Association between epicardial adipose tissue and incident heart failure mediating by alteration of natriuretic peptide and myocardial strain.

BACKGROUND: Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. METHODS: Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. RESULTS: Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19-1.72, P < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07-1.40], P = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92-0.98], P = 0.011) and GLS (HR [95% CI], 1.04 [1.01-1.07], P = 0.032). CONCLUSIONS: EAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases. TRIAL REGISTRATION: URL: https://clinicaltrials.gov . Identifier: NCT00005121.

Identification of a long noncoding RNA Gm17501 as a novel negative regulator of cardiac hypertrophy.

Pathological cardiac hypertrophy is an independent risk factor for the development of heart failure. Long noncoding RNAs (lncRNAs), an emerging class of non-protein-coding transcripts, are involved in regulation of multiple cardiac diseases through diverse molecular mechanism, whereas the role of cytoplasmic lncRNAs in regulating cardiac hypertrophy remains unclear. In this study, we identified a novel and functional long noncoding RNA Gm17501, which was predominantly expressed in the cytoplasm of cardiomyocytes. The expression level of lncRNA Gm17501 was altered in cardiac hypertrophy induced by pressure overload and phenylephrine treatment. Moreover, lncRNA Gm17501 expression was decreased in the heart tissue of patients with heart failure. Silencing lncRNA Gm17501 aggravated cardiac hypertrophy under pathological stress. Inhibition of lncRNA Gm17501 did not alter the expression of nearby genes but decreased mRNA level of calcium handling proteins which were involved in cardiac contraction. Therefore, the cytoplasmic lncRNA Gm17501 might protect cardiomyocytes against hypertrophy, possibly by maintaining calcium signaling pathway.

Puerarin Protects against Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis.

This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and reoxygenation (OGD/R) model and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.

Micro-RNAs in Human Placenta: Tiny Molecules, Immense Power.

Micro-RNAs (miRNAs) are short non-coding single-stranded RNAs that modulate the expression of various target genes after transcription. The expression and distribution of kinds of miRNAs have been characterized in human placenta during different gestational stages. The identified miRNAs are recognized as key mediators in the regulation of placental development and in the maintenance of human pregnancy. Aberrant expression of miRNAs is associated with compromised pregnancies in humans, and dysregulation of those miRNAs contributes to the occurrence and development of related diseases during pregnancy, such as pre-eclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), recurrent miscarriage, preterm birth (PTB) and small-for-gestational-age (SGA). Thus, having a better understanding of the expression and functions of miRNAs in human placenta during pregnancy and thereby developing novel drugs targeting the miRNAs could be a potentially promising method in the prevention and treatment of relevant diseases in future. Here, we summarize the current knowledge of the expression pattern and function regulation of miRNAs in human placental development and related diseases.

MicroRNA-3935 promotes human trophoblast cell epithelial-mesenchymal transition through tumor necrosis factor receptor-associated factor 6/regulator of G protein signaling 2 axis.

BACKGROUND: Insufficient migration and invasion during trophoblast epithelial-mesenchymal transition (EMT) results in the occurrence and development of preeclampsia (PE), and our previous study has screened 52 miRNAs, whose expression levels are altered in the placental samples from PE patients, compared with the normal group. Among those, miR-3935 is one of the miRNAs being most significantly down-regulated, indicating its involvement in PE. However, the exact effect and molecular mechanisms remain unknown. METHODS: In the present study, we investigate the roles and underlying mechanisms of miR-3935 in trophoblast EMT by use of the human extra-villous trophoblast cell line HTR-8/SVneo as well as human placental tissues and maternal blood samples obtained from 15 women with normal pregnancies and 15 women with PE. Experimental methods include transfection, quantitative reverse transcription-PCR (qRT-PCR), western blot, immunofluorescence staining, dual-luciferase assays, in vitro invasion and migration assays, RNA-Seq analysis, bisulfite sequencing and immunohistochemistry staining. RESULTS: MiR-3935 expression is significantly decreased in both placentas and peripheral blood specimens of PE, and functionally, miR-3935 promotes EMT of trophoblast cells. Mechanistically, TRAF6 is identified to be a direct target of miR-3935 and TRAF6 exerts its negative effect on EMT of trophoblast cells by inhibition of RGS2, which down-regulates the methylation status of promoter of CDH1 gene that encodes E-Cadherin protein through induction of ALKBH1, resulting in increase of E-Cadherin and subsequently insufficient trophoblast EMT. CONCLUSIONS: Together these results uncover a hitherto uncharacterized role of miR-3935/TRAF6/RGS2 axis in the function of human trophoblasts, which may pinpoint the molecular pathogenesis of PE and may be a prognostic biomarker and therapeutic target for such obstetrical diseases as PE.

