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Online teaching is not limited by time, but the problem of low learning efficiency is common. To address this problem, the study proposes an attention mechanism for multidimensional feature fusion, which first detects faces, uses a supervised gradient descent algorithm for face feature point detection, and improves the least-squares ellipse-fitting algorithm to detect the open/closed state of human eyes. The sight detection method is also improved, and the fuzzy inference method is used to identify students’ emotions, and the modules are fused to achieve multidimensional feature fusion attention detection for online teaching. The study found that the average accuracy rate was 84.5% with glasses and 92.0% without glasses. The research method with glasses had an average time consumption of 17 ms, while the method without glasses took 15 ms, indicating higher detection accuracy and faster real-time performance. The improved approach led to higher recognition accuracy and accuracy rate. The detection accuracy of a single feature and the research method was 74.1 and 91.9%, respectively. It shows that the research method helps in the detection of students’ attention in online teaching.

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP's emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD's underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches. [ABSTRACT FROM AUTHOR]

Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for non-small-cell lung cancer (NSCLC) with EGFR activating mutations, but inevitably, the clinical efficacy is impeded by the emergence of acquired resistance. The tumor suppressor gene FBXW7 modulates chemosensitivity in various human cancers. However, its role in EGFR-TKI therapy in NSCLC has not been well studied. Here, we demonstrate that the mice with deficient Fbxw7 have greater susceptibility to urethane-induced lung tumor development. Through analysis of The Cancer Genome Atlas data, we show that deletion of FBXW7 occurs in 30.9% of lung adenocarcinomas and 63.5% of lung squamous cell carcinomas, which significantly leads to decrease in FBXW7 mRNA expression. The reduction in FBXW7 mRNA level is associated with poor overall survival in lung cancer patients. FBXW7 knockdown dramatically promotes epithelial-mesenchymal transition, migration, and invasion in NSCLC cells. Moreover, with silenced FBXW7, EGFR-TKI-sensitive cells become resistant to gefitinib, which is reversed by the mammalian target of rapamycin inhibitor, rapamycin. Furthermore, xenograft mouse model studies show that FBXW7 knockdown enhances tumorigenesis and resistance to gefitinib. Combination of gefitinib with rapamycin treatment suppresses tumor formation of gefitinib-resistant (GR) FBXW7-knockdown cells. In conclusion, our findings suggest that loss of FBXW7 promotes NSCLC progression as well as gefitinib resistance and combination of gefitinib and rapamycin may provide an effective therapy for GR NSCLC.

Exposure to thirdhand smoke (THS) is a recently described health concern that arises in many indoor environments. However, the carcinogenic potential of THS, a critical consideration in risk assessment, remains untested. Here we investigated the effects of short-term early exposure to THS on lung carcinogenesis in A/J mice. Forty weeks after THS exposure from 4 to 7 weeks of age, the mice had increased incidence of lung adenocarcinoma, tumor size and, multiplicity, compared with controls. In vitro studies using cultured human lung cancer cells showed that THS exposure induced DNA double-strand breaks and increased cell proliferation and colony formation. RNA sequencing analysis revealed that THS exposure induced endoplasmic reticulum stress and activated p53 signaling. Activation of the p53 pathway was confirmed by an increase in its targets p21 and BAX. These data indicate that early exposure to THS is associated with increased lung cancer risk.

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeks after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.

Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut. We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts the microbiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

NUCKS1 is a 27 kD vertebrate-specific protein, with a role in the DNA damage response. Here, we show that after 4 Gy total-body X-irradiation, Trp53+/- Nucks1+/- mice more rapidly developed tumors, particularly thymic lymphoma (TL), than Trp53+/- mice. TLs in both cohorts showed loss of heterozygosity (LOH) of the Trp53+ allele in essentially all cases. In contrast, LOH of the Nucks1+ allele was rare. Nucks1 expression correlated well with Nucks1 gene dosage in normal thymi, but was increased in the majority of TLs from Trp53+/- Nucks1+/- mice, suggesting that elevated Nucks1 message may be associated with progression towards malignancy in vivo. Trp53+/- Nucks1+/- mice frequently succumbed to CD4- CD8- TLs harboring translocations involving Igh but not Tcra/d, indicating TLs in Trp53+/- Nucks1+/- mice mostly originated prior to the double positive stage and at earlier lineage than TLs in Trp53+/- mice. Monoclonal rearrangements at Tcrb were more prevalent in TLs from Trp53+/- Nucks1+/- mice, as was infiltration of primary TL cells to distant organs (liver, kidney and spleen). We propose that, in the context of Trp53 deficiency, wild type levels of Nucks1 are required to suppress radiation-induced TL, likely through the role of the NUCKS1 protein in the DNA damage response.

