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Background: Cervical cancer (CC) is the fourth most common malignancy among women globally and serves as the main cause of cancer-related deaths among women in developing countries. The early symptoms of CC are often not apparent, with diagnoses typically made at advanced stages, which lead to poor clinical prognoses. In recent years, numerous studies have shown that there is a close relationship between mast cells (MCs) and tumor development. However, research on the role MCs played in CC is still very limited at that time. Thus, the study conducted a single-cell multi-omics analysis on human CC cells, aiming to explore the mechanisms by which MCs interact with the tumor microenvironment in CC. The goal was to provide a scientific basis for the prevention, diagnosis, and treatment of CC, with the hope of improving patients' prognoses and quality of life. Method: The present study acquired single-cell RNA sequencing data from ten CC tumor samples in the ArrayExpress database. Slingshot and AUCcell were utilized to infer and assess the differentiation trajectory and cell plasticity of MCs subpopulations. Differential expression analysis of MCs subpopulations in CC was performed, employing Gene Ontology, gene set enrichment analysis, and gene set variation analysis. CellChat software package was applied to predict cell communication between MCs subpopulations and CC cells. Cellular functional experiments validated the functionality of TNFRSF12A in HeLa and Caski cell lines. Additionally, a risk scoring model was constructed to evaluate the differences in clinical features, prognosis, immune infiltration, immune checkpoint, and functional enrichment across various risk scores. Copy number variation levels were computed using inference of copy number variations. Result: The obtained 93,524 high-quality cells were classified into ten cell types, including T_NK cells, endothelial cells, fibroblasts, smooth muscle cells, epithelial cells, B cells, plasma cells, MCs, neutrophils, and myeloid cells. Furthermore, a total of 1,392 MCs were subdivided into seven subpopulations: C0 CTSG+ MCs, C1 CALR+ MCs, C2 ALOX5+ MCs, C3 ANXA2+ MCs, C4 MGP+ MCs, C5 IL32+ MCs, and C6 ADGRL4+ MCs. Notably, the C2 subpopulation showed close associations with tumor-related MCs, with Slingshot results indicating that C2 subpopulation resided at the intermediate-to-late stage of differentiation, potentially representing a crucial transition point in the benign-to-malignant transformation of CC. CNVscore and bulk analysis results further confirmed the transforming state of the C2 subpopulation. CellChat analysis revealed TNFRSF12A as a key receptor involved in the actions of C2 ALOX5+ MCs. Moreover, in vitro experiments indicated that downregulating the TNFRSF12A gene may partially inhibit the development of CC. Additionally, a prognosis model and immune infiltration analysis based on the marker genes of the C2 subpopulation provided valuable guidance for patient prognosis and clinical intervention strategies. Conclusions: We first identified the transformative tumor-associated MCs subpopulation C2 ALOX5+ MCs within CC, which was at a critical stage of tumor differentiation and impacted the progression of CC. In vitro experiments confirmed the inhibitory effect of knocking down the TNFRSF12A gene on the development of CC. The prognostic model constructed based on the C2 ALOX5+MCs subset demonstrated excellent predictive value. These findings offer a fresh perspective for clinical decision-making in CC.
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Araquidonato 5-Lipoxigenase , Progressão da Doença , Mastócitos , Análise de Célula Única , Microambiente Tumoral , Neoplasias do Colo do Útero , Humanos , Mastócitos/imunologia , Mastócitos/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Feminino , Análise de Célula Única/métodos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Sequência de RNA , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and is closely related to the early development and differentiation of neuroendocrine (NE) cells. The disease is mainly represented by high-risk NB, which has the characteristics of high mortality and difficult treatment. The survival rate of high-risk NB patients is not ideal. In this article, we not only conducted a comprehensive study of NB through single-cell RNA sequencing (scRNA-seq) but also further analyzed cuproptosis, a new cell death pathway, in order to find clinical treatment targets from a new perspective. MATERIALS AND METHODS: The Seurat software was employed to process the scRNA-seq data. This was followed by the utilization of GO enrichment analysis and GSEA to unveil pertinent enriched pathways. The inferCNV software package was harnessed to investigate chromosomal copy number variations. pseudotime analyses involved the use of Monocle 2, CytoTRACE, and Slingshot software. CellChat was employed to analyze the intercellular communication network for NB. Furthermore, PySCENIC was deployed to review the profile of transcription factors. RESULT: Using scRNA-seq, we studied cells from patients with NB. NE cells exhibited superior specificity in contrast to other cell types. Among NE cells, C1 PCLAF + NE cells showed a close correlation with the genesis and advancement of NB. The key marker genes, cognate receptor pairing, developmental trajectories, metabolic pathways, transcription factors, and enrichment pathways in C1 PCLAF + NE cells, as well as the expression of cuproptosis in C1 PCLAF + NE cells, provided new ideas for exploring new therapeutic targets for NB. CONCLUSION: The results revealed the specificity of malignant NE cells in NB, especially the key subset of C1 PCLAF + NE cells, which enhanced our understanding of the key role of the tumor microenvironment in the complexity of cancer progression. Of course, cell death played an important role in the progression of NB, which also promoted our research on new targets. The scrutiny of these findings proved advantageous in uncovering innovative therapeutic targets, thereby bolstering clinical interventions.
