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Abstract Background Various factors have been found to be associated with high levels of death anxiety experienced by oncology nurses. The aim of this study was to use a person-oriented approach to examine the death anxiety patterns of Chinese oncology nurses and to analyze the differences in anxiety characteristics and their associated influencing factors. Methods A cross-sectional survey regarding palliative care among registered oncology nurses was conducted in Jiangsu Province, China.Latent class analyses was applied to identify their patterns of death anxiety. The score of PCQN-C (The Chinese version of the Palliative Care Quiz for Nursing) and FATCOD-B-C (The Chinese version of the Frommelt Attitude Toward Care of the Dying scale), the demographic and working characteristics were further analyzed through covariance analysis (ANCOVA) and multivariate (or logistic) regression across the subgroups. Results A two-potential-category model was selected based on the fit index. The results showed that 79% of oncology nurses belonged to the high pressure and pain group and 21% belonged to the low death anxiety group. The high pressure and pain group had significantly higher scores in the dimensions of emotion, stress and pain, time awareness, and cognition compared to the low death anxiety group. Factors influencing the high pressure and pain group included shorter working years, non-national or provincial oncology nursing specialists, non-national palliative care specialists, never discussing the topic of death with patients or family members, no palliative care related training, and PCQN and FATCOD scores. Conclusions Our study suggests that oncology nurses’ death anxiety can be divided into two categories: low death anxiety and high stress pain, and certain factors, such as being female, having a short work experience, and lacking palliative care-related training, increase the likelihood of death anxiety.

Prefoldins (PFDs) are ubiquitous co-chaperone proteins that originated in archaea during evolution and are present in all eukaryotes, including yeast, mammals, and plants. Typically, prefoldin subunits form hexameric PFD complex (PFDc) that, together with class II chaperonins, mediate the folding of nascent proteins, such as actin and tubulin. In addition to functioning as a co-chaperone in cytoplasm, prefoldin subunits are also localized in the nucleus, which is essential for transcription and post-transcription regulation. However, the specific and critical roles of prefoldins in plants have not been well summarized. In this review, we present an overview of plant prefoldin and its related proteins, summarize the structure of prefoldin/prefoldin-like complex (PFD/PFDLc), and analyze the versatile landscape by prefoldin subunits, from cytoplasm to nucleus regulation. We also focus the specific role of prefoldin-mediated phytohormone response and global plant development. Finally, we overview the emerging prefoldin-like (PFDL) subunits in plants and the novel roles in related processes, and discuss the next direction in further studies.

Background: This study aims to assess whether sarcopenia can be used to predict prognosis in patients with heart failure (HF) and if different diagnostic criteria for sarcopenia and diverse regions where studies were conducted could affect prognostic outcomes, thus providing a preliminary basis for early identification and prediction of poor prognosis in HF. Methods: The PubMed, Cochrane, Embase, and CNKI (China National Knowledge Infrastructure) databases were searched from inception until March 2023. Cohort studies evaluating the prognostic effect of sarcopenia in patients with HF were included. Two authors independently assessed the studies according to the Newcastle-Ottawa Scale. The meta-analyses were performed using RevMan 5.3 software. The study results were reported using a checklist of Preferred Reporting Items for Systematic Reviews and Meta-analyses were used to report the study results. Results: A total of 12 studies with 3696 HF patients were included. The results showed that the sarcopenia population had a higher risk of all-cause mortality (HR (hazard ratio) = 1.98, 95% CI (confidence interval): 1.61–2.44) and major adverse cardiovascular events (MACE) (HR = 1.24, 95% CI: 1.06–1.45) compared to the non-sarcopenia population. Moreover, the subgroup analysis reported that different diagnostic criteria for sarcopenia and diverse regions were statistically significant for all-cause mortality, except for the Europe subgroup (HR = 1.34, 95% CI: 0.89–2.02). In the subgroup analysis of MACE, all subgroups were statistically significant except for the European Working Group on Sarcopenia in Older People (EWGSOP) (HR = 1.39, 95% CI: 0.86–2.25) and European subgroups (HR = 1.39, 95% CI: 0.86–2.25). Conclusions: Sarcopenia is associated with poor prognosis, including all-cause mortality and MACE, in patients with HF. However, due to the adoption of various diagnostic criteria in different regions of the world, these results need further validation.

