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Myocardial infarction (MI) caused by ischemic cardiomyocyte necrosis induces inflammatory responses that strongly affect ventricular remodeling. Tolerogenic dendritic cells (tDCs) can suppress this effect on inflammatory responses. However, the precise role of atorvastatin-induced tDCs in ventricular remodeling after MI remains unclear.To explore the effect of necrotic cardiomyocytes (SNC) and/or atorvastatin on DC function, the expression of CD40, CD80, CD86, and MHC-II was determined using flow cytometry. The protein levels of TLR-4/NF-κB-related molecules were evaluated using western blotting. The infarct area after MI was determined via 2,3,5-triphenyltetrazolium chloride staining. The TUNEL assay was employed to evaluate the apoptosis of cardiomyocytes in heart sections. Masson's trichrome method was used to determine the extent of fibrosis.Compared to the DCs co-cultured with PBS (control), cells co-cultured with Supernatant-IM or Supernatant-NH produced higher levels of inflammatory cytokines, including TNF-α, IL-1, IL-6, IL-12P40, and IL-8. This cytokine production was impaired by atorvastatin treatment. SNC treatment induced DC maturation and enhanced inflammatory cytokine secretion and oxidative stress through TLR-4/NF-κB pathway activation. Compared to that in the PBS-treated group, the left ventricular ejection fraction was significantly improved after tDC treatment. Additionally, compared to that in the PBS-treated group, tDC treatment reduced the left ventricular end-diastolic and end-systolic diameters in mice. Furthermore, treatment with tDCs improved the left ventricular systolic function, attenuated inflammatory cell infiltration, and reduced cardiomyocyte apoptosis, myocardial fibrosis, and infarct size compared to those in the control group.Adoptive transfer of atorvastatin-induced tDCs alleviated post-infarction cardiomyocyte apoptosis and myocardial fibrosis in association with decreased inflammatory cell infiltration and inhibited oxidative stress, likely by suppressing TLR-4/NF-κB activation after myocardial infarction.

Background Kounis syndrome is a rare clinical condition characterized by the occurrence of an acute coronary event induced by an acute allergic episode. The ongoing pandemic of coronavirus disease 2019 (COVID-19) has contributed to an increase in the incidence of allergic reactions to a certain extent, thereby increasing the incidence of Kounis syndrome. Timely diagnosis and effective management of this disease are important in clinical practice. Case presentation We report a 43-year-old woman who developed generalized pruritus, breathlessness, paroxysmal precordial crushing pain, and dyspnea after receiving the third dose of the COVID-19 vaccine. After anti-allergic treatment and therapy for acute myocardial ischemia, her symptoms resolved with improvement in cardiac function and resolution of ST-segment changes. The prognosis was satisfactory, and the final diagnosis was type I Kounis syndrome. Conclusion This patient with type I Kounis syndrome rapidly developed acute coronary syndrome (ACS) after an acute allergic reaction to the COVID-19 vaccine. ​Timely diagnosis of acute allergic reaction and ACS, and targeted treatment based on the relevant guidelines are the key to successful treatment of the syndrome.​

Previous studies have depicted that miR-322 can regulate the function of various stem cells. However, its role and mechanism in the ability of embryonic stem cells (ESCs) to differentiate into cardiomyocytes are still unknown. Celf1 can play vital roles in stem cell differentiation and may be a potential target of miR-322 in ESCs’ differentiation. An experiment was performed on mouse ESCs transfected with lentivirus-mediated miR-322 to study the function of miR-322. RT-PCR results indicated that miR-322 could increase NKX-2.5, MLC2V, and α-MHC mRNA expression, signifying that miR-322 might promote the differentiation of ESCs towards cardiomyocytes in vitro. Western blot and immunofluorescence results likewise confirmed this conclusion. In addition, the experiment found that the knockdown of miR-322 expression could inhibit ESCs’ differentiation towards cardiomyocytes in cultured ESCs in vitro. Western blot results presented that miR-322 could suppress celf1 protein expression. Furthermore, Western blot, RT-PCR, and immunofluorescence results manifested that celf1 might inhibit ESCs’ differentiation towards cardiomyocytes in vitro. Overall, the results signified that miR-322 might promote ESCs’ differentiation towards cardiomyocytes by regulating celf1 expressions.

Background Recent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes. Methods A meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression. Results ApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18–1.76) and progression (P Conclusions ApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin–angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.

