UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer's development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN's pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN's potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN's close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN's role in breast cancer's prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.

Mental health of general practitioners in Chongqing, China during COVID-19: a cross-sectional study.

OBJECTIVES: In the context of the COVID-19 pandemic, general practitioners (GPs) continue to face unprecedented challenges that affect their mental health. However, few studies have assessed the mental health status of GPs. This study aimed to provide preliminary understanding of stress, job burn-out and well-being levels among GPs to train and manage them during public health emergencies. DESIGN: We conducted a cross-sectional online self-report survey. SETTING: The survey was conducted in Chongqing, China from July to August 2022. PARTICIPANTS: Data were collected from 2145 GPs, with an effective response rate of 91.0%. PRIMARY AND SECONDARY OUTCOME MEASURES: The main evaluation indicators were stress (Cohen's Perceived Stress Scale), job burn-out (Maslach Burnout Inventory-Human Services Survey Scale) and well-being (WHO-5 Well-Being Index). Multiple linear regression analysis was used to compare the effect of different demographic characteristics on the impact of stress, job burn-out and decreased well-being. RESULTS: Stress, job burn-out and decreased well-being were common among GPs. In this study, 59.7% experienced job burn-out, 76.1% experienced high levels of stress and 52.0% may have experienced depression. The main factors that influenced stress, burn-out and well-being were differences in age, working hours per week, title, part-time management work, work-life balance, sleep disorders, whether GPs received adequate recognition by patients and the work team and mental toughness (p<0.05). CONCLUSION: This survey is the first to investigate stress, job burn-out and well-being levels among local GPs in China during the COVID-19 pandemic. Curbing stress and job burn-out levels and ensuring well-being among GPs could be achieved by reducing paperwork, management work and working hours; promoting life and work balance; and increasing resilience among GPs. The findings provide a basis for policy-makers to formulate strategies for developing general practice.

MED16 Promotes Tumour Progression and Tamoxifen Sensitivity by Modulating Autophagy through the mTOR Signalling Pathway in ER-Positive Breast Cancer.

Recent studies have shown that the mediator complex (MED) plays a vital role in tumorigenesis and development, but the role of MED16 (mediator complex subunit 16) in breast cancer (BC) is not clear. Increasing evidence has shown that the mTOR pathway is important for tumour progression and therapy. In this study, we demonstrated that the mTOR signalling pathway is regulated by the expression level of MED16 in ER+ breast cancer. With the analysis of bioinformatics data and clinical specimens, we revealed an elevated expression of MED16 in luminal subtype tumours. We found that MED16 knockdown significantly inhibited cell proliferation and promoted G1 phase cell cycle arrest in ER+ BC cell lines. Downregulation of MED16 markedly reduced the sensitivity of ER+ BC cells to tamoxifen and increased the stemness and autophagy of ER+ BC cells. Bioinformatic analysis of similar genes to MED16 were mainly enriched in autophagy, endocrine therapy and mTOR signalling pathways, and the inhibition of mTOR-mediated autophagy restored sensitivity to tamoxifen by MED16 downregulation in ER+ BC cells. These results suggest an important role of MED16 in the regulation of tamoxifen sensitivity in ER+ BC cells, crosstalk between the mTOR signalling pathway-induced autophagy, and together, with the exploration of tamoxifen resistance, may indicate a new therapy option for endocrine therapy-resistant patients.

Cell Division Cycle-Associated Protein 3 (CDCA3) Is a Potential Biomarker for Clinical Prognosis and Immunotherapy in Pan-Cancer.

CDCA3 is an essential regulator in cell mitosis and can regulate many physiological and pathological processes in the human body by stimulating certain proteins such as cell cycle regulatory proteins, transcription factors, and signal transduction molecules. Although several studies have shown that dysregulation of CDCA3 is a common phenomenon in human cancers, no systematic pan-cancer analysis has been performed. In this study, we comprehensively investigated the role of CDCA3 in 33 human cancer types by utilizing multiple cancer-related databases and bioinformatics analysis tools, including TCGA, GTEx, GEPIA, TIMER, STRING, Metascape, and Cytoscape. Evidence from bioinformatics databases shows that CDCA3 is overexpressed in almost all human cancer types, and its overexpression is significantly associated with survival in patients with more than ten cancer types. CDCA3 expression positively correlates with immune cell infiltration levels in multiple human cancer types. Furthermore, the results of the GSEA analysis revealed that overexpression of CDCA3 may promote the malignant progression of cancer by activating various oncogenic signaling pathways in human cancers. In conclusion, our pan-cancer analysis provides a comprehensive overview of the oncogenic role of CDCA3 in multiple human cancer types, suggesting that CDCA3 may serve as a potential therapeutic target and prognostic biomarker in multiple human cancer types.