Anthocyanin and proanthocyanidin play important roles in plant secondary metabolism. Although previous studies identified many transcription factors involved in anthocyanin and proanthocyanidin synthesis, the effects of MADS-box transcription factors are unclear in apple. Brassinosteroids (BRs) are steroid hormones that affect plant flavonoid biosynthesis, but the underlying regulatory mechanism is not yet well established. In this study, we identified a MADS-box transcription factor, MdJa2, which contained a highly conserved MADS-box domain and belonged to the STMADS11 subfamily. Additionally, MdJa2 was responsive to BR signal, and the overexpression of MdJa2 inhibited the synthesis of anthocyanin and proanthocyanidin. The silencing of MdJa2 in “Orin” calli promoted anthocyanin and proanthocyanidin accumulations. Moreover, MdJa2 interacted with MdBZR1. MdJa2 was revealed to independently regulate anthocyanin and proanthocyanidin synthesis pathways. The MdJa2–MdBZR1 complex enhanced the binding of MdJa2 to the promoters of downstream target genes. Our research provides new insights into how MADS-box transcription factors in the BR signaling pathway control the accumulations of anthocyanin and proanthocyanidin in red-fleshed apple.

Background: Dance interventions are considered beneficial for older patients with mild cognitive impairment in many aspects. We conducted a comprehensive systematic review and meta-analysis to assess the effects of dance on different aspects (cognitive function, emotions, physical function, and quality of life) of this population.Methods: A systematic search of PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Embase, American Psychological Association PsycInfo, ProQuest, Scopus, Cumulative Index to Nursing and Allied Health Literature, the Chinese BioMedical Literature Database, the VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data database was performed. Two reviewers independently assessed the study quality.Results: Fourteen studies were retrieved from the databases for analysis. The pooled results showed that dance interventions significantly improved global cognition (standardized mean difference [SMD] = 0.73, 95% confidence interval [CI]: 0.47 to 0.99, P < 0.00001), rote memory (mean difference [MD] = −2.12, 95% CI: −4.02 to −0.21, P = 0.03), immediate recall (SMD = 0.54, 95% CI: 0.30 to 0.78, P < 0.0001), delayed recall (SMD = 0.56, 95% CI: 0.26 to 0.86, P = 0.0002) and attention (SMD = 0.38, 95% CI: 0.13 to 0.64, P = 0.003). No significant improvement was found in executive function, language, depression, anxiety, dementia-related behavioral symptoms, motor function, and quality of life.Conclusion: Dance interventions benefit most aspects of cognitive functions. The evidence for the effects of dance on psycho-behavioral symptoms, motor function and quality of life remains unclear. More trials with rigorous study designs are necessary to provide this evidence.

Abstract The two-component system (TCS) consists of histidine kinase (HK), histidine phosphate transfer protein (HP), and response regulatory factor (RR). It is one of the most crucial components of signal transduction in plants, playing a significant role in regulating plant growth, development, and responses to various abiotic stresses. Although TCS genes have been extensively identified in a variety of plants, the genome-wide recognition and examination of TCS in switchgrass remain unreported. Accordingly, this study identified a total of 87 TCS members in the genome of switchgrass, comprising 20 HK(L)s, 10 HPs, and 57 RRs. Detailed analyses were also conducted on their gene structures, conserved domains, and phylogenetic relationships. Moreover, this study analysed the gene expression profiles across diverse organs and investigated their response patterns to adverse environmental stresses. Results revealed that 87 TCS genes were distributed across 18 chromosomes, with uneven distribution. Expansion of these genes in switchgrass was achieved through both fragment and tandem duplication. PvTCS members are relatively conservative in the evolutionary process, but the gene structure varies significantly. Various cis-acting elements, varying in types and amounts, are present in the promoter region of PvTCSs, all related to plant growth, development, and abiotic stress, due to the TCS gene structure. Protein-protein interaction and microRNA prediction suggest complex interactions and transcriptional regulation among TCS members. Additionally, most TCS members are expressed in roots and stems, with some genes showing organ-specific expression at different stages of leaf and inflorescence development. Under conditions of abiotic stress such as drought, low temperature, high temperature, and salt stress, as well as exogenous abscisic acid (ABA), the expression of most TCS genes is either stimulated or inhibited. Our systematic analysis could offer insight into the characterization of the TCS genes, and further the growth of functional studies in switchgrass.

