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In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.
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Triple-negative breast cancer (TNBC) is a malignant tumor with high degree of malignancy and lack of effective target treatment. The research aims to explore the role and mechanism of X collagen alpha-1 chain protein (COL10A1 gene) in TNBC. UALCAN and Kaplan-Meier were used to detect the expression of COL10A1 and its role in the prognosis of breast cancer patients. The cells with stably expressing high levels of COL10A1 were obtained by recombinant lentivirus infection. The expression of COL10A1 in cells was temporarily downregulated by siRNA interference fragments. Real-time quantitative polymerase chain reaction and western blot analysis were utilized to detect the changes of COL10A1 mRNA and protein expression. The biological functions of the cells were evaluated by colony formation, cell counting kit-8, cell invasion and wound healing experiments. In addition, the effect of COL10A1 on angiogenesis was investigated by tube formation assay. Xenograft tumor model was used to confirm the effect of COL10A1 on tumorigenicity in vivo and multiplex fluorescent immunohistochemistry to detect multiple proteins simultaneously. The possible molecular mechanism of the function of COL10A1 was speculated through the detection of proteins in functionally related pathways. COL10A1 is highly expressed and is significantly associated with worse overall survival (OS) and recurrence-free survival (RFS) in TNBC. Overexpression of COL10A1 increased the clone formation rate and cell migration capacity of TNBC cells. In the COL10A1 overexpression group, the clone formation rates of MD-MB-231 and BT-549 cells (21.5 ± 0.62, 27.83 ± 3.72)% were significantly higher than those in the control group(15.23 ± 2.79, 19.4 ± 1.47)%, and the relative migration ratio (47.40 ± 3.09, 41.26 ± 4.33)% were higher than those in the control group (34.48 ± 2.03, 21.80 ± 1.03)%. When the expression of COL10A1 was downregulated, the ability of clone formation and wound-healing migration capacity in TNBC cells was weakened. Upregulated COL10A1 in TNBC cells generated more junctions and longer total segments between vascular endothelial cells, and promoted angiogenesis of the cells, and thus enhanced the tumorigenesis. In TNBC, it was found that COL10A1 might affect epithelial-mesenchymal transition (EMT) of the cells through Wnt/ß-catenin signaling pathway by the detection of the related pathway proteins. COL10A1 is highly expressed in TNBC, and its high expression leads to poor OS and RFS. COL10A1 may enhance TNBC cell proliferation, migration and tumor-related angiogenesis, and promote tumorigenesis in vivo via Wnt/ß-catenin signaling.
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Movimento Celular , Proliferação de Células , Colágeno Tipo X , Regulação Neoplásica da Expressão Gênica , Neoplasias de Mama Triplo Negativas , Via de Sinalização Wnt , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Humanos , Feminino , Via de Sinalização Wnt/genética , Animais , Camundongos , Movimento Celular/genética , Linhagem Celular Tumoral , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Prognóstico , Regulação para Cima , Camundongos Nus , beta Catenina/metabolismo , beta Catenina/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Pessoa de Meia-Idade , Camundongos Endogâmicos BALB CRESUMO
INTRODUCTION: Anxiety and depression often co-occur in adolescents, with factors from family and school playing a significant role in the comorbidity. However, network analysis has not examined and clarified the detailed bridge and central symptoms of this comorbidity caused by online learning and perceived parental relationships across different COVID-19 times. METHODS: Over four months, 2,356 secondary school students completed the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7. Participants were divided into harmonious and disharmonious groups based on their answers to a question about parental conflicts. RESULTS: The results indicated that adolescents perceiving more parental conflicts showed a denser comorbidity network after four months of online learning. Significant bridge symptoms decreased from three to two across two waves in the harmonious group, while in the disharmonious group, they increased from two to three. The number of central symptoms increased from one in wave 1 to three in wave 2 for the harmonious group, while four in wave 1 decreased to two in wave 2 for the disharmonious group. Furthermore, the CLPN analysis revealed that the strongest positive cross-lagged edge intensity between symptoms was anhedonia-energy in the harmonious group, with anhedonia being the most trigger symptom. In contrast, for the disharmonious group, guilt-suicide and trouble relaxing-excessive worry were the strongest cross-lagged edge, and trouble relaxing was the most trigger symptom. CONCLUSION: These findings may have implications for interventions designed to promote adolescent mental health in the context of online learning and parental conflicts.
