192 research outputs found

    Dendritic Polyglycerol-Conjugated Gold Nanostars for Metabolism Inhibition and Targeted Photothermal Therapy in Breast Cancer Stem Cells

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    Breast cancer stem cells (CSCs) are believed to be responsible for tumor initiation, invasion, metastasis, and recurrence, which lead to treatment failure. Thus, developing effective CSC-targeted therapeutic strategies is crucial for enhancing therapeutic efficacy. In this work, GNSs-dPG-3BP, TPP, and HA nanocomposite particles are developed by simultaneously conjugating hexokinase 2 (HK2) inhibitor 3-bromopyruvate (3BP), mitochondrial targeting molecule triphenyl phosphonium (TPP), and CSCs targeting agent hyaluronic acid (HA) onto gold nanostars-dendritic polyglycerol (GNSs-dPG) nanoplatforms for efficient eradication of CSCs. The nanocomposite particles possess good biocompatibility and exhibit superior mitochondrial-bound HK2 binding ability via 3BP to inhibit metabolism, and further induce cellular apoptosis by releasing the cytochrome c. Therefore, it enhanced the therapeutic efficacy of CSCs-specific targeted photothermal therapy (PTT), and achieved a synergistic effect for the eradication of breast CSCs. After administration of the synergistic treatment, the self-renewal of breast CSCs and the stemness gene expression are suppressed, CSC-driven mammosphere formation is diminished, the in vivo tumor growth is effectively inhibited, and CSCs are eradicated. Altogether, GNSs-dPG-3BP, TPP, and HA nanocomposite particles have been developed, which will provide a novel strategy for precise and highly efficient targeted eradication of CSCs

    Allergic Asthma-Induced Cognitive Impairment is Alleviated by Dexamethasone

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    Allergic asthma is a typical chronic inflammatory disease of respiratory tract. Clinical data shows that patients with allergic asthma have different degrees of cognitive dysfunction. The molecular mechanism underlying the pathogenesis of asthma-induced cognitive disorder is not yet well defined. Dexamethasone (DEX), one of the first-line drugs being widely used in the treatment of asthma, has not been reported to have an effect on cognitive dysfunction in mice model. To investigate the effect of asthma on cognitive impairment as well as the effect of DEX on asthma-caused morphological and behavioral changes, C57BL/6J mice received treatment with house dust mites (HDM) for 60 days to become allergic asthma model mice, and a group of HDM-treated asthma model mice were treated with DEX. HDM-treated asthma model mice exhibited increased airway hyperresponsiveness (AHR) and inflammatory infiltration in lung tissue. An elevated level of IL-4, IL-5, and TNF-α was detected in bronchoalveolar lavage fluid (BALF) by Luminex liquid suspension chip. Asthma model mice also presented memory deficits accompanied with morphological changes at the synaptic levels in the cortex and hippocampus. Meanwhile, vascular edema and increased expression of HIF-1α and HIF-2α were found in the brain of asthma model mice. Interestingly, DEX treatment could reverse the inflammatory changes in asthma model mice airway, rescue the cognitive impairment and improve the synaptic plasticity. Besides, DEX significantly decreased the expression of HIF-1α and HIF-2α in mice brain and lung. These processes may be used to decipher the complex interplay and pathological changes between asthma and cognition. This study provides laboratory evidence for the prevention and treatment of cognitive malfunction induced by asthma

    Development of 5G-based Remote Ultrasound Education: Current Status and Future Trends

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    The rapid advancement of 5G technology has opened new possibilities for remote ultrasound education, offering the potential to enhance training, real-time consultation, and quality control for primary ultrasound doctors. The 5G remote ultrasound education has the potential to revolutionize the way primary ultrasound doctors are trained and supported, ultimately leading to improved patient care and outcomes. By understanding the current status and development trends of this cutting-edge educational approach, the medical community can better prepare for and contribute to its ongoing evolution. Looking towards the future, the development trends in 5G remote ultrasound education are expected to revolve around continuous improvement and innovation in educational methods and technologies. This includes the exploration of artificial intelligence and machine learning applications, the expansion of telemedicine and telementoring programs, and the development of personalized learning plans tailored to individual learners\u27 needs. This article aims to offer an overview of the current status and applications of 5G remote ultrasound education, including the development of theoretical courses and network construction within our institutes, and to discuss future trends in this field

    Geographical distribution and determining factors of different invasive ranks of alien species across China