The tumor suppressor gene FBXW7 is deleted and mutated in many different types of human cancers. FBXW7 primarily exerts its tumor suppressor activity by ubiquitinating different oncoproteins including mTOR. Here we used gene transcript profiling to gain a deeper understanding of the role of FBXW7 in tumor development and to determine the influence of mTOR inhibition by rapamycin on tumor transcriptome and biological functions. In comparison to tumors from p53 single heterozygous (p53+/-) mice, we find that radiation-induced thymic lymphomas from Fbxw7/p53 double heterozygous (Fbxw7+/-p53+/-) mice show significant deregulation of cholesterol metabolic processes independent of rapamycin treatment, while cell cycle related genes were upregulated in tumors from placebo treated Fbxw7+/-p53+/- mice, but not in tumors from rapamycin treated Fbxw7+/-p53+/- mice. On the other hand, tumors from rapamycin treated Fbxw7+/-p53+/- mice were enriched for genes involved in the integrated stress response, an adaptive mechanism to survive in stressful environments. Finally, we demonstrated that the Fbxw7 gene signatures identified in mouse tumors significantly overlap with FBXW7 co-expressed genes in human cancers. Importantly these common FBXW7 gene signatures between mouse and human are predictive for disease-free survival in human colon, breast and lung adenocarcinoma cancer patients. These results provide novel insights into the role of FBXW7 in tumor development and have identified a number of potential targets for therapeutic intervention.

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However, 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. Lastly, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.

The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genes involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed after LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight in this observation. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent gene cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.

The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.

FBXW7 acts as a tumor suppressor in numerous types of human cancers through ubiquitination of different oncoproteins including mTOR. However, how the mutation/loss of Fbxw7 results in tumor development remains largely unknown. Here we report that downregulation of mTOR by radiation is Fbxw7-dependent, and short-term mTOR inhibition by rapamycin after exposure to radiation significantly postpones tumor development in Fbxw7/p53 double heterozygous (Fbxw7+/-p53+/-) mice but not in p53 single heterozygous (p53+/-) mice. Tumor latency of rapamycin treated Fbxw7+/-p53+/- mice is remarkably similar to those of p53+/- mice while placebo treatedFbxw7+/-p53+/- mice develop tumor significantly earlier than placebo treated p53+/- mice. Furthermore, we surprisingly find that, although temporal treatment of rapamycin is given at a young age, the inhibition of mTOR activity sustainably remains in tumors. These results indicate that inhibition of mTOR signaling pathway suppresses the contribution of Fbxw7 loss toward tumor development.

Tissues are composed of diverse cell subpopulations each with distinct metabolic characteristics that influence overall behavior. Unfortunately, traditional histopathology imaging techniques are 'blind' to the spatially ordered metabolic dynamics within tissue. While mass spectrometry imaging enables spatial mapping of molecular composition, resulting images are only a static snapshot in time of molecules involved in highly dynamic processes; kinetic information of flux through metabolic pathways is lacking. To address this limitation, we developed kinetic mass spectrometry imaging (kMSI), a novel technique integrating soft desorption/ionization mass spectrometry with clinically accepted in vivo metabolic labeling of tissue with deuterium to generate images of kinetic information of biological processes. Applied to a tumor, kMSI revealed heterogeneous spatial distributions of newly synthesized versus pre-existing lipids, with altered lipid synthesis patterns distinguishing region-specific intratumor subpopulations. Images also enabled identification and correlation of metabolic activity of specific lipids found in tumor regions of varying grade.

