Swine pseudorabies virus attenuated vaccine reprograms the kidney cancer tumor microenvironment and synergizes with PD-1 blockade.

The global incidence rate of kidney cancer (KC) has been steadily increasing over the past 30 years. With the aging global population, kidney cancer has become an escalating concern that necessitates vigilant surveillance. Nowadays, surgical intervention remains the optimal therapeutic approach for kidney cancer, while the availability of efficacious treatments for advanced tumors remains limited. Oncolytic viruses, an emerging form of immunotherapy, have demonstrated encouraging anti-neoplastic properties and are progressively garnering public acceptance. However, research on oncolytic viruses in kidney cancer is relatively limited. Furthermore, given the high complexity and heterogeneity of kidney cancer, it is crucial to identify an optimal oncolytic virus agent that is better suited for its treatment. The present study investigates the oncolytic activity of the Pseudorabies virus live attenuated vaccine (PRV-LAV) against KC. The findings clearly demonstrate that PRV-LAV exhibits robust oncolytic activity targeting KC cell lines. Furthermore, the therapeutic efficacy of PRV-LAV was confirmed in both a subcutaneous tumor-bearing nude mouse model and a syngeneic mouse model of KC. Combined RNA-seq analysis and flow cytometry revealed that PRV-LAV treatment substantially enhances the infiltration of a diverse range of lymphocytes, including T cells, B cells, macrophages, and NK cells. Additionally, PRV-LAV treatment enhances T cell activation and exerts antitumor effects. Importantly, the combination of PRV-LAV with anti-PD-1 antibodies, an approved drug for KC treatment, synergistically enhances the efficacy against KC. Overall, the discovery of PRV-LAV as an effective oncolytic virus holds significant importance for improving the treatment efficacy and survival rates of KC patients.

Predictive role of glycocalyx components and MMP-9 in cardiopulmonary bypass patients for ICU stay.

Background: Shedding of glycocalyx is relevant to worse prognosis in surgical patients, and elevated levels of serum matrix metalloproteinase-9 (MMP-9) are associated with this phenomenon. This study aimed to investigate the dynamic alterations of serum glycocalyx components and MMP-9 during cardiopulmonary bypass (CPB), and evaluate their predictive capacities for prolonged intensive care unit (ICU) stay, as well as their correlation with coagulation dysfunction. Methods: This retrospective study analyzed serum levels of syndecan-1, heparan sulfate (HS), and MMP-9 at different time points during CPB, and assessed their association with prolonged ICU stay and coagulation dysfunction. Results: Syndecan-1, HS, and MMP-9 exhibited divergent changes during CPB. Serum levels of syndecan-1 (AUC = 78.0 %) and MMP-9 (AUC = 78.4 %) were validated as reliable predictors for prolonged ICU stay, surpassing the predictive value of creatinine (AUC = 70.0 %). Syndecan-1 (rho = 0.566, P < 0.01 at T1 and rho = 0.526, P < 0.01 at T2) and HS (rho = 0.403, P < 0.05 at T4) exhibited correlations with activated partial thromboplastin time (APTT) ratio beyond the normal range. Conclusions: Our findings advocate the potential efficacy of serum glycocalyx components and MMP-9 as early predictive indicators for extended ICU stay following cardiac surgery with CPB. Additionally, we observed a correlation between glycocalyx disruption during CPB and coagulation dysfunction. Further studies with expansive cohorts are warranted to consolidate our findings and explore the predictive potential of other glycocalyx components.

The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors.

BACKGROUND: Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. METHODS: PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. RESULTS: Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve ("cold") to inflamed ("hot"), thereby increasing immune cell infiltration and restoring CD8+ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. CONCLUSIONS: PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8+ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.

Thirdhand smoke beliefs, exposure status and associated factors among young people in China: A cross-sectional study.

