A mapped dataset of surface ocean acidification indicators in large marine ecosystems of the United States.

Mapped monthly data products of surface ocean acidification indicators from 1998 to 2022 on a 0.25° by 0.25° spatial grid have been developed for eleven U.S. large marine ecosystems (LMEs). The data products were constructed using observations from the Surface Ocean CO2 Atlas, co-located surface ocean properties, and two types of machine learning algorithms: Gaussian mixture models to organize LMEs into clusters of similar environmental variability and random forest regressions (RFRs) that were trained and applied within each cluster to spatiotemporally interpolate the observational data. The data products, called RFR-LMEs, have been averaged into regional timeseries to summarize the status of ocean acidification in U.S. coastal waters, showing a domain-wide carbon dioxide partial pressure increase of 1.4 ± 0.4 µatm yr-1 and pH decrease of 0.0014 ± 0.0004 yr-1. RFR-LMEs have been evaluated via comparisons to discrete shipboard data, fixed timeseries, and other mapped surface ocean carbon chemistry data products. Regionally averaged timeseries of RFR-LME indicators are provided online through the NOAA National Marine Ecosystem Status web portal.

The diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients with respiratory tract infections.

Metagenomic next-generation sequencing (mNGS) is an unbiased and rapid method for detecting pathogens. This study enrolled 145 suspected severe pneumonia patients who were admitted to the Affiliated Hospital of Jining Medical University. This study primarily aimed to determine the diagnostic performance of mNGS and conventional microbiological tests (CMTs) using bronchoalveolar lavage fluid samples for detecting pathogens. Our findings indicated that mNGS performed significantly higher sensitivity (97.54% vs 28.68%, P < 0.001), coincidence (90.34% vs 35.17%, P < 0.001), and negative predictive value (80.00% vs 13.21%, P < 0.001) but performed lower specificity than CMTs (52.17% vs 87.5%, P < 0.001). Streptococcus pneumoniae as the most common bacterial pathogen had the largest proportion (22.90%, 30/131) in this study. In addition to bacteria, fungi, and virus, mNGS can detect a variety of atypical pathogens such as Mycobacterium tuberculosis and non-tuberculous. Mixed infections were common in patients with severe pneumonia, and bacterial-fungal-viral-atypical pathogens were the most complicated infection. After adjustments of antibiotics based on mNGS and CMTs, the clinical manifestation improved in 139 (95.86%, 139/145) patients. Our data demonstrated that mNGS had significant advantage in diagnosing respiratory tract infections, especially atypical pathogens and fungal infections. Pathogens were detected timely and comprehensively, contributing to the adjustments of antibiotic treatments timely and accurately, improving patient prognosis and decreasing mortality potentially.IMPORTANCEMetagenomic next-generation sequencing using bronchoalveolar lavage fluid can provide more comprehensive and accurate pathogens for respiratory tract infections, especially when considering the previous usage of empirical antibiotics before admission or complicated clinical presentation. This technology is expected to play an important role in the precise application of antimicrobial drugs in the future.

Identification of diagnostic gene signatures and molecular mechanisms for non-alcoholic fatty liver disease and Alzheimer's disease through machine learning algorithms.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and Alzheimer's disease (AD) pose significant global health challenges. Recent studies have suggested a link between these diseases; however, the underlying mechanisms remain unclear. This study aimed to decode the shared molecular landscapes of NAFLD and AD using bioinformatic approaches. METHODS: We analyzed three datasets for NAFLD and AD from the Gene Expression Omnibus (GEO). This study involved identifying differentially expressed genes (DEGs), using weighted gene co-expression network analysis (WGCNA), and using machine learning for biomarker discovery. The diagnostic biomarkers were validated using expression analysis, receiver operating characteristic (ROC) curves, and nomogram models. Furthermore, Gene Set Enrichment Analysis (GSEA) and CIBERSORT were used to investigate molecular pathways and immune cell distributions related to GADD45G and NUPR1. RESULTS: This study identified 14 genes that are common to NAFLD and AD. Machine learning identified six biomarkers for NAFLD, four for AD, and two crucial shared biomarkers: GADD45G and NUPR1. Validation confirmed their expression patterns and robust predictive abilities. GSEA revealed the intricate roles of these biomarkers in disease-associated pathways. Immune cell profiling highlighted the importance of macrophages under these conditions. CONCLUSION: This study highlights GADD45G and NUPR1 as key biomarkers for NAFLD and AD, and provides novel insights into their molecular connections. These findings revealed potential therapeutic targets, particularly in macrophage-mediated pathways, thus enriching our understanding of these complex diseases.