Multiple primary lung cancer (MPLC) refers to patients with two or more primary lesions of lung cancer. It can be divided into synchronous MPLC (sMPLC) and metachronous MPLC (mMPLC) based on the timing of occurrence. In recent years, the detection rate of MPLC has gradually increased. However, considerable controversy exists in distinguishing MPLC from intrapulmonary metastasis (IM), especially when the histopathological types are identical. Given the significant differences in treatment strategies and prognosis in clinical practice currently, accurate diagnosis of MPLC is crucial for personalized precision therapy. Molecular genetics and sequencing technologies offer effective strategies for assessing the clonal origin of tumors. There have been reports of coexisting mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) fusion genes in non-small cell lung cancer, but case of EGFR mutation following an ALK mutation has not been mentioned. This article accurately diagnoses and retrospectively analyzes the clinical data of a case of ALK mutant adenocarcinoma in a male patient who developed an EGFR mutation with multiple metastases four years after surgery, and reviews the relevant literature. This paper aims to deepen the understanding of mMPLC and provide clinical references for the diagnosis and treatment of such patients.

Abstract T-BOX factors belong to an evolutionarily conserved family of transcription factors. T-BOX factors not only play key roles in growth and development but are also involved in immunity, cancer initiation, and progression. Moreover, the same T-BOX molecule exhibits different or even opposite effects in various developmental processes and tumor microenvironments. Understanding the multiple roles of context-dependent T-BOX factors in malignancies is vital for uncovering the potential of T-BOX-targeted cancer therapy. We summarize the physiological roles of T-BOX factors in different developmental processes and their pathological roles observed when their expression is dysregulated. We also discuss their regulatory roles in tumor immune microenvironment (TIME) and the newly arising questions that remain unresolved. This review will help in systematically and comprehensively understanding the vital role of the T-BOX transcription factor family in tumor physiology, pathology, and immunity. The intention is to provide valuable information to support the development of T-BOX-targeted therapy.

Objective: Chronic bowel disease has the characteristics of high recurrence rate, prolonged and non-healing, and the incidence has increased year by year in recent years. Cannabidiol (CBD) has significant anti-inflammatory and antioxidant activities, but it is limited by its characteristics of fat solubility and low bioavailability. This study aims to treat chronic inflammatory bowel disease by preparing a CBD-loaded hydrogel system (GelMA + CBD) that can deliver CBD in situ and improve its bioavailability through slow release. Method: The study designed and constructed GelMA + CBD, and its surface morphology was observed by scanning electron microscopy, and its pore size, swelling rate and release rate were evaluated to evaluate its bioactivity and biosafety. The expression of various inflammatory factors was detected by ELISA, and the expression of protein and reactive oxygen species were observed by laser confocal microscopy to evaluate their anti-inflammatory and antioxidant properties. Results: Our study found that GelMA + CBD with biosafety, could make CBD be slowly released, and effectively inhibit the M1-type polarization of macrophages in vitro, and promote the M2-type polarization. In addition, GelMA + CBD can also reduce the expression of pro-inflammatory factors (such as iNOS) in macrophages, and increase the expression of anti-inflammatory factors (such as Arg-1), clear intracellular reactive oxygen species (ROS), and relieve oxidative stress. Conclusion: The vitro experiments have confirmed that the CBD-loaded hydrogel system has good biosafety, and can alleviate inflammation by regulating the polarization direction of macrophages, and then inhibiting the secretion of pro-inflammatory factors, laying a strong foundation for the treatment of chronic enteritis.