INTRODUCTION: Thirdhand smoke is an emerging threat to global public health. There is no research on young people's exposure to thirdhand smoke in China. This study aims to investigate the exposure status and beliefs of thirdhand smoke among young Chinese people and provide a reference for policy regarding thirdhand smoke. METHODS: Data from the 2022 Chinese Resident Psychological and Behavioral Survey were used to select young people aged 15-24 years. A total of 11781 subjects were included in this study. Demographic information, beliefs about thirdhand smoke, and exposure status to thirdhand smoke were investigated. RESULTS: Among the participants, 47.8% reported being exposed to thirdhand smoke (males: 49.1%, females: 47.0%). Young people living in urban areas (AOR=0.84, 95% CI: 0.77-0.91, p<0.001) and those with a monthly family income >12000 RMB (AOR=0.81, 95% CI: 0.71-0.92, p=0.001) were less likely to be exposed to thirdhand smoke. Young people with junior high school education or higher, and current or former smokers, were more likely to be exposed to thirdhand smoke. There is room for improvement in the beliefs about thirdhand smoke among young people. CONCLUSIONS: Thirdhand smoke exposure is an issue that should be addressed in public health policy. Young people with low income and current or former smokers are populations that should be mainly focused on in public education and prevention work on thirdhand smoke.

Identification of potential biomarkers in cancer testis antigens for glioblastoma.

OBJECTIVE: To screen and validate cancer testis antigens (CTAs) as potential biomarkers and explore their molecular mechanisms in glioblastoma (GBM). METHODS: Ribonucleic acid sequencing (RNA-seq) and bioinformatics analyses were utilized to screen the highly expressed CTAs in GBM. Correlation analysis was used to identify potential biomarkers associated with tumor purity and prognosis. Immunohistochemistry was applied for detection of protein expression. Protein-protein interaction (PPI) network construction, functional enrichment analysis, and binding domain prediction were performed to investigate the underlying molecular mechanisms of GBM. RESULTS: A total of 8 highly expressed CTAs were identified in GBM. One of them was PDZ-binding kinase (PBK). PBK messenger RNA (mRNA) was most highly expressed in GBM and associated with tumor purity and prognosis, PBK protein expression was also significantly increased in GBM tissues and correlated with p53 expression. Functional enrichment analysis revealed that the PBK related genes were predominantly enriched in cell cycle pathway with 38 genes enriched. The proteins encoding by these 38 genes were performed by binding domain prediction analysis, which demonstrated 15 proteins interacting with PBK. Most of these proteins were up regulated in GBM. CONCLUSION: PBK is highly expressed in GBM. It may serve as a potential biomarker for GBM targeting therapy and the cell cycle modulator by interacting with certain key molecules of cell cycle in GBM.

Sustainable fashion: Design of the experiment assisted machine learning for the environmental-friendly resin finishing of cotton fabric.

Given the carcinogenic properties of formaldehyde-based chemicals, an alternative method for resin-finishing cotton textiles is urgently needed. Therefore, the primary objective of this study is to introduce a sustainable resin-finishing process for cotton fabric via an industrial procedure. For this purpose, Bluesign® approved a formaldehyde-free Knittex RCT® resin was used, and the process parameters were designed and optimized according to the Taguchi L27 method. XRD analysis confirmed the crosslinking formation between resin and neighboring molecules of cotton fabric, as no change in the cellulose crystallization phase. Several machine learning models were built in a sequence to predict the crease recovery angle (CRA), tearing strength (TE) and whiteness index (WI). Assessment of modelling was evaluated through the use of various metrics such as root mean square error (RMSE), mean absolute error (MAE), and the coefficient of determination (R2). Results were compared to those from other regression models, such as principal component regression (PCR), partial least squares regression (PLSR), and fuzzy modelling. Based on the results of our research, the LSSVR model predicted the CRA, TE, and WI with substantially more accuracy than other models, as shown by the fact that its RMSE and MAE values were significantly lower. In addition, it offered the greatest possible R2 values, reaching up to 0.9627.

Sustainable and eco-friendly dyeing of traditional grass cloth with a reactive dye in palm oil medium.