Meta-analysis of metabolic syndrome and its individual components with risk of atrial fibrillation in different populations.

BACKGROUND: Recent studies have reported the effects of metabolic syndrome (MetS) and its components on atrial fibrillation (AF), but the results remain controversial. Therefore, we performed a meta-analysis to evaluate the relationship between MetS and AF risk. METHODS: Studies were searched from the Cochrane library, PubMed, and Embase databases through May 2020. Adjusted hazard ratios (HRs) and its corresponding 95% confidence intervals (CIs) were extracted and then pooled by using a random effects model. RESULTS: A total of 6 observational cohort studies were finally included. In the pooled analysis, MetS was associated with an increased risk of AF (HR 1.57; 95% CI 1.40-1.77; P < 0.01). And the components of MetS including abdominal obesity (HR 1.37; 95% CI 1.36-1.38; P < 0.01), elevated blood pressure (HR 1.56; 95% CI 1.46-1.66; P < 0.01), elevated fasting glucose (HR 1.18; 95% CI 1.15-1.21; P < 0.01) and low high density cholesterol (HDL) (HR 1.18; 95% CI 1.06-1.32; P < 0.01) was also associated with an increased risk of AF, while high triglyceride (HR 0.99; 95% CI 0.87-1.11, P = 0.82) was not. CONCLUSIONS: Our present meta-analysis suggested that MetS, as well as its components including abdominal obesity, elevated blood pressure, elevated fasting glucose and low HDL cholesterol were associated with an increase in the risk of AF.

Evaluation of atherogenic lipoprotein-cholesterol to HDL cholesterol ratio as a prognostic test for ST-segment elevation myocardial infarction.

Background: The detectable component of triglyceride-rich lipoproteins (TGRLs), remnant lipoprotein cholesterol (RLP-c), has been proven being correlated with the progression of atherosclerosis and myocardial infarction. However, when taken as a risk predictor, the prognostic and diagnostic potential of RLP-c remains controversial in studies. In this study, we evaluated the hypothesis that atherogenic lipoprotein-cholesterol (AL-c), representing the sum of RLP-c and the sd-LDL-c, to the HDL-c ratio, could represent a better predictive indicator than RLP-c alone in ST-segment elevation myocardial infarction (STEMI). Methods: The 316 consecutive patients suffering from persistent chest discomfort admitted to the Shanghai General Hospital between January 2018 and June 2018 were enrolled. 149 STEMI patients (62% men, mean age 69.6 ± 13.3 years) were included as the study cohort. The AL-c/HDL-c ratio was calculated on admission in a cohort of electrocardiogram-confirmed STEMI patients and compared to other lipid profiles as a predictive indicator. Results: The AL-c/HDL-c ratio was significantly increased in STEMI patients compared with apparently healthy adults (0.93; IQR [0.71-1.18] vs 0.70; IQR [0.45-1.04]; p < 0.001). Gender dependency existed, and the male and female patients had median AL-c/HDL-c ratios of 1.01 and 0.79, respectively (p < 0.001). Compared to RLP-c, the AL-c/HDL-c ratio had a better prognostic value to predict STEMI risk in both sexes (AUC of 0.672 with a sensitivity of 0.794 in males and 0.613 with a sensitivity of 0.684 in females). Conclusions: The AL-c/HDL-c ratio could represent a convenient and sensitive biomarker for screening and predicting STEMI risk.

Choosing an appropriate glomerular filtration rate estimating equation: role of body mass index.

