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Although gastric cancer (GC) is one of the most frequent malignant tumors in the digestive tract with high morbidity and mortality, it remains a diagnostic dilemma due to its reliance on invasive biopsy or insensitive assays. Herein, we report a fluorescent gastric cancer reporter (FGCR) with activatable near-infrared fluorescence (NIRF) signals and high renal-clearance efficiency for the detection of orthotopic GC in a murine model via real-time imaging and remote urinalysis. In the presence of gastric-tumor-associated ß-galactosidase (ß-Gal), FGCR can be fluorescently activated for in vivo NIRF imaging. Relying on its high renal-clearance efficiency (â¼95% ID), it can be rapidly excreted through kidneys to urine for the ultrasensitive detection of tumors with a diameter down to â¼2.1 mm and for assessing the prognosis of oxaliplatin-based chemotherapy. This study not only provides a new approach for noninvasive auxiliary diagnosis and prognosis of GC but also provides guidelines for the development of fluorescence probes for cancer diagnosis.
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Corantes Fluorescentes , Imagem Óptica , Neoplasias Gástricas , beta-Galactosidase , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/urina , Neoplasias Gástricas/patologia , Animais , beta-Galactosidase/metabolismo , Corantes Fluorescentes/química , Humanos , Camundongos , Linhagem Celular Tumoral , Camundongos NusRESUMO
Surface plasmonic detectors have the potential to be key components of miniaturized chip-scale spectrometers. Graphene plasmons, which are highly confined and gate-tunable, are suitable forin situlight detection. However, the tuning of graphene plasmonic photodetectors typically relies on the complex and high operating voltage based on traditional dielectric gating technique, which hinders the goal of miniaturized and low-power consumption spectrometers. In this work, we report a tunable mid-infrared (MIR) photodetector by integrating of patterned graphene with non-volatile ferroelectric polarization. The polarized ferroelectric thin film provides an ultra-high surface electric field, allowing the Fermi energy of the graphene to be manipulated to the desired level, thereby exciting the surface plasmon polaritons effect, which is highly dependent on the free carrier density of the material. By exciting intrinsic graphene plasmons, the light transmittance of graphene is greatly enhanced, which improves the photoelectric conversion efficiency of the device. Additionally, the electric field on the surface of graphene enhanced by the graphene plasmons accelerates the carrier transfer efficiency. Therefore, the responsivity of the device is greatly improved. Our simulations show that the detectors have a tunable resonant spectral response of 9-14µm by reconstructing the ferroelectric domain and exhibit a high responsivity to 5.67 × 105A W-1at room temperature. Furthermore, we also demonstrate the conceptual design of photodetector could be used for MIR micro-spectrometer application.
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OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.
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Fluorescent probes are attractive in diagnosis and sensing. However, most reported fluorophores can only detect one or few analytes/parameters, notably limiting their applications. Here we have designed three phenanthridine-based fluorophores (i.e., B1, F1, and T1 with 1D, 2D, and 3D molecular configuration, respectively) capable of monitoring various microenvironments. In rigidifying media, all fluorophores show bathochromic emissions but with different wavelength and intensity changes. Under compression, F1 shows a bathochromic emission of over 163â nm, which results in organic fluorophore-based full-color piezochromism. Moreover, both B1 and F1 exhibit an aggregation-caused quenching (ACQ) behavior, while T1 is an aggregation-induced emission (AIE) fluorophore. Further, F1 and T1 selectively concentrate in cell nucleus, whereas B1 mainly stains the cytoplasm in live cell imaging. This work provides a general design strategy of versatile fluorophores for microenvironmental monitoring.
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Diagnóstico por Imagem , Corantes Fluorescentes , Núcleo Celular , CitoplasmaRESUMO
Chemiluminescence imaging has been recognized as a valuable tool for ultrasensitive detection of physio-pathological events through elimination of background autofluorescence. However, most chemiluminescent nanoprobes suffer from shallow imaging depths and slow clearance from living bodies, which impede their use in clinical settings. We herein report size-transformable nanoreporters (ADN1 and ADN2) that could be activated at disease site by superoxide anion (O2 â - ) to trigger nanostructure disassembly into renal excretable fluorescent fragments as well as chemiluminescence turn-on for crosstalk-free duplex chemo-fluorescence imaging and in vitro urinalysis. In peritonitis mouse model, we demonstrate that the representative nanoreporter ADN1 spontaneously accumulates at the disrupted peritoneum and is cleaved by upregulated O2 â - to initiate depolymerization and result in red chemiluminescence at 620â nm, enabling sensitive detection of peritonitis at least 19â h earlier than gold standard histological assays. Additionally, the incorporation of a near-infrared (NIR) dye into ADN1 results in ADN2 exhibiting intense and red-shifted chemiluminescence at ≈800â nm, which permits early detection of deeply seated diseases such as drug-induced hepatotoxicity. This study thus showcases a modular design strategy that is not only applicable to developing versatile chemiluminescent nanoprobes with switchable pharmacokinetics for early disease diagnosis, but also promising for future clinical translations.
