LncRNA AGPG Confers Endocrine Resistance in Breast Cancer by Promoting E2F1 Activity.

Resistance to endocrine therapy represents a major concern for patients with estrogen receptor α-positive (ERα+) breast cancer. Endocrine therapy resistance is commonly mediated by activated E2F signaling. A better understanding of the mechanisms governing E2F1 activity in resistant cells could reveal strategies for overcoming resistance. Here, we identified the long noncoding RNA (lncRNA) actin gamma 1 pseudogene 25 (AGPG) as a regulator of E2F1 activity in endocrine-resistant breast cancer. Expression of AGPG was increased in endocrine-resistant breast cancer cells, which was driven by epigenomic activation of an enhancer. AGPG was also abnormally upregulated in patient breast tumors, especially in the luminal B subtype, and high AGPG expression was associated with poor survival of patients with ERα+ breast cancer receiving endocrine therapy. The upregulation of AGPG mediated resistance to endocrine therapy and cyclin-dependent kinase 4/6 inhibition in breast cancer cells. Mechanistically, AGPG physically interacted with PURα, thus releasing E2F1 from PURα and leading to E2F1 signaling activation in ERα+ breast cancer cells. In patients with breast cancer, E2F1 target genes were positively and negatively correlated with expression of AGPG and PURα, respectively. Coadministration of chemically modified AGPG siRNA and tamoxifen strongly suppressed tumor growth in endocrine-resistant cell line-derived xenografts. Together, these results demonstrate that AGPG can drive endocrine therapy resistance and indicate that it is a promising biomarker and potential therapeutic target in breast cancer. SIGNIFICANCE: Blockade of formation of the PURα/E2F1 complex by lncRNA AGPG activates E2F1 and promotes endocrine resistance, providing potential strategies for combatting endocrine-resistant breast cancer.

A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer.

The WD40 repeat-containing F-box proteins (FBXWs) family belongs to three major classes of F-box proteins. Consistent with the function of other F-box proteins, FBXWs are E3 ubiquitin ligases to mediate protease-dependent protein degradation. However, the roles of several FBXWs remain elusive. In the present study, via integrative analysis of transcriptome profiles from The Cancer Genome Atlas (TCGA) datasets, we found that FBXW9 was upregulated in the majority of cancer types, including breast cancer. FBXW expression was correlated with the prognosis of patients with various types of cancers, especially for FBXW4, 5, 9, and 10. Moreover, FBXWs were associated with infiltration of immune cells, and expression of FBXW9 was associated with poor prognosis of patients receiving anti-PD1 therapy. We predicted several substrates of FBXW9, and TP53 was the hub gene in the list. Downregulation of FBXW9 increased the expression of p21, a target of TP53, in breast cancer cells. FBXW9 was also strongly correlated with cancer cell stemness, and genes correlated with FBXW9 were associated with several MYC activities according to gene enrichment analysis in breast cancer. Cell-based assays showed that silencing of FBXW9 inhibited cell proliferation and cell cycle progression in breast cancer cells. Our study highlights the potential role of FBXW9 as a biomarker and promising target for patients with breast cancer.

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma.

PURPOSE: To explore transcriptome and immunological features of patients with Ewing sarcoma (ES) using all publicly available microarray data. METHODS: Data of 479 ES tissues were integrated and normalized. Gene expression, immune infiltration, and cancer-specific pathways were analyzed. Genes of interest were knocked down, followed by cell proliferation and colony formation assays. RESULTS: Consistent with the previous reports of differential expressed genes (DEGs) in ES, our analysis identified CCND1, HMCN1, and NKX2-2 were among the most highly expressed, while TWNC1, MYBPC1, and CKM were among the lowest expressed genes. GO, KEGG, and GSEA enrichment analysis identified that the DEGs related to bone and muscle functioning, those that contributed to crucial cellular, and metabolism pathways such as actin binding, apoptosis, TCA cycle, and cell cycle were also significantly enriched. Immune infiltration analysis discovered that many T cell subsets including CD4T, CD8 T, and Gamma delta T cells were highly infiltrated, while monocytes and B cells were less infiltrated in tumors. A total of 138 genes were both significantly up-regulated in tumors and associated with decreased survival, while 38 significantly down-regulated genes were associated with increased survival, many of which were previously reported as oncogenes and tumor suppressors in ES and other cancers. Silencing of four newly identified top ranked up-regulated genes with decreased survivals in ES inhibited proliferation and colony formation of ES cells. CONCLUSION: This study may provide a clear representative transcriptome profile of ES, providing diagnostic biomarkers, pathways, and immune infiltrative characteristics targets for ES.