BACKGROUND: We aimed to investigate the accuracy of different equations in evaluating estimated glomerular filtration rate (eGFR) in a Chinese population with different BMI levels. METHODS: A total of 837 Chinese patients were enrolled, and the eGFRs were calculated by three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, three full-age spectrum (FAS) equations and two Modification of Diet in Renal Disease (MDRD) equations. Results of measured GFR (mGFR) by the 99Tcm-diathylenetriamine pentaacetic acid (99Tcm-DTPA) renal dynamic imaging method were the reference standards. According to BMI distribution, the patients were divided into three intervals: below 25th(BMIP25), 25th to 75th(BMIP25-75) and over 75th percentiles (BMIP75). RESULTS: The medium BMI of the three BMI intervals were 20.9, 24.8 and 28.9 kg/m2, respectively. All deviations from mGFR (eGFR) were correlated with BMI (p < 0.05). The percentage of cases in which eGFR was within mGFR ±30% (P30) was used to represent the accuracy of each equation. Overall, eGFRFAS_Cr_CysC and eGFREPI_Cr_2009 performed similarly, showing the best agreement with mGFR among the eight equations in Bland-Altman analysis (biases: 4.1 and - 4.2 mL/min/1.73m2, respectively). In BMIP25 interval, eGFRFAS_Cr got - 0.7 of the biases with 74.2% of P30, the kappa value was 0.422 in classification of CKD stages and the AUC60 was 0.928 in predicting renal insufficiency, and eGFREPI_Cr_2009 got 2.3 of the biases with 71.8% of P30, the kappa value was 0.418 in classification of CKD stages and the AUC60 was 0.920 in predicting renal insufficiency. In BMIP25-75 interval, the bias of eGFRFAS_Cr_CysC was 4.0 with 85.0% of P30, the kappa value was 0.501 and the AUC60 was 0.941, and eGFRFAS_Cr_CysC showed balanced recognition ability of each stage of CKD (62.3, 63.7, 68.0, 71.4 and 83.3% respectively). In BMIP75 interval, the bias of eGFREPI_Cr_CysC_2012 was 3.8 with 78.9% of P30, the kappa value was 0.484 the AUC60 was 0.919, and eGFREPI_Cr_CysC_2012 equation showed balanced and accurate recognition ability of each stage (60.5, 60.0, 71.4, 57.1 and 100% respectively). In BMIP75 interval, the bias of eGFRFAS_Cr_CysC was - 1.8 with 78.5% of P30, the kappa value was 0.485, the AUC60 was 0.922. However, the recognition ability of each stage of eGFRFAS_Cr_CysC eq. (71.1, 61.2, 70.0, 42.9 and 50.0% respectively) was not as good as GFREPI_Cr_CysC_2012 equation. CONCLUSION: For a Chinese population, we tend to recommend choosing eGFRFAS_Cr and eGFREPI_Cr_2009 when BMI was around 20.9, eGFRFAS_Cr_CysC when BMI was near 24.8, and eGFREPI_Cr_CysC_2012 when BMI was about 28.9.

Lipoprotein-Associated Phospholipase A2 in Cardiac Disease: a Potential Early Biomarker of Unstable Coronary Artery Disease.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a serine lipase that deteriorates the stability of atherosclerotic plaques. This study aims to investigate Lp-PLA2 activity and its diagnostic potential in the early period of acute coronary syndromes (ACS). METHODS: Two hundred sixty-two patients referred for acute chest pain within 6 hours of symptom onset were included. Among the candidates, 67 were diagnosed with ST-elevation myocardial infarction (STEMI) and 167 unstable angina (UA). The STEMI patients were divided into cardiac troponin I (cTnI) negative and cTnI positive groups according to the cTnI values at admission. As control, 184 stable coronary artery disease (CAD) patients were also enrolled. Blood samples were collected immediately after admission. The levels of Lp-PLA2 activity and lipids were measured. The diagnostic value of Lp-PLA2 was determined based on receiver operating characteristic curves. RESULTS: Lp-PLA2 activity levels of STEMI and UA groups were dramatically higher than that in CAD group. However, Lp-PLA2 values showed no marked difference between STEMI and UA groups. Similar results were obtained between cTnI negative and positive groups among STEMI patients. In the three groups combined, there was a significant correlation between LDL-C concentration and Lp-PLA2 activity. In the ACS group, the area under the curve was 0.719 (95% CI: 0.671 - 0.768), and the optimal Lp-PLA2 cutoff value was 306.4 U/L, with a sensitivity of 67% and specificity of 69%. CONCLUSIONS: Lp-PLA2 activity was significantly elevated in the early stage of ACS. The obtained statistical data suggest that Lp-PLA2 activity may represent a novel early marker of unstable coronary disease.

