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This study is to elucidate the effect of the LINC00663/EBF1/NR2F1 axis on inflammation and angiogenesis in bladder cancer (BC) and related molecular mechanisms. After transfection, functional experiments were conducted to test cell proliferation and invasion, tube formation ability, and content of inflammatory factors, Snail, E-cadherin, and VEGFA. Meanwhile, the relationships among LINC00663, EBF1, and NR2F1 were predicted and verified. In addition, xenograft experiments in nude mice were performed to observe the oncogenicity of 5637 BC cells in vivo. In BC tissues and cells, LINC00663 and NR2F1 were upregulated. Silencing NR2F1 or LINC00663 repressed cell proliferation and invasion, weakened vascular mimicry in vitro, decreased inflammatory factor, Snail, and VEGFA levels, and increased expression of E-cadherin. LINC00663 positively regulated NR2F1 expression through EBF1. Additionally, in vivo experiments showed that NR2F1 upregulation reversed the suppression effects of LINC00663 silencing on tumour growth, inflammation, and angiogenesis. Silencing LINC00663 decreased NR2F1 expression by mediating EBF1, thereby inhibiting BC inflammation and angiogenesis.

Summary: Background: Visepegenatide, a once-weekly glucagon-like peptide-1 receptor agonist injection, demonstrated effective glycaemic control and good tolerability without the requirement of dose titration in the two completed phase 2 studies. We aimed to evaluate the efficacy and safety of visepegenatide in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by metformin monotherapy in this phase 3 clinical study. Methods: This multicentre phase 3 clinical study included a 24-week, randomised, placebo-controlled, double-blind period followed by a 28-week open-label extended treatment period. Patients (N = 620) aged ≥18 and ≤75 years with glycated haemoglobin (HbA1c) ≥7.0% and ≤10.5% [≥53.0 and ≤91.27 mmol/mol], were randomized in a 1:1 ratio to receive visepegenatide 150-μg or placebo once-weekly subcutaneous injection during the double-blind period. Subsequently, the patients in the placebo group were switched to visepegenatide treatment (placebo→visepegenatide group), and the patients in the visepegenatide group continued the same treatment during the open-label extended treatment period. The primary endpoint was the change in HbA1c from baseline to week 24. Findings: At week 24, the placebo-adjusted least squares mean (LSM) change of HbA1c was −0.57% (95% CI −0.71 to −0.43) with visepegenatide (p

Abstract Introduction Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. Methods In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups—low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)—using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1β, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. Results At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1β significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1β among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1β exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. Conclusion IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Abstract The influence of environmental factors like smoking and alcohol on myopia and astigmatism is controversial. However, due to ethical concerns, alternative study designs are urgently needed to assess causal inference, as mandatory exposure to cigarettes and alcohol is unethical. Following comprehensive screenings, 326 single nucleotide polymorphisms (SNPs) related to myopia and astigmatism were included in the dataset. To validate the causal association between exposures such as cigarette smoking, alcohol consumption, and coffee intake, and outcomes namely astigmatism and myopia, five regression models were employed. These models encompassed MR-Egger regression, random-effects inverse-variance weighted (IVW), weighted median estimator (WME), weighted model, and simple model. The instrumental variables utilized in these analyses were the aforementioned SNPs. Apply Cochran’s Q test to determine heterogeneity of SNPs; if heterogeneity exists, focus on IVW model results. The IVW model showed a 1.379-fold increase in the risk of astigmatism (OR = 1.379, 95%CI 0.822~2.313, P = 0.224) and a 0.963-fold increase in the risk of myopia (OR = 0.963, 95%CI 0.666~1.393, P = 0.841) for each unit increase in smoking. For each unit increase in coffee intake, the risk of astigmatism increased 1.610-fold (OR = 1.610, 95%CI 0.444~5.835, P = 0.469) and the risk of myopia increased 0.788-fold (OR = 0.788, 95%CI 0.340~1.824, P = 0.578). For each additional unit of alcohol consumption, the risk of astigmatism increased by 0.763-fold (OR = 0.763, 95%CI 0.380~1.530, P = 0.446), and none of the differences were statistically significant. However, for each unit of alcohol consumption, the risk of myopia increased by 1.597 times, and the difference was statistically significant (OR = 1.597, 95%CI 1.023~2.493, P = 0.039). The findings indicate that alcohol consumption is a risk factor for myopia but smoking and coffee intake do not affect its development. Additionally, there is no association between smoking, alcohol consumption, coffee intake, and the risk of astigmatism.