Psychological responses and dietary changes of residents during the local outbreak of COVID-19 in the post-epidemic era: A cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on the psychological state and dietary behavior of individuals. Many previous studies have discussed the psychological and dietary problems during the first COVID-19 pandemic. However, few papers have discussed them during the local COVID-19 outbreak in the post-epidemic era. To explore the psychological responses and the influencing factors, dietary changes and the relationship with psychological responses during the local COVID-19 outbreak in the post-epidemic era. Methods: A total 3790 residents were surveyed by online questionnaire to collect information about social demography, health status, local outbreak related information, lifestyle changes, anxiety and depression. Binary logistic regression was used to discuss the influencing factors of anxiety and depression. Kendall tau-b correlation coefficient was used to discuss the relationship between anxiety, depression and dietary changes. Self-perceived physical condition, chronic disease, lockdown or quarantine, fear of COVID-19, changes in smoking, drinking and physical activity were the influencing factors of anxiety and depression. The top 3 foods with increased intake were drinking water, fresh fruits and fresh vegetables, while the top 3 foods with reduced intake were puffed foods, fried foods and sugary foods. Dietary changes were correlated with generalized anxiety disorder-7 and patient health questionnaire-9 scores. These findings provide experience and clues for local governments to improve the psychological status and dietary habits of residents during the local COVID-19 outbreak in the post-pandemic era.

Neoantigens and NK Cells: "Trick or Treat" the Cancers?

Immunotherapy has become an important treatment strategy for cancer patients nowadays. Targeting cancer neoantigens presented by major histocompatibility complex (MHC) molecules, which emerge as a result of non-synonymous somatic mutations with high immunogenicity, is one of the most promising cancer immunotherapy strategies. Currently, several therapeutic options based on the personalized or shared neoantigens have been developed, including neoantigen vaccine and adoptive T-cell therapy, both of which are now being tested in clinical trials for various malignancies. The goal of this review is to outline the use of neoantigens as cancer therapy targets, with an emphasis on neoantigen identification, clinical usage of personalized neoantigen-based cancer therapy agents, and the development of off-the-shelf products based on shared neoantigens. In addition, we introduce and discuss the potential impact of the neoantigen-MHC complex on natural killer (NK) cell antitumor function, which could be a novel way to boost immune response-induced cytotoxicity against malignancies.

The Difference in Learning Activities of Postgraduate Students of Different Qualification Types Under the COVID-19 Pandemic: A Multi-Group Latent Class Analysis.

Introduction: There are two types of master's qualifications in China. One is the academic qualification that pays more attention to academic research, aiming to cultivate research-oriented talents; while the other is the application-oriented qualification that focuses more on practical ability, aiming to cultivate applied-oriented talents. The purpose of this study is to explore the impact of the COVID-19 on the learning activities of postgraduate students, as well as the differences in the extent to which the learning activities of postgraduate students of different qualification types are affected and their mental health status. Methods: A self-constructed scale for the pandemic's impact on master's students, the self-rating anxiety scale and the self-rating depression scale were applied in the study. The single- and multi-group latent class analyses were used to investigate the impact of the pandemic on postgraduate students of different qualification types. Results: A total of 2818 responses were collected. The single-group latent class analysis identified four classes. The multi-group latent class analysis showed that no absolute homogeneity existed between different groups. In general, the number of academic master's students affected was greater than application-oriented master's students. Application-oriented master's students were more affected by course activities, while academic master's students were more affected by academic and social activities. Results show that individuals more affected had higher levels of anxiety and depression. Compared to course activities, impacts on social activities were more likely to cause anxiety and depression. Discussion: Universities can provide a more flexible way of assistance to different qualification types of postgraduate students. Furthermore, social activities play an important role in the mental health of postgraduate students. Therefore, under the background of normalization of pandemic prevention and control, schools should pay more attention to students' interpersonal communication activities to help relieve students' anxiety, depression, and other negative emotions.