Mechanistic target of rapamycin mTOR complex 1 (mTORC1) plays a key role in the integration of various environmental signals to regulate cell growth and metabolism. mTORC1 is recruited to the lysosome where it is activated by its interaction with GTP-bound Rheb GTPase. However, the regulatory mechanism of Rheb activity remains largely unknown. Here, we show that ubiquitination governs the nucleotide-bound status of Rheb. Lysosome-anchored E3 ligase RNF152 catalyzes Rheb ubiquitination and promotes its binding to the TSC complex. EGF enhances the deubiquitination of Rheb through AKT-dependent USP4 phosphorylation, leading to the release of Rheb from the TSC complex. Functionally, ubiquitination of Rheb is linked to mTORC1-mediated signaling and consequently regulates tumor growth. Thus, we propose a mechanistic model whereby Rheb–mediated mTORC1 activation is dictated by a dynamic opposing act between Rheb ubiquitination and deubiquitination that are catalyzed by RNF152 and USP4 respectively.

BackgroundLeft-sided heart failure (HF) is documented as a key prognostic factor in HF. However, the relative molecular mechanisms underlying left-sided HF is unknown. The purpose of this study is to unearth significant modules, pivotal genes and candidate regulatory components governing the progression of left-sided HF by bioinformatical analysis.MethodsA total of 319 samples in GSE57345 dataset were used for weighted gene correlation network analysis (WGCNA). ClusterProfiler package in R was used to conduct functional enrichment for genes uncovered from the modules of interest. Regulatory networks of genes were built using Cytoscape while Enrichr database was used for identification of transcription factors (TFs). The MCODE plugin was used for identifying hub genes in the modules of interest and their validation was performed based on GSE1869 dataset.ResultsA total of six significant modules were identified. Notably, the blue module was confirmed as the most crucially associated with left-sided HF, ischemic heart disease (ISCH) and dilated cardiomyopathy (CMP). Functional enrichment conveyed that genes belonging to this module were mainly those driving the extracellular matrix-associated processes such as extracellular matrix structural constituent and collagen binding. A total of seven transcriptional factors, including Suppressor of Zeste 12 Protein Homolog (SUZ12) and nuclear factor erythroid 2 like 2 (NFE2L2), adrenergic receptor (AR), were identified as possible regulators of coexpression genes identified in the blue module. A total of three key genes (OGN, HTRA1 and MXRA5) were retained after validation of their prognostic value in left-sided HF. The results of functional enrichment confirmed that these key genes were primarily involved in response to transforming growth factor beta and extracellular matrix.ConclusionWe uncovered a candidate gene signature correlated with HF, ISCH and CMP in the left ventricle, which may help provide better prognosis and therapeutic decisions and in HF, ISCH and CMP patients.

Traffic surveillance video is recorded in uncontrolled outdoor scenarios. If the camera view gets obstructed by the leaves, the video will fail to be used in vehicle tracking and recognition. It is required that the traffic video surveillance systems run self-checking in order to evaluate if the camera view is blocked by leaves or not. In view of this, a two-step learning framework is proposed in this paper to automatically determine whether the video is leaf degraded or leaf free. First, the proposed framework exploits the convolutional neural network to learn the discriminative features of leaf particles. Then the trained model is used to detect candidate leaf patches in the image. Second, a probabilistic approach is used to pool decisions of each candidate leaf patch to generate final leaf detection result in the video. Experimental results are provided to demonstrate that the proposed approach can effectively detect leaves in real-world traffic surveillance video.

Five new pyrazin-2(1H)-one derivatives, ochramides A-D (1-4) and ochralate A (5), as well as three known analogues (6-8) were isolated from the fermentation broth of the marine coral-derived halotolerant Aspergillus ochraceus LCJ11-102 in a nutrient-limited medium containing 10% NaI. Their chemical structures were determined by analyzing NMR and X-ray diffraction data. Compounds 2, 5 and 6 showed antimicrobial activities against Enterobacter aerogenes with the MIC values of 40.0, 18.9, and 20.1 μM, respectively.

An accurate understanding about the variation of sap flow and the interaction mechanisms of sap flow with environmental factors is essential when carrying out vegetation restoration projects in areas where rainfall is limited. A thermal dissipation probe (TDP) measured sap flow of Salix matsudana, growing in typical sandy and loess soils in the same semi-arid watershed on the Loess Plateau, China in 2012 and 2013 from May to October. Similar sap flow diurnal variation patterns occurred for both soils but, based on the sap flow, the calculated total transpiration of S. matsudana growing in the loess soil was about five times greater than that growing in the sandy soil due to differences in the sapwood cross-sectional area. Soil texture affected both the vertical distribution of S. matsudana fine roots and the soil water cycle, which led to the S. matsudana growing in the sandy soil being subjected more frequently to drought stress that stunted its growth. In contrast, S. matsudana grew well in the loess soil. Soil texture was the key factor responsible for the discrepancy in the total sap flow of S. matsudana in the study region due to its effect on soil water content. Therefore, if afforestation is planned for this or similar regions, soil texture should be taken into account.

Objective To investigate the factors that can accurately predict the prognosis for patients with FIGO stage-IB cervical squamous cell carcinoma treated with radical surgery.