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    Determination of the geographical distribution and life-form spectra of alien species with different invasive abilities are essential to understand the process of invasion and to develop measures to manage alien species. Based on six classifications of Chinese alien species, environmental and social data, we determined species density, life-form spectrum of alien species, and the relationship between species density of alien species and climatic or social factors. The species density of alien species increased from the northwest to the southeast regions of China for all the six ranks. The boundary line between low and high species density of alien species was consistent with the dividing line of population density (the “Hu Line”). Mean annual precipitation was the most important factor for species density in malignant invaders, serious invaders, local invaders, and species requiring further observation (Ranks I, II, III, and V, respectively). Gross domestic product per square kilometer and annual minimum temperature were the most important factors in mild invaders and cultivated aliens (Ranks IV and VI, respectively). Annual and biennial herbs made up 52.9% to 71.2% of total species in Ranks I to IV; shrubs and trees 3.7% to 14.7%. The annual and biennial herbs were 35.5% and 32.6%, and the shrubs and trees were 25.3% and 31.6% in Ranks IV and VI. Results implied that precipitation was the most important factor on species density for the invasive alien species. However, social factors and temperature were the most important factors for the non-invasive alien species. The invasive alien species had a high proportion of annual and biennial herbs and non-invasive alien had a high proportion of shrubs and trees. It is important to understand the geographical distribution and life-form spectra of various invasive alien species for alien species controls

    The De Novo Cytosine Methyltransferase DRM2 Requires Intact UBA Domains and a Catalytically Mutated Paralog DRM3 during RNA–Directed DNA Methylation in Arabidopsis thaliana

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    Eukaryotic DNA cytosine methylation can be used to transcriptionally silence repetitive sequences, including transposons and retroviruses. This silencing is stable between cell generations as cytosine methylation is maintained epigenetically through DNA replication. The Arabidopsis thaliana Dnmt3 cytosine methyltransferase ortholog DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) is required for establishment of small interfering RNA (siRNA) directed DNA methylation. In mammals PIWI proteins and piRNA act in a convergently evolved RNA–directed DNA methylation system that is required to repress transposon expression in the germ line. De novo methylation may also be independent of RNA interference and small RNAs, as in Neurospora crassa. Here we identify a clade of catalytically mutated DRM2 paralogs in flowering plant genomes, which in A.thaliana we term DOMAINS REARRANGED METHYLTRANSFERASE3 (DRM3). Despite being catalytically mutated, DRM3 is required for normal maintenance of non-CG DNA methylation, establishment of RNA–directed DNA methylation triggered by repeat sequences and accumulation of repeat-associated small RNAs. Although the mammalian catalytically inactive Dnmt3L paralogs act in an analogous manner, phylogenetic analysis indicates that the DRM and Dnmt3 protein families diverged independently in plants and animals. We also show by site-directed mutagenesis that both the DRM2 N-terminal UBA domains and C-terminal methyltransferase domain are required for normal RNA–directed DNA methylation, supporting an essential targeting function for the UBA domains. These results suggest that plant and mammalian RNA–directed DNA methylation systems consist of a combination of ancestral and convergent features

    A Survey of Marine Coastal Litters around Zhoushan Island, China and Their Impacts

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    Rapid development of the economy increased marine litter around Zhoushan Island. Social-ecological scenario studies can help to develop strategies to adapt to such change. To investigate the present situation of marine litter pollution, a stratified random sampling (StRS) method was applied to survey the distribution of marine coastal litters around Zhoushan Island. A univariate analysis of variance was conducted to access the amount of litter in different landforms that include mudflats, artificial and rocky beaches. In addition, two questionnaires were designed for local fishermen and tourists to provide social scenarios. The results showed that the distribution of litter in different landforms was significantly different, while the distribution of litter in different sampling points had no significant difference. The StRS survey showed to be a valuable method for giving a relative overview of beach litter around Zhoushan Island with less effort in a future survey. The questionnaire feedbacks helped to understand the source of marine litter and showed the impact on the local environment and economy. Based on the social-ecological scenarios, governance recommendations were provided in this paper

    Progress in evaluation of cervical metastatic lymph nodes of differentiated thyroid cancer with ultrasonography

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    Accurate evaluation of cervical metastatic lymph nodes is of great significance to the risk staging, treatment and prognosis of patients with differentiated thyroid cancer(DTC). Ultrasonography is the main examination method to evaluate cervical lymph nodes. In recent years, with the emergence and extensive application of new technologies such as elastic imaging, contrast-enhanced ultrasonography, fine needle aspiration cytology and artificial intelligence, the diagnostic effectiveness of cervical metastatic lymph nodes of DTC has been further improved
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