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The stem bark of Aquilaria sinensis(Thymelaeaceae), with the local name of "Li-Wa-Zi-Xing", is used in traditional Yi medicine for treating chronic gastritis and other diseases. However, its active ingredients remain currently unknown. In this study, Helicobacter pylori(Hp) is used in anti-bacterial experiments to test the active compounds derived from A. sinensis stem bark. Nineteen compounds were isolated from the stem bark of A. sinensis by column chromatography, high-performance liquid chromatography, recrystallization, etc. Aquilaridiester(1) is a new lignan. The other eighteen compounds were reported before, including docosyl caffeate(2), 6-hydroxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(3), qinanone A(4), 6-hydroxy-2-(2-phenylethyl)chromone(5), 6-hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(6), 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-1-benzopyran-4-one(7), 6-hydroxy-2-[2-(3,4-dimethoxyphenyl)ethyl]chromone(8), 6-hydroxy-2-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one(9), genkwanin(10), 5-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one(11), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(12),(+)-syringaresinol(13), zhebeiresinol(14), aquilarin A(15), caruilignan D(16),(-)-ficusal(17), pistaciamide(18), and protocatechuic acid(19). The anti-bacterial results show that compounds 2-7, 10-11, and 13 have inhibitory activity against Hp. Among them, 6-hydroxy-2-(2-phenylethyl)chromone(5) and 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-benzopyran-4-one(7) have superior inhibitory effects on Hp to others, with the same minimum inhibitory concentration(MIC) of 6.25 µmol·L~(-1). The 2-(2-phenylethyl)chromones are the major active ingredients in A. sinensis stem bark.
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Antibacterianos , Helicobacter pylori , Testes de Sensibilidade Microbiana , Casca de Planta , Thymelaeaceae , Helicobacter pylori/efeitos dos fármacos , Casca de Planta/química , Antibacterianos/farmacologia , Antibacterianos/química , Thymelaeaceae/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Caules de Planta/químicaRESUMO
BACKGROUND: Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations. METHODS: In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood. RESULTS: Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects. CONCLUSIONS: This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.
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Apoptose , Ouro , Nanopartículas Metálicas , Paládio , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Ouro/química , Humanos , Catálise , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Feminino , Paládio/uso terapêutico , Paládio/química , Paládio/farmacologia , Animais , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Peróxido de Hidrogênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Camundongos NusRESUMO
One-dimensional nanomaterials have become one of the most available nanoreinforcing agents for developing next-generation high-performance functional self-healing composites owing to their unique structural characteristics and surface electron structure. However, nanoscale control, structural regulation, and crystal growth are still enormous challenges in the synthesis of specific one-dimensional nanomaterials. Here, oxygen-defective MoO3-x nanowires with abundant surface dynamic bonding were successfully synthesized as novel nanofillers and photothermal response agents combined with a polyurethane matrix to construct composite elastomers, thus achieving mechanically enhanced and self-healing properties. Benefiting from the surface plasmon resonance of the MoO3-x nanowires and interfacial multiple dynamic bonding interactions, the composite elastomers demonstrated strong mechanical performance (with a strength of 31.45 MPa and elongation of 1167.73%) and ultrafast photothermal toughness self-healing performance (20 s and an efficiency of 94.34%). The introduction of MoO3-x nanowires allows the construction of unique three-dimensional cross-linked nanonetworks that can move and regulate interfacial dynamic interactions under 808 nm infrared laser stimulation, resulting in controlled mechanical and healing performance. Therefore, such special elastomers with strong photothermal responses and mechanical properties are expected to be useful in next-generation biological antibacterial materials, wearable devices, and artificial muscles.