Irisin improves diabetic cardiomyopathy-induced cardiac remodeling by regulating GSDMD-mediated pyroptosis through MITOL/STING signaling.

Diabetic cardiomyopathy (DCM) is a common complication of diabetes mellitus (DM). However, the mechanisms underlying DCM-induced cardiac injury remain unclear. Recently, the role of cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling and pyroptosis in DCM has been investigated. Based on our previous results, this study was designed to examine the impact of irisin, mitochondrial ubiquitin ligase (MITOL/MARCH5), and cGAS/STING signaling in DCM-induced cardiac dysfunction and the effect of gasdermin D (GSDMD)-dependent pyroptosis. High-fat diet-induced mice and H9c2 cells were used for cardiac geometry and function or pyroptosis-related biomarker assessment at the end of the experiments. Here, we show that DCM impairs cardiac function by increasing cardiac fibrosis and GSDMD-dependent pyroptosis, including the activation of MITOL and cGAS/STING signaling. Our results confirmed that the protective role of irisin and MITOL was partially offset by the activation of cGAS/STING signaling. We also demonstrated that GSDMD-dependent pyroptosis plays a pivotal role in the pathological process of DCM pathogenesis. Our results indicate that irisin treatment protects against DCM injury, mitochondrial homeostasis, and pyroptosis through MITOL upregulation.

Integrative analysis reveals chemokines CCL2 and CXCL5 mediated shear stress-induced aortic dissection formation.

Background: Aortic dissection (AD) is a critical emergency in cardiovascular disease. AD occurs only in specific sites of the aorta, and the variation of shear stress in different aortic segments is a possible cause not reported. This study investigated the key molecules involved in shear stress-induced AD through quantitative bioinformatic analysis of a public RNA sequencing database and clinical tissue sample validation. Methods: Gene expression data from the GSE153434, GSE147026, and GSE52093 datasets were downloaded from the Gene Expression Omnibus. Next, differently expressed genes (DEGs) in each dataset were identified and integrated to identify common AD DEGs. STRING, Cytoscape, and MCODE were used to identify hub genes and crucial clustering modules, and Connectivity Map (CMap) was used to identify positive and negative agents. The same procedure was performed for the GSE160611 dataset to obtain shear stress-induced human aortic endothelial cell (HAEC) DEGs. After the integration of these two DEGs sets to identify shear stress-associated hub DEGs in AD, Gene Ontology Enrichment Analysis was performed. The common chemokine receptors and ligands in AD were identified by analyzing AD's three RNA sequencing datasets. Their origin was verified by analyzing AD single-cell sequencing data and validated by immunoblotting and immunofluorescence. Results: We identified 100 down-regulated and 50 up-regulated AD common DEGs. Enrichment results showed that common DEGs were closely related to blood vessel morphogenesis, muscle structure development, muscle tissue development, and chemotaxis. Among those DEGs, MYC, CCL2, and SPP1 are the three molecules with the highest degree. A crucial cluster of 15 genes was identified using MCODE, which contained inflammation-related genes with elevated expression and muscle cell-related genes with decreased expression, and CCL2 is central to immune-related genes. CMap confirmed MEK inhibitors and ALK inhibitors as possible therapeutic agents for AD. Moreover, 366 shear stress-associated DEGs in HAEC were identified in the GSE160611 dataset. After taking the intersection, we identified five shear stress-associated hub DEGs in AD (ANGPTL4, SNAI2, CCL2, GADD45B, and PROM1), and the enrichment analysis indicated they were related to the endothelial cell apoptotic process. Chemokine CCL2 was the molecule with a high degree in both DEG sets. Besides CCL2, CXCL5 was the only chemokine ligand differentially expressed in the three datasets. Additionally, immunoblotting confirmed the increased expression of CCL2 and CXCL5 in clinical tissue samples. Further research at the single-cell level revealed that CCL2 has multiple origins, and CXCL5 is macrophage-derived. Conclusion: Through integrative analysis, we identified core common AD DEGs and possible therapeutic agents based on these DEGs. We elucidated that the chemokine CCL2 and CXCL5-mediated "Endothelial-Monocyte-Neutrophil" axis may contribute to the development of shear stress-induced AD. These findings provide possible therapeutic targets for the prevention and treatment of AD.

