic acid (OA) were selected for the improvements of mechanical properties. The results showed that PEG efficiently improves the tensile strength and elongation (%E) of zein films compared to OA, although PEG induced weaker water barrier properties of the films than OA. FTIR spectra confirmed the formation of the hydrogen bonds between zein and PEG/OA. The EO-embedded zein film showed better antimicrobial effects than EO themselves. CIN-embedded films showed the highest antimicrobial effect among the three EOs. The sizes of the inhibition zones against Staphylococcus aureus of PEG-added zein films with 1%, 3%, and 5% CIN were 5.67, 12.67, and 16.67 mm, which were larger than that of pure CIN, with the sizes of 0.00, 3.00, and 4.67 mm, respectively. The developed films demonstrate a gradual release of EOs and show antimicrobial effects up to 96 h, indicating their high potential for the applications as active food packaging.

Machine learning for the prediction of acute kidney injury in patients with sepsis.

BACKGROUND: Acute kidney injury (AKI) is the most common and serious complication of sepsis, accompanied by high mortality and disease burden. The early prediction of AKI is critical for timely intervention and ultimately improves prognosis. This study aims to establish and validate predictive models based on novel machine learning (ML) algorithms for AKI in critically ill patients with sepsis. METHODS: Data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC- III) database. Feature selection was performed using a Boruta algorithm. ML algorithms such as logistic regression (LR), k-nearest neighbors (KNN), support vector machine (SVM), decision tree, random forest, Extreme Gradient Boosting (XGBoost), and artificial neural network (ANN) were applied for model construction by utilizing tenfold cross-validation. The performances of these models were assessed in terms of discrimination, calibration, and clinical application. Moreover, the discrimination of ML-based models was compared with those of Sequential Organ Failure Assessment (SOFA) and the customized Simplified Acute Physiology Score (SAPS) II model. RESULTS: A total of 3176 critically ill patients with sepsis were included for analysis, of which 2397 cases (75.5%) developed AKI during hospitalization. A total of 36 variables were selected for model construction. The models of LR, KNN, SVM, decision tree, random forest, ANN, XGBoost, SOFA and SAPS II score were established and obtained area under the receiver operating characteristic curves of 0.7365, 0.6637, 0.7353, 0.7492, 0.7787, 0.7547, 0.821, 0.6457 and 0.7015, respectively. The XGBoost model had the best predictive performance in terms of discrimination, calibration, and clinical application among all models. CONCLUSION: The ML models can be reliable tools for predicting AKI in septic patients. The XGBoost model has the best predictive performance, which can be used to assist clinicians in identifying high-risk patients and implementing early interventions to reduce mortality.

MicroRNA-24-3p alleviates cardiac fibrosis by suppressing cardiac fibroblasts mitophagy via downregulating PHB2.

Cardiac fibrosis is a pathological process of multiple cardiovascular diseases, which may lead to heart failure. Studies have shown that microRNAs (miRNAs) play critical roles in regulating mitophagy and cardiac fibrosis. We found that miR-24-3p expression was significantly downregulated in transverse aortic constriction (TAC) mice and cardiac fibroblasts (CFs) treated with Ang Ⅱ. We also found that, apart from improving cardiac structure and function, forced expression of miR-24-3p not only reduced the levels of collagen and α-SMA but also inhibited proliferation and migration of CFs. Next, our research proved that miR-24-3p suppressed the progression of mitophagy, autophagic flux, and the levels of mitophagy-related proteins in cardiac fibrosis models. Further analysis showed that PHB2 was a direct target of miR-24-3p. Finally, experiments showed that the knockdown of PHB2 reversed Ang Ⅱ-induced fibrosis in CFs. The results of our study suggests that increased expression of miR-24-3p contributes to the reduction of cardiac fibrosis and that it might be targeted therapeutically to alleviate cardiac fibrosis.

Current status of and barriers to the treatment of advanced-stage liver cancer in China: a questionnaire-based study from the perspective of doctors.