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Luminescência , Superóxidos , Animais , Camundongos , Corantes Fluorescentes/química , Imagem Óptica/métodos , RimRESUMO
Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.
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Carbocianinas , Doenças Inflamatórias Intestinais , Imagem Óptica , Animais , Camundongos , Prognóstico , Imagem Óptica/métodos , Corantes Fluorescentes , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Diagnóstico PrecoceRESUMO
Generally, we consider chitosan being a safe, nontoxic natural polymer with wide clinical applications. However, allergic reactions caused by chitosan have been reported on rare occasions. We report here a case of allergy and perform a literature review.
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The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA+ IGLC2+ plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8+ cycling B cells/CCR5+ T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.
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Neoplasias Colorretais/imunologia , Neoplasias Colorretais/fisiopatologia , Transdução de Sinais/fisiologia , Microambiente Tumoral/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Efficient and inexpensive bifunctional catalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are essential for water splitting. Herein, we successfully prepare porous Fe-Mo oxide hybrid nanorods through a hydrothermal method followed by annealing at high temperature. They exhibit excellent catalytic activity for OER and HER in alkaline media, and produce a current density of 10 mA cm-2 at overpotentials of 200 and 66 mV. Besides, they work as bifunctional electrode materials for overall water splitting, achieving a current density of 10 mA cm-2 at a voltage of 1.52 V, and maintaining a current density of 60 mA cm-2 for 60 h. The unique morphology with self-supported structure can expose more active sites and facilitate charge transfer, and is not easy to peel off, thus it improves the catalytic activity and stability. This work therefore provides a valuable route for designing and fabricating inexpensive and high-performance catalytic materials for overall water splitting.
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BACKGROUND: Recently, multiple lines of evidence have demonstrated that linc00662 serves as an oncogene in various cancers. However, the exact mechanism of oncogenesis mediated by linc00662 in colorectal cancer (CRC) remains unknown. In this study, we aimed to explore the biological role of linc00662 in the regulation of CRC progression. METHODS: Both gene expression omnibus (GEO) and the cancer genome atlas (TCGA) datasets were used to evaluate the expression of linc00662. RT-qPCR was used to analyze the expression of linc00662, miR-497-5p, and AVL9 in CRC clinical samples and cell lines. Cell Counting Kit-8 (CCK-8), flow cytometry, transwell assay, and xenograft model were used to investigate the effect of linc00662 on CRC cell proliferation, cell cycle, and metastasis. Western blot analysis was used to analyze the expression of the epithelial-mesenchymal transition (EMT)-associated markers. Furthermore, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. Dual-luciferase reporter assays were used to analyze the regulatory relationships among linc00662, miR-497-5p, and AVL9. RESULTS: In this study, we found that the expression of linc00662 was significantly upregulated in CRC tissues compared to normal tissues and positively correlated with tissue differentiation, T stage, and lymphatic metastasis. Further, our data showed that the expression of linc00662 was positively associated with lymph node metastasis, TMN stage, and poor-moderate differentiation. Patients with higher linc00662 expression level were more likely to have poorer overall survival. Knockdown of linc00662 inhibited CRC cell growth, induced cell apoptosis, triggered cell cycle arrest at G2/M phase, and suppressed cell migration and invasion through regulating the EMT pathway. Further, mechanistic studies revealed that knockdown of linc00662 significantly reduced the expression of AVL9, a direct target of miR-497-5p. CONCLUSIONS: Linc00662 was significantly upregulated in CRC, and mediated CRC progression and metastasis by competing with miR-497-5p to modulate the expression of AVL9. Therefore, our result sheds light on the potential application of linc00662 in CRC diagnosis and therapy.
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OBJECTIVE: Although the role of microRNA-17 (miR-17) has been identified as a tumour biomarker in various studies, its prognostic value in cancers remains unclear. Therefore, we performed a systematic review and meta-analysis to analyse and summarise the relationship between the miR-17 status and clinical outcome in a variety of human cancers. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science and Embase from the first year of records to 15 May 2017. OUTCOMES: The patients' survival results were pooled, and pooled HRs with 95% CIs were calculated and used for measuring the strength of association between miR-17 and the prognosis of cancers, including hepatocellular carcinoma, lung cancer, osteosarcoma, glioma, T-cell lymphoblastic lymphoma and colon cancer. Heterogeneity, publication bias and subgroup analysis were also conducted. RESULTS: A total of 1096 patients were included in this meta-analysis from 12 articles. The results indicated that the increased expression of miR-17 played an unfavourable role in overall survival in various human carcinomas with the HR of 1.342 taking into account the publication bias. In subgroup analysis, HR of ethnicity (non-Asian HR=1.48 and Asian HR=1.40), disease (digestive system HR=1.36 and blood system cancer (HR=2.38) were significant with P<0.05. For the analysis of disease-free survival and recurrence-free survival, the increased expression of miR-17 was associated with unfavourable prognosis (HR=1.40). CONCLUSIONS: miR-17 may be a useful biomarker in predicting the clinical outcome of human cancers, but due to the limitations of the current studies, further verification of the role of miR-17 in human malignancies is urgently needed. PROSPERO REGISTRATION NUMBER: CRD42017065749.