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Objective: The aim of this research was to gain a thorough understanding of the processes involved in cell communication and discover potential indicators for treating multiple myeloma (MM) through the use of single-cell RNA sequencing (scRNA-seq). And explored the expression of multiple myeloma-related subgroups on metal ion-related pathways to explore the relationship between MM and metal ions. Methods: We performed a fair examination using single-cell RNA sequencing on 32 bone marrow specimens collected from 22 individuals at different points of MM advancement and 9 individuals without any health issues. To analyze the scRNA-seq data, we employed advanced computational algorithms, including Slingshot, Monocle2, and other methodologies. Specifically, Slingshot and Monocle2 enabled us to simulate the biological functionalities of different cell populations and map trajectories of cell developmental pathways. Additionally, we utilized the UMAP algorithm, a powerful dimension reduction technique, to cluster cells and identify genes that were differentially expressed across clusters. Results: Our study revealed distinct gene expression patterns and molecular pathways within each patient, which exhibited associations with disease progression. The analysis provided insights into the tumor microenvironment (TME), intra- and inter-patient heterogeneity, and cell-cell interactions mediated by ligand-receptor signaling. And found that multiple myeloma-related subgroups were expressed higher levels in MMP and TIMP pathways, there were some associations. Conclusion: Our study presents a fresh perspective for future research endeavors and clinical interventions in the field of MM. The identified gene expression patterns and molecular pathways hold immense potential as therapeutic targets for the treatment of multiple myeloma. The utilization of scRNA-seq technology has significantly contributed to a more precise understanding of the complex cellular processes and interactions within MM. Through these advancements, we are now better equipped to unravel the underlying mechanisms driving the development and progression of this complex disease.
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Mieloma Múltiplo , Análise de Célula Única , Microambiente Tumoral , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Humanos , Análise de Célula Única/métodos , Microambiente Tumoral/genética , Regulação Neoplásica da Expressão Gênica , Análise de Sequência de RNA , Perfilação da Expressão Gênica , Masculino , Feminino , Pessoa de Meia-Idade , Transcriptoma , Idoso , Biologia Computacional/métodos , Algoritmos , Biomarcadores Tumorais/genéticaRESUMO
OBJECTIVES: Simnotrelvir is a small molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction (DDI) potential of simnotrelvir/ritonavir should be investigated. METHODS: This DDI study was an open-label, fixed-sequence, two-period Phase I clinical trial in Chinese healthy adult subjects, divided into 3 cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam). RESULTS: The results demonstrated that compared to administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (AUC0-t) of simnotrelvir by 25% (GMR 125%, 90% confidence interval (CI) 114% - 137%), whereas co-administration with rifampicin significantly decreased the AUC0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4% - 20.9%). Notably, simnotrelvir/ritonavir increased the AUC0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551% - 2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity. CONCLUSIONS: The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, while the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam. GOV IDENTIFIER: NCT05665647.
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Mechanochromic light control technology that can dynamically regulate solar irradiation is recognized as one of the leading candidates for energy-saving windows. However, the lack of spectrally selective modulation ability still hinders its application for different scenarios or individual needs. Here, inspired by the generation of structure color and color change of living organisms, a simple layer-by-layer assembly approach toward large-area fabricating mechanically responsive film for visible and near-infrared multiwavelength spectral modulation smart windows is reported here. The assembled SiO2 nanoparticles and W18O49 nanowires enable the film with an optical modulation rate of up to 42.4% at the wavelength of 550 nm and 18.4% for the near-infrared region, separately, and the typical composite film under 50% stretching shows ≈41.6% modulation rate at the wavelength of 550 nm with NIR modulation rate less than 2.7%. More importantly, the introduction of the multilayer assembly structure not only optimizes the film's optical modulation but also enables the film with high stability during 100 000 stretching cycles. A cooling effect of 21.3 and 6.9 °C for the blackbody and air inside a model house in the real environmental application is achieved. This approach provides theoretical and technical support for the new mechanochromic energy-saving windows.
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Background: Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. Materials and methods: Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion. Results: Our study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn't received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group. Conclusion: This research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.
