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Background We investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis. Methods A total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits. Results According to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P P P P Conclusions Increased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.

Objective V-set and transmembrane domain-containing protein 1 (VSTM1) is negatively correlated with inflammation. However, its effect on atherosclerosis (AS) remains largely unexplored. In this study, we aimed to assess the effect of VSTM1 on the biological function of human peripheral blood mononuclear cells /macrophages stimulated by oxidized low-density lipoprotein (ox-LDL). Methods U937 cells were divided into three groups as follows: control group, pLenti-VSTM1 shRNA group (VSTM1 depletion), and pLenti-VSTM1 group (VSTM1 overexpression). Cellular migration, chemotaxis, apoptosis, and secretion of inflammatory factors of monocytes/macrophages stimulated by ox-LDL were studied. Results Overexpression of VSTM1 decreased the proliferation of U937 cells and induced cellular apoptosis. Depletion of VSTM1 enhanced the invasiveness and chemotaxis, increased the inflammatory response, and reduced the incidence of cell necrosis and apoptosis. Nuclear factor κ of B cells (NF-κB) was activated in VSTM1-depleted U937 cells. Conclusion VSTM1 might play an important role in the activation of monocytes/macrophages and participate in the pathogenesis of AS via regulating NF-κB activity.

Predicting the estimated time of arrival (ETA) plays an essential role in decision support (conflict detection, arrival sequencing, or trajectory optimization) for air traffic controllers. In this paper, a new multiple stages strategy for ETA prediction is proposed based on radar trajectories, including arrival pattern identification, arrival pattern classification, and flight time estimation. First, an intention-oriented trajectory clustering method is developed based on a new trajectory representation technique. Such a proposed trajectory clustering method can group trajectories into different arrival patterns in an efficient way. Second, an arrival pattern classification model is constructed based on random forest and XGBoost algorithms. Then, a flight time regression model is trained for each arrival pattern by using the XGBoost algorithm. Information on current states, historical states, and traffic situations is considered to build the feature set during these processes. Finally, the arrival operation toward Guangzhou International Airport is chosen as a case study. The results illustrate that the proposed method and feature engineering approach could improve the performance of ETA prediction. The proposed multiple stages strategy is superior to the single-model-based ETA prediction.

The aim of this study was to investigate the correlation between v-set and transmembrane domain-containing 1 (VSTM1) expression and incidence of major adverse cardiac events (MACE) in patients with coronary heart disease (CHD). A total of 310 patients were divided into a non-acute coronary syndrome (non-ACS) group (containing the stable angina group, and the asymptomatic coronary artery diseaseand other patients group) and an ACS group (containing unstable angina and acute myocardial infarction patients). Monocytic VSTM1 expression levels (assessed via average fluorescence intensity derived from antibody binding to VSTM1) in each group were detected and analyzed. The cut-off value of monocytic VSTM1 expression to predict the onset of ACS and MACE was confirmed. VSTM1 expression in monocytes from the ACS group was lower than that of the non-ACS group. The incidence of MACEs in the high VSTM1-expression group was much less than that of those in the low VSTM1 expression group at the 1 year follow-up stage. VSTM1 expression had an independent-inversed association with increased incidence of MACE and ACS. VSTM1 expression in monocytes may help to predict the occurrence of ACS in patients with CHD, and moreover it may provide the means to evaluate MACE prognosis during CHD patient follow-up.

International audience; This article deals with event-triggered filter design of positive systems subject to state saturation. An event-triggering condition in the form of 1-norm is established based on the error and the measurable output. Under the presented event-triggering condition, the filter systems are transformed into interval uncertain systems. The positivity of the filter and error dynamics is achieved by considering the lower bound of the interval systems. Using a linear copositive Lyapunov function, the stability is guaranteed by considering the upper bound of the interval systems. By virtue of linear programming, an l 1 -gain filter is designed for the systems subject to exogenous disturbance. Then, multiplicative and additive gain fluctuations are introduced. Two classes of nonfragile filters are proposed, and a cone is constructed to guarantee that the states of the systems with state saturation can keep inside it. Finally, two examples are given to illustrate the effectiveness of the proposed approach.

Two-dimensional (2D) monolayer-bilayer (ML-BL) lateral junctions (LJs) have recently attracted attention due to their straightforward synthesis and resulting clean interface. Such systems consist of an extended ML with a secondary layer present only over half of the system, leading to an interface that is associated with the terminating edge of the secondary half layer. Our first-principles calculations reveal that the edges of the half layer completely lack reconstruction in the presence of unintentional dopants, in this case, Re. This observation is in startling contrast to the known physics of three-dimensional (3D) semiconductor surfaces where reconstruction has been widely observed. Herein, the electrostatics of the reduced dimensionality allows for greater separation between compensating defects, enabling dopants to remotely passivate edge states without needing to directly participate in the chemistry.

Background Serum free fatty acid (FFA) concentrations are associated with coronary heart disease and diabetes mellitus (DM). Few studies focused on the relationship between serum FFA levels and coronary artery calcification (CAC). Methods This was a retrospective, single-centered study recruiting patients underwent FFA quantification, coronary angiography and intravascular ultrasound (IVUS). CAC severity was assessed with the maximum calcific angle (arc) of the calcified plaque scanned by IVUS. Patients with an arc ≥ 180° were classified into the severe CAC (SCAC) group, and those with an arc Results Totally, 426 patients with coronary artery disease were consecutively included. Serum FFA levels were significantly higher in the SCAC group than non-SCAC group (6.62 ± 2.17 vs. 5.13 ± 1.73 mmol/dl, p p p = 0.003) and the DM group (OR 1.939, CI 1.388–2.710, p p p p Conclusions Serum FFA levels were independently associated with SCAC, and could have some predictive capacity for SCAC. The association was strongest in the DM group.

