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BACKGROUND: Legionella maceachernii pneumonia is a severe respiratory infection with low incidence but high mortality. However, the optimal treatment for this disease remains unclear. We report a case of successful treatment of Legionella maceachernii pneumonia, which is the first report of such a case in China. CASE PRESENTATION: An 87-year-old man with concomitant chronic obstructive pulmonary disease, liver cirrhosis, and history of left nephrectomy was diagnosed with Legionella maceachernii pneumonia using Dano-seq pathogen metagenomic testing. After two weeks of treatment with cefoperazone/sulbactam combined with quinolone antibiotics, the patient showed improvement and was discharged. The patient continued to take oral quinolone antibiotics for one week after discharge and recovered during outpatient follow-up. CONCLUSIONS: Dano-seq pathogen metagenomic testing can rapidly diagnose Legionella maceachernii pneumonia, and taking quinolone antibiotics is an effective treatment.
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Introduction: Exit selection is crucial in indoor emergency evacuation. Domestic and foreign scholars have found that exit choice behavior is influenced by three factors: environmental factors, social interactions, and individual internal factors. Previous studies have shown that in addition to a single environmental factor affecting exit decisions, the influence of other available exit options in the context can ultimately lead to a reversal of exit decisions -The context effect. However, the impact of context effects on exit decisions in emergency situations has not been thoroughly explored. Therefore, this article identifies three basic independent variables: context effects, crowd flows, and gender differences, to study the exit decisions of different gender groups facing different crowd flows, as well as how context effects affect existing exit decisions. Methods: In this paper, we used virtual reality technology to construct an indoor fire scene and designed a total of 15 virtual experiments with different crowd distribution or context effects. 131 participants were divided into two groups, male and female, and their exit decisions were observed under different crowd flows and contextual effects. Results: The research results show that: 1) Both men and women have an innate preference to avoid crowded exits, and the proportion of following crowd evacuation significantly decreases when there are crowded crowds in the scene; 2) The exit decisions of female participants are more influenced by the crowd, while men tend to be more influenced by context effects when evacuating independently; 3) The context effects on exit decisions in emergency situations is statistically significant, and this performance is more significant in the male population. Further analysis reveals that similarity effects have a more significant impact on exit decisions than attraction effects. Discussions: These findings provide deeper insights into the exit choice behavior of the population and may contribute to the design of safe exits in indoor buildings. In addition, this article emphasizes the importance of context effects and provides a foundation for future research.
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High-value utilization of bleached lignin has been widely used in different fields, whereas the investigation on darkened lignin in composite materials was often ignored. In this work, a sort of eco-friendly and structurally robust sodium carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA)/sodium lignosulfonate (SLS) black composite mulch film was elaborately designed. The chelation and redox reaction effect between Fe ions and SLS lead to the formation of a more quinones structure on lignin, darkening both lignin and the mulch films. The chelation effect between Fe ions and biopolymer formed three-dimensional structures, which can be used as sacrifice bonds to dissipate energy and improve the mechanical properties of the composite films. In particular, the maximum elongation at break and toughness increased from 48.4 % and 1141 kJ/m3 for the CMC/PVA film to 210.9 % and 1426 kJ/m3 for the optimized CMC/PVA/SLS/Fe black mulch film, respectively. In addition, the optimized black mulch film also possesses good soil water retention, thermal preservation effect, controlled urea release, and well biodegradability. This work offered a novel strategy for designing eco-friendly black mulch with reinforced mechanical strength, slow-release urea, soil moisture retention, and heat preservation performances.