Mediating role of resilience between family functioning and quality of life in patients with advanced colorectal cancer.

To better understand the relationship between family functioning, resilience, and quality of life (including physical and mental component score, PCS and MCS) in patients with advanced colorectal cancer (CRC) to predict and improve their quality of life.A cross-sectional study was conducted in which a total of 165 patients with advanced colorectal cancer participated in a one-time survey. Measures included the Family Functioning Assessment Device, the 10-item Connor-Davidson Resilience Scale, and the SF-12 Health Survey Assessment Scale. The data analysis methods included descriptive analysis, pearson's correlation analysis, t-tests, and nonparametric tests.Of the patients with advanced CRC, 47.27% and 72.73% had moderate or low mental and physical health components, respectively. The results indicated that in patients with advanced CRC, family function was negatively correlated with resilience (p < 0.01), family functioning was negatively correlated with MCS (p < 0.01), and resilience was positively correlated with PCS (p < 0.05) and MCS (p < 0.01). The mediating analysis revealed that family functioning regulated MCS through resilience (effect value = 13.17%).Our findings suggest that the MCS of patients with advanced CRC is influenced by both family functioning and resilience. PCS in patients with advanced CRC appears to be influenced by resilience but not by family functioning.

Tetrahydrocurcumin ameliorates postinfarction cardiac dysfunction and remodeling by inhibiting oxidative stress and preserving mitochondrial function via SIRT3 signaling pathway.

BACKGROUND: Myocardial infarction (MI) often leads to sudden cardiac death. Persistent myocardial ischemia increases oxidative stress and impairs mitochondrial function, contributing significantly to postinfarction cardiac dysfunction and remodeling, and the subsequent progression to heart failure (HF). Tetrahydrocurcumin (THC), isolated from the rhizome of turmeric, has antioxidant properties and has been shown to protect against cardiovascular diseases. However, its effects on HF after MI are poorly understood. PURPOSE: The objective was the investigation of the pharmacological effects of THC and its associated mechanisms in the pathogenesis of HF after MI. METHODS: A total of 120 mice (C57BL/6, male) were used for the in vivo experiments. An MI mouse model was created by permanent ligation of the left anterior descending coronary artery. The mice received oral dose of THC at 120 mg/kg/d and the effects on MI-induced myocardial injury were evaluated by assessment of cardiac function, histopathology, myocardial oxidative levels, and mitochondrial function. Molecular mechanisms were investigated by intraperitoneal injection of 50 mg/kg of the SIRT3 selective inhibitor 3-TYP. Meanwhile, mouse neonatal cardiomyocytes were isolated and cultured in a hypoxic incubator to verify the effects of THC in vitro. Lastly, SIRT3 and Nrf2 were silenced using siRNAs to further explore the regulatory mechanism of key molecules in this process. RESULTS: The mouse hearts showed significant impairment in systolic function after MI, together with enlarged infarct size, increased myocardial fibrosis, cardiac hypertrophy, and apoptosis of cardiomyocytes. A significant reversal of these changes was seen after treatment with THC. Moreover, THC markedly reduced reactive oxygen species generation and protected mitochondrial function, thus mitigating oxidative stress in the post-MI myocardium. Mechanistically, THC counteracted reduced Nrf2 nuclear accumulation and SIRT3 signaling in the MI mice while inhibition of Nrf2 or SIRT3 reversed the effects of THC. Cell experiments showed that Nrf2 silencing markedly reduced SIRT3 levels and deacetylation activity while inhibition of SIRT3 signaling had little impact on Nrf2 expression. CONCLUSION: This is the first demonstration that THC protects against the effects of MI. THC reduced both oxidative stress and mitochondrial damage by regulating Nrf2-SIRT3 signaling. The results suggest the potential of THC in treating myocardial ischemic diseases.

The regulatory effects of the apelin/APJ system on depression: A prospective therapeutic target.