BACKGROUND: Liver cancer is a severe public health problem worldwide, and it creates a relatively higher disease burden in China than in the Western world. Despite achieving notable progress in China, potential differences in some aspects of medical services for liver cancer may persist across different regions and hospitals. This warrants serious consideration of the actual status of and barriers to liver cancer treatment. We intended to explore the present status of and obstacles in liver cancer treatment especially for advanced-stage liver cancer. METHODS: In February 2021, a national multicenter cross-sectional study was conducted among 1500 doctors from 31 provinces of mainland China using a self-administered online questionnaire. Participants completed the questionnaire about their general information, perspectives on the current status of liver cancer treatment, and expectations for future treatment. Chi-square and logistic regression analyses were performed to explore the differences associated with the regions, doctors' professional ranks, and hospital levels. RESULTS: Treatment conditions, medications, and treatment strategies were inconsistent across different economic regions and hospital of different levels. With respect to obstacles in treatment, 76.6% of the doctors were unsatisfied with the current treatment for liver cancer. Important factors that influenced their satisfaction with the treatment for liver cancer included early diagnosis and the disclosure of true conditions to patients. CONCLUSIONS: There persists differences in the treatment of liver cancer in China, besides barriers to treatment. More attention should be paid to the detection and treatment of liver cancer and the propagation of novel progress among doctors in underdeveloped areas.

Association of Red Cell Distribution Width-to-Platelet Ratio and Mortality in Patients with Sepsis.

Background: As a novel inflammatory index, the ratio of red cell distribution width (RDW) to platelet count (RPR) may have prognostic value in some critical illnesses. However, studies on the prognostic influence of RPR in patients with sepsis are few. This study is aimed at investigating the association between RPR levels and 28-day mortality in patients with sepsis. Methods: Data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care III database. The best cut-off value was calculated by establishing the receiver operating characteristic curve (ROC), and the predictive ability of different indicators was compared through the area under the curve (AUC). The association between RPR levels and 28-day mortality was assessed using the Cox proportional hazards model. Restrictive cubic spline analysis was applied to the multivariable Cox model to investigate the nonlinear relationship between RPR and 28-day mortality. Results: A total of 3367 patients with sepsis were included in the study. A nonlinear relationship was observed between RPR and 28-day mortality, showing a trend of a first rapid increase and a gradual increase. For the prediction of mortality, the best cut-off value for RPR was 0.109, with an AUC of 0.728 (95% confidence interval [CI]: 0.709-0.747). The predictive capability of RPR was superior to those of RDW, platelet, SOFA score, and SAPS II score. After adjusting for various confounding factors, high RPR was significantly associated with increased mortality with adjusted hazard ratios of 1.210 (95% CI: 1.045-1.400) for categorical variables and 2.826 (95% CI: 2.025-3.944) for continuous variables. Conclusion: Elevated RPR level is significantly correlated with a high risk of 28-day mortality in patients with sepsis and can be a new predictor of patient prognosis.

CaWRKY28 Cys249 is Required for Interaction with CaWRKY40 in the Regulation of Pepper Immunity to Ralstonia solanacearum.

WRKY transcription factors have been implicated in plant response to pathogens but how WRKY-mediated networks are organized and operate to produce appropriate transcriptional outputs remains largely unclear. Here, we identify a member of the WRKY family from pepper (Capsicum annuum), CaWRKY28, that physically interacts with CaWRKY40, a positive regulator of pepper immunity and thermotolerance. We confirmed CaWRKY28-CaWRKY40 interaction by coimmunoprecipitation, bimolecular fluorescence complementation, and microscale thermophoresis. Our findings supported the idea that CaWRKY28 is a nuclear protein that acts as positive regulator in pepper responses to infection by the pathogenic bacterium Ralstonia solanacearum. It performs its function not by directly modulating the W-box containing immunity-related genes but by promoting CaWRKY40 via physical interaction to bind and activate its immunity-related target genes, including CaPR1, CaNPR1, CaDEF1, and CaABR1, but not its thermotolerance-related target gene, CaHSP24. All of these data indicate that CaWRKY28 interacts with and potentiates CaWRKY40 in regulating immunity against R. solanacearum infection but not thermotolerance. Importantly, we discovered that CaWRKY28 Cys249, shared by CaWRKY28 and its orthologs probably only in the family Solanaceae, is crucial for the CaWRKY28-CaWRKY40 interaction. These results highlight how CaWRKY28 associates with CaWRKY40 during the establishment of WRKY networks, and how CaWRKY40 achieves its functional specificity during pepper responses to R. solanacearum infection.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