Opacification of lentoid bodies derived from human induced pluripotent stem cells is accelerated by hydrogen peroxide and involves protein aggregation.

Despite the recent breakthrough in cataract drug development, further improvements have been limited by the lack of human in vitro cataract disease models. This study, therefore, aims to generate a qualified cataract disease model. Mature lentoid bodies (LBs) on Day 25 (D25), which were differentiated from human induced pluripotent stem cells (iPSCs) using the "fried egg" method, were continually culturing (control) or extra treated with either ultraviolet (UV) radiation or hydrogen peroxide (H2 O2 ). The LBs' shape alteration and opacity were examined using light microscopy and mean gray value evaluation. Their structure and crystallin expression were examined using immunofluorescence and transmission electron microscopy (TEM). Real-time polymerase chain reaction and western blot were used to investigate the potential role of autophagy in cloudy LBs. Mature LBs became cloudy with time which was accelerated by H2 O2 . Immunofluorescence examinations and TEM showed that the H2 O2 -treated and control LBs had similar shapes, lens capsule, and monolayer lens epithelial cell (LEC) structures. However, we were unable to do further assessment of the UV-treated LBs as the structures of LBs were easily damaged when treated with UV radiation. Cells containing aggregated protein (αA-crystallin and αB-crystallin) puncta were more abundant in the H2 O2 -treated LBs as compared with control LBs. Moreover, LC3B expression decreased with age in anterior lens capsules obtained from age-related cataracts (ARCs) patients as compared with LC3B levels in primary LECs, which is consistent with that LC3B expression in LBs was lower on D45 than on D25. Our study found that human iPSCs-derived LBs became cloudy with time which was accompanied by protein aggregation, and this phenomenon was accelerated by H2 O2 , suggesting that LBs with extending culture may serve as a human model for in vitro ARCs.

Therapeutic Effects of Bipolar Coagulation Forceps on Open Thyroid Surgery.

BACKGROUND: The aim was to compare the therapeutic effects of bipolar coagulation forceps, harmonic scalpel, and conventional thyroidectomy on open thyroid surgery. METHODS: A total of 527 patients who received open thyroid surgery in the Affiliated Drum Tower Hospital of Nanjing University Medical School between February 2013 and February 2016 were randomly divided into three groups: bipolar coagulation forceps, harmonic scalpel, and conventional thyroidectomy. There were no statistically significant differences in gender, age, disease constituents or mass diameter between the three groups. All surgeries were performed by the same surgeon. The surgical time, intraoperative blood loss, postoperative volume of drainage, postoperative hospital stay, and postoperative complications of the three surgical methods were compared. RESULTS: The bipolar coagulation forceps and harmonic scalpel groups were significantly superior to the conventional thyroidectomy group (p < 0.05) in terms of surgical time, intraoperative blood loss, postoperative volume of drainage, and postoperative hospital stay, but the first two groups had similar outcomes (p > 0.05). There were significant differences between the three groups in temporary recurrent laryngeal nerve palsy and temporary hypoparathyroidism, and the results of the bipolar coagulation forceps group were significantly better than those of the other two groups (p < 0.05). No significant differences were found in airway depression due to postoperative bleeding or irritating cough induced by superior laryngeal nerve palsy between the three groups (p > 0.05). None of the patients in the three groups suffered from permanent recurrent laryngeal nerve palsy or permanent hypoparathyroidism. CONCLUSIONS: The effects of bipolar coagulation forceps on open thyroid surgery exceeded those of the harmonic scalpel and conventional thyroidectomy. This method is worthy of promotion in clinical practice.

Incidence and analysis of intraoperative complications in femtosecond laser-assisted cataract surgery: a large-scale cohort study to establish the learning curve.