An automated approach for predicting glioma grade and survival of LGG patients using CNN and radiomics.

Objectives: To develop and validate an efficient and automatically computational approach for stratifying glioma grades and predicting survival of lower-grade glioma (LGG) patients using an integration of state-of-the-art convolutional neural network (CNN) and radiomics. Method: This retrospective study reviewed 470 preoperative MR images of glioma from BraTs public dataset (n=269) and Jinling hospital (n=201). A fully automated pipeline incorporating tumor segmentation and grading was developed, which can avoid variability and subjectivity of manual segmentations. First, an integrated approach by fusing CNN features and radiomics features was employed to stratify glioma grades. Then, a deep-radiomics signature based on the integrated approach for predicting survival of LGG patients was developed and subsequently validated in an independent cohort. Results: The performance of tumor segmentation achieved a Dice coefficient of 0.81. The intraclass correlation coefficients (ICCs) of the radiomics features between the segmentation network and physicians were all over 0.75. The performance of glioma grading based on integrated approach achieved the area under the curve (AUC) of 0.958, showing the effectiveness of the integrated approach. The multivariable Cox regression results demonstrated that the deep-radiomics signature remained an independent prognostic factor and the integrated nomogram showed significantly better performance than the clinical nomogram in predicting overall survival of LGG patients (C-index: 0.865 vs. 0.796, P=0.005). Conclusion: The proposed integrated approach can be noninvasively and efficiently applied in prediction of gliomas grade and survival. Moreover, our fully automated pipeline successfully achieved computerized segmentation instead of manual segmentation, which shows the potential to be a reproducible approach in clinical practice.

Latest Performance Improvement Strategies and Techniques Used in 5G Antenna Designing Technology, a Comprehensive Study.

In the recent era, fifth-generation technology (5G) has not been fully implemented in the realm of wireless communication. To have excellent accessible bandwidth feasibility, and in order to achieve the aims of 5G standards, such as higher data rates and ultrahigh-definition video streaming, the millimeter wave (mmWave) band must be employed. Services with minimal latency and many other features are feasible only in the mmWave spectrum. To avoid numerous communication complexities such as high connection losses, short wavelength, and restricted bandwidth, as well as path-loss challenges in the mmWave range, an antenna with wide bandwidth, high gain, narrow steerable beam, high isolation, low side-lobe levels, and multiband features is required to alleviate these difficulties and meet 5G communication standards. To overcome these challenges, specific strategies and techniques should be employed in the traditional antenna designing procedure to excellently improve the performance of the antenna in terms of bandwidth, gain, and efficiency and to reduce the mutual coupling effect between the closely colocated antenna elements in MIMOs and arrays. The researchers reported on a variety of bandwidth and gain improvement approaches. To gain broader coverage, traditional antenna design techniques must be modified. In this study, the latest state-of-the-art work is reviewed, such as the role of the metamaterials (MMTs), parasitic patches, hybrid feeding, EBG structure, impact of the slots with different geometrical shapes in the radiator to achieve the goal of wide bandwidth, boosted gain, reduced side-lobes level, as well as stable radiation properties. Mutual coupling reduction techniques are also briefly reported. The role of reconfigurability is focused on in this study, and at the end, the future challenges in the field of antenna design and possible remedies to such issues are reviewed.

Comprehensive Analysis of Necroptosis-Related Genes as Prognostic Factors and Immunological Biomarkers in Breast Cancer.

Breast cancer (BC) is a lethal malignancy with a poor prognosis. Necroptosis is critical in the progression of cancer. However, the expression of genes involved in necroptosis in BC and their association with prognosis remain unclear. We investigated the predictive potential of necroptosis-related genes in BC samples from the TCGA dataset. We used LASSO regression to build a risk model consisting of twelve necroptosis-related genes in BC. Using the necroptosis-related risk model, we were able to successfully classify BC patients into high- and low-risk groups with significant prognostic differences (p = 4.872 × 10 -7). Additionally, we developed a matched nomogram predicting 5, 7, and 10-year overall survival in BC patients based on this necroptosis-related risk model. Our next step was to perform multiple GSEA analyses to explore the biological pathways through which these necroptosis-related risk genes influence cancer progression. For these twelve risk model genes, we analyzed CNV, SNV, OS, methylation, immune cell infiltration, and drug sensitivity in pan-cancer. In addition, immunohistochemical data from the THPA database were used to validate the protein expression of these risk model genes in BC. Taken together, we believe that necroptosis-related genes are considered potential therapeutic targets in BC and should be further investigated.