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Hierro , Lignina , Agricultura/métodos , Suelo , Alcohol Polivinílico/química , Urea , SodioRESUMEN
Heart transplantation is the gold standard for treating patients with advanced heart failure. Although improvements in immunosuppressive therapies have significantly reduced the frequency of cardiac graft rejection, the incidences of T cell-mediated rejection (TCMR) and antibody-mediated rejection remain almost unchanged. A four-archetype analysis (4AA) model, developed by Philip F. Halloran, illustrated this problem well. It provided a new dimension to improve the accuracy of diagnoses and an independent system for recalibrating the histology guidelines. However, this model was based on the invasive method of endocardial biopsy, which undoubtedly increased the postoperative risk of heart transplant patients. Currently, little is known regarding the associated genes and specific functions of the different phenotypes. We performed bioinformatics analysis (using machine-learning methods and the WGCNA algorithm) to screen for hub-specific genes related to different phenotypes, based Gene Expression Omnibus accession number GSE124897. More immune cell infiltration was observed with the ABMR, TCMR, and injury phenotypes than with the stable phenotype. Hub-specific genes for each of the four archetypes were verified successfully using an external test set (accession number GSE2596). Logistic-regression models based on TCMR-specific hub genes and common hub genes were constructed with accurate diagnostic utility (area under the curve > 0.95). RELA, NFKB1, and SOX14 were identified as transcription factors important for TCMR/injury phenotypes and common genes, respectively. Additionally, 11 Food and Drug Administration-approved drugs were chosen from the DrugBank Database for each four-archetype model. Tyrosine kinase inhibitors may be a promising new option for transplant rejection treatment. KRAS signaling in cardiac transplant rejection is worth further investigation. Our results showed that heart transplant rejection subtypes can be accurately diagnosed by detecting expression of the corresponding specific genes, thereby enabling precise treatment or medication.
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Trasplante de Corazón , Trasplante de Riñón , Humanos , Trasplante de Corazón/efectos adversos , Rechazo de Injerto , Trasplante de Riñón/métodos , Medicina de Precisión , Donantes de Tejidos , Biopsia , Biología Computacional , Factores de Transcripción SOXB2RESUMEN
Thyroid cancer (TC) is a kind of cancer with high heterogeneity, which leads to significant difference in prognosis. The prognostic molecular processes are not well understood. Cancer cells and tumor microenvironment (TME) cells jointly determine the heterogeneity. However, quite a little attention was paid to cells in the TME in the past years. In this study, we not only reveal that endothelial cells (ECs) are strongly associated with the progress of papillary thyroid cancer (PTC) using single-cell RNA-seq (scRNA-seq) data downloaded from Gene Expression Omnibus (GEO) and WGCNA, but also screen 5 crucial genes of ECs: CLDN5, ABCG2, NOTCH4, PLAT, and TMEM47. Furthermore, the 5-gene molecular prognostic model is constructed, which can predict how well a patient will do on PD-L1 blockade immunotherapy for TC and evaluate prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrates that PLAT is decreased in TC and the increase of PLAT can restrain the migratory capacity of TC cells. Meanwhile, in TC cells, PLAT suppresses VEGFa/VEGFR2-mediated human umbilical vascular endothelial cell (HUVEC) proliferation and tube formation. Totally, we construct the 5-gene molecular prognostic model from the perspective of EC and provide a new idea for immunotherapy of TC.
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ARN Citoplasmático Pequeño , Neoplasias de la Tiroides , Humanos , Células Endoteliales , Pronóstico , Neoplasias de la Tiroides/genética , ARN , Análisis de la Célula Individual , Microambiente Tumoral/genéticaRESUMEN
Comprehensive and exceedingly precise centralized patient monitoring has become essential to advance predictive, preventive, and efficient patient care in contemporary healthcare. Millimeter-wave (mmWave) technology, boasting high-frequency and high-speed wireless communication, holds promise as a viable solution to this challenge. This paper presents a new approach that combines mmWave communication and computer vision (CV) to achieve real-time patient monitoring and data transmission in indoor medical environments. The system comprises a transmitter, a reflective surface, and multiple communication targets, and utilizes the high-frequency, low-latency features of mmWave as well as CV-based target detection and depth estimation for precise localization and reliable data transmission. A machine learning algorithm analyses real-time images captured by an optical camera to identify target distance and direction and establish clear line-of-sight links. The system proactively adapts its transmission power and channel allocation based on the target's movements, guaranteeing complete coverage, even in potentially obstructive areas. This methodology tackles the escalating demand for high-speed, real-time data processing in modern healthcare, significantly enhancing its delivery.