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Ansiedade , COVID-19 , Depressão , Educação a Distância , Relações Pais-Filho , Estudantes , Humanos , Adolescente , Masculino , Feminino , Depressão/epidemiologia , Depressão/psicologia , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/psicologia , COVID-19/epidemiologia , Instituições AcadêmicasRESUMO
Onion (Allium cepa), a member of the genus Allium, is widely cultivated throughout the world including China (Zhang et al. 2022). In July 2022, stunted onion (A. cepa 'Weiwang') plants showing typical symptoms of yellow stripe and leaves distortion (Fig. S1) were observed in a vegetable garden in Hohhot, Inner Mongolia, China. The garden is approximately 0.24 ha with around 20,000 onion plants, out of which 140 plants were symptomatic. Diagnosis of the symptomatic plants using negative stain electron microscopy revealed the association of long flexuous virus particles measuring about 11 to 12 nm × 820 to 1000 nm (Fig. S2), which was suggestive of the presence of potyvirus (Chen et al. 2002). Subsequently, the pathogen was identified as the leek yellow stripe virus through RT-PCR combined with Sanger sequencing as described below. The total RNA of each sample was extracted using the MiniBEST plant RNA extraction kit (TaKaRa, Dalian, China), serving as template for synthesis of cDNA using the ABScriptIII RT master mix (ABclonal Biotechnology, Wuhan, China). We then amplified a fragment at the 3' terminus of LYSV using a M5 Hiper superluminal mix (Mei5 Biotechnology, Beijing, China) with the primer pair LYSV-F / LYSV-R (Santosa and Ertunc 2020) which flank the partial NIb gene, the complete coat protein gene and partial 3' untranslated region of LYSV. A unique PCR product of about 1 kb was seen for 10 out of the 140 samples. Five out of the 10 PCR products were randomly selected and cloned using a Zero Background pTOPO-TA cloning kit (Aidlab Technologies, Beijing, China) and E. coli JM109 competent cells were then transformed. Positive colonies were screened by PCR detection of the insert fragments using the primers LYSV-F/-R, and the inserts were sequenced at BGI Genomics (Beijing) using the M13(-21) Forward and M13 Reverse primers. All the obtained sequences were 1032 nt in length, and shared nucleotide sequence identities of 99.2% to 100% (two out of the five sequences were identical to each other). The query sequences were submitted to BLASTn to retrieve homologous sequences from NCBI GenBank databases, and the results showed that the four sequences were homologous to LYSV, suggesting the occurrence of LYSV on onions in Inner Mongolia, China. The sequences were then deposited in GenBank under accession numbers of OQ969953-56, named LYSV isolate Hohhot-1, -2, -3, and -4. In comparison with other published LYSV isolates, the LYSV Hohhot-1, -2, -3, and -4 had the highest nucleotide sequence identity of 87.23%, 86.97%, 87.33%, and 87.23% with LYSV G66 (GenBank accession no. MN059493), respectively, which infects garlic in China. Phylogeny analysis was performed based on 41 complete sequences of the CP gene of LYSV, including the four in this work and another 37 from GenBank of which six isolates were discovered in onions in Turkey (MN070124, MN070126, MN070130, MN070131, MN864794 and MN864795) and the others 31 isolates were from garlics or leeks in 15 different countries (Argentina, Australia, Brazil, China, Ethiopia, Germany, India, Iran, Japan, Mexico, Netherlands, New Zealand, Serbia, South Korea, and Spain), while the CP gene of onion yellow dwarf virus (AJ510223) was employed as an outgroup reference. The tree was reconstructed using the neighbor-joining method of MEGA11 with a bootstrap value of 1,000 replicates. On the tree (Fig. S3), the LYSV Hohhot-1, -2, -3, and -4 were closely related to each other and were distinct from other LYSV isolates including the six isolates in onions in Turkey, suggesting a specific genetic variation of the LYSV isolates in Hohhot. According to Santosa et al. (2023), LYSV Hohhot-1, -2, -3, and -4 were within the S-type lineage. This was the first record of LYSV infecting onions in China, expanding the natural host range of LYSV in China, which offered important information for the management of onion diseases.