Purpose: To study the effect and mechanism of action of electro-acupuncture (EA) on nerve regeneration by analyzing the behavior, inflammation and cell death in spinal cord injury (SCI) rat model. Methods: SCI model was established according to Allen’s falling strike method. Electroacupuncture was performed on Jiaji (EX-B2)/Mingmen (GV4) acupoint with a 1 mA current intermittent wave at a frequency of 2Hz for 20 min daily. Interleukin (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using ELISA kits. Apoptosis-induced DNA strand breaks were evaluated by TUNEL assay while relative mRNA expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were measured by western blot. Results: Relative mRNA and protein expressions of DUSP14 decreased in SCI rats with time but increased by EA treatment. Further, partial locomotor functional recovery was presented in SCI rats by EA treatment. Moreover, intraspinal injection of DUSP14 over-expression viral supernatants/EA treatment ameliorated inflammation and apoptosis in SCI rats. Meanwhile, the protein levels of NF-κB p65 (nucleus) and phosphorylated TGF-activated kinase 1 (p-TAK1) increased in SCI rats following EA treatment but were decreased by EA treatment and intraspinal injection of DUSP14 over-expression viral supernatants. Conclusion: EA acupoint treatment exerts neuroprotective effects in SCI rats via the reduction of inflammation and apoptosis, and induction of DUSP14.

Aims Heart failure with preserved ejection fraction (HFpEF) develops in response to hypertensive left ventricular (LV) hypertrophy and is associated with increased cardiovascular events. Although the progression to systolic heart failure is a known consequence of LV hypertrophy and HFpEF, few data are available on the LV geometry change and frequency of deterioration to systolic dysfunction in this population. Methods and results We evaluated the baseline and follow‐up characteristics in 680 patients with LV hypertrophy and HFpEF in this prospective cohort study. The primary endpoint was 5 year all‐cause mortality. The changes of LV geometry and heart failure transition were analysed. Systolic dysfunction [left ventricular ejection fraction (LVEF)

The immersed boundary method (IBM) is often adopted to simulate various flow systems. The two key steps in IBM, namely the force distribution and velocity interpolation steps, are both performed in...

Background: Reperfusion therapy is known to improve prognosis and limit myocardial damage after myocardial infarction (MI). The administration of antiplatelet drugs prior to percutaneous coronary intervention also proves beneficial to patients with acute MI (AMI). However, a good number of AMI patients do not receive reperfusion therapy, and it is not clear if they would benefit from antiplatelet pre-treatment. Methods: Experimental C57BL/6 mice were randomly allocated to five groups: the sham group, control, post-treatment, pre-treatment, and pre- and post-treatment groups. Acetylsalicylic acid (15 mg/kg), clopidogrel (11 mg/kg), ticagrelor (27 mg/kg), and prasugrel (1.5 mg/kg) were intragastrically administered in the treatment groups. On day 7 post MI, cardiac function and cardiac fibrosis were evaluated using echocardiography and Masson’s trichrome staining, respectively. Histopathological examinations were performed on tissue sections to grade inflammatory cell infiltration. Platelet inhibition was monitored by measuring thrombin-induced platelet aggregation. Results: Left ventricular ejection fraction and fractional shortening improved significantly (p < 0.01) in the pre-treatment groups when compared to the post-treatment and control groups. A significant (p < 0.01) decrease in cardiac fibrosis was observed in the pre-treatment group, compared with the posttreatment and control groups. Inflammatory cell infiltration significantly decreased in the pre-treatment group compared with the control group (p < 0.05). Thrombin-induced platelet aggregation was significantly inhibited by antiplatelet drugs, but increased with the exposure to H2O2. Conclusions: In the absence of reperfusion therapy, pre-treatment with antiplatelet drugs successfully improved cardiac function, reduced cardiac fibrosis and inflammatory cell infiltration, and inhibited oxidative stress-induced platelet aggregation after MI in the mouse model.

Atopic dermatitis is a severe, chronic relapsing inflammatory disease of the skin with family clustering. It is characterized into acute phase, which is dominated by T helper 2-type immune responses, and chronic phase, which is dominated by T helper 1-type immune responses. Studies have shown that 3,3'-diindolylmethane not only has antitumor effects but also can relieve symptoms of inflammatory diseases by inhibiting the nuclear factor-κB signaling pathway and regulating T cell differentiation. To study the effect of 3,3'-diindolylmethane on atopic dermatitis and the underlying mechanism, a mouse model of acute atopic dermatitis was established using 2,4-dinitrofluorobenzene. After intraperitoneal injection of 3,3'-diindolylmethane, skin erythema and edema in mice were significantly alleviated. Furthermore, 3,3'-diindolylmethane reduced immune activation, probably by inhibiting the secretion of thymic stromal lymphopoietin by keratinocytes. 3,3'-Diindolylmethane also promoted the differentiation of regulatory T cells and inhibited the activation of T helper 2 and T helper 17 cells to reduce atopic dermatitis-related immune responses. However, it showed no significant effect on the differentiation of T helper 1 cells. These results indicate that 3,3'-diindolylmethane has a significant inhibitory effect on T helper 2 cells in the acute phase of atopic dermatitis. Our findings may provide not only more insights into the pathological mechanism of AD, but also a new candidate medicine for it.