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Algoritmos , Comunicación , Humanos , Computadores , Instituciones de Salud , Atención a la SaludRESUMEN
Polyphyllin D (PD), one of the important steroid saponins in traditional medicinal herb Paris polyphylla, has been demonstrated to have anticancer activity both in vitro and in vivo. However, the mechanisms through which PD exerts its anticancer effects in triple-negative breast cancer (TNBC) remain unclear. Our study was presented to evaluate the anticancer effect and the potential mechanisms of PD in two TNBC cell lines, BT-549 and MDA-MB-231. Through comprehensively comparing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data of PD-treated and untreated BT-549 and MDA-MB-231 cells, we found that PD could induce apoptosis of TNBC cells by activating oxidative phosphorylation pathway in BT-549 cells, as well as inhibiting spliceosome function alteration in MDA-MB-231 cells. These results suggested that the mechanisms underlying the pro-apoptotic effect of PD on TNBC may be cell type-specificity-dependent. Moreover, we found that nodal modulator 2/3 (NOMO2/3) were downregulated both in PD-treated BT-549 and MDA-MB-231 cells, suggesting that NOMO2/3 may be the potential target of PD. Verification experiments revealed that PD deceased NOMO2/3 expression at protein level, rather than mRNA level. Whether NOMO2/3 are the upstream modulators of oxidative phosphorylation pathway and spliceosome needs further validation. In conclusion, a comprehensive proteomics study was performed on PD-treated or untreated TNBC cells, revealing the anticancer mechanisms of PD.
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BACKGROUND: This study aimed to explore the risk factors of acute renal failure (ARF) after Stanford type A aortic dissection (AAD) surgery, establish a nomogram prediction model and calculate the risk of ARF. MATERIAL AND METHODS: 241 AAD patients who received aortic surgery in the department of cardiovascular surgery, Zhongnan Hospital of Wuhan University were enrolled in this study. All enrolled patients were divided into the ARF group and non-ARF group. The clinical data of the two groups were collected and compared. The independent risk factors of ARF after aortic surgery were analyzed by univariate and multivariate logistic regression analyses. Moreover, a nomogram prediction model was generated. The calibration curve, ROC curve and independent external validation were performed to evaluate the nomogram prediction model. RESULTS: 67 patients were diagnosed with ARF within 48 h after the operation. Univariate and multivariate logistic regression analyses showed that hypertension, preoperative renal artery involvement, CPB time extension and postoperative decreased platelet lymphocyte ratio were the independent risk factors of ARF after AAD surgery. The nomogram model could predict the risk of ARF with a sensitivity of 81.3% and a specificity of 78.6%. The calibration curve displayed good agreement of the predicted probability with the actual observed probability. AUC of the ROC curve was 0.839. External data validation was performed with a sensitivity of 79.2% and a specificity of 79.8%. CONCLUSIONS: Hypertension, preoperative renal artery involvement, CPB time extension and postoperative decreased platelet lymphocyte ratio could predict the risk of ARF after AAD surgery.
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BACKGROUND: The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients. METHODS: We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1-2 months of follow-up. RESULTS: 27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50-2.15; P < .00001; I2 = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40-0.80; P = .001; I2 = 76%). There was a lower risk of CALs during 1-2 months follow-up for those who started IVIG administration within 10 days from the onset. CONCLUSIONS: Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.