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BACKGROUND: This study aims to determine the satisfaction and future training needs of general practice residents participating in a novel model of ambulatory teaching aligned with the specifications for standardized residency training in outpatient management issued by the Chinese Medical Doctor Association (CMDA). METHODS: A cross-sectional survey of the satisfaction and training needs was conducted among general practice residents at West China Hospital, Sichuan University. Patient characteristics and preceptors' feedback on the residents' performance were also analyzed. RESULTS: The study involved 109 residents (30.28% men) and 161 patients (34.78% men; age: 52.63 ± 15.87 years). Residents reported an overall satisfaction score of 4.28 ± 0.62 with the ambulatory teaching program. Notably, residents scored lower in the Subjective-Objective-Assessment-Plan (SOAP) evaluation when encountering patients with the greater the number of medical problems (P < 0.001). Residents encountering patients with a shorter duration of illness (< 3 months) achieved higher scores than those with longer illness durations (≥ 3 months, P = 0.044). Residency general practitioners (GPs) were most challenged by applying appropriate and effective patient referrals (43/109; 39.45%). GPs expressed a strong desire to learn how to make decisions when facing challenging patient situations (4.51 ± 0.63). CONCLUSION: This study suggests selecting patients with multiple comorbidities for ambulatory teaching and enhancing training on practical problem-solving abilities for GPs. The findings provide insights for the development of future ambulatory teaching programs.
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Assistência Ambulatorial , Medicina Geral , Internato e Residência , Humanos , Estudos Transversais , China , Masculino , Medicina Geral/educação , Feminino , Pessoa de Meia-Idade , Adulto , Competência Clínica , Educação de Pós-Graduação em MedicinaRESUMO
BACKGROUND: Nursing students are faced with multiple challenges and have a higher probability of suffering from anxiety. The current study aims to explore the relation between empathy and anxiety, examining the mediation and moderation effects of insomnia and self-compassion, respectively. METHODS: This study employed a convenient sampling method, recruiting 1,161 nursing students (female = 923, male = 238, Meanage = 18.37, SDage = 2.38) from three universities in China. These students completed the questionnaires online, including General Anxiety Disorder -7 (GAD-7), Jefferson Scale of Physician Empathy-Nursing student (JSPE-NS), Youth Self-rating Insomnia Scale -8 (YSIS-8), and Self-Compassion Scale (SCS). The study employed latent variable structural equation models to analyze the relation and mechanisms between empathy and anxiety. Then, the mediated role of insomnia and the moderated role of self-compassion were examined. RESULTS: The prevalence rates of anxiety and insomnia in the current sample are 18.24% and 26.76%, respectively. The results showed that empathy could negatively predict anxiety, with a significant mediating effect of insomnia between them (B = -0.081, p < 0.05, 95% CI [-0.197, -0.063]). Additionally, it was proven that self-compassion moderated the positive relation between insomnia and anxiety. With a higher level of self-compassion, the indirect effect of empathy on anxiety through insomnia was weaker (B = -0.053, p < 0.01, 95% CI [-0.095, -0.019]). When individuals showed a lower level of self-compassion, the indirect effect of empathy on anxiety through insomnia was stronger (B = -0.144, p < 0.01, 95% CI [-0.255, -0.059]). CONCLUSION: The analysis of this research proved that empathy was negatively related to anxiety, and insomnia served as a mediator between empathy and anxiety. Besides, the protective role of self-compassion on individuals' mental health was identified. The findings of the study suggest that the education of nursing students should highlight the significance of fostering empathy and self-compassion. The intervention on insomnia may be helpful in reducing the levels of anxiety since insomnia is a risky factor for anxiety.