Excessive alcohol intake can cause sustained or severe alcoholic liver injury (alcoholic liver disease). The purpose of this study was to explore the effect of Camellia vietnamensis active peptide (CMAP) A1-2 on alcohol-induced liver injury cells. Alcohol at 200 mmol/L reduced the survival rate of L-02 liver cells and caused a large amount of apoptosis. CMAP A1-2 component at 200 μg/mL was not toxic to normal cells and restored alcohol-induced cell survival. The main mechanisms of action of the CMAP A1-2 component included inhibiting alcohol-activated enzymes, such as alcohol-activated acetaldehyde dehydrogenase and cytochrome P4502E1, restoring glutathione content reduced by the action of alcohol, reducing intracellular reactive oxygen species level and inhibiting oxidative damage caused by ethanol. Moreover, CMAP A1-2 component activated p38 to regulate nuclear transcription factor, promote the expression of antioxidant enzyme (Hemeoxygenase-l) and protein kinase C, and reduce cell damage caused by alcohol.

Fine particulate air pollution

Colloidal quantum dots and graphene oxide composite are promising semiconductor nanomaterials for optoelectronic devices due in part to their tunable light absorption and extraordinary carrier tran...

Background: Infection by multi–drug-resistant (MDR) bacteria is a high-risk factor for poor clinical results. Pancreatoduodenectomy (PD) has been associated with a high rate of complications, inclu...

Deep learning plays a major task in classification of unsupervised data, which utilises network enhanced learning. This technique proves to be powerful in remote sensing (RS) field for spatial data classification. In the existing environment, huge amounts of data from the earth observation satellites known as satellite images time series (SITS) are gathered, which can be utilised for observing the areas related to geography over through time. In this proposed model the time series model utilised is based on geography. There exists a challenge on how these types of information can be analysed in the field of remote sensing. Notable, techniques related to deep learning substantiated in dealing with remote sensing usually for classification of scene . In this paper, we propose an enhanced classification method involving Recurrent Neural Network (RNN) along with Random forest (RF) for land classification using satellite images, which are publicly available for various research purposes. We utilised spatial data gathered from the satellite images (i.e. time series). Our experimental classification is based on pixel and object-based classification. The attained analysis illustrates that the proposed model outperforms the other present day remote sensing classification techniques by producing 87% target accuracy of classification scene from satellite images.

In a tactical wargame, the decisions of the artificial intelligence (AI) commander are critical to the final combat result. Due to the existence of fog-of-war, AI commanders are faced with unknown and invisible information on the battlefield and lack of understanding of the situation, and it is difficult to make appropriate tactical strategies. The traditional knowledge rule-based decision-making method lacks flexibility and autonomy. How to make flexible and autonomous decision-making when facing complex battlefield situations is a difficult problem. This paper aims to solve the decision-making problem of the AI commander by using the deep reinforcement learning (DRL) method. We develop a tactical wargame as the research environment, which contains built-in script AI and supports the machine–machine combat mode. On this basis, an end-to-end actor–critic framework for commander decision making based on the convolutional neural network is designed to represent the battlefield situation and the reinforcement learning method is used to try different tactical strategies. Finally, we carry out a combat experiment between a DRL-based agent and a rule-based agent in a jungle terrain scenario. The result shows that the AI commander who adopts the actor–critic method successfully learns how to get a higher score in the tactical wargame, and the DRL-based agent has a higher winning ratio than the rule-based agent.

There is no effective serologic parameter to distinguish different types of pancreatitis now. To distinguish between acute pancreatitis (AP) and acute exacerbations of chronic pancreatitis (CP) and to determine whether fibrosis occurs in CP, we evaluated the ability to produce white blood cells (WBCs), the neutrophil-to-retinol-binding protein (RBP) ratio (called the WNR), the product of the gamma-glutamyl transpeptidase (GGT) level, and the 5′-nucleotide-to-RBP ratio (called the GNR). We evaluated the newly proposed difference index RBP and analyzed the effectiveness of the WNR and GNR in 691 patients with pancreatic diseases. We performed univariate and multivariate analyses of serological indices and their correlations with RBP and performed receiver operating characteristic (ROC) curve analyses of the WNR and GNR. The serum RBP level decreased markedly in AP compared with that in the acute stage of CP (p < 0.05). The GGT, alkaline phosphatase (ALP), total protein (TP), albumin (ALB), prealbumin (PA), 5′-nucleotide, and uric acid (UC) serum levels were significantly higher for fibrotic CP than for the acute stage of CP without fibrosis (p < 0.05). With progressing to pancreatic fibrosis, the liver injury-related indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-Dimer, aspartate aminotransferase (AST), and GGT, gradually increased (p < 0.05). ROC curve analysis suggests that both the WNR (area under the curve [AUC] = 0.821) and GNR (AUC = 0.778) can be used to differentiate pancreatitis types., Graphical Abstract, To distinguish different types of pancreatitis by serological index, Luo and colleagues evaluated the ability to produce white blood cells (WBCs), the neutrophil-to-retinol-binding protein (RBP) ratio (called the WNR), the product of the gamma-glutamyl transpeptidase (GGT) level, and the 5′-nucleotide-to-RBP ratio (called the GNR). Both can be used to differentiate pancreatitis types.