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Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Humanos , Lactante , Inmunoglobulinas Intravenosas/uso terapéutico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Infusiones Intravenosas , Estudios RetrospectivosRESUMEN
The conjecture of breast cancer is uncertain because of its explosive growth and the complicated molecular mechanisms. Circular RNAs (circRNAs) are regulatory RNA sequences present in the genome and their regulatory mechanism involves the sponging of microRNAs (miRNAs). In this study, we explored the regulation between circular forms of dedicator of cytokinesis 1 (circDOCK1) (hsa_circ_0007142) and miR-128-3p, and its implication on the pathogenesis of breast cancer modulated by never in mitosis (NIMA) related kinase 2 (NEK2). We revealed an increase in circDOCK1 and NEK2 expression, and a decrease in miR-128-3p expression in breast cancer tissues and cell lines. Bioinformatics analysis and experimental validation indicated a positive correlation between circDOCK1 and NEK2 expression but a negative correlation was recorded between miR-128-3p and circDOCK1 or NEK2, respectively. Furthermore, inhibition of circDOCK1 expression was followed by an increase in miR-128-3p and a decrease in NEK2 levels in vitro and in vivo. The luciferase assay concluded that miR-128-3p was a direct target of circDOCK1 while NEK2 was the direct target of miR-128-3p. Furthermore, circDOCK1 inhibition hindered breast cancer development by repressing NEK2 and thus promoting the increased expression of miR-128-3p both in vitro and in vivo. We therefore conclude that circDOCK1 promotes breast cancer progression by targeting miR-128-3p-mediated downregulation of NEK2 and that the circDOCK1/hsa-miR-128-3p/NEK2 axis may be a novel therapeutic target for breast cancer treatment.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , Neoplasias de la Mama/genética , Citocinesis/genética , Proliferación Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Mitosis/genética , Movimiento Celular/genética , Quinasas Relacionadas con NIMA/genética , Quinasas Relacionadas con NIMA/metabolismoRESUMEN
Storage is necessary for rice to ensure the year-round consumption of rice. With the increase in storage time, the taste quality and commercial value of rice gradually decrease. The accurate determination of the freshness of rice is critical to the rice trade. However, it is difficult to distinguish aging rice from fresh rice, so a quick and simple method is needed to identify the freshness of the rice. In this study, a combination of near-infrared spectroscopy (NIR) and various algorithms, such as partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and classification and regression trees (CART), were used to differentiate the freshness of rice. PLS-DA and SVM demonstrated excellent classification ability in identifying the freshness of rice, with sensitivity and specificity of 1. The original spectra were used with 100% accuracy in the test set to determine the freshness of the rice. As a result, PLS-DA and SVM can be used to determine the freshness of the rice.
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Oryza , Espectroscopía Infrarroja Corta , Espectroscopía Infrarroja Corta/métodos , Oryza/química , Análisis Discriminante , Algoritmos , Análisis de los Mínimos Cuadrados , Máquina de Vectores de SoporteRESUMEN
BACKGROUND: Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. METHODS: The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ''TyG index'' and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. RESULTS: A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22-1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19-1.89) and increased risk of mortality (OR 1.40 95% CI 1.14-1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88-1.43) and neurological worsening (OR: 1.76; 95% CI 0.79-3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I2 = 77.20%). CONCLUSIONS: TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Calidad de Vida , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Bases de Datos Factuales , Glucosa , Triglicéridos , Glucemia , Biomarcadores , Factores de RiesgoRESUMEN
OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a globally aggressive malignant tumor. This study aimed to investigate the mechanism of JUND in ESCC development via MAPRE2. METHODS: ESCC cells (KYSE-450 and ECA109) were transfected with small interfering RNA (si)-JUND, si-MAPRE2, si-JUND, or pcDNA3.1-MAPRE2. JUND and MAPRE2 expression in ESCC cells was detected with quantitative real-time polymerase chain reaction and western blot. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to determine ESCC cell proliferation. Dual-luciferase reporter gene and chromatin immunoprecipitation assays were performed to assess binding between JUND and MAPRE2. Human umbilical vein endothelial cells (HUVECs) were co-cultured with ESCC cell supernatants. Angiogenesis was assessed with an in vitro angiogenesis assay. Western blot was conducted to evaluate the expression of angiogenic proteins [vascular endothelial growth factor A (VEGFA), matrix metallopeptidase 9 (MMP-9), and angiopoietin-2 (ang2)]. RESULTS: The levels of expression of JUND and MAPRE2 were high in ESCC cells. Mechanistically, JUND bound to MAPRE2 promoter and increased MAPRE2 transcription. Downregulation of JUND or MAPRE2 inhibited KYSE-450 and ECA109 cell proliferation and reduced the levels of expression of VEGFA, MMP-9, and ang2 and tube formation in HUVECs co-cultured with ESCC cell supernatants. MAPRE2 upregulation counteracted the inhibitory effects of JUND silencing on cell proliferative and angiogenic capabilities in ESCC. CONCLUSIONS: JUND promoted MAPRE2 transcription, thereby facilitating cell proliferative and angiogenic abilities in ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , Proteínas Asociadas a Microtúbulos , Proteínas Proto-Oncogénicas c-jun , Humanos , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Células Endoteliales/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , ARN Interferente Pequeño , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismoRESUMEN
Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though its prevalence in dementia has been studied, its occurrence in mild cognitive impairment (MCI) has not been well established. As MCI is often a prelude to dementia, our study aims to investigate the prevalence of MCI among individuals with sarcopenia and to also ascertain whether sarcopenia is independently associated with MCI. The Cochrane Library, PubMed, Ovid, Embase and Web of Science were systematically searched for articles on MCI and/or sarcopenia published from inception to 1 February 2022. We reviewed the available literature on the number of individuals with MCI and/or sarcopenia and calculated odds ratios (ORs) of sarcopenia in MCI and MCI in sarcopenia, respectively. Statistical analyses were performed using the meta package in Stata, Version 12.0. A total of 13 studies and 27 428 patients were included in our analysis. The pooled prevalence of MCI in participants with sarcopenia was 20.5% (95% confidence interval [CI]: 0.140-0.269) in a total sample of 2923 cases with a high level of heterogeneity (P < 0.001; I2 = 95.4%). The overall prevalence of sarcopenia with MCI was 9.1% (95% CI: 0.047-0.134, P < 0.001; I2 = 93.0%). For overall ORs, there were 23 364 subjects with a mean age of 73 years; the overall adjusted OR between MCI and sarcopenia was 1.46 (95% CI: 1.31-1.62). Slight heterogeneity in both adjusted ORs (P = 0.46; I2 = 0%) was noted across the studies. The prevalence of MCI is relatively high in patients with sarcopenia, and sarcopenia may be a risk factor for MCI.
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Disfunción Cognitiva , Demencia , Sarcopenia , Humanos , Anciano , Sarcopenia/epidemiología , Sarcopenia/complicaciones , Prevalencia , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/complicaciones , Factores de Riesgo , Demencia/complicacionesRESUMEN
Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.
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MicroARNs , ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , ARN Largo no Codificante/genética , Docetaxel/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Proliferación CelularRESUMEN
Cytotoxic chemotherapy is the major strategy to prevent and reduce triple-negative breast cancer (TNBC) progression and metastasis. Hypoxia increases chemoresistance and is associated with a poor prognosis for patients with cancer. Based on accumulating evidence, microRNAs (miRNAs) play an important role in acquired drug resistance. However, the role of miRNAs in hypoxia-induced TNBC drug resistance remains to be clarified. Here, we found that hypoxia induced TNBC docetaxel resistance by decreasing the miR-494 level. Modulating miR-494 expression altered the sensitivity of TNBC cells to DTX under hypoxic conditions. Furthermore, we identified Survivin as a direct miR-494 target. Hypoxia upregulated survivin expression. In a clinical study, the HIF-1α/miR-494/Survivin signaling pathway was also active in primary human TNBC, and miR-494 expression negatively correlated with HIF-1α and survivin expression. Finally, in a xenograft model, both miR-494 overexpression and the HIF-1α inhibitor PX-478 increased the sensitivity of TNBC to DTX by suppressing the HIF-1α/miR-494/Survivin signaling pathway in vivo. In conclusion, treatments targeting the HIF-1α/miR-494/Survivin signaling pathway potentially reverse hypoxia-induced drug resistance in TNBC.