Effects of the COVID-19 Pandemic on Chinese Graduate Students' Learning Activities: A Latent Class Analysis.

To investigate the impact of the pandemic on graduate students' learning activities, a series of questionnaires were distributed to graduate students in universities across China, and 2,818 responses were collected. A latent class analysis was performed to classify the effects of the pandemic on graduate students' learning activities. Then, a multinomial logistic regression analysis and an analysis of variance analysis were carried out to explore the impact of demographic variables on the classification and their mental health status. The analysis identified four latent classes: "the overall less affected" (34.83%), "the overall more affected" (31.97%), "course activities were more affected" (19.40%), and "social activities were more affected" (13.79%). The multinomial logistic regression analysis indicated that during the pandemic, the learning activities of graduate students in all grades were affected to varying degrees, and the impacts on second-year and third-year graduate students were greater than those of first-year graduate students. The analysis of variance revealed that the scores for anxiety, depression, and social anxiety of "the overall more affected" were significantly greater than those of the other three groups, and nearly one-third of students belonged to this class, suggesting that more attention and care should be given to these students. As a result of the COVID-19 pandemic, a number of graduate students have suffered mental problems (anxiety and depression). Under the current backdrop of a new normal, schools and teachers should pay attention to graduate students' mental health, providing targeted assistance to different types of students.

Preliminary Study of microRNAs Allele-specific Targeting in Allergic Rhinitis Patients from Central China.

BACKGROUND: Abnormal expression of miRNA is a common feature in many diseases. Some studies have also emphasized that miRNAs play an important role in asthma and Allergic Rhinitis (AR). This study attempts to reveal the differences between miRNAs expression and normal nasal mucosa in AR patients by microarray method so as to further understand the molecular mechanism of AR development. METHODS: MiRNA microarrays were used for analyzing six samples of the nasal mucosa of AR and six samples of nonallergic patients. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of some differently expressed miRNAs was used to confirm the array results. Furthermore, pathway analysis was carried out. RESULTS: The microarray identified that 64 miRNAs showed altered expression in the nasal mucosa of the AR group when compared with the control group. Moreover, the expression levels of ten miRNAs were significantly altered in the AR group. To verify the results of microarray, three differentially expressed miRNA were determined by RT-PCR, and the results also confirmed these changes. Ten differentially expressed miRNAs were present in the nasal mucosa of AR patients compared with the control group, and three differentially expressed miRNAs as miR-1244, miR- 4651, and miR-7641 were determined by RT-PCR. The results also confirmed the changes, indicating that they play important roles in the process of AR. CONCLUSION: MiR-1244, miR-4651, and miR-7641 may play important roles in the process of AR. Sequencing analysis indicated that three kinds of mutations existed in MAPK8 3'UTR, which may play a role in binding with miR-7641, and then influence the AR process. Single miRNA or, more probably, their sets hold the promise for their use as biomarkers of allergic rhinitis. They are also a promising target of future therapies.

The Impact of the COVID-19 Pandemic on Chinese Postgraduate Students' Mental Health.

To understand the mental health status of Chinese postgraduate students during the COVID-19 pandemic, we used three online questionnaires: self-rating anxiety (SAS) scale, self-rating depression (SDS) scale, and social avoidance and distress (SAD) scale. A total of 3137 postgraduate students from different regions of China participated in our study. We explored the relationship between participant characteristics and mental health using an analysis of variance (ANOVA). We found that the proportions of respondents with severe, mild, and moderate depression were 1.4%, 10.48%, and 21.99%, respectively, and the corresponding proportions of respondents with anxiety were 1.56%, 4.65%, and 14.69%, respectively. A one-way ANOVA revealed that the mental health statuses of the participants were different between the subgroups based on majors, classes, degree types, and the method of communication with advisors and students. A two-way ANOVA revealed significant effects on interaction and the method of communication with advisors and peers. These findings suggest that the mental health of postgraduate students should be monitored during the pandemic, especially when they are unable to communicate directly with their advisors or peers, and targeted psychological counselling must be focused on anxiety and depression.