Depression is a debilitating neuropsychological disorder characterized by high incidence, high recurrence, high suicide, and high disability rates, which poses serious threats to human health and imposes heavy psychological and economic burdens on family and society. The pathogenesis of depression is extremely complex, and its etiology is multifactorial. Mounting evidence suggests that apelin and apelin receptor APJ, which compose the apelin/APJ system, are related to the development of depression. However, the specific mechanism is still unclear, and research in this area in human is still insufficient. Acceleration of research into the regulatory effects and underlying mechanisms of the apelin/APJ system in depression may identify attractive therapeutic targets and contribute to the development of novel intervention strategies against this devastating psychological disorder. In this review, we mainly discuss the regulatory effects of apelin/APJ system on depression and its potential therapeutic applications.

Predicting Extrathyroidal Extension in Papillary Thyroid Carcinoma Using a Clinical-Radiomics Nomogram Based on B-Mode and Contrast-Enhanced Ultrasound.

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. PTC patients with extrathyroidal extension (ETE) are associated with poor prognoses. The preoperative accurate prediction of ETE is crucial for helping the surgeon decide on the surgical plan. This study aimed to establish a novel clinical-radiomics nomogram based on B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) for the prediction of ETE in PTC. A total of 216 patients with PTC between January 2018 and June 2020 were collected and divided into the training set (n = 152) and the validation set (n = 64). The least absolute shrinkage and selection operator (LASSO) algorithm was applied for radiomics feature selection. Univariate analysis was performed to find clinical risk factors for predicting ETE. The BMUS Radscore, CEUS Radscore, clinical model, and clinical-radiomics model were established using multivariate backward stepwise logistic regression (LR) based on BMUS radiomics features, CEUS radiomics features, clinical risk factors, and the combination of those features, respectively. The diagnostic efficacy of the models was assessed using receiver operating characteristic (ROC) curves and the DeLong test. The model with the best performance was then selected to develop a nomogram. The results show that the clinical-radiomics model, which is constructed by age, CEUS-reported ETE, BMUS Radscore, and CEUS Radscore, showed the best diagnostic efficiency in both the training set (AUC = 0.843) and validation set (AUC = 0.792). Moreover, a clinical-radiomics nomogram was established for easier clinical practices. The Hosmer-Lemeshow test and the calibration curves demonstrated satisfactory calibration. The decision curve analysis (DCA) showed that the clinical-radiomics nomogram had substantial clinical benefits. The clinical-radiomics nomogram constructed from the dual-modal ultrasound can be exploited as a promising tool for the pre-operative prediction of ETE in PTC.

[Double-column Die-punch fractures of distal radius treated with butterfly plate fixation via Henry approach].

OBJECTIVE: To explore clinical effect of open reduction and internal fixation with Henry's approach butterfly plate in treating double-column Die-punch fractures of distal radius. METHODS: From January 2018 to June 2021, 26 patients with double-column Die-column distal radius were treated with open reduction and internal fixation through Henry's surgical approach and using distal radius volar column plate(butterfly plate), including 14 males and 12 females, aged from 20 to 75 years old with an average age of (44.2±3.4) years old. Postopertaive complications were observed, Gartland-Werley score at 12 months after opertaion was used to evaluate wrist joint function. RESULTS: All 26 patients were followed up from 10 to 18 months with an average of(13.4±0.8) months. All fractures were obtained fracture union, the time ranged from 8.5 to 15.8 weeks with an average of (11.4±0.5) weeks. All incisions healed at stageⅠwithout infection, nerve injury and internal fixation failure occurred. Postoperative Gartland-Werley score at 12 months was (3.65±0.36), and 16 patients got excellent result, 8 good and 2 moderate. CONCLUSION: Open reduction and internal fixation with butterfly plate for the treatment of double-column Die-punch fractures of the distal radius through volar Henry approach could obtain satisfactory clinical outcomes.

Clinical-Radiomics Nomogram Based on Contrast-Enhanced Ultrasound for Preoperative Prediction of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma.