This study aims to investigate the specific predictive role of the preoperative Nutritional Risk Index (NRI) in oligometastatic prostate cancer (OM-PC) patients, who have undergone cytoreductive radical prostatectomy (cRP), and explored its prognostic index values. A total 89 OM-PC patients, who were identified between 2013 and 2019, were included in the present study. The Kaplan-Meier method and Cox regression analysis were used to separately assess the prostate specific antigen (PSA) progression-free survival (PFS). Overall accuracy was determined by analyzing the area under the receiver operating characteristic curve (AUC). The analysis of patients in these three different groups indicated that patients with lower NRI values were significantly associated with a higher Gleason score and more neoadjuvant androgen deprivation therapy (

Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure. This study was designed to evaluate the influences of long-term xanthine oxidase inhibitor (febuxostat) prescription on left ventricular hypertrophy (LVH), left ventricular (LV) diastolic function, and new-onset heart failure with preserved ejection fraction (HFpEF) in these patients. Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared febuxosatat prescription (n = 96) and non-urate-lowering therapy (n = 192) in patients with hypertensive left ventricular hypertrophy (LVH) and asymptomatic hyperuricemia. With a follow-up of 36 months, febuxostat significantly decreased the level of serum uric acid as well as generated more prominent improvement in LVH and LV diastolic function. Besides, the new-onset symptomatic HFpEF occurred in 2 of 96 patients in febuxostat group and 13 of 192 patients in non-urate-lowering group (P = 0.091). No increased risk for major adverse cardiovascular events in patients prescribed with febuxostat was noted. In conclusion, long-term febuxostat exposure was associated with protective effects in terms of LVH or LV diastolic dysfunction in patients with hypertensive LVH and asymptomatic hyperuricemia. Febuxostat also displayed a trend for reduced risk of new-onset HFpEF in this population.

Perineural invasion is a common feature of pancreatic ductal adenocarcinoma (PDAC). Here, we investigated the effect of perineural invasion on the microenvironment and how this affects PDAC progression. Transcriptome expression profiles of PDAC tissues with different perineural invasion status were compared, and the intratumoral T-cell density and levels of neurotransmitters in these tissues were assessed. Perineural invasion was associated with impaired immune responses characterized by decreased CD8+ T and Th1 cells, and increased Th2 cells. Acetylcholine levels were elevated in severe perineural invasion. Acetylcholine impaired the ability of PDAC cells to recruit CD8+ T cells via HDAC1-mediated suppression of CCL5. Moreover, acetylcholine directly inhibited IFNγ production by CD8+ T cells in a dose-dependent manner and favored Th2 over Th1 differentiation. Furthermore, hyperactivation of cholinergic signaling enhanced tumor growth by suppressing the intratumoral T-cell response in an orthotopic PDAC model. Conversely, blocking perineural invasion with bilateral subdiaphragmatic vagotomy in tumor-bearing mice was associated with an increase in CD8+ T cells, an elevated Th1/Th2 ratio, and improved survival. In conclusion, perineural invasion–triggered cholinergic signaling favors tumor growth by promoting an immune-suppressive microenvironment characterized by impaired CD8+ T-cell infiltration and a reduced Th1/Th2 ratio. Significance: These findings provide a promising therapeutic strategy to modulate the immunosuppressive microenvironment of pancreatic ductal adenocarcinoma with severe perineural invasion.

Background Type 2 diabetes mellitus (T2DM) and hypertension are independently related to increasing risk of subsequent incident heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term metformin prescription in these patients. Methods Using a propensity score matching of 1:2 ratio, this retrospective claims database study compared metformin prescription (n = 130) and non-metformin therapy (n = 260) in patients with T2DM and hypertension and without clinical signs or symptoms of heart failure. Results With a follow-up of 6 years, the new-onset symptomatic HFpEF occurred in 6 of 130 patients in metformin group and 31 of 260 patients in non-metformin group (P = .020). Metformin also generated more prominent improvement in left ventricular (LV) diastolic function and hypertrophy. And Cox proportional hazards regression model revealed that metformin prescription (HR 0.351, 95% CI: 0.145–0.846, P = .020) was associated with a reduced risk of new onset of symptomatic HFpEF. Conclusions Long-term metformin exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and hypertrophy in patients with T2DM and hypertension, which might be beneficial for the delay of HFpEF progression.

The polysaccharide (OJP1), extracted from the root of Ophiopogon japonicus, is a well-known traditional Chinese medicine used to treat cardiovascular diseases. The present study was set up to investigate the cardioprotective effect of OJP1 on isoproterenol (ISO)-induced myocardial ischemia injury in rats. Results showed that pretreatment with OJP1 (100, 200 and 300 mg/kg) significantly reduced ISO-induced ST-segment elevation and the heart index, attenuated the levels of marker enzymes (AST, LDH, CK and CK-MB), along with a significantly enhanced the activities of ATPases. Moreover, pretreatment with OJP1 not only enhanced the activities of SOD, GPx and CAT in serum and myocardium, but also decreased the level of MDA. The biochemical and histopathological analysis also showed that OJP1 can alleviate the myocardial injury induced by ISO. Taken together, our results indicated that oral administration of OJP1 offered significant cardioprotective effect against the damage induced by ISO through enhancement of endogenous antioxidants.

Facial landmark detection aims to locate keypoints for facial images, which typically suffer from variations caused by arbitrary pose, diverse facial expressions, and partial occlusion. In this article, we propose a coarse-to-fine framework that joins a stacked hourglass network and salient region attention refinement for robust face alignment. To achieve this goal, we first present a multi-scale region learning module to analyze the structure information at a different facial region and extract a strong discriminative deep feature. Then we employ a stacked hourglass network for heatmap regression and initial facial landmarks prediction. Specifically, the stacked hourglass network introduces an improved Inception-ResNet unit as a basic building block, which can effectively improve the receptive field and learn contextual feature representations. Meanwhile, a novel loss function takes into account global weights and local weights to make the heatmap regression more accurate. Different from existing heatmap regression models, we present a salient region attention refinement module to extract a precise feature based on the heatmap regression, and utilize the filtered feature for landmarks refinement to achieve accurate prediction. Extensive experimental results of several challenging datasets (including 300 Faces in the Wild, Caltech Occluded Faces in the Wild, and Annotated Facial Landmarks Faces in the Wild) confirm that our approach can achieve more competitive performance than the most advanced algorithms.