Abstract Despite the success of immunotherapy in treating hepatocellular carcinoma (HCC), HCC remains a severe threat to health. Here, a crucial transcription factor, SOX12, is revealed that induces the immunosuppression of liver tumor microenvironment. Overexpressing SOX12 in HCC syngeneic models increases intratumoral regulatory T‐cell (Treg) infiltration, decreases CD8+T‐cell infiltration, and hastens HCC metastasis. Hepatocyte‐specific SOX12 knockout attenuates DEN/CCl4‐induced HCC progression and metastasis, whereas hepatocyte‐specific SOX12 knock‐in accelerates these effects. Mechanistically, SOX12 transcriptionally activates C‐C motif chemokine ligand 22 (CCL22) expression to promote the recruitment and suppressive activity of Tregs. Moreover, SOX12 transcriptionally upregulates CD274 expression to suppress CD8+T‐cell infiltration. Either knockdown of CCL22 or PD‐L1 dampens SOX12‐mediated HCC metastasis. Blocking of CC chemokine receptor 4 (CCR4), a receptor for CCL22, by inhibitor C‐021 or Treg‐specific knockout of CCR4 inhibits SOX12‐mediated HCC metastasis. Transforming growth factor‐β1 (TGF‐β1)/TGFβR1‐Smad2/3/4 is identified as a key upstream signaling for SOX12 overexpression in HCC cells. Combining C‐021 or TGFβR1 inhibitor galunisertib with anti‐PD‐L1 exhibits an enhanced antitumor effect in two HCC models. Collectively, the findings demonstrate that SOX12 contributes to HCC immunosuppression through the CCL22/CCR4‐Treg and PD‐L1‐CD8+T axes. Blocking of CCR4 or TGFβR1 improves the efficacy of anti‐PD‐L1 in SOX12‐mediated HCC.

Abstract The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes the physiological function of the SOX family and their multiple roles in tumors, with a focus on the relationship between the SOX family and TIME, aiming to propose their potential role in cancer and promising methods for treatment.

Abstract Background The small YABBY plant-specific transcription factor has a prominent role in regulating plant growth progress and responding to abiotic stress. Results Here, a total of 16 PvYABBYs from switchgrass (Panicum virgatum L.) were identified and classified into four distinct subgroups. Proteins within the same subgroup exhibited similar conserved motifs and gene structures. Synteny analyses indicated that segmental duplication contributed to the expansion of the YABBY gene family in switchgrass and that complex duplication events occurred in rice, maize, soybean, and sorghum. Promoter regions of PvYABBY genes contained numerous cis-elements related to stress responsiveness and plant hormones. Expression profile analysis indicated higher expression levels of many PvYABBY genes during inflorescence development and seed maturation, with lower expression levels during root growth. Real-time quantitative PCR analysis demonstrated the sensitivity of multiple YABBY genes to PEG, NaCl, ABA, and GA treatments. The overexpression of PvYABBY14 in Arabidopsis resulted in increased root length after treatment with GA and ABA compared to wild-type plants. Conclusions Taken together, our study provides the first genome-wide overview of the YABBY transcription factor family, laying the groundwork for understanding the molecular basis and regulatory mechanisms of PvYABBY14 in response to ABA and GA responses in switchgrass.

Abstract Transcription factor BTB domain and CNC homology 1 (BACH1) belongs to the Cap ‘n’ Collar and basic region Leucine Zipper (CNC-bZIP) family. BACH1 is widely expressed in mammalian tissues, where it regulates epigenetic modifications, heme homeostasis, and oxidative stress. Additionally, it is involved in immune system development. More importantly, BACH1 is highly expressed in and plays a key role in numerous malignant tumors, affecting cellular metabolism, tumor invasion and metastasis, proliferation, different cell death pathways, drug resistance, and the tumor microenvironment. However, few articles systematically summarized the roles of BACH1 in cancer. This review aims to highlight the research status of BACH1 in malignant tumor behaviors, and summarize its role in immune regulation in cancer. Moreover, this review focuses on the potential of BACH1 as a novel therapeutic target and prognostic biomarker. Notably, the mechanisms underlying the roles of BACH1 in ferroptosis, oxidative stress and tumor microenvironment remain to be explored. BACH1 has a dual impact on cancer, which affects the accuracy and efficiency of targeted drug delivery. Finally, the promising directions of future BACH1 research are prospected. A systematical and clear understanding of BACH1 would undoubtedly take us one step closer to facilitating its translation from basic research into the clinic.