Bio-Conjugated Quantum Dots for Cancer Research: Detection and Imaging.

Ultrasound, computed tomography, magnetic resonance, and gamma scintigraphy-based detection and bio-imaging technologies have achieved outstanding breakthroughs in recent years. However, these technologies still encounter several limitations such as insufficient sensitivity, specificity and security that limit their applications in cancer detection and bio-imaging. The semiconductor quantum dots (QDs) are a kind of newly developed fluorescent nanoparticles that have superior fluorescence intensity, strong resistance to photo-bleaching, size-tunable light emission and could produce multiple fluorescent colors under single-source excitation. Furthermore, QDs have optimal surface to link with multiple targets such as antibodies, peptides, and several other small molecules. Thus, QDs might serve as potential, more sensitive and specific methods of detection than conventional methods applied in cancer molecular targeting and bio-imaging. However, many challenges such as cytotoxicity and nonspecific uptake still exist limiting their wider applications. In the present review, we aim to summarize the current applications and challenges of QDs in cancer research mainly focusing on tumor detection, bio-imaging, and provides opinions on how to address these challenges.

Psychometric Properties and Factor Structures of the CERQ, DERS, and RESE Measures: A Bifactor Approach.

This study aims to simultaneously compare the psychometric properties and examine the factor structures of 3 emotion regulation (ER) strategy scales using a bifactor approach. Due to good reliability and validity, extensive use, and the same scoring method, the Cognitive Emotion Regulation Questionnaire, Difficulties in Emotion Regulation Scale, and Regulatory Emotional Self-Efficacy Scale were used to assess ER strategies in 1,036 Chinese respondents. A bifactor confirmatory factor analysis was designed to address the multidimensionality of the factor structure, and the corresponding bifactor structures were then applied in a subsequent bifactor multidimensional item response theory (MIRT) analysis. Finally, bifactor MIRT was used to compare the psychometric properties of the 3 measures. The results indicated that bifactor structures were appropriate for the 3 ER strategy measures, which performed well overall. Different measures provide the highest accuracy for specific groups and designs. Some strengths and limitations of this article are discussed.

Impact of Academic Support on Anxiety and Depression of Chinese Graduate Students During the COVID-19 Pandemic: Mediating Role of Academic Performance.

INTRODUCTION: The COVID-19 pandemic broke out and has spread globally since 2019. It became a public health concern. This pandemic has brought tremendous changes in students' lives and modes of learning. Graduate students are likely to be more affected as they are a part of a special training program. According to the main-effect model, social support has a positive effect on mental health. The pandemic has exerted a negative impact on the social support of individuals, and as a result, the behavior of a person is more likely to be at risk and has resulted in psychological crisis in people/individuals. METHODS: A sample of 3137 graduate students responded to the instrument developed to assess the impact of the pandemic on the academic activities and performance, Self-rating Anxiety Scale and Self-rating Depression Scale. RESULTS: The results showed that: 1) the pandemic impacted the academic support and performance of graduate students in varying degrees, 21% of graduate students experienced anxiety, and 33.9% of graduate students experienced depressive symptoms in varying degrees; 2) academic support variables (ie, academic exchange with mentors and peers) and academic performance variables (ie, data collection and thesis writing) were significantly associated with anxiety and depressive symptoms; 3) the model fitted the data well (RMSEA = 0.029; SRMR = 0.014; TLI = 0.99; CFI = 0.996). The direct effects of academic support on anxiety and depressive symptoms were significant. The impact on academic performance played a mediating role between the impact on academic support, anxiety, and depressive symptoms. DISCUSSION: Academic support significantly affected academic performance, which in turn affected anxiety and depressive symptoms. So, it implies that, due to the pandemic, the academic support for graduate students had decreased, resulting in deterioration in academic performance, causing anxiety and depressive symptoms.