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PURPOSE: Automatic segmentation of brain tumors by deep learning algorithm is one of the research hotspots in the field of medical image segmentation. An improved FPN network for brain tumor segmentation is proposed to improve the segmentation effect of brain tumor. MATERIALS AND METHODS: Aiming at the problem that the traditional full convolutional neural network (FCN) has weak processing ability, which leads to the loss of details in tumor segmentation, this paper proposes a brain tumor image segmentation method based on the improved feature pyramid networks (FPN) convolutional neural network. In order to improve the segmentation effect of brain tumors, we improved the model, introduced the FPN structure into the U-Net structure, captured the context multi-scale information by using the different scale information in the U-Net model and the multi receptive field high-level features in the FPN convolutional neural network, and improved the adaptability of the model to different scale features. RESULTS: Performance evaluation indicators show that the proposed improved FPN model has 99.1% accuracy, 92% DICE rating and 86% Jaccard index. The performance of the proposed method outperforms other segmentation models in each metric. In addition, the schematic diagram of the segmentation results shows that the segmentation results of our algorithm are closer to the ground truth, showing more brain tumour details, while the segmentation results of other algorithms are smoother. CONCLUSIONS: The experimental results show that this method can effectively segment brain tumor regions and has certain generalization, and the segmentation effect is better than other networks. It has positive significance for clinical diagnosis of brain tumors.
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Neoplasias Encefálicas , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Algoritmos , Neoplasias Encefálicas/diagnóstico por imagem , EncéfaloRESUMO
INTRODUCTION: Several studies have demonstrated a directional link between rage rumination and aggression. However, recent research suggests that this relationship is bidirectional. The current study examined the complex relationships between anger rumination and aggression using a moderated network approach in a longitudinal design while considering personal relative deprivation. METHOD: A total of 665 participants (59.25% female, agemean±SD = 19.01 ± 1.25) were enrolled at two-time points. Assessments included self-report measures of the Anger Rumination Scale, Buss-Perry Aggression Questionnaire, and Relative Deprivation Scale. A Moderated Network Model (MMN) was used to test the complex links among anger rumination, aggression, and personal relative deprivation. RESULTS: The analysis revealed that the link between anger rumination and aggression was complex and bidirectional. Notably, as the level of personal relative deprivation increased, verbal aggression had a positive conditional effect on anger afterthoughts in Wave 2, and thoughts of revenge had a positive conditional effect on verbal aggression in Wave 2. Moreover, as the first discovery, anger afterthoughts and anger had a negative conditional effect on each other across levels of personal relative deprivation in Wave 2. In addition, network comparison indicates that the MNMs structure was significantly different across timepoints, implying that anger rumination and aggression were inextricably linked in college students during isolation and that this complicated relationship was weakened after isolation. CONCLUSIONS: This study deepens our understanding of the bidirectional relationships between anger rumination and aggression and recognizes the moderating role of personal relative deprivation.
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COVID-19 , Pandemias , Humanos , Feminino , Masculino , Controle de Doenças Transmissíveis , Agressão , IraRESUMO
INTRODUCTION: To determine the effectiveness of the Star Family Doctors Training Program, a comprehensive Continuing professional development (CPD) program for general practitioners (GPs) in a compact medical consortium. PATIENTS AND METHODS: Observational cohort study with a quantitative analyses in primary health care institutions in Sichuan Province. The interventions were as following: (1) The Star Family Doctors Training Program is a full-time, local government allocation program certified by the Health Department of Sichuan Province, emphasizing small group learning and practice, and using standard patients and medical patient simulators; 30 participants were selected by their institutions. (2) The control group underwent a self-financed after-work CPD program using conventional lectures; 50 participants were self-selected. Short-term effectiveness assessed using immediate post-training tests and self-evaluations; long-term (1 year) effectiveness evaluated using self-reported surveys. RESULTS: The study involved 80 GPs (28.75% men; mean age: 38.2 ± 9.2 years). The average post-training total score was higher in the STAR group than in the control group (72.83 ± 5.73 vs. 68.18 ± 7.64; p = 0.005). Compared to the controls, STAR participants reported seeing more patients (all p < 0.05), and had more patients who signed family-doctor contracts (p = 0.001) as well as increased patient satisfaction (p = 0.03), respectively. STAR-group trainees appraised the program higher and were more willing to recommend it to colleagues (90% vs. 64%, p = 0.011). CONCLUSION: The Star Family Doctors Training Program achieved good responses and provides a reference for future CPD programs.