To address the issues of illegal trading vulnerabilities and data leakage among security personnel resulting from the traditional governance in the security crowdsourcing ecosystem, this study introduces a “novel” credit supervision mechanism. By constructing a tripartite evolutionary game model involving the government, security crowdsourcing platforms, and security personnel, we analyze factors and mechanisms influencing the strategic choices of the three entities. The impact of different mechanisms on the system’s evolutionary path is explored by numerical simulation. The results show that: 1) enhancing credibility benefits, reducing regulation costs, and strengthening governance efforts of the regulators can promote “good behavior” of the three entities; 2) the security crowdsourcing ecosystem is able to achieve an ideal stable state under certain conditions; 3) the “novel” credit supervision mechanism can be operated effectively based on the credit feedback mechanism; 4) improved collaborative governance effectively restrains security personnel from engaging in the illegal trading of vulnerabilities; 5) the government implementing a reasonable reward and punishment mechanism for platforms is optimal for achieving an ideal stable state. This study provides insights for enhancing the governance system in the security crowdsourcing ecosystem.

For quality control improvement of medicine and food homology (MFH) health food, the concept of functional quality control and rapid screening strategy of functional compounds were proposed based on the dual identity characteristics. Taking Wuweisanqi Capsule as the research object, firstly, a modified method “syndrome correlation-network analysis” based on network pharmacology was used for analysis. Functions related targets were collected from common medical databases, while the clustering algorithm was used to extract the information of clinical records related to daily health care from traditional Chinese medicine (TCM) database to obtain the targets. The bioactive compounds and related targets were retrieved from the TCM Systems Pharmacology Database and Analysis Platform around the five materials included in formula. Protein-protein interaction (PPI) network and pathway enrichment analysis were performed on the intersection targets. According to the constructed formula material-compound-target-pathway network, the potential functional compounds were preliminarily identified. Secondly, key targets and compounds were analyzed by molecular docking to further screen functional compounds. Finally, combined with references, the screening and establishing determination methods of functional compounds containing total saponins, astragaloside IV, puerarin and schisandrin were finished. The rapid screening strategy adequately utilizes the advantage of TCM background for MFH health food and the effective extracting ability of massive data by the algorithm. It links three aspects of health food functions, formula materials and functional compounds, providing an efficient solution for the realization of function-formula-component integrated functional quality control, which has great application potential in health food industry.

Abstract With the development of the Internet of Things (IoT), more and more devices are connected in edge-cloud environment, and spectrum scarcity has become a major bottleneck for the employment of IoT devices in the end side of cloud computing. In addition, due to the broadcast nature of RF link, the potential eavesdropper may be presented in the wireless environment. To improve spectrum efficiency (SE) and ensure safe transmission of the users, in this paper, the two-way relay cooperative Cognitive Radio Non-Orthogonal Multiple Access (CR-NOMA) with massive multiple-in multiple-out (MIMO) is proposed. Our objective is to maximize the security energy efficiency (SEE) of the cognitive system subject to the quality of service (QoS) of users. Specifically, the multi-objective optimization problem is decomposed into three subproblems, i.e., the optimization of transmit power, power allocation, and antenna selection, respectively. The Lagrange dual algorithm based on the first-order Taylor series expansion function is proposed to solve the non-convex problem. Moreover, a novel orthogonal antenna selection algorithm is proposed to decrease the cost of radio frequency chains and limit the interference to the primary user. The simulation results show that the proposed scheme has significant performance gain on SEE. It can effectively increase the number of access for cloud computing edge IoT users. In addition, due to the impact of correlation between the antennas, as the number of relay antennas increases, the SEE converges to a specific value, which exists the optimal number of antenna.

Electrical resistivity tomography is a non-destructive and efficient geophysical exploration method that can effectively reveal the geological structure and sliding surface characteristics inside landslide bodies. This is crucial for analyzing the stability of landslides and managing associated risks. This study focuses on the Lijiazu landslide in Zhuzhou City, Hunan Province, employing the electrical resistivity tomography method to detect effectively the surrounding area of the landslide. The resistivity data of the deep strata were obtained, and the corresponding geophysical characteristics are inverted. At the same time, combined with the existing drilling data, the electrical structure of the landslide body is discussed in detail. The inversion results reveal significant vertical variations in the landslide body’s resistivity, reflecting changes in rock and soil physical properties. Combined with geological data analysis, it can be concluded that the sliding surface is located in the sandy shale formation. Meanwhile, by integrating various geological data, we can conclude that the landslide is currently in a creeping stage. During the rainy season, with rainfall infiltration, the landslide will further develop, posing a risk of instability. It should be promptly addressed through appropriate remediation measures. Finally, based on the results of two-dimensional inversion, this article constructs a three-dimensional surface morphology of the landslide body, which can more intuitively compare and observe the internal structure and material composition of the landslide body. This also serves as a foundation for the subsequent management and stability assessment of landslides, while also paving the way for exploring new perspectives on the formation mechanisms and theories of landslides.