As a two-dimensional direct band gap semiconductor with unique electronic and magnetic properties, monolayer chromium triiodide (CrI3) has a great potential for spintronic applications. Under the g...

Rationale: Tumor vascular normalization (TVN) is emerging to enhance the efficacy of anticancer treatment in many cancers including glioblastoma (GBM). However, a common and severe challenge being currently faced is the transient TVN effect, hampering the sustained administration of anticancer therapy during TVN window. Additionally, the lack of non-contrast agent-based imaging biomarkers to monitor TVN process postpones the clinical translation of TVN strategy. In this study, we investigated whether dual inhibition of VEGF and the glycolytic activator PFKFB3 could reinforce the TVN effect in GBM. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM)-MRI were performed to monitor TVN process and to identify whether IVIM-MRI is a candidate or complementary imaging biomarker for monitoring TVN window without exogenous contrast agent administration. Methods: Patient-derived orthotopic GBM xenografts in mice were established and treated with bevacizumab (BEV), 3PO (PFKFB3 inhibitor), BEV+3PO dual therapy, or saline. The vascular morphology, tumor hypoxia, and lactate level were evaluated before and at different time points after treatments. Doxorubicin was used to evaluate chemotherapeutic efficacy and drug delivery. Microarray of angiogenesis cytokines and western blotting were conducted to characterize post-treatment molecular profiling. TVN process was monitored by DCE- and IVIM-MRI. Correlation analysis of pathological indicators and MRI parameters was further analyzed. Results: Dual therapy extended survival and delayed tumor growth over each therapy alone, concomitant with a decrease of cell proliferation and an increase of cell apoptosis. The dual therapy reinforces TVN effect, thereby alleviating tumor hypoxia, reducing lactate production, and improving the efficacy and delivery of doxorubicin. Mechanistically, several angiogenic cytokines and pathways were downregulated after dual therapy. Notably, dual therapy inhibited Tie1 expression, the key regulator of TVN, in both endothelial cells and tumor cells. DCE- and IVIM-MRI data showed that dual therapy induced a more homogenous and prominent TVN effect characterized by improved vascular function in tumor core and tumor rim. Correlation analysis revealed that IVIM-MRI parameter D * had better correlations with TVN pathological indicators compared with the DCE-MRI parameter K trans. Conclusions: Our results propose a rationale to overcome the current limitation of BEV monotherapy by integrating the synergistic effects of VEGF and PFKFB3 blockade to enhance chemotherapy efficacy through a sustained TVN effect. Moreover, we unveil IVIM-MRI parameter D * has much potential as a complementary imaging biomarker to monitor TVN window more precisely without exogenous contrast agent injection.

Synchronous resection of primary pancreatic ductal adenocarcinoma (PDAC) and liver metastases in highly selective patients is being accepted based on oncology research progress showing safe surgical outcomes with low morbidity and mortality. We also tried to determine patients who would benefit from the operation.From January 2012 to October 2017, 48 patients who underwent synchronous resection of primary PDAC and liver metastases were retrospectively evaluated. Twenty-three of them underwent oligometastatic synchronous resection.The majority of synchronous resection PDAC patients underwent hepatic wedge resection, and no oligometastatic patient was treated with hemihepatectomy. The median overall survival (OS) of the synchronous resection patients was 7.8 months. Hepatic oligometastatic PDAC patients had a longer OS than that of non-oligometastatic synchronous resection patients, systemic chemotherapy patients and palliative patients (16.1 vs 6.4 months, P = 0.02; 16.1 vs 7.6 months, P = 0.02; 16.1 vs 4.3 months, P 0.0001; respectively). Further analysis showed that localized pancreatic body/tail PDAC had a better OS in oligometastatic patients than in non-oligometastatic synchronous resection patients (16.8 months vs 7.05 months, P = 0.0004) and systemic chemotherapy patients (16.8 months vs 8 months, P = 0.003).Patients with pancreatic body/tail PDAC with liver oligometastases can benefit from synchronous resection.

Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, CDC5L was also found to act as a candidate oncogene in osteosarcoma and cervical tumours. However, the role of CDC5L expression in bladder cancer remains unclear. Here, we analysed the expression and clinical significance of CDC5L in bladder cancer tissues. The expression of CDC5L in fresh bladder cancer tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in bladder cancer. The expression of CDC5L was significantly associated with bladder cancer pathology grade and Ki67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for the survival of bladder cancer patients. To determine whether CDC5L could regulate the proliferation of bladder cancer cells, we transfected bladder cancer cells with an interfering RNA targeting CDC5L and then investigated cell proliferation with a cell counting kit (CCK)-8, flow cytometry assays, colony formation and xenograft assay analyses. Our results indicate that knockdown of CDC5L inhibits proliferation of bladder cancer cells. In addition, reduced expression of CDC5L induced apoptosis of bladder cancer cells and inhibited their migration, invasion and EMT. These findings suggest that CDC5L might play an important role in bladder cancer and thus be a promising therapeutic target of bladder cancer.

