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Background Emerging evidence suggest the critical role of circular RNAs (circRNAs) in disease development especially in various cancers. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) is still largely unknown. Methods RNA sequencing was performed to identify significantly upregulated circRNAs in paired HCC tissues and non-tumor tissues. CCK-8 assay, colony formation, transwell, and xenograft mouse models were used to investigate the role of circRNAs in HCC proliferation and metastasis. Small interfering RNA (siRNA) was used to silence gene expression. RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assay and western blot were used to explore the underlying molecular mechanisms. Results Hsa_circ_0095868 , derived from exon 5 of the MDK gene (named circMDK), was identified as a new oncogenic circRNA that was significantly upregulated in HCC. The upregulation of circMDK was associated with the modification of N6-methyladenosine (m 6 A) and poor survival in HCC patients. Mechanistically, circMDK sponged miR-346 and miR-874-3p to upregulate ATG16L1 (Autophagy Related 16 Like 1), resulting to the activation of PI3K/AKT/mTOR signaling pathway to promote cell proliferation, migration and invasion. Poly (β-amino esters) (PAEs) were synthesized to assist the delivery of circMDK siRNA (PAE-siRNA), which effectively inhibited tumor progression without obvious adverse effects in four liver tumor models including subcutaneous, metastatic, orthotopic and patient-derived xenograft (PDX) models. Conclusions CircMDK could serve as a potential tumor biomarker that promotes the progression of HCC via the miR-346/874-3p-ATG16L1 axis. The PAE-based delivery of siRNA improved the stability and efficiency of siRNA targeting circMDK. The PAE-siRNA nanoparticles effectively inhibited HCC proliferation and metastasis in vivo. Our current findings offer a promising nanotherapeutic strategy for the treatment of HCC. Graphical Abstract

For oriented object detection, the existing CNN-based methods typically rely on a substantial and diverse dataset, which can be expensive to acquire and demonstrate limited capacity for generalization when faced with new categories that lack annotated samples. In this case, we propose MOCA-Net, a few-shot oriented object detection method with a multi-oriented enhancement branch and context-aware module, utilizing a limited number of annotated samples from novel categories for training. Especially, our method generates multi-oriented and multi-scale positive samples and then inputs them into an RPN and the detection head as a multi-oriented enhancement branch for enhancing the classification and regression capabilities of the detector. And by utilizing the context-aware module, the detector can effectively extract contextual information surrounding the object and incorporate it into RoI features in an adaptive manner, thereby improving its classification capability. As far as we know, our method is the first to attempt this in this field, and comparative experiments conducted on the public remote sensing dataset DOTA for oriented object detection showed that our method is effective.

Recent years have witnessed rapid development and remarkable achievements on deep learning object detection in remote sensing (RS) images. The growing improvement of the accuracy is inseparable from the increasingly complex deep convolutional neural network and the huge amount of sample data. However, the under-fitting neural network will damage the detection performance facing the difficulty of sample acquisition. Thus, it evolves into few-shot object detection (FSOD). In this article, we first briefly introduce the object detection task and its algorithms, to better understand the basic detection frameworks followed by FSOD. Then, FSOD design methods in RS images for three important aspects, such as sample, model, and learning strategy, are respectively discussed. In addition, some valuable research results of FSOD in computer vision field are also included. We advocate a wide research technique route, and some advice about feature enhancement and multi-modal fusion, semantics extraction and cross-domain mapping, fine-tune and meta-learning strategies, and so on, are provided. Based on our stated research route, a novel few-shot detector that focuses on contextual information is proposed. At the end of the paper, we summarize accuracy performance on experimental datasets to illustrate the achievements and shortcomings of the stated algorithms, and highlight the future opportunities and challenges of FSOD in RS image interpretation, in the hope of providing insights into future research.