Abstract Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A + epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8+ TRM cells, and CCL2 + immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8+ TEX cells, and STMN1 + tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1 + TGM2 +) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.

Cancers of the digestive system (DS), including esophageal, gastric, colorectal, liver, and pancreatic cancers, have a high incidence and mortality worldwide. Current cancer models cannot faithfully recapitulate the critical features of the original tumor, resulting in the failure of translation from basic research into clinical practice. More advanced cancer models are in urgent need of pathogenesis exploration and anticancer medicine development. Organoids are in vitro cultured three dimensional (3D) self-organizing organotypic structures derived from tissues and pluripotent stem cells, which faithfully mimic the histological features and preserve the genetic heterogeneity of the original tissues. Both normal and malignant organoids can now be efficiently established from the DS tissues of patients. In this review, we summarize the general methods to generate human DS organoids and their applications as a novel model in basic cancer research, preclinical medical practice, and precision medicine.

The global imaginary contributes to the perpetuation of neo-colonial and neoliberal mentalities, which reinforce the political, cultural, and social dominance over international students. Through an exploration guided by interrelated theories of agency and transnational social fields, this study employs a narrative inquiry methodology with a constructivist research approach to comprehend and investigate the agency of international graduate students of Color amidst transnational mobility during the COVID-19 pandemic within a four-year public research institution in the United States. The research findings demonstrate that specific contexts and spaces shape the agency of international graduate students and (trans)form their present and future. This article reveals four distinct forms of agency: agency as negotiation in uncertainties, agency as resistance to forms of (neo)racism, agency for personal growth and (trans)formation, and agency within transnational futures.

Coal is the most abundant and widely distributed fossil energy source on the planet [...]

Sentiment analysis is one of the significant application fields of natural language processing. Researchers divide the sentiment into explicit sentiment and implicit sentiment according to whether the expression contains sentiment words or not. Most of the existing research focuses on explicit sentiment tasks. However, implicit sentiment analysis is difficult to study because of its implicit tendency to express sentiment and the problem of “weak features” and “multi-confounding weak features”. We develop a novel model based on “Hierarchical Knowledge Enhancement and Multi-pooling”(HKEM), which fully integrates the knowledge information of different levels in the text through hierarchical knowledge enhancement to alleviate the “weak feature” problem. At the same time, the multi-pooling method is used to extract and analyze multiple features, and the “multi-confounding weak features” are modeled. In this paper, comparative experiments have been conducted on the SMP-ECISA2019 dataset, and the results show that the accuracy of this model is comparable to that of the current best model, and the F1 score is 5.9% higher than that of the best model, indicating that the model proposed in this paper can accurately analyze Chinese implicit sentiment and achieve the state-of-the-art in the comprehensive performance evaluation, which proves the effectiveness and superiority of the model in this paper.

Abstract Background Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies. Methods We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole‐exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC‐101 and CUDC‐907, were evaluated in vitro and in vivo. Results The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single‐cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC‐907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids. Conclusions Patient‐derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.

In the field of object detection, domain adaptation is one of popular solution to align the distribution between the real scene (target domain) and the training scene (source domain) by adversarial training. However, only global features are applied to the Domain Adaptive Faster R-CNN (DA Faster R-CNN) method. The lack of local features reduces the performance of domain adaptation. Therefore, a novel method for domain adaptive detection called Skip-Layer Network with Optimization (SLNO) method is proposed in this paper. Three improvements are presented in SLNO. Firstly, different level convolutional features are fused by a multi-level features fusion component for domain classifier. Secondly, a multi-layer domain adaptation component is developed to align the image-level and the instance-level distributions simultaneously. Among this component, domain classifiers are used in both image-level and instance-level distributions through the skip layer. Thirdly, the cuckoo search (CS) optimization method is applied to search for the best coefficient of SLNO. As a result, the capability of domain alignment is strengthened. The Cityscapes, Foggy Cityscapes, SIM10K, KITTI data sets are applied to test our proposed novel approach. Consequently, excellent results are achieved by our proposed methods against state-of-the-art object detection methods. The results demonstrate our improvements are effective on domain adaptation detection.