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Clínicos Gerais , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Feminino , Clínicos Gerais/educação , Educação Médica Continuada , Médicos de Família , Aprendizagem , EstudantesRESUMO
Older adults are more likely to live alone and engage in solitary activities than young adults, leading to decrement in their well-being. However, researchers have discovered beneficial implications of solitude, and some of them even have established that the negative and positive effects of solitude coexist. The study's purposes are to investigate the relationship between solitude and well-being among older adults and to further examine the inter-individual differences in this relationship. In the database of Google Scholar, the systematic review methods are used and 17 articles meet the inclusion criteria. The study concludes that older adults experience solitude both negatively and positively; the complex relationship between solitude and well-being can be better understood and explained by inter-individual differences based on intrapersonal, interpersonal, and cultural factors. This systematic review adopts a perspective that spans individual and social/cultural levels and helps grasp the link between solitude and well-being in older adults. Based on this review, the researcher can develop appropriate interventions to help older people maximize the benefits of solitude while minimizing the drawbacks to further achieve a higher quality of life.
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Individualidade , Qualidade de Vida , Adulto Jovem , Humanos , IdosoRESUMO
Based on previous findings in a U.S. sample, the present study validated the relationship between childhood trauma and dissociation, as well as the mediating role of disorganized attachment and the moderating role of mentalizing (i.e. self-concept clarity and reflective functioning) in a group of 569 Chinese adults (i.e. a community sample). Results demonstrated a mediating role for disorganized attachment relationships in linking childhood maltreatment and dissociative symptoms. Moreover, self-concept clarity moderated this mediating relationship. An interesting finding that differs from the U.S. sample is that reflective functioning did not play a moderating role between insecure attachment and dissociation in Chinese adults. Chinese culture places greater emphasis on collectivism, altruism, and other-oriented, and thus the protective effect of the reflective function may not be as effective as in an individualistic culture. This study provides evidence for a better understanding of the relationship between childhood trauma, attachment, dissociation, and the moderating role of mentalizing in an Eastern culture, and it opens the door to further research examining whether more Western (such as the U.S.) and Eastern (particularly Chinese) relationships are similar in both social and clinical psychology.
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Experiências Adversas da Infância , Maus-Tratos Infantis , Transtornos Dissociativos , Mentalização , Adulto , Criança , Humanos , Experiências Adversas da Infância/psicologia , Maus-Tratos Infantis/psicologia , Transtornos Dissociativos/psicologia , População do Leste Asiático/psicologia , Apego ao Objeto , Autoimagem , Comparação TransculturalRESUMO
Land space is an important link between human social-economic activities and the evolution of the natural environment. Its changes can directly reflect the transformation process of mankind's activities on the surface system, and it is a core element of the study of global environmental change. In the research, based on the "three districts and three lines" classification method of national land spatial, the urban space, agricultural space, and ecological space of Tianjin were divided. Natural trend, economic development, cultivated land protection, and ecological priority were set as four simulation scenarios, which were predicted by the Markov-Plus model for the spatial pattern of national land in 2030. Data statistics and the MSPA model were used to quantitatively analyze Tianjin's future land space from two aspects of structure and pattern. The main conclusions were as follows: (1) The overall accuracy of the simulation results of the Markov-Plus model was 0.971, and its kappa value was 0.948. The simulation accuracy was relatively high, which provides a reference for future spatial simulation prediction in this area. (2) In different simulation scenarios, the changing trend of Tianjin's land space scale from 2020 to 2030 was that urban space continues to increase, while agricultural space and ecological space decrease successively. (3) Each simulation scenario achieves good results for spatial prediction under the condition of setting limiting factors. In the natural trend scenario, the spatial variability of the types is more complex, the boundaries are more fragmented, and the spatial reference value of the territory is lower.