Colonoscopy is widely used for the screening, diagnosis and treatment of intestinal diseases. Adequate bowel preparation is a prerequisite for high-quality colonoscopy. However, the rate of adequate bowel preparation in outpatients is low. Several studies on supplementary education methods have been conducted to improve the rate of adequate bowel preparation in outpatients. However, the controversial results presented encourage us to perform this meta-analysis. According to the PRISMA statement (2020), the meta-analysis was registered on PROSPERO. We searched all studies up to August 28, 2021, in the three major electronic databases of PubMed, Web of Science and Cochrane Library. The primary outcome was adequate bowel preparation rate, and the secondary outcomes included bowel preparation quality score, polyp detection rate, adenoma detection rate, cecal intubation time, withdrawal time, nonattendance rate and willingness to repeat rate. If there was obvious heterogeneity, the funnel plot combined with Egger's test, meta-regression analysis, sensitivity analysis and subgroup analysis were used to detect the source of heterogeneity. RevMan 5.3 and Stata 17.0 software were used for statistical analysis. A total of 2061 records were retrieved, and 21 full texts were ultimately included in the analysis. Our meta-analysis shows that supplementary education can increase the rate of adequate bowel preparation for outpatients (79.9% vs 72.9%, RR = 1.14, 95% CI: 1.08-1.20, I2 = 87%, p<0.00001). Supplementary education shortened the withdrawal time (MD: -0.80, 95% CI: -1.54 to -0.05, p = 0.04) of outpatients, increased the Boston Bowel Preparation Scale (MD: 0.40, 95% CI: 0.36 to 0.44, p<0.00001), reduced the Ottawa Bowel Preparation Scale (MD: -1.26, 95% CI: -1.66 to -0.86, p<0.00001) and increased the willingness to repeat (91.9% vs 81.4%, RR:1.14, 95% CI: 1.04 to 1.25, p = 0.004). Supplementary education for outpatients based on the standard of care can significantly improve the quality of bowel preparation.

The timely injection of gangue slurry into the mining space formed after coal mining can scale up the disposal of gangue and control surface deformation. However, the waterproof effect of gangue slurry in the mining space remains unclear, necessitating urgent investigation into the permeability characteristics of compacted backfill bodies of gangue slurry under the action of overburden. In this study, a multi-field coupled seepage test system for backfill materials was developed based on Forchheimer’s nonlinear seepage law, and a laboratory preparation method for compacted backfill body (CBB) of gangue slurry after grouting and backfilling in mining space under pseudo-triaxial conditions was proposed. Additionally, the pressure bleeding characteristics of gangue slurry under the action of overburden were studied, the variation law of permeability of the CBB with the axial pressure, a particle size range, and cement dosage was revealed, and the determination method for the permeability level of the CBB and its optimization method were put forward. The research results indicate that there are obvious staged characteristics in the pressure bleeding changes in gangue slurry. Axial pressure, particle size range, and cement dosage all have a significant impact on the permeability of the CBB. The permeability level of the CBB of gangue slurry is within the range of poor permeability and extremely poor permeability. After backfilling into the mining space, gangue slurry exhibits a significant water-blocking effect.

This study aimed to investigate the relationship between the epicardial fat area (EFA), and both the occurrence and severity of atrial fibrillation (AF), and explore the potential factors associated with AF development. Three hundred hospitalized patients with AF (100 paroxysmal, 100 persistent, and 100 permanent) and 200 patients with sinus rhythm (SR), who were admitted during the same period, were retrospectively included. The EFA was quantified using chest computed tomography images analyzed with the sliceOmatic software. Then, the demographic, laboratory, echocardiographic, and EFA data were collected and compared between groups. Afterwards, logistic regression and receiver-operating characteristic (ROC) analyses were performed to identify the factors associated with AF. The body mass index, neutrophil-to-lymphocyte ratio, red blood cell distribution width, blood urea nitrogen, serum creatinine, blood glucose, left ventricular end-diastolic diameter, and left atrial volume index (LAVI) were higher in AF patients, when compared with SR controls (all,  < 0.05). The EFA was significantly elevated in AF patients [13.42 [9.06-17.72] 7.30 [5.29-9.32],  < 0.001], with a progressive increase from paroxysmal to persistent, to permanent AF. The multivariate analysis identified EFA (odds ratio: 1.307, 95% confidence interval: 1.214-1.407) and LAVI (odds ratio: 1.057, 95% confidence interval: 1.034-1.081) as independent factors associated with AF occurrence. In the AF subgroups, EFA and LAVI were also identified as independent factors associated with AF severity. Furthermore, age, body mass index, red blood cell distribution width, serum creatinine, and LAVI were identified as independent determinants of EFA. The ROC analyses revealed good predictive performance for AF, with EFA showing an area under the ROC curve of 0.836 (cut-off: 10.08 cm , sensitivity: 69.30%, specificity: 83.00%) and LAVI showing an area under the ROC curve of 0.812 (cut-off: 30.82 mL/m , sensitivity: 74.00%, specificity: 80.50%). EFA is closely associated with both the occurrence and severity of AF. Along with LAVI, EFA may serve as a valuable independent factor associated with the risk of AF.