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Progressão da Doença , Células Epiteliais , Neoplasias Ovarianas , Análise de Célula Única , Microambiente Tumoral , Feminino , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Transativadores/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Biomarcadores Tumorais/genética , Análise de Sequência de RNA , Prognóstico , Proteínas de Ligação a DNA/genética , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , RNA-Seq , Pessoa de Meia-Idade , DNA Topoisomerases Tipo IIRESUMO
Underwater friction stir welding (UFSW) achieves reliable joining between dissimilar materials and meets the welding demand for function and properties in lightweight structures of modern engineering. A defect monitoring method based on Variational Mode Decomposition optimized by Beluga Whale Optimization and Hilbert-Huang Transform (BWO-VMD-HHT) is proposed to solve the unclear feature of AE signal in UFSW due to the aqueous medium. UFSW experiments on Al alloy and carbon fiber reinforced thermoplastic (CFRTP) are carried out with AE signals measured. The time-frequency domain features of AE signals are extracted by BWO-VMD-HHT. The experimental results show that the main frequency of the AE signal is 22.5 kHz, and surface crack defects, shallow hole defects, and deep hole defects are accompanied by the transfer phenomena of different frequency components. Then, the feature vectors are built by frequency components in the BWO-VMD-HHT spectrum and reduced by principal component analysis, including 22.5 kHz, 24 kHz, 20.6 kHz, 18.4 kHz, 17.3 kHz, and 15.6 kHz. The feature vectors are divided into the train and test sets, and the welding defect prediction model (ResNet18-attention) is built by ResNet18 and trained by feature vectors. In the test set, the ResNet18-attention is compared with the BP, SVM, and RBF. Test results show that the precision of models has improved by at least 10%, which are trained by BWO-VMD-HHT features vector. Also, ResNet18-attention has achieved an average precision of 0.906 and recognizes the category of weld defect accurately, and this method can be applied to the defect monitoring of UFSW.
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Decapod iridescent virus 1 (DIV1) stands as a significant pathogen affecting crustaceans, posing a grave threat to the shrimp industries in aquaculture dependent nations. Within the Iridoviridae family, the conserved envelope protein DIV1-168L plays a pivotal role in virion entry. Nonetheless, the host factors that interact with 168L remain unidentified. To address this gap, we established a cDNA library derived from Litopenaeus vannamei gill tissue and conducted yeast two-hybrid screening to identify host factors that interact with 168L. Additionally, we performed co-immunoprecipitation assays to verify the interaction between cuticle protein 8 (CP8) and 168L. Expression pattern analysis revealed the presence of CP8 transcripts in the gill and epidermis. Furthermore, immunohistochemistry results demonstrated the expression of CP8 in gill cells and its localization in the gill filament epithelium. Fluorescence analysis indicated that full-length CP8 colocalized with 168L in the cytoplasm of Sf9 cells. Removal of the signal peptide from the N-terminal of CP8 eliminated its concentration in the cytoplasm. Additionally, CP8 expression was significantly inhibited during DIV1 infection. Therefore, our research contributes to a better understanding of the entry mechanism of iridovirids. The GenBank accession number for the DIV1 sequence is MF197913.1.
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Iridoviridae , Penaeidae , Animais , Penaeidae/virologia , Iridoviridae/fisiologia , Proteínas de Artrópodes/metabolismo , Proteínas de Artrópodes/genéticaRESUMO
Lung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Neoplasias , Células-Tronco Neoplásicas , Fenótipo , Receptor ErbB-2 , Animais , Humanos , Camundongos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Linhagem Celular Tumoral , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , FemininoRESUMO
BACKGROUND: Verticillium wilt, caused by the fungus Verticillium dahliae, is a soil-borne vascular fungal disease, which has caused great losses to cotton yield and quality worldwide. The strain KRS010 was isolated from the seed of Verticillium wilt-resistant Gossypium hirsutum cultivar "Zhongzhimian No. 2." RESULTS: The strain KRS010 has a broad-spectrum antifungal activity to various pathogenic fungi as Verticillium dahliae, Botrytis cinerea, Fusarium spp., Colletotrichum spp., and Magnaporthe oryzae, of which the inhibition rate of V. dahliae mycelial growth was 73.97% and 84.39% respectively through confrontation test and volatile organic compounds (VOCs) treatments. The strain was identified as Bacillus altitudinis by phylogenetic analysis based on complete genome sequences, and the strain physio-biochemical characteristics were detected, including growth-promoting ability and active enzymes. Moreover, the control efficiency of KRS010 against Verticillium wilt of cotton was 93.59%. After treatment with KRS010 culture, the biomass of V. dahliae was reduced. The biomass of V. dahliae in the control group (Vd991 alone) was 30.76-folds higher than that in the treatment group (KRS010+Vd991). From a molecular biological aspect, KRS010 could trigger plant immunity by inducing systemic resistance (ISR) activated by salicylic acid (SA) and jasmonic acid (JA) signaling pathways. Its extracellular metabolites and VOCs inhibited the melanin biosynthesis of V. dahliae. In addition, KRS010 had been characterized as the ability to promote plant growth. CONCLUSIONS: This study indicated that B. altitudinis KRS010 is a beneficial microbe with a potential for controlling Verticillium wilt of cotton, as well as promoting plant growth.