Adaptive orthogonal frequency division multiplexing (OFDM) systems are promising for high-bit-rate short-reach communication by optimizing the allocation of modulation format and power to each subcarrier. Because adaptive OFDM systems involve multiple modulation formats, automatic modulation format identification (AMFI) is significant for subsequent signal processing and symbol decision of OFDM receivers. In this work, we proposed and experimentally demonstrated a blind modulation format identification technique based on constellation diagrams achieved from channel estimation of OFDM system. In the proposed AMFI scheme, the identification feature is the number of signals’ constellation clusters. First, we use the peak-density clustering algorithm to track the centers of signals’ constellation clusters by plotting the density–distance graph, where the clusters’ centers have much larger density and distance values than that of the other clusters’ points. Then, we use the K nearest neighbor regression algorithm to automatically calculate the number of signals’ constellation clusters. Finally, we evaluated and measured the identification accuracies of QPSK, 8-QAM, 8-PSK, 16-QAM, 64-QAM and 128 QAM signals in simulation and experiment.

Background Microglial polarization toward pro-inflammatory M1 phenotype are major contributors to the development of perioperative neurocognitive disorders (PNDs). Metabolic reprogramming plays an important role in regulating microglial polarization. We therefore hypothesized that surgical trauma can activate microglial M1 polarization by metabolic reprogramming to induce hippocampal neuroinflammation and subsequent postoperative cognitive impairment. Methods We used aged mice to establish a model of PNDs, and investigated whether surgical trauma induced metabolic reprograming in hippocampus using PET/CT and GC/TOF–MS based metabolomic analysis. We then determined the effect of the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) on hippocampal microglial M1 polarization, neuroinflammation, and cognitive function at 3 d after surgery. Results We found that surgery group had less context-related freezing time than either control or anesthesia group (P 0.05). The level of Iba-1 fluorescence intensity in hippocampus were significantly increased in surgery group than that in control group (P, Highlights Surgical trauma impaired the hippocampus-dependent contextual memory in age mice.Surgical trauma induced microglial M1 polarization and subsequent neuroinflammation.Metabolic reprogramming was crucial for regulating microglial M1 polarization in PNDs.Modulating microglial metabolism might provide a valuable approach for treating PNDs.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033).Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF.Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e′ level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF).Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

With the wide application of computer, internet and big data in the field of education in China, the traditional teaching mode in university of finance and economics faces some new challenges. They may undergo fundamental changes in educational concept, teaching mode, teaching method and learning method, etc. Innovating the application of computer network teaching is very important and urgent in university of finance and economics. In this study, firstly, we explored the necessary for the combination of the computer internet and teaching in university of finance and economics. Secondly, in 2018, based on 690 national excellent undergraduate online courses, we analyze the agglomeration of national excellent undergraduate online courses of finance and economics university in provinces of China adopting the Location Quotient (LQ) method. The results showed that Jiangxi province has the highest agglomeration of national excellent undergraduate online courses of finance and economics university in China, while Shanghai and Beijing have low agglomeration of national excellent undergraduate online courses of finance and economics university. Thirdly, from the four aspects of unreasonable teaching course designed, backward teaching mode, difficult to judge whether students master the knowledge learned and weak computer internet teaching faculty, this study showed the existing problems of teaching in university of finance and economics under the context of computer network. Lastly, this study innovated the application mode of computer network teaching in university of finance and economics by restructuring curriculum system, changing the teaching mode, building a high-quality computer internet teaching team and innovating evaluation system of the computer internet teaching.

The traffic dynamics of complex networks is closely related to network structure. By changing network structure, the traffic dynamics behavior can be optimized. Faced with the network congestion problem, we focus on the relationship between network traffic capacity and its structure. The multilayer networks are studied, which are composed of high-speed and low-speed layers. A link rewiring strategy is proposed to change the low-speed layer structure and improve the network traffic capacity. Compared with the random link rewiring strategy, the purposeful link rewiring strategy can improve network traffic capacity. A large number of simulations are carried out under the effective traffic-flow assignment strategy to prove the effectiveness of the link rewiring strategy. This strategy improves packet transmission efficiency of low-speed layer, and reduces the average length of effective path, which indicates that adjustment of low-speed layer structure can improve traffic capacity of multilayer networks.

Upstream stimuli for myofibroblast activation are of considerable interest for understanding the mechanisms underlying renal fibrosis. Activin B, a member of the TGF-β family, exists as a homodimer of inhibin subunit beta B (INHBB), but its role in renal fibrosis remains unknown. We found that INHBB expression was significantly increased in various renal fibrosis models and human chronic kidney disease specimens with renal fibrosis. Notably, the increase of INHBB occurred mainly in the tubular epithelial cells (TECs). In vivo, inhibiting INHBB blocked the activation of interstitial fibroblasts and ameliorated the renal fibrosis induced by unilateral ureteral obstruction or ischemia-reperfusion injury, while ectopic expression of INHBB in the TECs was able to activate interstitial fibroblasts and initiate interstitial fibrosis. In vitro, overexpression of INHBB in TECs led to the secretion of activin B, thereby promoting the proliferation and activation of interstitial fibroblasts through activin B/Smad signaling. Furthermore, inhibition of activin B/Smad signaling attenuated the fibrotic response caused by tubular INHBB. Mechanistically, the upregulation of INHBB depended on the transcription factor Sox9 in the injured TECs. Clinical analyses also identified a positive correlation between Sox9 and INHBB expression in human specimens, suggesting the Sox9/INHBB axis as a positive regulator of renal fibrosis. In conclusion, tubule-derived INHBB is implicated in the pathogenesis of renal fibrosis by activating the surrounding fibroblasts in a paracrine manner, thereby exhibiting as a potential therapeutic target. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Brain, guarded by the most rigorous barrier — blood‐brain barrier (BBB), is the most critical and sophisticated control center in the body. The dead bodies from melanoma cells, small apoptotic bodies with membrane embedded CD44v6 molecules could pass through BBB and deliver drugs for the cure of Parkinson's disease. The apoptotic body might be a new type of carrier for efficient in vivo drug delivery. More details can be found in article number 2004929 by Chunming Wang, Junfeng Zhang, Lei Dong, and co‐workers. [Image: see text]