Background Venous thromboembolism (VTE) is a critical yet preventable complication during pregnancy. However, evidence on pregnant women’s knowledge, attitudes, and practices (KAP) toward VTE and its influencing factors remains limited. This study aimed to assess the KAP levels of VTE among pregnant women and identify key determinants to inform targeted interventions. Methods A hospital-based cross-sectional study was conducted among 1384 pregnant women in a tertiary women’s and children’s hospital in Sichuan Province, China. Data were collected using a structured questionnaire covering sociodemographic characteristics and a validated maternal KAP scale for VTE. Descriptive statistics and multiple linear regression analyses were performed to evaluate KAP scores and their influencing factors. Results A total of 1,384 women were included with a mean age of 29.4 ± 4.3 years. The mean total KAP score was 113.11 ± 16.82, with knowledge 33.49 ± 5.19(IQRs: 32.00–38.00), attitudes 46.93 ± 5.09(IQRs: 43.75 -75.00), and practices 32.69 ± 6.54(IQRs: 29.00–39.00). Multivariable regression indicated that knowledge was positively associated with second-trimester pregnancy (β = 0.38, 95% CI: 0.32–0.44), higher education (β = 0.15 to 0.26), and proactive learning (β = 0.06, 95% CI: 0.00–0.12), but lower among women without prior VTE education (β = − 0.16, 95% CI: − 0.21 to − 0.10). Attitudes were reduced in late pregnancy and postpartum (β = − 0.12, 95% CI: − 0.18 to − 0.06; β = − 0.09, 95% CI: − 0.16 to − 0.03) and improved with proactive learning (β = 0.11, 95% CI: 0.04–0.17). Preventive practices were lower in late pregnancy (β = − 0.17, 95% CI: − 0.23 to − 0.11) and postpartum (β = − 0.08, 95% CI: − 0.15 to − 0.02), but higher in women with undergraduate or postgraduate education (β = 0.14 to 0.18) and those with proactive learning (β = 0.14, 95% CI: 0.08–0.21). Conclusions Pregnant women in Southwest China demonstrated moderate knowledge, generally positive attitudes, but relatively low levels of preventive practices regarding VTE. Tailored interventions should prioritize women in early pregnancy stages, integrate VTE education into routine prenatal care, and leverage family support (e.g., spouse engagement). Healthcare systems should establish standardized VTE training programs and optimize individualized risk communication to reduce pregnancy-related VTE morbidity.