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Bacillus , Gossypium , Doenças das Plantas , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Bacillus/fisiologia , Gossypium/microbiologia , Gossypium/crescimento & desenvolvimento , Ascomicetos/fisiologia , Verticillium/fisiologia , Filogenia , Agentes de Controle BiológicoRESUMO
In order to investigate the failure modes and instability mechanism of fractured rock. Uniaxial compression tests were conducted on sandstone specimens with different dip angles. Based on rock energy dissipation theory and fractal theory, the energy evolution characteristics and fragmentation fractal characteristics in the process of deformation and failure of specimens were analyzed. The results show that the peak strength and elastic modulus of fractured rock mass are lower than those of intact samples, and both show an exponential increase with the increase of fracture dip angle. The energy evolution laws of different fracture specimens are roughly similar and can be classified into four stages based on the stress-strain curve: pressure-tight, elastic, plastic, and post-destructive. The total strain energy, elastic strain energy, and dissipated strain energy of the specimen at the peak stress point increased exponentially with crack inclination, and the dissipated strain energy and compressive strength conformed to a power function growth relationship. The distribution of the fragments after the failure of the fracture sample has fractal characteristics, and the fractal dimension increases with the increase of the fracture dip angle. In addition, the higher the compressive strength of the specimen, the greater the energy dissipation, the more serious the degree of fragmentation, and the greater the fractal dimension. The data fitting further shows that there is a power function relationship between the dissipated strain energy and the fractal dimension. The research results can provide a theoretical basis for the stability of rock mass engineering and structural deformation control.
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The impact of anthropogenic global warming has induced significant upward dispersal of trees to higher elevations at alpine treelines. Assessing vertical deviation from current uppermost tree distributions to potential treeline positions is crucial for understanding ecosystem responses to evolving global climate. However, due to data resolution constraints and research scale limitation, comprehending the global pattern of alpine treeline elevations and driving factors remains challenging. This study constructed a comprehensive quasi-observational dataset of uppermost tree distribution across global mountains using Google Earth imagery. Validating the isotherm of mean growing-season air temperature at 6.6 ± 0.3°C as the global indicator of thermal treeline, we found that around two-thirds of uppermost tree distribution records significantly deviated from it. Drought conditions constitute the primary driver in 51% of cases, followed by mountain elevation effect which indicates surface heat (27%). Our analyses underscore the multifaceted determinants of global patterns of alpine treeline, explaining divergent treeline responses to climate warming. Moisture, along with temperature and disturbance, plays the most fundamental roles in understanding global variation of alpine treeline elevation and forecasting alpine treeline response to ongoing global warming.
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Ecossistema , Árvores , Árvores/fisiologia , Temperatura , Temperatura Baixa , Clima , AltitudeRESUMO
Automated segmentation of liver tumors in CT scans is pivotal for diagnosing and treating liver cancer, offering a valuable alternative to labor-intensive manual processes and ensuring the provision of accurate and reliable clinical assessment. However, the inherent variability of liver tumors, coupled with the challenges posed by blurred boundaries in imaging characteristics, presents a substantial obstacle to achieving their precise segmentation. In this paper, we propose a novel dual-branch liver tumor segmentation model, SBCNet, to address these challenges effectively. Specifically, our proposed method introduces a contextual encoding module, which enables a better identification of tumor variability using an advanced multi-scale adaptive kernel. Moreover, a boundary enhancement module is designed for the counterpart branch to enhance the perception of boundaries by incorporating contour learning with the Sobel operator. Finally, we propose a hybrid multi-task loss function, concurrently concerning tumors' scale and boundary features, to foster interaction across different tasks of dual branches, further improving tumor segmentation. Experimental validation on the publicly available LiTS dataset demonstrates the practical efficacy of each module, with SBCNet yielding competitive results compared to other state-of-the-art methods for liver tumor segmentation.