Traditional grass cloth has been used in China for a long time for the manufacturing of various household furnishing textiles and ladieswear. However, traditionally the grass cloth is dyed with reactive dyes in an aqueous medium, but the dyeing process is not sustainable because of high energy and water usage and the production of coloured effluent. In this work, the possibility of palm oil/water dual-phase dyeing of traditional grass cloth with a reactive dye, C.I. Reactive Blue 194 (Reactive Blue 194), was explored. The grass cloth soaked in an alkaline solution with 80-140% pick-up was dyed in a palm oil dyebath containing dye powder dispersed in a palm oil medium. The initial study confirmed that the pre-treatment of the fabric with an alkaline solution with 140% pick-up was beneficial for the uniform distribution of the dye in the fibres. The dyeing process parameters (e.g., fixation temperature, solution pH, and fixation time) for the grass cloth dyeing with the Reactive Blue 194 were optimised by using the Taguchi method. The pH of the alkali pre-treatment solution was found to be the most influential factor, as confirmed by the analysis of variance in terms of the percentage of contribution (94.41%), which was statistically significant (P < 0.05). The confirmation tests were carried out under optimal settings, and a higher K/S (24.06) was found compared with the initial condition (21.51). X-ray diffraction analysis indicated that the dyeing process did not affect the crystallinity of the grass cloth fibres. Furthermore, the recovery of palm oil from the spent dyebath was around 99%, and up to five times recycling and reuse of palm oil were studied for the dyeing of grass cloth. The colour strength of the grass cloths dyed in the palm oil recycled up to five times was similar to the cloth dyed in fresh palm oil. The results show that palm oil can be used as a dyeing medium for the sustainable dyeing of grass cloth with effluent reduction, which can be extended to the dyeing of other textile fibres.

Adsorption Behaviour of Reactive Blue 194 on Raw Ramie Yarn in Palm Oil and Water Media.

As an edible oil, palm oil is also safe and reliable in dyeing, and the residual palm oil after dyeing can be recycled and used continuously, which is green and environmentally friendly and has great research prospects. In this research, raw ramie yarn, used for traditional grass cloth, was dyed in a palm oil medium using Reactive Blue 194. Studying the adsorption and diffusion behaviour in the dyeing process is necessary. Additionally, the kinetics and isotherm model of dyeing raw ramie yarn with Reactive Blue 194 in palm oil is studied, and the adsorption behaviour between them is discussed. For a better understanding, the raw ramie yarn dyeing adsorption behaviour was also carried out in a water medium. It was found that the dyeing rates in palm oil are distinctly faster than in water. Kinetics data suggested that the pseudo-second-order model fitted for both dyeing mediums (palm oil and water) of the adsorption of the Reactive Blue 194 dye onto raw ramie yarn. Afterward, the adsorption isotherms' results denote that the Langmuir model was suitable for palm oil dyeing medium while the Freundlich model was suited for water medium. Overall, this study has demonstrated that raw ramie yarn dyeing in a palm oil medium could be a sustainable colouration route for textile fibres with a greater dye exhaustion percentage.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Confirmation of lung adenocarcinoma as the primary cancer with detection of EML4-ALK rearrangement using next-generation sequencing: a case study.

We report a female patient, who presented as a carcinoma of unknown primary site with multiple tumors in breast, lung, stomach, and ovary, was confirmed to be lung adenocarcinoma as primary cancer through detecting EML4-ALK rearrangement by the next generation sequencing (NGS). The patient was treated with crizotinib and resulted in significant regression of the primary and metastatic tumors, but resistance to crizotinib was developed 5 months after the treatment. Targeted therapy was, therefore, switched to alectinib, one of the second-generation of anaplastic lymphoma kinase (ALK) inhibitors, with excellent therapeutic response till November 16th, 2021. This study suggested that NGS be recommended to detect ALK rearrangement in the patients with carcinoma of unknown primary site, and that resistance to targeted therapy with ALK inhibitors should be considered for personalized precision medicine.

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma.

Objective: The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma. Methods: The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo. Results: MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma. Conclusion: MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Analyses.

OBJECTIVE: Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker. METHODS: Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis. RESULTS: Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis. CONCLUSION: MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

Structures of pseudorabies virus capsids.

Pseudorabies virus (PRV) is a major etiological agent of swine infectious diseases and is responsible for significant economic losses in the swine industry. Recent data points to human viral encephalitis caused by PRV infection, suggesting that PRV may be able to overcome the species barrier to infect humans. To date, there is no available therapeutic for PRV infection. Here, we report the near-atomic structures of the PRV A-capsid and C-capsid, and illustrate the interaction that occurs between these subunits. We show that the C-capsid portal complex is decorated with capsid-associated tegument complexes. The PRV capsid structure is highly reminiscent of other α-herpesviruses, with some additional structural features of ß- and γ-herpesviruses. These results illustrate the structure of the PRV capsid and elucidate the underlying assembly mechanism at the molecular level. This knowledge may be useful for the development of oncolytic agents or specific therapeutics against this arm of the herpesvirus family.