BackgroundTobacco smoking is a carcinogen for many cancers including bladder cancer. The microbiota is involved in the occurrence, development, and treatment of tumors. We explored the composition of male urinary microbiome and the correlation between tobacco smoking and microbiome in this study.MethodsAlpha diversity, principal component analysis (PCA) and Adonis analysis, linear discriminant analysis (LDA) coupled with effect size measurement, and PICRUSt function predictive analysis were used to compare different microbiome between smokers and non-smokers in men.ResultsThere were 26 qualified samples included in the study. Eleven of them are healthy controls, and the others are from men with bladder cancer. Simpson index and the result of PCA analysis between smokers and non-smokers were not different (P > 0.05) in healthy men. However, the abundance of Bacteroidaceae, Erysipelotrichales, Lachnospiraceae, Bacteroides, and so on in the urinary tract of smokers is much higher than that of non-smokers. Compared to non-smokers, the alpha diversity in smokers was elevated in patients with bladder cancer (P < 0.05). PCA analysis showed a significant difference between smokers and non-smokers (P < 0.001), indicating that tobacco smoking plays a vital role in urinary tract microbial composition.ConclusionThe composition of microbiome in the urinary tract is closely related to tobacco smoking. This phenomenon is more significant in patients with bladder cancer. This indicates tobacco smoking may promote the occurrence and development of bladder cancer by changing urinary tract microbiome.

Long non‐coding RNA MIR503 host gene (MIR503HG) is located on chromosome Xq26.3, and has been found to be deregulated in many types of human malignancy and function as tumour suppressor or promoter based on cancer types. The role of MIR503HG in breast cancer was still unknown. In our study, we found MIR503HG expression was significantly decreased in triple‐negative breast cancer tissues and cell lines. Furthermore, we observed low MIR503HG expression was correlated with late clinical stage, lymph node metastasis and distant metastasis. In the survival analysis, we observed that triple‐negative breast cancer patients with low MIR503HG expression had a statistically significant worse prognosis compared with those with high MIR503HG expression, and low MIR503HG expression was a poor independent prognostic factor for overall survival in triple‐negative breast cancer patients. The study in vitro suggested MIR503HG inhibits cell migration and invasion via miR‐103/OLFM4 axis in triple negative breast cancer. In conclusion, MIR503HG functions as a tumour suppressive long non‐coding RNA in triple negative breast cancer.

This study was design to examine the diagnostic performance of cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen (CTX-II), and matrix metalloproteinase-3 (MMP-3) as biomarker for knee and hip OA.Systematic search on multiple databases was completed in January 2018 using certain keywords. COMP, CTX-II, MMP-3 levels in knee and hip OA patients and healthy individuals were collected and calculated. Differences between subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare COMP, CTX-II, and MMP-3 performance between measuring sources, genders, large and small sample size and diagnostic criteria for OA patients.A moderate performance of COMP in distinguishing between knee (SMD: 0.68; 95% confidence intervals (CI): 0.43-0.93; P 0.0001) or hip (SMD: 0.25; 95% CI, 0.10, 0.40; P = 0.0008) OA patients and controls were found. CTX-II showed a moderated standardised mean differences (SMD) of 0.48 (95% CI, 0.32, 0.64; P 0.0001) in the detection of knee OA and a large SMD of 0.76 (95% CI, 0.09, 1.42; P = 0.03) in diagnosing hip OA. A small SMD of 0.32 (95% CI, -0.03, 0.67; P = 0.07) was found for MMP-3 performance and the results did not reach statistic significance. Progression study revealed potential effectiveness of serum COMP in predicting OA progression. Subgroup analysis showed that serum COMP and urinary CTX-II performed better in male than female. Study size and diagnostic criteria did not significantly influence the pooled SMD, but they might be the sources of heterogeneity among studies.The overall results indicates that serum COMP and urinary CTX-II can distinguish between knee or hip OA patients and control subjects. Serum COMP is effective in predicting OA progression.Further researches with rigorous study design and a larger sample size are required to validate our findings.

This paper reviews China’s achievements in energy efficiency improvements and air emissions reductions from the electric power sector during the 11th five-year plan (FYP) (2006–2010) and 12th FYP (2011–2015) periods, and discusses the remaining challenges and opportunities for policy formulation. Mandates for closure of small coal-fired power plants (CFPPs), and replacement with large ones, together with the promulgation of air emissions standards and the development of renewable energy projects, have resulted in an improvement of 15% in energy efficiency and a reduction of 91%, 89% and 96% in emission rates of SO2, NOx and PM from China’s electric power sector over the last decade. Compared to the United States, the Chinese electric power generation fleet is more energy efficient and has lower average emissions rates of SO2 and NOx. Despite these achievements, two characteristics of the current system pose serious challenges for China’s clean power development: a) two thirds of China’s power generation still rely on coal, and more CFPPs are being built and approved to be built; and b) high curtailment of renewable energy limits its benefits. We review the root causes of these challenges and highlight opportunities for enacting policies to address them.