How Course Support and Academic Support Impact on Chinese Graduate Students during the COVID-19: The Multiple Mediating Roles of Thesis Writing and Anxiety.

Because of the impact of the COVID-19 pandemic, the learning style of graduate students has changed considerably, making them more susceptible to psychological problems. This study aimed to explore the mediating roles of thesis writing and anxiety between course support (including course-arrangement, course-assessment, and course-learning), academic support (including academic exchange with colleges, tutors and schoolmates) and depression. There were 3137 graduate students investigated by self-developed Graduate Students' Academic Affected Questionnaire, Self-Rating Anxiety Scale and Self-Rating Depression Scale. The results showed that (1) 82% of graduate students reported their course support, academic support and thesis writing were affected to varying degrees; (2) course support and academic support correlated with thesis writing, anxiety and depression (p < 0.001); (3) the mediation model fitted well, the mediating effect of anxiety between academic support and depression was significant (ß = 0.086, SE = 0.02, p < 0.001), the serial multiple mediating effects of thesis writing and anxiety between academic support and depression were significant (ß = 0.02, SE = 0.008, p = 0.013) and the serial multiple mediating effects of thesis writing and anxiety between course support and depression were also found to be significant (ß = 0.014, SE = 0.006, p = 0.014).

A quantum dot-based lateral flow immunoassay for the rapid, quantitative, and sensitive detection of specific IgE for mite allergens in sera from patients with allergic rhinitis.

The prevalence of allergic rhinitis (AR) is increasing worldwide. However, the current systems used to measure levels of immunoglobulin E (IgE) in sera are associated with several disadvantages that limit their further application. Consequently, there is a need to develop novel highly sensitive strategies that can rapidly detect IgE in a quantitative manner. The development of such systems will significantly enhance our ability to diagnose, treat, and even prevent AR. Herein, we describe our experience of using quantum dot-based lateral flow immunoassay (QD-LFIA), combined with a portable fluorescence immunoassay chip detector (PFICD), to detect serum-specific IgE against Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae (Der-f), two common mite allergens in China. Our data showed that our system could detect serum-specific levels of IgE against Der-p and Der-f as low as 0.093 IU/mL and 0.087 IU/mL, respectively. We also established a standard curve to determine serum-specific IgE concentrations that correlated well with the clinical BioIC microfluidics system. The sensitivity of our assay was 96.7% for Der-p and 95.5% for Der-f, while the specificity was 87.2% for Der-p and 85.3% for Der-f. Collectively, our results demonstrate that QD-LFIA is a reliable system that could be applied to detect serum-specific IgE in accordance with clinical demands. This QD-LFIA strategy can be applied at home, in hospitals, and in pharmacies, with reduced costs and time requirements when compared with existing techniques. In the future, this system could be developed to detect other types of allergens and in different types of samples (for example, whole blood). Graphical abstract We describe our experiment using a quantum dot-based lateral flow immunoassay combined with a portable fluorescence immunoassay chip detector for both qualitative and quantitative detection of serum-specific IgE against two common mite allergens. This strategy can be applied at home, in hospitals, and in pharmacies, with reduced costs and time requirements. In the future, this system could be developed to detect other types of allergens and in different types of samples.

Multiwalled Carbon Nanotubes Prevent Tumor Metastasis Through Switching M2-Polarized Macrophages to M1 via TLR4 Activation.