RIP1 Regulates Mitochondrial Fission during Skeletal Muscle Ischemia Reperfusion Injury.

BACKGROUND: Dynamin related protein-1 (Drp1)-mediated mitochondrial fission relates to ischemia reperfusion (IR) injury, and its association with necroptosis is implied. We hypothesized that receptor-interacting protein 1 (RIP1), a key kinase in necroptosis, acted as an upstream of Drp1-mediated mitochondrial fission during skeletal muscle IR. METHODS: Thirty rats were randomized into the SM, IR, NI, MI, and DI group (n = 6). The rats in the SM group were shamly operated, and those in the IR group were subjected to 4-hour ischemia of the right hindlimb that was followed by 4-hour reperfusion. Intraperitoneal administration of Nec-1 1 mg/kg, Mdivi-1 1.2 mg/kg and same volume of DMSO were given before ischemia in the NI, MI and DI groups, respectively. Upon reperfusion, the soleus muscles were harvested to determine morphological changes and the expression of RIP1, total Drp1 and p-Drp1 (Ser616). Moreover, the muscular oxidative stress indicators and plasma muscle damage biomarkers were detected. RESULTS: IR led to impaired histopathological structures and mitochondrial fragmentation in the soleus muscle tissue, accompanied with increased muscular oxidative stress and muscle injury biomarkers, which could be similarly alleviated by Mdivi-1 and Nec-1 (p < 0.05). RIP1 and p-Drp1 (Ser616) protein levels were significantly upregulated in the soleus muscle subjected to IR injury, this upregulation was attenuated in the NI group, and Mdivi-1 downregulated the protein expression of p-Drp1 (Ser616) but not of RIP1 (p < 0.05). CONCLUSION: RIP1 functions as an upstream of Drp1-mediated mitochondrial fission in the execution of necroptosis during skeletal muscle IR.

Knockdown of DPP4 promotes the proliferation and the activation of the CREB/aromatase pathway in ovarian granulosa cells.

Dipeptidyl peptidase 4 (DPP4) has been revealed to be upregulated in women suffering from polycystic ovary syndrome (PCOS), which is a common reproductive disorder. The present study was designed to investigate the effects of inhibition of DPP4 expression on the proliferation of ovarian granulosa cells as well as on the activation of the cAMP response element­binding protein (CREB)/aromatase pathway. The expression levels of DPP4 in rat serum samples with or without PCOS and ovarian granulosa cells (KGN cells) were detected using reverse transcription­quantitative PCR (RT­qPCR) and western blot analyses. Cell viability and cell cycle progression were detected using the Cell Counting Kit­8 assay and flow cytometric analysis, respectively. The 5­ethynyl­2'­deoxyuridine assay was employed to detect the proliferation of glycolaldehyde­bovine serum albumin (GOA­BSA)­treated KGN cells. In addition, RT­qPCR and western blot analyses were applied to detect the expression levels of CREB, specific cell cycle­associated proteins and cytochrome P450 (CYP) 19A1 and CYP11A1 enzymes in KGN cells. The expression levels of DPP4 were upregulated in rats with PCOS. Inhibition of DPP4 expression promoted the proliferation and cell cycle arrest of KGN cells. It was also revealed that the expression levels of cell cycle­associated proteins were upregulated in DPP4­silenced KGN cells. In addition, their proliferation was decreased following treatment with GOA­BSA, while the addition of sitagliptin partially reversed these effects. Additionally, sitagliptin reversed the inhibitory effects caused by GOA­BSA treatment on the cell cycle progression and on the activation of the CREB/aromatase pathway in KGN cells, as determined by the increased expression levels of the cell cycle­associated proteins as well as those of the CREB protein and the CYP19A1 and CYP11A1 enzymes. In conclusion, inhibition of DPP4 expression promoted the proliferation of KGN cells and the activation of the CREB/aromatase pathway.

Will personality traits affect the use of e-cigar among college students? A cross-sectional study in Guangdong Province, China.