In recent years, green financing has attracted global attention. Many countries and international organizations have proposed frameworks for developing green financing, and an increasing number of ...

We propose a new method to discriminate and identify the modulation format of signals based on an unsupervised neural network named convolutional Gaussian-Bernoulli restricted Boltzmann machine (CGBRBM). Tests are performed to demonstrate how the proposed method works and to evaluate the discrimination/identification accuracy for different input combinations. Signals of five modulation formats are used to test the CGBRBM-based algorithm including QPSK, 8QAM, 16QAM, 32QAM, and 64QAM. The results indicate the performance of the proposed method when dealing with various application scenarios and reveal the relation between discrimination accuracy and identification accuracy.

Fat embolism syndrome (FES) is characterized by high mortality and lack of effective treatment, the symptomatic therapy is most used to relieve clinical symptoms. Some studies have shown that inflammation is one of the main pathogeneses of FES. Lipoxin A4 is an endogenous-derived anti-inflammatory substance which was discovered recently. It can alleviate inflammatory response and promote inflammation resolution, and is referred as brake signal of inflammation. Therefore we hypothesize that lipoxin A4 may have a remission and therapeutic effect on FES by attenuating FES-induced inflammatory responses.

It has become increasingly clear that the development of cancer, a multifactorial disease, cannot be explained by a single molecule or gene mutation. As a new discipline, metabolomics focuses on the body's metabolite changes, and attempts to find differences to explain the development of cancer; it has proven to be effective and credible. Metabolic studies of bladder cancer (BCa) lag behind those of other tumors. This review systematically outlines the specific process of metabolomics and the use of metabolomics in BCa studies in recent years. We have reviewed the in vitro cell line, bladder tumor tissue and biofluid (urine, plasma and serum) studies used in metabolomics analyses of BCa. The advantages and drawbacks of the use of different samples were compared. Based on the available studies, we have further described the aberrant metabolic pathways of BCa and have suggested some metabolites that may be potential biomarkers for BCa detection.

Background An increase in blood flow in the forearm arteries has been reported after brachial plexus block (BPB). However, few studies have quantitatively analysed the blood flow of the forearm arteries after BPB or have studied only partial haemodynamic parameters. The purpose of the present study was to comprehensively assess blood flow changes in the distal radial artery (RA) and ulnar artery (UA) after BPB performed via a new costoclavicular space (CCS) approach using colour Doppler ultrasound. Methods Thirty patients who underwent amputated finger replantation and received ultrasound-guided costoclavicular BPB were included in the study. The haemodynamic parameters of the RA and UA were recorded before the block and 10 min, 20 min, and 30 min after the block using colour Doppler ultrasound to determine the peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (Vmean), pulsatility index (PI), resistance index (RI) and area. The volumetric flow rate (VFR) was calculated using the formula Q = area×Vmean. The aforementioned parameters were compared not only before and after the BPB but also between the RA and UA. Results Compared with those of the respective baselines, there was a significant increase in the PSV, EDV, Vmean, area, and VFR and a significant decrease in the PI and RI of the RA and UA 10 min, 20 min, and 30 min post-block. The increase 30 min post-block in EDV (258.68 % in the RA, 279.63 % in the UA) was the most notable, followed by that in the Vmean (183.36 % in the RA, 235.24 % in the UA), and the PSV (139.11 % in the RA, 153.15 % in the UA) changed minimally. The Vmean and VFR of the RA were significantly greater than those of the UA before the BPB; however, there was no significant difference in the VFR between the RA and UA after the BPB. Conclusions A costoclavicular BPB can increase blood flow in the forearm arteries. The RA had a higher volumetric flow rate than the UA before the BPB; however, the potential blood supply capacity of the UA was similar to that of the RA after a BPB. Trial registration This study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/searchproj.aspx, clinical trial number: ChiCTR 1900023796, date of registration: June 12, 2019)

Highlights • A multi-task multi-instance learning framework is proposed to jointly assess the severity of the COVID-19 patients and segment lung lobe. • A unique hierarchical multi-instance learning strategy is developed to predict the severity of patients in a weakly supervised manner for 3D CT images. • An embedding-level multi-instance learning method is proposed to predict labels beyond the instance-level. • The proposed method achieving promising results in severity assessment in a real-world COVID-19 dataset compared to several state-of-the-art methods., Understanding chest CT imaging of the coronavirus disease 2019 (COVID-19) will help detect infections early and assess the disease progression. Especially, automated severity assessment of COVID-19 in CT images plays an essential role in identifying cases that are in great need of intensive clinical care. However, it is often challenging to accurately assess the severity of this disease in CT images, due to variable infection regions in the lungs, similar imaging biomarkers, and large inter-case variations. To this end, we propose a synergistic learning framework for automated severity assessment of COVID-19 in 3D CT images, by jointly performing lung lobe segmentation and multi-instance classification. Considering that only a few infection regions in a CT image are related to the severity assessment, we first represent each input image by a bag that contains a set of 2D image patches (with each cropped from a specific slice). A multi-task multi-instance deep network (called M2UNet) is then developed to assess the severity of COVID-19 patients and also segment the lung lobe simultaneously. Our M2UNet consists of a patch-level encoder, a segmentation sub-network for lung lobe segmentation, and a classification sub-network for severity assessment (with a unique hierarchical multi-instance learning strategy). Here, the context information provided by segmentation can be implicitly employed to improve the performance of severity assessment. Extensive experiments were performed on a real COVID-19 CT image dataset consisting of 666 chest CT images, with results suggesting the effectiveness of our proposed method compared to several state-of-the-art methods.