Population genomics reveals variable patterns of immune gene evolution in monarch butterflies (Danaus plexippus).

Humoral and cellular immune responses provide animals with major defences against harmful pathogens. While it is often assumed that immune genes undergo rapid diversifying selection, this assumption has not been tested in many species. Moreover, it is likely that different classes of immune genes experience different levels of evolutionary constraint, resulting in varying selection patterns. We examined the evolutionary patterns for a set of 91 canonical immune genes of North American monarch butterflies (Danaus plexippus), using as an outgroup the closely related soldier butterfly (Danaus eresimus). As a comparison to these immune genes, we selected a set of control genes that were paired with each immune for approximate size and genomic location. As a whole, these immune genes had a significant but modest reduction in Tajima's D relative to paired-control genes, but otherwise did not show distinct patterns of population genetic variation or evolutionary rates. When further partitioning these immune genes into four functional classes (recognition, signalling, modulation, and effector), we found distinct differences among these groups. Relative to control genes, recognition genes exhibit increased nonsynonymous diversity and divergence, suggesting reduced constraints on evolution, and supporting the notion that coevolution with pathogens results in diversifying selection. In contrast, signalling genes showed an opposite pattern of reduced diversity and divergence, suggesting evolutionary constraints and conservation. Modulator and effector genes showed no statistical differences from controls. These results are consistent with patterns found in immune genes in fruit flies and Pieris butterflies, suggesting that consistent selective pressures on different classes of immune genes broadly govern the evolution of innate immunity among insects.

[Effects of Different Land Use Practices on Nitrogen Loss from Runoff During Rainfall Events].

To understand the effect of nitrogen from runoff during rainfall events for different land uses, sub-catchments A and B in the small Shipanqiu watershed in Zhong County, Chongqing-which were managed using different land use practices-were taken as research objects. Runoff flow and nitrogen levels at the outlet of the catchment were monitored. Sub-catchment A is an agroforestry-water complex and sub-catchment B is the site of traditional agriculture. EMC was used to evaluate the average concentration of runoff nitrogen during rainfall events, and the effect of this runoff nitrogen on the small watershed with different land use systems was analyzed. The results showed that the TN concentration in catchment B (1.37-15.17 mg·L-1) > catchment A (0.84-9.28 mg·L-1); the ratio of the first peak to the second peak in catchment A was 62%, which was far less than the 97% in catchment B; the average DN/TN values were 69% and 75% in catchments A and B, respectively; and the average NN/DN values were 67% and 80% in catchments A and B, respectively. The different land use practices have significant impacts on nitrogen loss. Compared with the catchment where traditional agricultural practices were followed, the agroforestry-water complex catchment effectively reduced the loss of nitrogen and decreased the first TN peak value and DN/TN and NN/DN values. This study provides a scientific basis for the prevention and control of non-point source pollution in small watersheds in the area of the Three Gorges Reservoir.

Transcriptomics of monarch butterflies (Danaus plexippus) reveals that toxic host plants alter expression of detoxification genes and down-regulate a small number of immune genes.

Herbivorous insects have evolved many mechanisms to overcome plant chemical defences, including detoxification and sequestration. Herbivores may also use toxic plants to reduce parasite infection. Plant toxins could directly interfere with parasites or could enhance endogenous immunity. Alternatively, plant toxins could favour down-regulation of endogenous immunity by providing an alternative (exogenous) defence against parasitism. However, studies on genomewide transcriptomic responses to plant defences and the interplay between plant toxicity and parasite infection remain rare. Monarch butterflies (Danaus plexippus) are specialist herbivores of milkweeds (Asclepias spp.), which contain toxic cardenolides. Monarchs have adapted to cardenolides through multiple resistance mechanisms and can sequester cardenolides to defend against bird predators. In addition, high-cardenolide milkweeds confer monarch resistance to a specialist protozoan parasite (Ophryocystis elektroscirrha). We used this system to study the interplay between the effects of plant toxicity and parasite infection on global gene expression. We compared transcriptional profiles between parasite-infected and uninfected monarch larvae reared on two milkweed species. Our results demonstrate that monarch differentially express several hundred genes when feeding on A. curassavica and A. incarnata, two species that differ substantially in cardenolide concentrations. These differentially expressed genes include genes within multiple families of canonical insect detoxification genes, suggesting that they play a role in monarch toxin resistance and sequestration. Interestingly, we found little transcriptional response to infection. However, parasite growth was reduced in monarchs reared on A. curassavica, and in these monarchs, several immune genes were down-regulated, consistent with the hypothesis that medicinal plants can reduce reliance on endogenous immunity.