AIMS: To assess the safety of femtosecond laser-assisted cataract surgery (FLACS) based on surgical parameters and intraoperative complications analysis and to determine the length of the learning curve for FLACS. METHODS: A prospective consecutive cohort study was conducted on Chinese patients who underwent either FLACS (3289 cases) or contemporaneous conventional phacoemulsification cataract surgery (2130 cases). The laser group was divided into four subgroups in chronological order. We recorded intraoperative complication incidences and compared with surgical parameters between groups. Subgroup analysis was conducted to explore the learning curve of FLACS. RESULTS: The laser group had a 4.93% incidence of incomplete capsulotomies and a 1.22% incidence of anterior capsule tears. Subgroup analysis showed significant differences in 8 aspects between the first 250 cases (50 cases per surgeon) and the last 2539 cases, but only 2 aspects differed between the second 250 cases (50 cases per surgeon) and the last 2539 cases. There were no significant differences between the third 250 cases (50 cases per surgeon) and the last 2539 cases. CONCLUSIONS: The intraoperative complications of FLACS were reported, and the learning curve is associated with a significant reduction in the incidence of intraoperative complications. The length of the basic learning curve of FLACS is 100 cases, and the length of the advanced learning curve was 150 cases. This study demonstrated that FLACS is characterised by a relatively straightforward and secure operative technique.

Drag reduction using bionic groove surface for underwater vehicles.

Introduction: The reduction of drag is a crucial concern within the shipping industry as it directly influences energy consumption. This study addresses this issue by proposing a novel approach inspired by the unique ridge structure found on killer whale skin. The objective is to develop a non-smooth surface drag reduction method that can effectively decrease drag and improve energy efficiency for ships. Methods: The study introduces a technique involving the creation of transverse bionic groove surfaces modeled after the killer whale skin's ridge structure. These grooves are aligned perpendicular to the flow direction and are intended to modify the behavior of turbulent boundary layer flows that form around the ship's hull. Numerical simulations are employed using the Shear Stress Transport k-ω model to analyze the effects of the proposed groove surface across a wide range of flow conditions. The research investigates the impact of various parameters, such as the width-to-depth ratio (λ/A), groove depth, and inlet velocity, on the drag reduction performance of the bionic groove surface. Results: The study reveals several key findings. Optimal shape parameters for the bionic groove surface are determined, enabling the most effective drag reduction. The numerical simulations demonstrate that the proposed groove surface yields notable drag reduction benefits within the velocity range of 2∼12 m/s. Specifically, the friction drag reduction ratio is measured at 26.91%, and the total drag reduction ratio at 9.63%. These reductions signify a substantial decrease in the forces opposing the ship's movement through water, leading to enhanced energy efficiency. Discussion: Comparative analysis is conducted between the performance of the bionic groove surface and that of a smooth surface. This investigation involves the examination of velocity gradient, streamwise mean velocity, and turbulent intensity. The results indicate that the bionic groove structure effectively mitigates viscous stress and Reynolds stress, which in turn reduces friction drag. This reduction in drag is attributed to the alteration in flow behavior induced by the non-smooth surface. Conclusion: The study proposes a novel approach for drag reduction in the shipping industry by emulating the ridge structure of killer whale skin. The transverse bionic groove surface, aligned perpendicular to flow direction, demonstrates promising drag reduction outcomes across diverse flow conditions. Through systematic numerical simulations and analysis of key parameters, the research provides insights into the drag reduction mechanism and identifies optimal design parameters for the groove surface. The potential for significant energy savings and improved fuel efficiency in maritime transportation underscores the practical significance of this research.

RGS2 promotes estradiol biosynthesis by trophoblasts during human pregnancy.

Production of estradiol (E2) by the placenta during human pregnancy ensures successful maintenance of placental development and fetal growth by stimulating trophoblast proliferation and the differentiation of cytotrophoblasts into syncytiotrophoblasts. Decreased levels of E2 are closely associated with obstetrical diseases such as preeclampsia (PE) in the clinic. However, the mechanisms underlying the inhibition of placental E2 biosynthesis remain poorly understood. Here, we report that regulator of G-protein signaling 2 (RGS2) affects E2 levels by regulating aromatase, a rate-limiting enzyme for E2 biosynthesis, by using human trophoblast-derived JEG-3 cells and human placental villus tissues. RGS2 enhanced the protein degradation of the transcription factor heart and neural crest derivatives expressed 1 (HAND1) by suppressing ubiquitin-specific protease 14 (USP14)-mediated deubiquitination of HAND1, resulting in the restoration of HAND1-induced trans-inactivation of the aromatase gene and subsequent increases in E2 levels. However, aromatase bound to RGS2 and repressed RGS2 GTPase activating protein (GAP) activity. Moreover, we observed a positive correlation between RGS2 and aromatase expression in clinical normal and preeclamptic placental tissues. Our results uncover a hitherto uncharacterized role of the RGS2-aromatase axis in the regulation of E2 production by human placental trophoblasts, which may pinpoint the molecular pathogenesis and highlight potential biomarkers for related obstetrical diseases.