It is difficult for users to understand the complex cloud product information for product selection. Using this information to recommend satisfactory cloud products is a challenge. Previous studies focused on similar information of users and products while neglecting relevance; therefore, they could not create recommendation approaches that account for functional dependencies among cloud products. To overcome this challenge, this study proposes a cloud product set recommendation model based on a hierarchical knowledge graph (KG) with a pre-post correlation of product functionality. There are two main contributions: First, we constructed a cloud product functionality and performance KG using the dependency information of layers and entities to represent complicated pre-post logical connections. The KG was designed according to the cloud service model. Second, we designed an improved PageRank algorithm to obtain the importance weight for each functionality and performance, which replaces the original average method with the proportion of connection weight. We considered the release time of the functionality, launch time of the product, and last update time of the product as crucial factors in the recommendation score to reflect the importance of the functionality and current development stage of the product. Finally, our method recommended a product set based on the weighted scores from the above results. In addition, we constructed a cloud product functionality dataset containing 339 functionalities. The experimental results show that the proposed method can generate a closely related set of products, leading to improved accuracy and higher satisfaction compared to mainstream methods.

Time series classification is a key problem in data mining, most of existing classification methods directly extract one-dimensional data from one-dimensional features, which cannot effectively express the inter-relation between different time points. Besides, some classification methods extract two-dimensional features through encoding raw one-dimensional data into two-dimensional images, and part of information is lost due to the difference of encoding methods. How to make full use of one-dimensional and two-dimensional features to extract valuable information and integrate them in an optimal fashion remains a promising challenge. In this paper, we propose a multi-scale convolutional network to extract one-dimensional features from time series for obtaining more feature information based on multi-scale convolution kernels. Two-dimensional features are constructed in terms of two-dimensional image coding based on ${G}$ ramian angular field, ${M}$ arkov transition field and ${R}$ ecurrence plot (GMR) methods. We develop a multi-dimensional feature fusion approach leveraging ${S}$ queeze-and- ${E}$ xcitation (SE) and ${S}$ elf- ${A}$ ttention (SA) mechanism to effective fusing one-dimensional multi-scale features and two-dimensional image features in terms of weight setting. We conduct experimental verification based on 84 complete data traces from a typical UCR dataset in the field. Experimental results show that the accuracy of our proposed approach improves by 3.35% compared with existing benchmark methods. The Grad ient-weighted ${C}$ lass ${A}$ ctivation ${M}$ apping (Grad-CAM) visualization analysis method is adopted, where our proposed approach extracts more accurate features and effectively distinguishes different time series data categories.

Abstract Background Metastasis is a major determinant of death in patients with hepatocellular carcinoma (HCC). Dissecting key molecular mediators that promote this malignant feature may help yield novel therapeutic insights. Here, we investigated the role of E-twenty-six transformation-specific variant 1 (ETV1), a member of the E-twenty-six transformation-specific (ETS) family, in HCC metastasis. Methods The clinical significance of ETV1 and its target genes in two independent cohorts of HCC patients who underwent curative resection were assessed by Kaplan–Meier analysis and Multivariate Cox proportional hazards model. Luciferase reporter assay and chromatin immunoprecipitation assay were used to detect the transcriptional regulation of target gene promoters by ETV1. The effect of ETV1 on invasiveness and metastasis of HCC were detected by transwell assays and the orthotopically metastatic model. Results ETV1 expression was frequently elevated in human HCC specimens. Increased ETV1 expression was associated with the malignant biological characteristics and poor prognosis of HCC patients. ETV1 facilitated invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ETV1 promoted HCC metastasis via upregulating metastasis-related genes, including protein tyrosine kinase 2 (PTK2) and MET. Down-regulated the expression of PTK2 or tyrosine protein kinase Met (c-MET) decreased ETV1-mediated HCC metastasis. Hepatocyte growth factor (HGF) upregulated ETV1 expression through activating c-MET-ERK1/2-ELK1 pathway. Notably, in two independent cohorts, patients with positive coexpression of ETV1/PTK2 or ETV1/c-MET had worse prognosis. Furthermore, the combination of PTK2 inhibitor defactinib and c-MET inhibitor capmatinib significantly suppressed HCC metastasis induced by ETV1. Conclusion This study uncovers functional and prognostic roles for ETV1 in HCC and exposes a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. Targeting this pathway may provide a potential therapeutic intervention for ETV1-overexpressing HCC.