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Conservação dos Recursos Naturais , Ecossistema , Humanos , Conservação dos Recursos Naturais/métodos , Monitoramento Ambiental , Simulação por Computador , Desenvolvimento Econômico , China , CidadesRESUMO
Effortless print-sound integration is essential to reading development, and the superior temporal cortex (STC) is the most critical brain region. However, to date, the conclusion is almost restricted to alphabetic orthographies. To examine the neural basis in non-alphabetic languages and its relationship with reading abilities, we conducted a functional magnetic resonance imaging study in typically developing Chinese children. Two neuroimaging-based indicators of audiovisual processing-additive enhancement (higher activation in the congruent than the average activation of unimodal conditions) and neural integration (different activations between the congruent versus incongruent conditions)-were used to investigate character-sounds (opaque) and pinyin-sounds (transparent) processing. We found additive enhancement in bilateral STCs processing both character and pinyin stimulations. Moreover, the neural integrations in the left STC for the two scripts were strongly correlated. In terms of differentiation, first, areas beyond the STCs also showed additive enhancement in processing pinyin-sounds. Second, while the bilateral STCs, left inferior/middle frontal and parietal regions manifested a striking neural integration (incongruent > congruent) for character-sounds, no significant clusters were revealed for pinyin-sounds. Finally, the neural integration in the left middle frontal gyrus for characters was specifically associated with silent reading comprehension proficiency, indicating automatic semantic processing during implicit character-sound integration. In contrast, the neural integration in the left STC for pinyin was specifically associated with oral reading fluency that relies on grapho-phonological mapping. To summarize, this study revealed both script-universal and script-specific neurofunctional substrates of print-sound integration as well as their processing- and region-dependent associations with reading abilities in typical Chinese children.
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Idioma , Fonética , Encéfalo/fisiologia , Mapeamento Encefálico , Criança , China , Humanos , Imageamento por Ressonância Magnética/métodos , LeituraRESUMO
BACKGROUND: Pyroptosis is a newly discovered form of cell programmed necrosis, but its role and mechanism in cancer cells remain unclear. The aim of this study is to systematically analyze the transcriptional sequencing data of breast cancer (BC) to find a pyroptosis-related prognostic marker to predict the survival of BC patients. METHODS: The original RNA sequencing (RNA-seq) expression data and corresponding clinical data of BC were downloaded from The Cancer Genome Atlas (TGCA) database, followed by differential analysis. The pyroptosis-related differentially expressed genes (DE-PRGs) were employed to perform a computational difference algorithm and Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) was utilized to avoid overfitting. A total of 4 pyroptosis-related genes (PRGs) with potential prognostic value were identified, and a risk scoring formula was constructed based on these genes. According to the risk scores, the patients could be classified into high- and low-risk score groups. The potential molecular mechanisms and properties of PRGs were explored by computational biology and verified in Gene Expression Omnibus (GEO) datasets. In addition, the quantitative real time PCR (RT-qPCR) and Human Protein Atlas (HPA) were performed to validate the expression of the key genes. RESULTS: A PRGs signature, which was an independent prognostic factor, was constructed, and could divide patients into high- and low-risk groups. The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group both in TCGA and in GEO, indicating that the signature is valuable for survival prediction and personalized immunotherapy of BC patients. CONCLUSIONS: The pyroptosis-related biomarkers were identified for BC prognosis. The findings of this study provide new insights into the development of the efficacy of personalized immunotherapy and accurate cancer treatment options.
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Neoplasias da Mama , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Piroptose/genética , Microambiente Tumoral/genéticaRESUMO
T-cell-based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD-1) inhibitor on triple-negative breast cancer (TNBC). Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs-ACT) were applied in combination with a PD-1 inhibitor to the TNBC mouse model. The pre- and post-therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. We found that TILs exhibited higher IFN-γ and TNF-α secretion than conventional T cells. The TILs-ACT combined with PD-1 inhibitor promoted active T-cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD-1 on TILs. In conclusion, PD-1 blockade regulated T-cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.