RIPK1 is aberrantly expressed in multiple B-cell cancers and implicated in the underlying pathogenesis.

According to the latest epidemiology of the US, B-cell cancers account for > 3% of all new cancer cases and > 80% of non-Hodgkin lymphomas. However, the disease-modifying small molecular drug suitable for most B-cell cancers is still lacking. RIPK1 (receptor-interacting serine/threonine-protein kinase 1) has been observed to be dysregulated and implicated in the pathogenesis of multiple solid cancers, of which, however, the roles in blood cancers are quite unclear. In our study, to identify multi-function targets for B-cell cancer treatment, we reanalyzed a public transcriptomic dataset from the database of Gene Expression Omnibus, which includes CD19+ B-cell populations from 6 normal donors and patients of 5 CLL, 10 FL, and 8 DLBCL. After overlapping three groups (CLL vs. normal, FL vs. normal, and DLBCL vs. normal) of differentially expressed genes (DEGs), we obtained 69 common DEGs, of which 3 were validated by real-time quantitative PCR, including RIPK3, IGSF3, TGFBI. Interestingly, we found that the loss function of RIPK1 significantly increases the proliferation and viability of GM12878 cells (a normal human B lymphocyte cell line). Consistently, overexpression of RIPK1 in TMD8 and U2932 cells effectively inhibited cell proliferation and growth. More importantly, modifying RIPK1 kinase activity by a small molecule (such as necrostain-1, HOIPIN-1, etc.) alters the cell growth status of B-cell lymphoma, showing that RIPK1 exhibits anti-tumor activity in the context of B-cell lymphoma. Taken together, we consider that RIPK1 may be a potential target in the clinical application of B-cell lymphoma (including CLL, DLBCL, and FL) treatment.

Robust Representation Learning for Power System Short-Term Voltage Stability Assessment Under Diverse Data Loss Conditions.

With the help of neural network-based representation learning, significant progress has been recently made in data-driven online dynamic stability assessment (DSA) of complex electric power systems. However, without sufficient attention to diverse data loss conditions in practice, the existing data-driven DSA solutions' performance could be largely degraded due to practical defective input data. To address this problem, this work develops a robust representation learning approach to enhance DSA performance against multiple input data loss conditions in practice. Specifically, focusing on the short-term voltage stability (SVS) issue, an ensemble representation learning scheme (ERLS) is carefully designed to achieve data loss-tolerant online SVS assessment: 1) based on an efficient data masking technique, various missing data conditions are handled and augmented in a unified manner for lossy learning dataset preparation; 2) the emerging spatial-temporal graph convolutional network (STGCN) is leveraged to derive multiple diversified base learners with strong capability in SVS feature learning and representation; and 3) with massive SVS scenarios deeply grouped into a number of clusters, these STGCN-enabled base learners are distinctly assembled for each cluster via multilinear regression (MLR) to realize ensemble SVS assessment. Such a divide-and-conquer ensemble strategy results in highly robust SVS assessment performance when faced with various severe data loss conditions. Numerical tests on the benchmark Nordic test system illustrate the efficacy of the proposed approach.

A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis.

Postoperative endophthalmitis (POE) has been the most threatening complication after cataract surgery, which perhaps can be solved by the antibiotic-loaded intraocular lens (IOL). However, most drug-loaded IOLs demonstrate insufficient drug quantity, short release time, increased implantation-related difficulties or other noticeable drawbacks. To prevent POE and to address these deficiencies, a drug-loaded copolymer IOL, prepared from poly (urethane acrylate) prepolymer, isobornyl methacrylate (IBOMA), N-vinyl-2-pyrrolidone (NVP), Irgacure 819, RUVA-93, and gatifloxacin (GAT), was rapidly fabricated via photocuring and by using a 3D-printed mold. This composite displayed an outstanding and controllable GAT release behavior in vitro, a high light transmittance, and a moderate refractive index. Also, it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material. In vivo tests demonstrated satisfying released drug concentration at the early treatment stage. In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL, which also displayed good biocompatibility. These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE, also the proposed methods could inspire more designs for various medical applications.