This study aimed to establish a new clinical-radiomics nomogram based on ultrasound (US) for cervical lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC). We collected 211 patients with PTC between June 2018 and April 2020, then we randomly divided these patients into the training set (n = 148) and the validation set (n = 63). 837 radiomics features were extracted from B-mode ultrasound (BMUS) images and contrast-enhanced ultrasound (CEUS) images. The maximum relevance minimum redundancy (mRMR) algorithm, least absolute shrinkage and selection operator (LASSO) algorithm, and backward stepwise logistic regression (LR) were applied to select key features and establish a radiomics score (Radscore), including BMUS Radscore and CEUS Radscore. The clinical model and clinical-radiomics model were established using the univariate analysis and multivariate backward stepwise LR. The clinical-radiomics model was finally presented as a clinical-radiomics nomogram, the performance of which was evaluated by the receiver operating characteristic curves, Hosmer-Lemeshow test, calibration curves, and decision curve analysis (DCA). The results show that the clinical-radiomics nomogram was constructed by four predictors, including gender, age, US-reported LNM, and CEUS Radscore. The clinical-radiomics nomogram performed well in both the training set (AUC = 0.820) and the validation set (AUC = 0.814). The Hosmer-Lemeshow test and the calibration curves demonstrated good calibration. The DCA showed that the clinical-radiomics nomogram had satisfactory clinical utility. The clinical-radiomics nomogram constructed by CEUS Radscore and key clinical features can be used as an effective tool for individualized prediction of cervical LNM in PTC.

The Ocean Carbon and Acidification Data System.

The Ocean Carbon and Acidification Data System (OCADS) is a data management system at the National Oceanic and Atmospheric Administration (NOAA) National Centers for Environmental Information (NCEI). It manages a wide range of ocean carbon and acidification data, including chemical, physical, and biological observations collected from research vessels, ships of opportunity, and uncrewed platforms, as well as laboratory experiment results, and model outputs. Additionally, OCADS serves as a repository for related Global Ocean Observing System (GOOS) biogeochemistry Essential Ocean Variables (EOVs), e.g., oxygen, nutrients, transient tracers, and stable isotopes. OCADS endeavors to be one of the world's leading providers of ocean carbon and acidification data, information, products, and services. To provide the best data management services to the ocean carbon and acidification research community, OCADS prioritizes adopting a customer-centric approach and gathering knowledge and expertise from the research community to improve its data management practices. OCADS aims to make all ocean carbon and acidification data accessible via a single portal, and welcomes submissions from around the world: https://www.ncei.noaa.gov/products/ocean-carbon-acidification-data-system/.

GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy.

The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women.

Application of metagenomic next-generation sequencing in cutaneous tuberculosis.

Tuberculous infection in a skin wound is a rare but well-known condition. This study describes a child infected with tuberculosis after being wounded. Because of swelling and pain in his wrist tissue, he was admitted to the Affiliated Hospital of Jining Medical University of Shandong Province on 16 October 2021. His medical history only included a wound. He was discharged after debridement. The laboratory data were normal. Two months after surgery, his wound was still swollen and painful. Secretions from the wound were sent for metagenomic next-generation sequencing (mNGS), which revealed three reads related to the Mycobacterium tuberculosis complex group (MTBC). A diagnosis of cutaneous tuberculosis (TB) was made. The wound disappeared after anti-TB drugs were administered. This case demonstrates that, while TB presenting as a severe cutaneous wound is rare, it should be considered in the clinical diagnosis. Clinicians should also pay attention to extrapulmonary infection with MTBC in patients, particularly in some long-suffering patients, and identify the specific pathogen as soon as possible. mNGS could help to identify pathogens and facilitate early treatment, thereby improving the prognosis.

1-Deoxynojirimycin attenuates septic cardiomyopathy by regulating oxidative stress, apoptosis, and inflammation via the JAK2/STAT6 signaling pathway.