CaAIL1 Acts Positively in Pepper Immunity against Ralstonia solanacearum by Repressing Negative Regulators.

APETALA2 (AP2) subfamily transcription factors participate in plant growth and development, but their roles in plant immunity remain unclear. Here, we discovered that the AP2 transcription factor CaAIL1 functions in immunity against Ralstonia solanacearum infection (RSI) in pepper (Capsicum annuum). CaAIL1 expression was upregulated by RSI, and loss- and gain-of-function assays using virus-induced gene silencing and transient overexpression, respectively, revealed that CaAIL1 plays a positive role in immunity to RSI in pepper. Chromatin immunoprecipitation sequencing (ChIP-seq) uncovered a subset of transcription-factor-encoding genes, including CaRAP2-7, CaGATA17, CaGtf3a and CaTCF25, that were directly targeted by CaAIL1 via their cis-elements, such as GT or AGGCA motifs. ChIP-qPCR and electrophoretic mobility shift assays confirmed these findings. These genes, encoding transcription factors with negative roles in immunity, were repressed by CaAIL1 during pepper response to RSI, whereas genes encoding positive immune regulators such as CaEAS were derepressed by CaAIL1. Importantly, we showed that the atypical EAR motif (LXXLXXLXX) in CaAIL1 is indispensable for its function in immunity. These findings indicate that CaAIL1 enhances the immunity of pepper against RSI by repressing a subset of negative immune regulators during the RSI response through its binding to several cis-elements in their promoters.

Comparisons of simulation results between passive and active fluid structure interaction models for left ventricle in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Patient-specific active fluid-structure interactions (FSI) model is a useful approach to non-invasively investigate the hemodynamics in the heart. However, it takes a lot of effort to obtain the proper external force boundary conditions for active models, which heavily restrained the time-sensitive clinical applications of active computational models. METHODS: The simulation results of 12 passive FSI models based on 6 patients' pre-operative and post-operative CT images were compared with corresponding active models to investigate the differences in hemodynamics and cardiac mechanics between these models. RESULTS: In comparing the passive and active models, it was found that there was no significant difference in pressure difference and shear stress on mitral valve leaflet (MVL) at the pre-SAM time point, but a significant difference was found in wall stress on the inner boundary of left ventricle (endocardium). It was also found that pressure difference on the coapted MVL and the shear stress on MVL were significantly decreased after successful surgery in both active and passive models. CONCLUSION: Our results suggested that the passive models may provide good approximated hemodynamic results at 5% RR interval, which is crucial for analyzing the initiation of systolic anterior motion (SAM). Comparing to active models, the passive models decrease the complexity of the modeling construction and the difficulty of convergence significantly. These findings suggest that, with proper boundary conditions and sufficient clinical data, the passive computational model may be a good substitution model for the active model to perform hemodynamic analysis of the initiation of SAM.

Diverticulum of mitral valve.

Diverticulum arising from the heart is an uncommon finding. They are incidentally detected by echocardiography as masses arising from the cardiac valves. We present a case of an incidental finding of a diverticulum arising from the mitral valve. This was initially detected by Transthoracic echocardiography and later confirmed by transesophageal echocardiography and pathologic appearance.