Energy effective utilization of circulating fluidized bed fly ash to prepare silicon-aluminum composite aerogel and gypsum.

To reduce the cost of Si-Al aerogels preparation, circulating fluidized bed fly ash (CFA) was developed to be as the alternative to synthetic precursors. High energy consumption of alkali-melting and secondary wastes production were the major challenges. Here, a technique characterized by effective energy consumption and non-secondary waste was developed to convert CFA into Si-Al aerogel. The process consists two stages, preparation of Si-Al sol by sintering of CFA and Na2CO3 followed by sulfuric acid leaching, and synthesis of Si-Al aerogel by so-gel with trimethyl chlorosilane modification and ambient pressure drying. The optimization results of proportion and sintering temperature showed that the optimal temperature of sintering of Na2CO3 and CFA with the mass ratio of 0.7 was 750 °C, 100 °C lower than that of most other waste aluminosilicate materials. CaSO4·0.5H2O which meet building gypsum requirement was obtained by specifying the drying temperature of acid-leached residue at 126 °C for 2 h. The modification procedure was explored to obtain Si-Al aerogel with a large specific surface area of 857 m2/g and hydrophobic angle of 139.3°. Thermal and mechanical properties tests indicated that the Si-Al aerogels and gypsum produced from CFA exhibited promising thermal insulation and the potential application in construction.

Role of ARID1A in the Regulation of Human Trophoblast Migration and Invasion.

Migration and invasion of trophoblasts is critical for human placental development, trophoblastic differentiation, and pregnancy-associated diseases. AT-rich interactive domain-containing protein 1A (ARID1A), a subunit of the SWI-SNF complex, has been suggested to participate in the regulation of fertility via placental disruption in mice. However, whether ARID1A regulates human placental development and function remains unknown. Here, using human trophoblast-like JEG-3 cell line, we report that ARID1A controls trophoblast cell migration and invasion. Overexpression of ARID1A inhibits JEG-3 cell migration and invasion, whereas knockdown of ARID1A promotes migration and invasion in JEG-3 cells. Mechanistically, while ARID1A reduces JEG-3 cell migration by down-regulation of Snail transcription, it restrains JEG-3 cell invasion by binding to and destabilization of MMP-9 protein. Finally, ARID1A is apparently up-regulated in placental tissues of preeclampsia compared to that of normal pregnancies. Our results thereby imply that ARID1A acts as a critical gene in supporting the physiological function of human mature placenta.

Tianma Gouteng Decoction Exerts Pregnancy-Protective Effects Against Preeclampsia via Regulation of Oxidative Stress and NO Signaling.

Preeclampsia (PE), a pregnancy-specific syndrome with the major molecular determinants of placenta-borne oxidative stress and consequently impaired nitric oxide (NO) generation, has been considered to be one of the leading causes of maternal morbidity as well as mortality and preterm delivery worldwide. Several medical conditions have been found to be associated with increased PE risk, however, the treatment of PE remains unclear. Here, we report that Tianma Gouteng Decoction (TGD), which is used clinically for hypertension treatment, regulates oxidative stress and NO production in human extravillous trophoblast-derived TEV-1 cells. In human preeclamptic placental explants, reactive oxygen species (ROS) levels were elevated and NO production was inhibited, while TGD treatment at different periods effectively down-regulated the H2O2-induced ROS levels and significantly up-regulated the H2O2-suppressed NO production in human TEV-1 cells. Mechanistically, TGD enhanced the activity of total nitric oxide synthase (TNOS), which catalyze L-arginine oxidation into NO, and simultaneously, TGD promoted the expression of neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS), two isoforms of nitric oxide synthetases (NOS) in human placenta, resulting in the increased NO generation. More importantly, TGD administration not only increased the weight gain during pregnancy and revealed a hypotensive effect, but also improved the placental weight gain and attenuated fetal growth restriction in an NG-nitro-L-arginine methyl ester (L-NAME)-induced mouse PE-like model. Our results thereby provide new insights into the role of TGD as a potentially novel treatment for PE.