Endothelial cell dysfunction is a fundamental injury of atherosclerosis cardiovascular disease (ASCVD), closely linked to ferroptosis, which is a novel type of cell death induced by iron-dependent lipid peroxidation. Several clinical trials have suggested that empagliflozin, a selective inhibitor of sodium glucose co-transporter 2, reduces the risk of hospitalization for heart failure and cardiovascular death in patients with type 2 diabetes. However, little is known about the mechanism of EMPA in endothelial cell ferroptosis in ASCVD. The aim of the present study was to evaluate the potential mechanism of EMPA against ferroptosis induced by RAS-selective lethal 3 (RSL3) in endothelial cells. EA.hy926 human umbilical vein endothelial cells were cultured in vitro and were divided into four groups: The Control, RSL3, RSL3 + low-concentration EMPA intervention and RSL3 + high-concentration EMPA intervention groups. Iron-dependent lipid peroxidation was assessed by detecting the fluorescence intensity of ferrous ion (Fe 2+ ), lipid reactive oxygen species (ROS) and content of malondialdehyde (MDA). The expression of ferroptosis-related genes was assessed by RT-qPCR and western blotting. siRNA nuclear factor erythroid 2-related factor 2 (NRF2) was transfected into EA.hy926 cells to measure the expression of target genes. It was demonstrated that the level of MDA, Fe 2+ and lipid ROS was higher in the RSL3-treated group compared with the EMPA intervention group, while EMPA markedly mitigated that effect. In addition, EMPA can reverse the RSL3-induced low expression of glutathione peroxidase 4 (GPX4) and high expression of ACSL4 in endothelial cells, as evidenced by the upregulation of nuclear factor transcription factor nuclear factor, erythroid 2 (NFE2)-related factor 2 and heme oxygenase-1 expression, while siNRF2 transfection impaired the antiferroptosis effect of EMPA. The present study indicated that EMPA may inhibit RSL3-induced ferroptosis in endothelial cells by activating the NRF2/heme oxygenase 1 gene pathway.

The mining of coal resources is accompanied by a large amount of solid waste such as gangue, which seriously affects the ecological environment. The gangue grouting backfilling technique can achieve the dual goals of gangue disposal and surface deformation control by injecting gangue slurry into the underground. The bearing mechanical characteristics of gangue slurry directly affect the surface deformation control effect of the grouting backfilling technique. In this study, a loading simulation system of grouting backfilling materials was designed, uniaxial confined compression tests were conducted, and the self–bearing mechanism of large particle–sized gangue slurry with different fluidities under instantaneous and creep loading modes was investigated. Additionally, the mechanical characteristics of the compacted body (i.e., the gangue slurry after creep loading) were analyzed. The results indicate that the self–bearing process of gangue slurry can be divided into three stages: the rapid compression and drainage stage, the pore compaction and water bleeding stage, and the particle crushing and elastic–plastic deformation stage. The uniaxial compressive stress–strain curve of a compacted body can be classified into four stages: elastic stage, yield stage, reinforcement stage, and crushing stage, and the strength of the compacted body is affected by the loading time and fluidity of the slurry. When the slurry with a fluidity of 240 mm is subjected to constant pressure for 3 h, the compressive strength of the slurry reaches the maximum value of 4.98 MPa, and 13.1% stress damage occurs when the constant pressure reaches 4 h. This research provides a theoretical basis for the improvement of the proportion and bearing characteristics of gangue grouting materials.

Influenza vaccines, which are recommended by the World Health Organization (WHO), are the most effective preventive measure against influenza virus infection. Madin–Darby canine kidney (MDCK) cell culture is an emerging technology used to produce influenza vaccines. One challenge when purifying influenza vaccines using this cell culture system is to efficiently remove impurities, especially host cell double-stranded DNA (dsDNA) and host cell proteins (HCPs), for safety assurance. In this study, we optimized ion-exchange chromatography methods to harvest influenza viruses from an MDCK cell culture broth, the first step in influenza vaccine purification. Bind/elute was chosen as the mode of operation for simplicity. The anion-exchange Q chromatography method was able to efficiently remove dsDNA and HCPs, but the recovery rate for influenza viruses was low. However, the cation-exchange SP process was able to simultaneously achieve high dsDNA and HCP removal and high influenza virus recovery. For the SP process to work, the clarified cell culture broth needed to be diluted to reduce its ionic strength, and the optimal dilution rate was determined to be 1:2 with purified water. The SP process yielded a virus recovery rate exceeding 90%, as measured using a hemagglutination units (HAUs) assay, with removal efficiencies over 97% for HCPs and over 99% for dsDNA. Furthermore, the general applicability of the SP chromatography method was demonstrated with seven strains of influenza viruses recommended for seasonal influenza vaccine production, including H1N1, H3N2, B (Victoria), and B (Yamagata) strains, indicating that the SP process could be utilized as a platform process. The SP process developed in this study showed four advantages: (1) simple operation, (2) a high recovery rate for influenza viruses, (3) a high removal rate for major impurities, and (4) general applicability.