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Linfócitos do Interstício Tumoral , Neoplasias de Mama Triplo Negativas , Animais , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Camundongos , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/uso terapêutico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Chinese cabbage [Brassica rapa L. subsp. pekinensis (Lour.) Hanelt] has been grown commercially for many decades in Huade County, Inner Mongolia. In 2018 and 2019, an unusual stem and leaf wilt disease with an average disease incidence of approximately 3% was observed. Diseased plants with spindle-shaped stem lesions were collected and small pieces (0.3 × 0.3 cm) of the diseased tissues were cut from the margins of stem lesions, surface sterilized with 75% alcohol for 3 to 5 s, 0.1% NaClO for 2 to 3 min, and washed three times with sterilized water. The treated tissues were placed on 1.5% (w/v) water agar plates and incubated at 25°C for 3 days. The mycelia were cut and transferred onto potato dextrose agar (PDA) for culture purification. Three isolates with similar morphology were obtained and named as BC-2, BC3-2 and BG2. To confirm their pathogenicity, Chinese cabbage (cv. Chunqiuhuang) seed was planted into plugs. After 30 days, the fibrous roots were wounded with a fruit knife and root-dipped in the conidium suspension (1 × 106 conidia/ml) for 20 min. Inoculated seedlings were transplanted in pots (30 × 25 cm) with sterilized nursery soil, with one seeding per pot. The roots of control plants were also wounded and dipped in sterilized water. Five seedlings were inoculated with each isolate and the experiment was repeated three times. Treated seedlings were maintained in a greenhouse at 25 to 28°C under a 12-h photoperiod. Chlorosis and wilting were observed approximately 4 weeks after inoculation, and the outer layer of leaves of the inoculated seedlings developed discoloration and wilted symptoms after 50 days. The symptoms induced by all three isolates were the same as the symptoms observed in the field, whereas no symptoms developed on the control plants. To confirm the Koch's postulates, the fungus was successfully re-isolated from the infected leaves and had similar growth and morphology as the original isolates. The three isolates were cultured for both morphology and molecular identification. The 14-day-old colonies on PDA were buff or salmon pink with few aerial hyphae, and slimy surfaces. Aerial hyphae were sparse with simple or branched conidiophores. Conidia were ellipsoidal, hyaline, surface smooth, septate or aseptate, and (4.0 to 9.7 µm × 2.0 to 3.9 µm). Such characteristics are typical of Plectosphaerella spp. (Palm et al. 1995). For molecular identification, the internal transcribed spacer (ITS) region of rDNA was amplified using the primer pair ITS1/ITS4 (White et al. 1990), and the products were directly sequenced. BLAST analysis showed that the sequences of Isolates BC-2 (511 bp out of 515 bp), BC3-2 (512 bp out of 516 bp) and BG2 (503 bp out of 505 bp) showed 99% identity to an isolate of P. cucumerina (acc. no. KT826571.1) from Bottle gourd [Lagenaria siceraria (Molina) Standl.] (Yan et al. 2016). The sequences of Isolates BC-2, BC3-2 and BG2 were deposited in GenBank (acc. nos. MW320463, MW320462 and MW320464). Although P. cucumerina was reported causing root rot of cabbage (B. oleracea) in Gansu, China (Li et al. 2017), to our knowledge, this is the first report of P. cucumerina causing Chinese cabbage wilt in Inner Mongolia, China. The presence of the disease could cause significant economic losses in Chinese cabbage production. For this reason, strategies for the management and control of this disease should be implemented.
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The evolution of land-use spatial conflict is a comprehensive reflection of regional development and a common phenomenon in urbanization. The research on land-use spatial conflicts can provide theoretical basis and practical support for spatial control. The present study employs Tianjin as the research object, and ecological risk assessment model was improved based on landscape pattern analysis by selecting appropriate indicators that may bring conflict risk problems. The spatial conflict measurement model of land-use based on the coordination of human-land-landscape elements was preliminarily constructed. The spatial and temporal evolution of land-use spatial conflict degree, and spatial autocorrelation from 2000 to 2020 was preliminarily analyzed. Results showed that (1) the conflict measurement level of the model was verified by Google Earth remote sensing image platform and field survey, and the results were relatively consistent with the actual situation, which proves that this method was feasible. (2) The areas with low intensity of land-use conflict were mainly distributed in remote mountainous areas with less human activities, while the areas with high comprehensive conflict index were mainly distributed in the central urban area with more active human activities and urbanization, the urban fringe area, the water-land ecotone, and some landscape transition areas. (3) There was a close relationship between land use spatial conflict and land-use change. Areas with severe and frequent land-use changes were often areas with noticeable land-use conflict changes. In the period of high land-use change intensity and frequent land-use mode conversion, it was also a period of a large area where regional land-use conflict was enhanced. (4) The overall level of conflict showed an average trend year by year, and the high conflict fluctuates greatly with first rising and then falling, but the change range was small. Moderate conflict mainly showed a decreasing trend, with an extensive change range. The early stage of the mild conflict was relatively stable, and the later stage changed significantly.