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Algoritmos , Neoplasias Hepáticas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Fígado/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Redes Neurais de Computação , Aprendizado ProfundoRESUMO
PURPOSE: To identify risk factors of chemotherapy-related cognitive impairment (CRCI) and construct and validate a visual prediction model of such for patients with breast cancer. METHODS: A multicenter, descriptive, and cross-sectional design was adopted. Data were collected from ten public tertiary hospitals in China. Cognitive function was assessed by using Functional Assessment of Cancer Therapy-cognitive function. Socio-demographic, clinical, psychological, and physical indicators were also assessed. The logistic prediction model was constructed by fivefold cross-validation. Then, a nomogram was utilized to visualize the prediction model, which was also evaluated via discrimination, calibration, and decision curve analysis. RESULTS: A total of 71 breast cancer patients had CRCI with a prevalence of 9.58%. This visual prediction model was constructed based on education background, exercise frequency, chemotherapy times, and fatigue and demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.882. The calibration curve indicated good agreement between experimental and projected values, and the decision curve proved good clinical applicability. CONCLUSION: Education background, exercise frequency, chemotherapy times, and fatigue were associated with high incidence of CRCI. The prediction model exhibits superior performance and has promise as a useful instrument for assessing the likelihood of CRCI in breast cancer patients. IMPLICATIONS FOR CANCER SURVIVORS: Our findings could provide breast cancer survivors with risk screening based on CRCI predictors to implement prevention and early intervention, and help patients integrate into society and achieve comprehensive recovery.
RESUMO
BACKGROUND: NF2-schwannomatosis (NF2) is an autosomal dominant disorder prone to hearing loss. Auditory brainstem implants (ABIs) offer a promising solution for hearing rehabilitation in NF2. OBJECTIVE: To synthesize existing literature on ABI implantation in NF2, focusing on audiological outcomes and ABI-related complications. METHODS: The systematic review followed PRISMA guidelines and was registered in the PROSPERO database (CRD42022362155). Relevant studies were identified by searching PubMed, EMBASE, CENTRAL, CMB, and CNKI from inception to August 2023. Data on environmental sound discrimination, open-set discrimination, closed-set discrimination, and ABI-related complications were extracted and subjected to meta-analysis. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Thirty-three studies were included. The pooled estimate was 58% (95% CI 49-66%) for environmental sound discrimination and 55% (95% CI 40-69%) for closed-set discrimination. Regarding open-set discrimination, the pooled estimates were 30% (95% CI 19-42%) for sound only, 46% (95% CI 37-54%) for lip-reading only, and 63% (95% CI 55-70%) for sound plus lip-reading. The pooled occurrence of ABI-related complications was 33% (95% CI 15-52%). CONCLUSION: This meta-analysis underscores the effectiveness and safety of ABIs in NF2, providing valuable insights for evidence-based decision-making and hearing rehabilitation strategies.
Assuntos
Implante Auditivo de Tronco Encefálico , Implantes Auditivos de Tronco Encefálico , Neurilemoma , Neurofibromatoses , Neurofibromatose 2 , Neoplasias Cutâneas , Humanos , Neurofibromatose 2/complicações , Neurofibromatose 2/cirurgia , Resultado do Tratamento , Audição , Estudos RetrospectivosRESUMO
PURPOSE: Glucose not only provides energy for tumor cells, but also provides various biomolecules that are essential for their survival, proliferation and invasion. Therefore, it is of great clinical significance to understand the mechanism of how tumor cells adapt to metabolic stress and maintain their survival. The aim of this research was to study the critical role of OGT and TRIM29 O-GlcNAc modification driven adaptability of PDAC cells to low glucose stress, which might have important medical implications for PDAC therapy. METHODS: Western blotting, mass spectrometry and WGA-immunoprecipitation were used to examined the levels of OGT and O-GlcNAc glycosylated proteins in BxPC3 and SW1990 cells in normal culture and under glucose deprivation conditions. Crystal violet assay, flow cytometry, RIP, RT-qPCR, protein stability assay, biotin pull down were used to investigate the mechanism of OGT and TRIM29-mediated adaptive response to glucose deficiency in PDAC cells. RESULTS: The current study found that under the condition of low glucose culture, the levels of OGT and O-GlcNAc glycosylation in PDAC cells were significantly higher than those in normal culture. Moreover, the high expression of OGT has a protective effect on PDAC cells under low glucose stress. This study confirmed that there was no significant change in mRNA level and protein degradation of OGT under low glucose stress, which was mainly reflected in the increase of protein synthesis. In addition, O-GlcNAc modification at T120 site plays a critical role in the metabolic adaptive responses mediated by TRIM29. CONCLUSIONS: Taken together, our study indicated that O-GlcNAcylation of TRIM29 at T120 site and OGT translation forms a loop feedback to facilitate survival of PDAC under glucose deficiency.