Oil oxidation products can react with food substrates to produce harmful substances, and oil saturation is closely related to oil oxidation in the process of frying. Therefore, the influence of the composition of fatty acids in oil on the formation of harmful substances in fried pork balls was explored. The five frying oils with the lowest unsaturated fatty acid (UFA) content, ranked in ascending order, were palm oil, peanut oil, soybean oil, corn oil, and colza oil (64.94%, 79.94%, 82.65%, 83.07%, and 92.26%, respectively). The overall levels of four harmful substances (acrylamide, polycyclic aromatic hydrocarbons, heterocyclic amines, and trans fatty acids) found in the oil used to fry pork balls followed a descending order: canola oil, corn oil, peanut oil, soybean oil, and palm oil (33.66 μg/kg, 27.17 μg/kg, 23.45 μg/kg, 18.67 μg/kg, and 13.19 μg/kg, respectively). This order was generally consistent with the trend in the content of UFAs. Therefore, the formation of harmful substances is closely related to the saturation of oil. Compared with other frying oils, soybean oil as a household oil produces relatively low amounts of harmful substances and has less negative impact on the quality (oil content, moisture content, and higher protein digestibility) of fried products.

Background: Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive.Method: We obtained patients’ RNA expression data and follow-up information from University of California Santa Cruz (UCSC) and The Cancer Genome Atlas (TCGA). We analyzed the mRNA level of Cuproptosis-related genes (CRGs) and performed univariate Cox analysis. Liver hepatocellular carcinoma (LIHC) was chosen for further investigation. Real-Time quantitative PCR (RT-qPCR), Western blotting (WB), Immunohistochemical (IHC), and Transwell assays were used to determine expression patterns and functions of CRGs in LIHC. Next, we identified CRGs-related lncRNAs (CRLs) and differentially expressed CRLs between HCC and normal cases. Univariate Cox analysis, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to construct the prognostic model. Univariate and multivariate Cox analysis was used to assess whether the risk model can act as an independent risk factor of overall survival duration. Different risk groups performed immune correlation analysis, tumor mutation burden (TMB), and Gene Set Enrichment Analysis (GSEA) analysis were performed in different risk groups. Finally, we assessed the performance of the predictive model in drug sensitivity.Results: CRGs expression levels have significant differences between tumor and normal tissues. High expression of Dihydrolipoamide S-Acetyltransferase (DLAT) correlated to metastasis of HCC cells and indicated poor prognosis for HCC patients. Our prognostic model consisted of four cuproptosis-related lncRNA (AC011476.3, AC026412.3, NRAV, MKLN1-AS). The prognostic model performed well in predicting survival rates. The results from Cox regression analysis suggested that risk score can serve as an independent prognostic element for survival durations. Survival analysis revealed that low risk patients have extended survival periods compared with those with high risk. The results of the immune analysis indicated that risk score has a positive correlation with B cell and CD4+ T cell Th2, while has a negative relationship with endothelial cell and hematopoietic cells. Besides, immune checkpoint genes have higher expression folds in the high-risk set than in the low-risk set. The high-risk group had higher rates of genetic mutation than the low-risk set while having a shorter survival time. GSEA revealed the signaling pathways enriched in the high-risk group were mostly immune-related, while metabolic-related pathways were enriched in the low-risk group. Drugs sensitivity analysis indicated that our model has the ability to predict the efficacy of clinical treatment.Conclusion: The Cuproptosis-related lncRNAs prognostic formula is a novel predictor of HCC patients’ prognosis and drug sensitivity.