Simultaneous localization and mapping (SLAM) algorithm is a prerequisite for unmanned ground vehicle (UGV) localization, path planning, and navigation, which includes two essential components: frontend odometry and backend optimization. Frontend odometry tends to amplify the cumulative error continuously, leading to ghosting and drifting on the mapping results. However, loop closure detection (LCD) can be used to address this technical issue by significantly eliminating the cumulative error. The existing LCD methods decide whether a loop exists by constructing local or global descriptors and calculating the similarity between descriptors, which attaches great importance to the design of discriminative descriptors and effective similarity measurement mechanisms. In this paper, we first propose novel multi-channel descriptors (CMCD) to alleviate the lack of point cloud single information in the discriminative power of scene description. The distance, height, and intensity information of the point cloud is encoded into three independent channels of the shadow-casting region (bin) and then compressed it into a two-dimensional global descriptor. Next, an ORB-based dynamic threshold feature extraction algorithm (DTORB) is designed using objective 2D descriptors to describe the distributions of global and local point clouds. Then, a DTORB-based similarity measurement method is designed using the rotation-invariance and visualization characteristic of descriptor features to overcome the subjective tendency of the constant threshold ORB algorithm in descriptor feature extraction. Finally, verification is performed over KITTI odometry sequences and the campus datasets of Jilin University collected by us. The experimental results demonstrate the superior performance of our method to the state-of-the-art approaches.

While critical scholars have attempted to decenter internationalization, limited research has aimed to understand internationalization efforts in the context of the socio-historical particularities of the postcolonial condition. This paper takes a decolonial perspective in the study of internationalization, in light of the Eurocentric tendencies of modernity, whose major manifestation in higher education is neoliberal globalization. We unpack internationalization in the U.S. and examine how it is embedded in and reproduces neoliberalism, racism, and colonialism. Since decolonization is not merely deconstructive but also regenerative, we reconceive what it means to be international and recommend how internationalization can be deployed as a tool of decolonization, considering various possibilities for hopeful and ethical praxis. We identify promising practices to spark ongoing reflection and action about ways to contest coloniality/modernity and rethink mobility. This paper can benefit educators seeking to reclaim internationalization and [re]align it with an ethos of mutuality and practices geared at strengthening cooperation, rather than competition.

The COVID-19 pandemic threatens to exacerbate the school psychology personnel crisis. There is a dearth of knowledge regarding how the pandemic has impacted school psychology trainers and course delivery. In this national study, 92 school psychology trainers completed an online questionnaire regarding technological instructional changes, job satisfaction, and their own mental health well-being during the pandemic. Findings suggest that during the portion of the pandemic assessed most trainers reported that they: (a) switched from in-person instruction to primarily online instruction, (b) were mostly satisfied with their jobs, and (c) generally experienced a positive sense of well-being. Furthermore, a sizable portion of those that switched to a mixture of hybrid and online instruction during the pandemic endorsed that they are likely to continue to use these modalities after the pandemic subsides. Unfortunately, although school psychology trainers presented as generally resilient workforce during the pandemic, almost 20% participants screened positive for possible depression.

Minghui Hou Old Dominion University, USA As an international student, until recently I had never thought about educational equality for international students because it seemed impossible for an international student to have the same opportunities or resources as domestic students. However, Tannock claims that UK law does not require international students to pay higher tuition fees than home students, but only requires "international students not receive a public subsidy for their education" (p. 132). In light of market-centric competition, nation-state equality legislation has provided equality and justice protection for international students in the UK to attract more international students. [Extracted from the article]