Targeting tumor-associated macrophages (TAMs) has emerged as a novel therapeutic strategy for cancer metastasis. Here, we investigated whether carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) prevent tumor metastasis through regulating macrophage polarization. In Lewis lung carcinoma (LLC) or B16F10 melanoma-bearing mice, intratracheal instillation of MWCNTs-COOH significantly reduced metastatic burden in the lungs. MWCNTs-COOH promoted the expression of M1 markers (iNOS and CXCR10) and inhibited the expression of M2 markers (CD206 and Arg-1) along with an increased expression of Th1 cytokines (TNF-α and IL-12) and decreased expression of Th2 cytokines (TGF-ß and IL-10). Such changes were accompanied with TLR4 mRNA and protein elevation. Importantly, macrophage depletion in mice lungs reversed the anti-metastatic effects of MWCNTs-COOH. In vitro, MWCNTs-COOH switched IL-4/13-treated macrophages to the M1 phenotype and thus prevented the migration and invasion of LLC cells, accompanied by the upregulation of toll-like receptor (TLR)-4/NF-κB p65 signaling. Moreover, TAK-242 (resatorvid), a specific TLR4 inhibitor, reversed the effects of MWCNTs-COOH on macrophage polarization. In summary, MWCNTs-COOH effectively prevent tumor metastasis through skewing M2-polarized macrophages to M1 via activating TLR4/NF-κB signaling. Thus, targeting TAMs by MWCNTs-COOH is a potential therapeutic approach against tumor metastasis.

The Protective and Immunomodulatory Effects of Fucoidan Against 7,12-Dimethyl benz[a]anthracene-Induced Experimental Mammary Carcinogenesis Through the PD1/PDL1 Signaling Pathway in Rats.

Fucoidan is a sulfated polysaccharide that is extracted from brown algae seaweed. This study was designed to evaluate the protective and immunomodulatory effects of dietary fucoidan on 7,12-dimethyl benz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Sixty Sprague-Dawley rats were randomly assigned to four equal groups: the control group (control group), the cancer model group (model group), and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg·body weight, respectively. We found that fucoidan treatment decreased the tumor incidence and mean tumor weight and prolonged the tumor latency. Flow cytometric analyses revealed that the number of blood natural killer cells was higher after fucoidan treatment and that the proportions of CD4 and CD8 T cells were also increased. The serum levels of interleukin (IL)-6, IL-12p40, and interferon (IFN)-γ were higher in the rats treated with fucoidan compared to those of model rats. Moreover, the percentage of CD3+ Foxp3+ regulatory T cells in the blood and the levels of IL-10 and transforming growth factor ß in the serum were lower in the rats treated with fucoidan. Furthermore, fucoidan treatment decreased the expression of Foxp3 and programmed cell death 1 ligand 1 (PDL1) in tumor tissues. The levels of p-phosphatidyl inositol kinase 3 and p-AKT in tumor tissues were also lower than those of model rats. These results suggest that a fucoidan-supplemented diet can inhibit DMBA-induced tumors in rats. This study provides experimental evidence toward elucidating the immune enhancement induced by fucoidan through the programmed cell death 1/PDL1 signaling pathway. The immunomodulatory effect is one of the possible mechanisms of the protective effect of fucoidan against mammary carcinogenesis.

Breast cancer suppression by aplysin is associated with inhibition of PI3K/AKT/FOXO3a pathway.

Aplysin, a bromosesquiterpene isolated from Aplysia kurodai, was explored as a potential anti-breast cancer agent by us. However, the mechanisms underlying the anticarcinogenic effect of aplysin remain unclear. Here, aplysin was found to remarkably suppress tumor growth in vivo, inhibit cell proliferation and promote apoptosis in vitro. Additionally, we demonstrated that aplysin attained these effects in part by down-regulating PI3K/AKT/FOXO3a signaling pathway. Aplysin treatment inhibited the phosphorylation levels of AKT (Ser-473) and AKT-dependent phosphorylation of FOXO3a (Ser-253) in breast cancer cell lines and breast cancer tissues. The expression levels of FOXO3a-targeted genes were also destabilized by aplysin, cyclin D1 and Bcl-XL were declined; however, p21CIP1, p27KIP1, Bim, TRAIL and FasL were increased both in vivo and in vitro. Furthermore, activation of the PI3K/AKT signaling pathway by an activator and silencing of FOXO3a by shRNA protected the cells from aplysin mediated growth suppression and apoptosis. In summary, our findings revealed that aplysin could suppress breast cancer progression by inhibiting PI3K/AKT/FOXO3a pathway, thereby suggesting a potential role of aplysin as a chemoprevention drug for patients with breast cancer.