Background: The prevalence of e-cigar among adolescents and young adults around the world is increasing rapidly, which has a serious impact on the health of young people. This study assessed the prevalence of e-cigar among college students and to explore the relationship between e-cigar use and personality traits. Methods: This study conducted an electronic questionnaire survey on college students who were from three undergraduate universities and three junior colleges in Guangdong Province from January 2022 to March 2022. The survey was conducted by stratified cluster sampling, and the respondents were 1362. Statistical descriptions are used to describe the demographic characteristics and personality traits of participants. Mann-Whitney U tests, and Chi-square tests were used to compare the differences between current e-cigar users and non e-cigar users. Two-step hierarchical Logistic regression was used to predict the associated factors with e-cigar use. Results: The prevalence of current e-cigar users was 5.1%. Agreeableness showed statistically significant higher in non-users (Z = 2.585, P < 0.01). Moreover, gender (AOR = 0.312, 95%CI: 0.174-0.562), the relationship with mother (AOR = 5.887, 95%CI: 1.460-23.748), friends who use e-cigar (AOR = 3.808, 95%CI: 2.159-6.719), allowance per month (AOR = 2.482, 95%CI: 1.371-4.490), and agreeableness (AOR = 0.957, 95%CI: 0.918-0.997) were related to the use of e-cigar. Conclusion: The level of agreeableness is associated with the use of e-cigar among college students. All these provided an important theoretical basis for future intervention.

SOAT1 enhances lung cancer invasiveness by stimulating AKT-mediated mitochondrial fragmentation.

Sterol O-acyltransferase 1 (SOAT1) is a key enzyme in lipid metabolism, which mediates cholesterol esterification metabolism and is closely associated with many cancers. However, the role of SOAT1 in lung cancer invasion remains unclear. We found that SOAT1 expression was positively correlated with lung cancer invasion. Downregulation of SOAT1 inhibited invasion, mitochondrial fragmentation, AKT phosphorylation, and phospho-Drp (Ser616) in lung cancer cells and promoted intracellular free cholesterol accumulation. Mechanistically, the AKT phosphorylation inhibitor MK-2206 alleviated both SOAT1 overexpression and high expression-induced mitochondrial fragmentation and lung cancer cell invasion. Furthermore, intracellular free cholesterol accumulation reduced AKT phosphorylation, SREBP1 mRNA expression, cell invasion, and mitochondrial fragmentation in lung cancer cells with high SOAT1 expression. In summary, our findings suggest that SOAT1 promotes lung cancer invasion by activating the PI3K/AKT signaling pathway by downregulating intracellular free cholesterol levels, thereby affecting the regulation of mitochondrial fragmentation.

Cancer-testis antigen ACRBP expression and serum immunoreactivity in ovarian cancer: Its association with prognosis.

INTRODUCTION: Cancer testis (CT) antigens are attractive targets for cancer immunotherapy because of their expression restriction and immunogenicity. The acrosin binding protein (ACRBP) is a member of CT antigens. This study aimed to evaluate ACRBP expression and immunogenicity in ovarian cancer (OC). METHODS: The expression level of ACRBP in OC tissues, normal ovarian tissues, and cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. We determined the levels of ACRBP antigen and antibody in serum samples collected from patients with OC and healthy donors using enzyme-linked immunosorbent assays (ELISA), the level of ACRBP in cell-cultured medium was also tested. RESULTS: ACRBP mRNA and protein expressions were upregulated in OC tissues relative to normal tissue, especially highly expressed in epithelial ovarian cancer (EOC). Moreover, ACRBP expression was significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and chemosensitivity. Serological analysis showed that anti-ACRBP antibody was detected in the sera of 16 of the 56 (28.5%) patients with OC but not in healthy donors. The area under the receiver operating characteristic curve for ACRBP antibody was 0.802 (95% confidence interval [CI]: 0.708-0.876), and the sensitivity and specificity for ACRBP antibody was 85.71% and 55.0%, respectively. Kaplan-Meier analysis revealed that the overall survival (OS) and disease-free survival (DFS) in OC patients with high ACRBP expression were significantly lower than those with low expression (p = 0.040, p = 0.021). However, ACRBP antibody level was not associated with prognosis. CONCLUSION: ACRBP expression was upregulated in OC tissues and induced humoral immune response in patients with OC, suggesting that ACRBP is a potential prognostic biomarker and a target of tumor immunotherapy for OC.