The Aurora-A kinase gene is frequently amplified and/or overexpressed in a variety of human cancers, leading to major efforts to develop therapeutic agents targeting this pathway. Here, we show that Aurora-A is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7 in a process that is regulated by GSK3β. Using a series of truncated Aurora-A proteins and site-directed mutagenesis, we identified distinct FBXW7 and GSK3β-binding sites in Aurora-A. Mutation of critical residues in either site substantially disrupts degradation of Aurora-A. Furthermore, we show that loss of Pten results in the stabilization of Aurora-A by attenuating FBXW7-dependent degradation of Aurora-A through the AKT/GSK3β pathway. Moreover, radiation-induced tumor latency is significantly shortened in Fbxw7(+/-)Pten(+/-) mice as compared with either Fbxw7(+/-) or Pten(+/-) mice, indicating that Fbxw7 and Pten appear to cooperate in suppressing tumorigenesis. Our results establish a novel posttranslational regulatory network in which the Pten and Fbxw7 pathways appear to converge on the regulation of Aurora-A level.

FBXW7 acts as a tumor suppressor through ubiquitination and degradation of multiple oncoproteins. Loss of FBXW7 expression, which could be partially attributed by the genomic deletion or mutation of FBXW7 locus, is frequently observed in various human cancers. However, the mechanisms regulating FBXW7 expression still remain poorly understood. Here we examined the 5' region of FBXW7 gene to investigate the regulation of FBXW7 expression. We identified seven alternative splicing (AS) 5'-UTR forms of FBXW7α that are composed of multiple novel non-coding exons. A significant difference in translational efficiency among these 5'-UTRs variants was observed by in vivo Luciferase reporter assay and Western blot. Furthermore, we found that the mRNA level of the AS form with high translational efficiency was specifically reduced in more than 80% of breast cancer cell lines and in more than 50% of human primary cancers from various tissues. In addition, we also identified mutations of FBXW7 in prostate cancers (5.6%), kidney cancers (16.7%), and bladder cancers (18.8%). Our results suggest that in addition to mutation, differential expression of FBXW7α AS forms with different translational properties may serve as a novel mechanism for inactivation of FBXW7 in human cancer.

As a wave of innovation, arising from the post-industrial society in the West, the Maker Movement is showing its unique characteristics in China after being transmitted from the West. The sudden rise of the “Chinese version of Maker Movement” (the Movement) is closely related to the national strategy of “widespread entrepreneurship and innovation”. Through festivalmaking activities and the localization of makerspaces, China has redefined the international maker culture. The impact of the Movement in China has extended extensively and profoundly to the fields of economy, education and culture. In the economic field, the Movement has promoted the popularization of the means of production, changed the relations of production, and created the new economic engine through innovations in economic systems. In the field of education, it has fostered innovative talents through the promotion of deeper learning and educational fairness. In terms of culture, it has enriched the spirit of culture, improved cultural patterns, and innovated cultural concepts. In the coming years, the Movement in China is likely to power the following trends: First, it will develop rapidly as a new economic model and business form; second, it will be more popular in forms of popularization and entertainment; third, the Movement will spread from cities to villages; fourth, even though the Movement may be temporarily halted due to potential failures to break through constraints such as technology, markets, policies, and funds, the Movement in China will generally present a spiraling upward trend.

Atherosclerosis (AS) is a chronic inflammatory disease, which leads to atherosclerotic rupture, lumen stenosis and thrombosis, and often endangers life. Circular RNAs (circRNAs) are a special class of non-coding RNA molecules, whose abnormal expression has been proved to be closely related to human diseases, including AS. Both the abnormal regulation of circRNAs and the sponging effect on miRNAs would lead to changes in gene expression in the form of epigenetic modification, ultimately leading to the formation of AS. CircRNAs can be used as peripheral blood markers of AS, and play an important regulatory role in the proliferation, migration, inflammation and apoptosis of vascular smooth muscle cells, endothelial cells and macrophage, which are key cells for the development of AS. The in-depth understanding of circRNAs in AS not only provides a new method for the diagnosis of AS, but also provides a new idea for the treatment of AS. [ABSTRACT FROM AUTHOR]