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MicroARNs , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Docetaxel , Regulación Neoplásica de la Expresión Génica , Humanos , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia , Transducción de Señal , SurvivinRESUMEN
PURPOSE: The International Association for the Study of Lung Cancer (IASLC) of TNM staging system has been well accepted as a precise model. However, the latest American Joint Committee on Cancer (AJCC) staging system to solve the different survival and prognosis of lung adenocarcinoma in the same period is still controversial. Therefore, it is necessary to thoroughly explore the applicability between the new system and survival prediction in terms of lung adenocarcinoma. METHODS: We recruited 52,517 patients with lung adenocarcinoma from the Surveillence, Epidemiology, and End Results database. Cox regression analysis was performed to determine survival related factors. The mortality rate per 1000 persons per year of the T4N2M0 lung adenocarcinoma stage and other stages were compared. Survival curves were obtained using the Kaplan-Meier analysis and log-rank test. RESULTS: The results of Cox proportional hazards regression analysis showed that age at diagnosis, race, T stage, distant metastasis, extrathoracic extension, radiotherapy, chemotherapy, and surgery are independent factors related to cancer-specific survival (CSS) and all-cause survival. Furthermore, patients with stage IIIA disease (P<0.001) and IIIB disease (P<0.001) excluding stage at T4N2M0 had a significantly lower risk of CSS and all-cause survival than those staged with T4N2M0 disease. The mortality rates per 1000 person-years with patients staged at T4N2M0 lung adenocarcinoma had higher mortality than patients in the same period. The CSS curves of patients with stage T4N2M0 reflected an obvious decline compared with those of stages IIIA disease and IIIB excluding T4N2M0, and there is no significant difference between this curve and stage IIIC patients (P>0.05). CONCLUSION: The survival rate of patients with T4N2M0 stage was significantly lower than that of patients with IIIA and IIIB stages excluding T4N2M0, there was no significant difference between T4N2M0 and IIIC. It was suggested that this group of patients with stage T4N2M0 were upgraded in the 8th IASLC system.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/terapia , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , PronósticoRESUMEN
A visible-light-promoted atomic substitution reaction for transforming thiocacids into carboxylic acids with dimethyl sulfoxide (DMSO) as the oxygen source has been developed, affording various alkyl and aryl carboxylic acids in over 90% yields. The atomic substitution process proceeds smoothly through the photochemical reactivity of the formed hydrogen-bonding adduct between thioacids and DMSO. A DMSO-involved proton-coupled electron transfer (PCET) and the simultaneous generation of thiyl and hydroxyl radicals are proposed to be key steps for realizing the transformation.
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Ácidos Carboxílicos , Dimetilsulfóxido , Transporte de Electrón , Oxidación-Reducción , Protones , Compuestos de AzufreRESUMEN
Diagnosis of Alzheimer's disease (AD) is a complex task, and at present, neuroimaging such as magnetic resonance imaging and positron emission tomography is commonly used for the diagnosis of AD. This research work developed a new biosensing method with gold nanomaterial to identify AD biomarker of miRNA-137. Gold nanourchin (GNU) was attached on the interdigitated electrode through the silane linker and COOH-ended capture oligonucleotide was immobilized on the GNU surface. This surface helps to quantify the target sequence of miRNA-137 and the detection limit reached to 0.01 pM on the linear range of 0.01-100 pM. With 3δ calculation on the linearity, the determination coefficient was noticed as y = 1.2867x - 2.2697; R2 = 0.9059. The control performances did not show a significant response, indicating the specific identification of target.