How symbiosis and ecological context influence the variable expression of transgenerational wing induction upon fungal infection of aphids.

Aphids, like most animals, mount a diverse set of defenses against pathogens. For aphids, two of the best studied defenses are symbiont-conferred protection and transgenerational wing induction. Aphids can harbor bacterial symbionts that provide protection against pathogens, parasitoids and predators, as well as against other environmental stressors. In response to signals of danger, aphids also protect not themselves but their offspring by producing more winged than unwinged offspring as a way to ensure that their progeny may be able to escape deteriorating conditions. Such transgenerational wing induction has been studied most commonly as a response to overcrowding of host plants and presence of predators, but recent evidence suggests that pea aphids (Acyrthosiphon pisum) may also begin to produce a greater proportion of winged offspring when infected with fungal pathogens. Here, we explore this phenomenon further by asking how protective symbionts, pathogen dosage and environmental conditions influence this response. Overall, while we find some evidence that protective symbionts can modulate transgenerational wing induction in response to fungal pathogens, we observe that transgenerational wing induction in response to fungal infection is highly variable. That variability cannot be explained entirely by symbiont association, by pathogen load or by environmental stress, leaving the possibility that a complex interplay of genotypic and environmental factors may together influence this trait.

The Effects of Milkweed Induced Defense on Parasite Resistance in Monarch Butterflies, Danaus plexippus.

Many plants express induced defenses against herbivores through increasing the production of toxic secondary chemicals following damage. Phytochemical induction can directly or indirectly affect other organisms within the community. In tri-trophic systems, increased concentrations of plant toxins could be detrimental to plants if herbivores can sequester these toxins as protective chemicals for themselves. Thus, through trophic interactions, induction can lead to either positive or negative effects on plant fitness. We examined the effects of milkweed (Asclepias spp.) induced defenses on the resistance of monarch caterpillars (Danaus plexippus) to a protozoan parasite (Ophryocystis elektroscirrha). Milkweeds contain toxic secondary chemicals called cardenolides, higher concentrations of which are associated with reduced parasite growth. Previous work showed that declines in foliar cardenolides caused by aphid attack render monarch caterpillars more susceptible to infection. Here, we ask whether cardenolide induction by monarchs increases monarch resistance to disease. We subjected the high-cardenolide milkweed A. curassavica and the low-cardenolide A. syriaca to caterpillar grazing, and reared infected and uninfected caterpillars on these plants. As expected, monarchs suffered less parasite growth and disease when reared on A. curassavica than on A. syriaca. We also found that herbivory increased cardenolide concentrations in A. curassavica, but not A. syriaca. However, cardenolide induction in A. curassavica was insufficient to influence monarch resistance to the parasite. Our results suggest that interspecific variation in cardenolide concentration is a more important driver of parasite defense than plasticity via induced defenses in this tri-trophic system.

Restoration of an endangered plant, Hygrophila pogonocalyx, leads to an adaptive host shift of the chocolate pansy (Junonia iphita iphita).

Anthropogenic introduction of a plant species may cause novel encounters between the plant and local herbivores, and initiate evolutionary changes in host plant usage by herbivores. Until recently the endemic aquatic plant Hygrophila pogonocalyx was endangered and had a restricted distribution in Taiwan. Massive restoration efforts since 1997 have led to an expansion of the plant's distribution and a novel encounter between it and an Asian butterfly, the chocolate pansy, Junonia iphita (Nymphalidae). This butterfly appears to have colonized H. pogonocalyx, switching from its original host, Strobilanthes penstemonoides var. formosana. In the present study, we aimed to investigate whether the utilization of H. pogonocalyx as a host plant has initiated a differentiation between butterflies using the novel and the original hosts. To this purpose we collected butterflies from patches of the two host plants which grow sympatrically. We tested oviposition preference for the two hosts and larval performance on them. Female adults exhibited distinct oviposition preference toward the host plant their mothers preferred. Offspring showed greater survivorship and pupal weight when fed on the host plant their mothers preferred. Male adults displayed territorial behaviors on the host plant that their mothers had preferred. Finally, the survival rate of offspring produced from cross-mating between individuals with different host plant preference was lower than that of non-hybrids. Taken together, we suggest that genetic differentiation has occurred between individuals preferring H. pogonocalyx versus S. penstemonoides as host plants via host shifting. This process was likely induced by the mass restoration of the formerly rare and endangered plant species.