Cardiac dysfunction caused by sepsis is the predominant reason for death in patients with sepsis. However, the effective drugs for its prevention and the molecular mechanisms remain elusive. 1-Deoxynojirimycin (DNJ), a natural iminopyranose, exhibits various biological properties, such as hypoglycemic, antitumor, antiviral, and anti-inflammatory activities. However, whether DNJ can mediate biological activity resistance in sepsis-induced myocardial injury and the underlying mechanisms are unclear. Janus kinase and signal transducer and activator of transcription (JAK/STAT) signaling is an important pathway for the signal transduction of several key cytokines in the pathogenesis of sepsis, which can transcribe and modulate the host immune response. This study was conducted to confirm whether DNJ mediates oxidative stress, apoptosis, and inflammation in cardiomyocytes, thereby alleviating myocardial injury in sepsis via the JAK2/STAT6 signaling pathway. Septic cardiomyopathy was induced in mice using lipopolysaccharide (LPS), and they were then treated with DNJ. The results showed that DNJ markedly improved sepsis-induced cardiac dysfunction, attenuated reactive oxygen species generation, reduced cardiomyocyte apoptosis, and mitigated inflammation. Mechanistically, increased JAK2/STAT6 phosphorylation was observed in the mouse sepsis models, which decreased significantly after DNJ oral treatment. To further confirm whether DNJ mediates the JAK2/STAT6 pathway, the selective inhibitor fedratinib was used to block the JAK2 signaling pathway in vitro, which enhanced the protective effects of DNJ against the sepsis-induced cardiac damage. Collectively, these findings suggest that DNJ attenuates sepsis-induced myocardial injury by decreasing myocardial oxidative damage, apoptosis, and inflammation via the regulation of the JAK2/STAT6 signaling pathway.

Tetrahydrocurcumin improves lipopolysaccharide-induced myocardial dysfunction by inhibiting oxidative stress and inflammation via JNK/ERK signaling pathway regulation.

BACKGROUND: Acute myocardial dysfunction in patients with sepsis is attributed to oxidative stress, inflammation, and cardiomyocyte loss; however, specific drugs for its prevention are still lacking. Tetrahydrocurcumin (THC) has been proven to contribute to the prevention of various cardiovascular diseases by decreasing oxidative stress and inflammation. This study was performed to investigate the functions and mechanism of action of THC in septic cardiomyopathy. METHODS: After the oral administration of THC (120 mg/kg) for 5 consecutive days, a mouse model of sepsis was established via intraperitoneal lipopolysaccharide (LPS, 10 mg/kg) injection. Following this, cardiac function was assessed, pathological section staining was performed, and inflammatory markers were detected. RESULTS: Myocardial systolic function was severely compromised in parallel with the accumulation of reactive oxygen species and enhanced cardiomyocyte apoptosis in mice with sepsis. These adverse changes were markedly reversed in response to THC treatment in septic mice as well as in LPS-treated H9c2 cells. Mechanistically, THC inhibited the release of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-6, by upregulating mitogen-activated protein kinase phosphatase 1, to block the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK). Additionally, THC enhanced the levels of antioxidant proteins, including nuclear factor-erythroid 2-related factor 2, superoxide dismutase 2, and NAD(P)H quinone oxidoreductase 1, while decreasing gp91phox expression. Furthermore, upon THC treatment, Bcl-2 expression was significantly increased, along with a decline in Bax and cleaved caspase-3 expression, which reduced cardiomyocyte loss. CONCLUSION: Our findings indicate that THC exhibited protective potential against septic cardiomyopathy by reducing oxidative stress and inflammation through the regulation of JNK/ERK signaling. The findings of this study provide a basis for the further evaluation of THC as a therapeutic agent against septic cardiomyopathy.

Management of Chronic Myeloid Leukemia and Pregnancy: A Bibliometric Analysis (2000-2020).

Background: Given the increasing number and survival rates of reproductive-age patients with chronic myeloid leukemia (CML), several studies aimed to elucidate optimum disease management in pregnancy. This study aimed to use bibliometric analysis to assess focus and reported insights, as well as future trends, in CML and pregnancy research. Methods: We extracted all studies related to CML and pregnancy from the Web of Science database from 2001 to 2020. VOS Viewer, CiteSpace, Python, and R-bibliometrix were used for bibliometric analysis, revealing the leading research countries, institutions, and authors, as well as distribution of keywords (frequency greater than five). Results: A total of 196 records, published in 137 journals by 1,105 authors from 421 research institutes in 50 countries, were identified for analysis. The United States was the leader in the number of publications. Imperial College London and National Research Center for Hematology were the most influential institutions. In addition, Apperley J, Cortes J, Abruzzese E and Kantarjian H were the leading authors in the field. Keyword analysis identified four research hotspot clusters. Conclusions: This study systematically analyzed the progress in CML and pregnancy research in the last 20 years. The present findings suggest that the management of planned and unplanned pregnancies in patients with CML will remain a research focus, as further evidence is required for the development of treatment guidelines.

