Search

Abstract Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.

Abstract Okara protein (OP) was extracted by alkali solution and acid-isolation method using bean dregs as raw materials. With OP as the main raw material, the mixed gelatin and modified starch as the gelling agent, xylitol as the sweetener, and buffered lactic acid as the sour agent, the elasticity, hardness, stickiness and chewiness of the texture analyzer were analyzed by the single-factor test and orthogonal test. Combined with sensory evaluation, the optimal formula for the preparation of OP gel gummies was comprehensively obtained as: the ratio of gelatin to modified starch was 9:1; the xylitol addition was 18 g; the addition of buffered lactic acid was 0.7mL, and the addition of OP solution was 16mL, respectively. The gel gummies prepared under this formula have the advantages of suitable sweetness and sourness, good taste, good stickiness and uniform color. It also has special physiological functions, such as immune regulation and antihypertensiveness.

The five recognized zoonotic foodborne pathogens, namely, Listeria monocytogenes, Staphylococcus aureus, Streptococcus suis, Salmonella enterica and Escherichia coli O157:H7, pose a major threat to global health and social–economic development. These pathogenic bacteria can cause human and animal diseases through foodborne transmission and environmental contamination. Rapid and sensitive detection for pathogens is particularly important for the effective prevention of zoonotic infections. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) combined with recombinase polymerase amplification (RPA) were developed for the simultaneous quantitative detection of five foodborne pathogenic bacteria. Multiple T lines were designed in a single test strip for increasing the detection throughput. After optimizing the key parameters, the single-tube amplified reaction was completed within 15 min at 37 °C. The fluorescent strip reader recorded the intensity signals from the lateral flow strip and converted the data into a T/C value for quantification measurement. The sensitivity of the quintuple RPA-EuNP-LFSBs reached a level of 101 CFU/mL. It also exhibited good specificity and there was no cross-reaction with 20 non-target pathogens. In artificial contamination experiments, the recovery rate of the quintuple RPA-EuNP-LFSBs was 90.6–101.6%, and the results were consistent with those of the culture method. In summary, the ultrasensitive bacterial LFSBs described in this study have the potential for widespread application in resource-poor areas. The study also provides insights in respect to multiple detection in the field.

The basic unit of rural revitalization is the village. Rural revitalization can be comprehensively promoted by using rural typology as an instrument for rural zoning planning, which is a significant factor. This study clarified the relationship between rural revitalization and basic public services, constructed evaluation index systems, and analyzed the symbiotic mode. The comprehensive development level and the symbiotic mode were incorporated to determine the type of village. The results showed the following: (1) The thriving industry and affluent life of Tangfang Town obviously contributed to its rural revitalization; the achievement of basic environmental improvement was eminent. (2) There are differences in the comprehensive development level of rural revitalization and basic public services among administrative villages, with an overall trend of “high in the north and low in the south”, corresponding to the industrial layout of “north industry and south agriculture” in Tangfang Town. (3) The symbiosis coefficients of all the administrative villages in Tangfang Town were between 0 and 0.5, and there was a positive symmetric mutualism relationship overall, indicating that basic public services have a significant impact and can effectively promote the process of rural revitalization. (4) Villages in Tangfang Town are divided into five functional areas—the comprehensive coordination area, potential improvement area, restricted development area, unbalanced allocation area, and backward guarantee area—and various types of optimization development strategies are proposed. As one of the top 100 demonstration towns for rural revitalization in Shaanxi Province, Tangfang Town plays a leading and exemplary role. Within the context of rural revitalization strategies, solving the problem of how to realize differentiated development in the next five years has become urgent. This study aimed to effectively promote the process of rural revitalization, provide theoretical guidance for scientific development in Tangfang Town, and promote research ideas for other towns in China.

Abstract Background Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients. Methods Expression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice. Results We found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-β-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM. Conclusions These findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.

This paper aims to explore the trends and hot topics of American applied linguistics by the content analysis of AAAL annual conferences’ handbooks. Making a diachronic research on topical strands of AAAL Conference from 1999 to 2019, the paper studies the dynamics and the trends of American applied linguistics by analyzing the changes of the strands in the conferences under study in 20 years. Based on self-built corpora of titles and abstracts of the presented papers in 2019 AAAL Annual Conference, high-frequency vocabulary and their collocations are detected by TagCrowd and AntConc in order to find the current hot topics of applied linguistics research. The conclusion is that the development of applied linguistics has speeded up in the past four years. Educational linguistics, corpus linguistics, research methodology, teacher education, lexical research, phonetics/phonology and oral communication are the new trends in this field. The hot words of applied linguistics in 2019 include academic writing, teacher education, Chinese and translanguaging. Finally, the study found that retrospective review study of international conferences could be a new research method in the field of review study, providing scholars with a comprehensive understanding of the discipline dynamics over a period of time