Assuntos
Ecossistema , Monitoramento Ambiental , China , Atividades Humanas , Humanos , UrbanizaçãoRESUMO
Symptoms of depression and anxiety usually co-occur and are inextricably linked to sleep disturbance. However, little is known about the symptom-to-symptom relationships among these three mental disorders. Hence, to improve our understanding of concurrent depression, anxiety, and sleep disturbance, we used the network analysis approach to construct an interplay relationship among the above three mental disorders and identify which specific symptoms bridge these aggregations. We collected data from a large sample (N = 6710, male = 3074, female = 3636; mean age = 19.28) at a university. We estimated the symptom network structure of depression, anxiety, and sleep disturbance as assessed by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Youth Self-Rating Insomnia Scale during the COVID-19 lockdown. We further investigated four goals: first, identifying the individual core symptoms in the network by the index of "expected influence"; second, determining the bridge symptoms that play roles in linking different mental disorders by the index of bridge expected influence (1-step); third, examining the robustness of all results; and fourth, providing an overall structure that may or may not differ by sex. The network structure was stable, accurate, and predictable. Items referring to sleep dissatisfaction, poor sleep quality, and uncontrollable worry were potentially core symptoms in the interplay among depression, anxiety, and sleep disturbance. Sleep, guilt, restlessness, irritability, and feeling afraid can function as bridges among depression, anxiety, and sleep disturbance, which is clinically relevant and theoretically important. The results suggested that the network structures significantly differed between the female and male networks. Robustness tests also revealed that the results were reliable.
RESUMO
Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR-182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR-182 expression were determined in the clinical BC tissues. CircRNA_000554 acted as a sponge of miR-182, and miR-182 directly targeted ZFP36. After that, in order to evaluate the effects of circRNA_000554, miR-182, and ZFP36 on cellular process, we evaluated in vitro epithelial-mesenchymal transition (EMT) and in vivo tumor growth after delivering a series of overexpression plasmids, mimic, inhibitor, or shRNAs into BC cells. Increasing circRNA_000554 suppressed EMT, cell invasion and migration during BC by depleting miR-182 and increasing ZFP36. The inhibitory effect of circRNA_000554 on tumor growth was validated in vivo. Taken together, the present study confirms that circRNA_000554 functioned as an inhibitor of EMT in BC and suggests a molecular mechanism that circRNA_000554 bound to miR-182 to upregulate ZFP36 in this process.
Assuntos
Neoplasias da Mama/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Circular/genética , Tristetraprolina/genética , Adulto , Idoso , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Tristetraprolina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Concern for the psychological health of people affected by the COVID-19 pandemic is necessary. Previous studies suggested that self-compassion contributes to life-satisfaction. However, little is known about the mechanism underlying this relation. This study investigated the relationship between self-compassion and life-satisfaction among Chinese self-quarantined residents during the COVID-19 pandemic. Furthermore, we examined the mediating effect of positive coping and the moderating role of gender in this relation. Participants consist of 337 self-quarantined residents (129 men, 208 women) from a community in China, who completed measures of demographic information, Self-Compassion Scale, Satisfaction with Life Scale, and Simplified Coping Style Questionnaire. The results revealed that self-compassion was positively linked with life-satisfaction. Moreover, positive coping partially mediated the relationship between self-compassion and life-satisfaction for males and not females. In the female group, self-compassion was positively linked with positive coping and life-satisfaction; however, positive coping and life-satisfaction were not significantly linked. These findings indicated that intervention focus on self-compassion could increase life-satisfaction in self-quarantined people during the COVID-19, and self-compassion may contribute to life-satisfaction via positive coping only in the male.