G Protein-Coupled Estrogen Receptor 30 Reduces Transverse Aortic Constriction-Induced Myocardial Fibrosis in Aged Female Mice by Inhibiting the ERK1/2 -MMP-9 Signaling Pathway.

The incidence of cardiovascular diseases was significantly increased in postmenopausal women. The protection of estrogen in the cardiovascular system has been further reported for decades. Although menopausal hormone therapy has been used in many clinical trials, the debatable results indicate that the studies for elucidating the precise molecular mechanism are urgently required. G protein-coupled estrogen receptor 30 (GPR30) is a membrane receptor of estrogen and displays protective roles in diverse cardiovascular diseases. Previous studies have revealed that ERK1/2-mediated MMP-9 signaling was involved in ischemic heart diseases. However, the role of ERK1/2-mediated MMP-9 signaling in the protection of GPR30 against cardiac hypertrophy in aged female mice has not been investigated. Our present study demonstrated that GPR30 overexpression and its agonist G1 co-administration reduced transverse aortic constriction-induced myocardial fibrosis and preserved cardiac function in aged female mice. MMP-9 expression was markedly increased via ERK1/2 phosphorylation in transverse aortic constriction-injured myocardium of aged female mice. Further results showed that GPR30/G1 activation decreased MMP-9 expression via ERK1/2 inhibition, which further reduced TGF-ß1 expression. Inhibition of the ERK1/2 signaling pathway by its inhibitor PD98059 suppressed the induction of the cardiomyocyte MMP-9 level caused by the GRP30 antagonist G15 and inhibited TGF-ß1 expression in cardiac fibroblast in vitro. In summary, our results from in vivo and in vitro studies indicated that GPR30 activation inhibited myocardial fibrosis and preserved cardiac function via inhibiting ERK-mediated MMP-9 expression. Thus, the present study may provide the novel drug targets for prevention and treatment of cardiac pathological hypertrophy in postmenopausal women.

circ_0023461 Silencing Protects Cardiomyocytes from Hypoxia-Induced Dysfunction through Targeting miR-370-3p/PDE4D Signaling.

BACKGROUND: Acute myocardial infarction (AMI) is a common cardiovascular disease with high disability and mortality. Circular RNAs (circRNAs) are implicated in the pathomechanism of multiple human diseases, including AMI. This study intended to explore the function and working mechanism of a novel circRNA circ_0023461 in hypoxia-induced cardiomyocytes. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were implemented to detect RNA and protein expression. Cell counting kit-8 (CCK8) assay and 5-ethynyl-2'-deoxyuridine (Edu) assay were conducted to analyze cell viability and proliferation ability. Cell migration and apoptosis were assessed by Transwell assay and flow cytometry. Cell oxidative stress was analyzed using the commercial kits. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze cell inflammation. Cell glycolytic metabolism was evaluated using the commercial kits. Dual-luciferase reporter assay and RNA pull-down assay were conducted to verify the intermolecular interactions. RESULTS: circ_0023461 expression was upregulated in AMI patients and hypoxia-induced AC16 cells. Hypoxia restrained the viability, proliferation, migration, and glycolysis and induced the apoptosis, oxidative stress, and inflammation of AC16 cells, and these effects were attenuated by the silence of circ_0023461. MicroRNA-370-3p (miR-370-3p) was verified as a target of circ_0023461, and circ_0023461 silencing-mediated protective effects in hypoxia-induced cardiomyocytes were partly alleviated by the knockdown of miR-370-3p. miR-370-3p interacted with the 3' untranslated region (3' UTR) of phosphodiesterase 4D (PDE4D), and PDE4D overexpression partly reversed miR-370-3p overexpression-induced protective effects in hypoxia-induced cardiomyocytes. circ_0023461 can upregulate PDE4D expression by acting as a molecular sponge for miR-370-3p in AC16 cells. CONCLUSION: circ_0023461 knockdown attenuated hypoxia-induced dysfunction in AC16 cells partly by targeting the miR-370-3p/PDE4D axis.