In recent years, foodborne disease outbreaks have caused huge losses to the economy and have had severe impacts on public health. The accuracy and variety of detection techniques is crucial to controlling the outbreak and spread of foodborne diseases. The need for instruments increases the difficulty of field detection, while manually-handled samples are subject to user error and subjective interpretation. Here, we use a mini automatic nucleic acid extractor combined with recombinant polymerase amplification (RPA) and lateral flow immunoassay (LFIA) for simultaneous quantitative detection of five major foodborne pathogens. The pre-treatment device using the magnetic bead method allows for nucleic acid extraction of the reagent tank without manual operation, which is highly efficient and stable for preventing aerosol contamination. The nuc gene of Staphylococcus aureus, the toxR gene of Vibrio parahaemolyticus, the rfbE gene of Escherichia coli O157:H7, the hlyA gene of Listeria monocytogenes, and the fimY gene of Salmonella enterica were used as target fragments. The labeled antibody concentration is optimized on the LFIA to find the equilibrium point for the binding capacity of the five chemical markers and to efficiently and accurately visualize the bands. The RPA assay shows an optimal performance at 37 °C for 15 min. The optimized RPA-LFIA detection limit can reach 101 CFU/mL. There was no cross-reactivity among forty-eight strains. Furthermore, the average recoveries in spiked food samples were 90.5–104.5%. In summary, the RPA-LFIA established in this study can detect five pathogenic bacteria simultaneously with little dependence on laboratory equipment, and it has promising prospects for screening in low-resource areas.

Taking the Giant Panda National Park as an example, this paper uses factor analysis to measure residents’ financial awareness and mediating effect models to investigate the influence paths of community governance, financial awareness, and residents’ willingness to participate in the construction and development of national parks. Finally, it suggests potential solutions for national park development and biodiversity conservation. The results indicated that financial awareness and community governance levels had a positive effect on residents’ willingness to participate, and satisfaction with community governance played a significant partially mediating role in their financial awareness, which in turn influenced their level of willingness.

The deterioration of grassland ecology is threatening the livelihood of herdsmen and increasing their rates of poverty. This study aims to explore the characteristics of herdsmen’s livelihood and the impact of livelihood capital and environmental perception on livelihood strategy selection. Based on 453 herdsmen households in the Province of Gansu and Qinghai, five types of livelihood capital were measured under the sustainable livelihoods framework. The influence of herdsmen’s livelihood capital on their decisions regarding their livelihood strategies was evaluated in multiple logistic functions. Meanwhile, hierarchical regression analysis and grouping regression methods were used to explore the moderating effects of two dimensions of environmental perception: ecological consciousness and sense of responsibility. The following results were obtained: First, all types of livelihood capital have a significant influence on the livelihood diversification of herdsmen; second, the direction and strength of these effects differ among types of livelihood capital. Moreover, environmental perception played a negative moderating role in the relationship between herdsmen’s livelihood capital and livelihood strategies. Therefore, it is expected to introduce policies ensuring the development of herdsmen’s livelihood capital and improve their environmental cognition, which can help realize the coordinated economic and ecological development of grassland.

CdS with well-defined crystallinity is anchored on carbon nitride photoelectrodes by a successive chemical bath deposition. And the as-synthesized samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible diffuse reflection spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy techniques. The effect of the amount of CdS on the catalytic activity for the degradation of acid Orange II is investigated under visible light irradiation. Results show that the photoelectrodes composed of CdS/CN exhibit much higher catalytic activity than pure CN photoelectrodes. A possible photocatalytic mechanism of the CdS/CN electrodes is proposed under visible light irradiation.

A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM) revealed the NGs to be spherical with core-shell structures, in the range of 32–40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF) compared with simulated gastric fluid (SGF). From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes.

Abstract Background Heat shock protein 70, a stress protein, has been implicated in tumor progression. However, its role in nasopharyngeal carcinoma (NPC) progression has not yet been clearly investigated. Methods Immunohistochemistry (IHC) was employed to examine the expression patterns of Hsp70, human leukocyte antigen –A (HLA-A) in NPC tissue samples. Results The expression of Hsp70 exhibited different spatial patterns among nuclear, membrane and cytoplasm in 507 NPC tumor tissues. Kaplan-Meier survival analysis demonstrated that different Hsp70 expression patterns are correlated with different patient outcomes. High membranal and cytoplasmic levels of Hsp70 predicted good survival of patients. In contrast, high nuclear abundance of Hsp70 correlated with poor survival. Moreover, the membranal and cytoplasmic levels of Hsp70 were positively correlated with levels of the MHC I molecule HLA-A. Conclusions Different Hsp70 expression patterns had distinct predictive values. The different spatial abundance of Hsp70 may imply its important role in NPC development and provide insight for the development of novel therapeutic strategies involving immunotherapy for NPC.

Abstract Background Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is a common malignancy in southern China, especially in Guangdong. Dietary habit is regarded as an important modifier of NPC risk in several endemic areas and may partially explain the geographic distribution of NPC incidence. In China, rapid economic development during the past few decades has changed the predominant lifestyle and dietary habits of the Chinese considerably, requiring a reassessment of diet and its potential influence on NPC risk in this NPC-endemic area. Methods To evaluate the association between dietary factors and NPC risk in Guangdong, China, a large-scale, hospital-based case-control study was conducted. 1387 eligible cases and 1459 frequency matched controls were recruited. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated using a logistic regression model, adjusting for age, sex, education, dialect, and habitation household type. Results Observations made include the following: 1) consumption of canton-style salted fish, preserved vegetables and preserved/cured meat were significantly associated with increased risk of NPC, with enhanced odds ratios (OR) of 2.45 (95% CI: 2.03-2.94), 3.17(95% CI: 2.68-3.77) and 2.09 (95% CI: 1.22-3.60) respectively in the highest intake frequency stratum during childhood; 2) consumption of fresh fruit was associated with reduced risk with a dose-dependent relationship (p = 0.001); and 3) consumption of Canton-style herbal tea and herbal slow-cooked soup was associated with decreased risk, with ORs of 0.84 (95% CI: 0.68-1.03) and 0.58 (95% CI: 0.47-0.72) respectively in the highest intake frequency stratum. In multivariate analyses, these associations remained significant. Conclusions It can be inferred that previously established dietary risk factors in the Cantonese population are still stable and have contributed to the incidence of NPC.

Uncovering the immune response to an inactivated SARS‐CoV‐2 vaccine (In‐Vac) and natural infection is crucial for comprehending COVID‐19 immunology. Here we conducted an integrated analysis of single‐cell RNA sequencing (scRNA‐seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In‐Vac compared with those from COVID‐19 patients. Our study reveals that In‐Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In‐Vac modestly upregulates IFN‐α but downregulates NF‐κB pathways, while natural infection triggers hyperactive IFN‐α and NF‐κB pathways. Both In‐Vac and natural infection alter T/B cell receptor repertoires, but COVID‐19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL‐15RA/IL‐15 receptor pathway after In‐Vac boost, suggesting its potential role in enhancing In‐Vac‐induced immunity. Collectively, our study illuminates multifaceted immune responses to In‐Vac and natural infection, providing insights for optimizing SARS‐CoV‐2 vaccine efficacy. [ABSTRACT FROM AUTHOR]

Ovarian cancer is characterized by aberrant activation of the mitogen-activated protein kinase (MAPK), highlighting the importance of targeting the MAPK pathway as an attractive therapeutic strategy. However, the clinical efficacy of MEK inhibitors is limited by intrinsic or acquired drug resistance. Here, we established patient-derived ovarian cancer models resistant to MEK inhibitors and demonstrated that resistance to the clinically approved MEK inhibitor trametinib was associated with enhancer reprogramming. We also showed that enhancer decommissioning induced the downregulation of negative regulators of the MAPK pathway, leading to constitutive ERK activation and acquired resistance to trametinib. Epigenetic compound screening uncovered that HDAC inhibitors could alter the enhancer reprogramming and upregulate the expression of MAPK negative regulators, resulting in sustained MAPK inhibition and reversal of trametinib resistance. Consequently, a combination of HDAC inhibitor and trametinib demonstrated a synergistic antitumor effect in vitro and in vivo, including patient-derived xenograft mouse models. These findings demonstrated that enhancer reprogramming of the MAPK regulatory pathway might serve as a potential mechanism underlying MAPK inhibitor resistance and concurrent targeting of epigenetic pathways and MAPK signaling might provide an effective treatment strategy for advanced ovarian cancer., Introduction Epithelial ovarian cancer (OV) is the leading cause of mortality from gynecological malignancies (1); the overall survival rate has remained poor at 30% to 50% for decades, mainly owing [...]