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Backgrounds: The integrator complex (INT) is a multiprotein assembly in gene transcription. Although several subunits of INT complex have been implicated in multiple cancers, the complex's role in gastric cancer (GC) is poorly understood. Methods: The gene expressions, prognostic values, and the associations with microsatellite instability (MSI) of INT subunits were confirmed by GEO and The Cancer Genome Atlas (TCGA) databases. cBioPortal, GeneMANIA, TISIDB, and MCPcounter algorithm were adopted to investigate the mutation frequency, protein-protein interaction network, and the association with immune cells of INT subunits in GC. Additionally, in vitro experiments were performed to confirm the role of INTS11 in pathogenesis of GC. Results: The mRNA expression levels of INTS2/4/5/7/8/9/10/11/12/13/14 were significantly elevated both in GSE183904 and TCGA datasets. Through functional enrichment analysis, the functions of INT subunits were mainly associated with snRNA processing, INT, and DNA-directed 5'-3' RNA polymerase activity. Moreover, these INT subunit expressions were associated with tumor-infiltrating lymphocytes and MSI in GC. In vitro experiments demonstrated that knockdown of the catalytic core INTS11 in GC cells inhibits cell proliferation ability. INTS11 overexpression showed opposite effects. Conclusions: Our data demonstrate that the INT complex might act as an oncogene and can be used as a prognosis biomarker for GC.
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The gold inner shell of Turbo argyrostomus is an important morphological classification characteristic in Gastropoda. However, the gene sets responsible for shell formation in gastropods remain poorly explored. In this study, we investigated the microstructure using scanning electron microscopy (SEM), hematoxylin-eosin (HE) and Alcian blue staining-periodic acid-Schiff (AB-PAS) staining. The SEM results illustrated that the T. argyrostomus shell exhibited a special "sandwich" microstructure. The results of histological observation demonstrated two major cell types: adipocytes and mucin cells. A total of 318 differentially expressed genes were identified between edge mantle and central mantle, among which whey acidic protein, N66, and nacre-like proteins, and Lam G and EGF domains may be related to shell microstructure. 22.39% - 25.20% of the mucin genes had biomineralization related domains, which supported for the relationship between mucins and shell formation. Moreover, this study revealed energy distribution differences between the edge mantle and central mantle. These results provide insights for further understanding of the biomineralization mechanism in Gastropoda.
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Exoesqueleto , Gastrópodos , Perfilación de la Expresión Génica , Transcriptoma , Animales , Exoesqueleto/ultraestructura , Exoesqueleto/metabolismo , Gastrópodos/genética , Gastrópodos/metabolismo , Gastrópodos/ultraestructura , Perfilación de la Expresión Génica/métodos , Mucinas/genética , Mucinas/metabolismo , Biomineralización/genética , Microscopía Electrónica de RastreoRESUMEN
Considering the key role of myeloid cell differentiation-related genes in the tumor microenvironment (TME), we aimed to build a prognostic risk model using these genes for Lung adenocarcinoma (LUAD). The mRNA gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were downloaded as the training and validation sets. Then, "edgeR" R package was applied to screen out the differentially expressed genes (DEGs) and univariate cox regression, backward stepwise selection analyses were performed to construct a prognostic model for LUAD. ESTIMATE, TIMER, XCELL, CIBERSORT abs, QUANTISEQ, MCPCOUNTER, EPIC, and CIBERSORT algorithms were conducted to access the association of risk levels with the stromal and immune cell infiltration levels in LUAD. Six genes (F2RL1, PRKDC, TNFSF11, INHA, PLA2G3 and TUBB1) were utilized to construct the prognostic model. The risk model showed excellent prognostic performance for LUAD in both TCGA and GEO datasets. Also, compared to the low-risk patients, the high-risk patients had higher expression of immune checkpoint molecules and showed a lower IC50 value to the chemotherapy agents. Our findings provided a myeloid cell differentiation-related gene signature that could effectively predict prognosis and guide treatment strategies for LUAD patients.
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Adenocarcinoma del Pulmón , Diferenciación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Células Mieloides , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Pronóstico , Células Mieloides/metabolismo , Células Mieloides/inmunología , Diferenciación Celular/genética , Biomarcadores de Tumor/genética , Femenino , Transcriptoma , Perfilación de la Expresión Génica , Masculino , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
Learning invariant representations via contrastive learning has seen state-of-the-art performance in domain generalization (DG). Despite such success, in this paper, we find that its core learning strategy - feature alignment - could heavily hinder model generalization. Drawing insights in neuron interpretability, we characterize this problem from a neuron activation view. Specifically, by treating feature elements as neuron activation states, we show that conventional alignment methods tend to deteriorate the diversity of learned invariant features, as they indiscriminately minimize all neuron activation differences. This instead ignores rich relations among neurons - many of them often identify the same visual concepts despite differing activation patterns. With this finding, we present a simple yet effective approach, Concept Contrast (CoCo), which relaxes element-wise feature alignments by contrasting high-level concepts encoded in neurons. Our CoCo performs in a plug-and-play fashion, thus it can be integrated into any contrastive method in DG. We evaluate CoCo over four canonical contrastive methods, showing that CoCo promotes the diversity of feature representations and consistently improves model generalization capability. By decoupling this success through neuron coverage analysis, we further find that CoCo potentially invokes more meaningful neurons during training, thereby improving model learning.
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As a prevalent pathogenic fungus, Aspergillus westerdijkiae poses a threat to both food safety and human health. The fungal growth, conidia production and ochratoxin A (OTA) in A. weterdijkiae are regulated by many factors especially transcription factors. In this study, a transcription factor AwSclB in A. westerdijkiae was identified and its function in asexual sporulation and OTA biosynthesis was investigated. In addition, the effect of light control on AwSclB regulation was also tested. The deletion of AwSclB gene could reduce conidia production by down-regulation of conidia genes and increase OTA biosynthesis by up-regulation of cluster genes, regardless under light or dark conditions. It is worth to note that the inhibitory effect of light on OTA biosynthesis was reversed by the knockout of AwSclB gene. The yeast one-hybrid assay indicated that AwSclB could interact with the promoters of BrlA, ConJ and OtaR1 genes. This result suggests that AwSclB in A. westerdijkiae can directly regulate asexual conidia formation by activating the central developmental pathway BrlA-AbaA-WetA through up-regulating the expression of AwBrlA, and promote the light response of the strain by activating ConJ. However, AwSclB itself is unable to respond to light regulation. This finding will deepen our understanding of the molecular regulation of A. westerdijkiae development and secondary metabolism, and provide potential targets for the development of new fungicides.
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Aspergillus , Factores de Transcripción , Humanos , Metabolismo Secundario/genética , Aspergillus/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/genéticaRESUMEN
Ascorbic acid (AA) is an essential vitamin in humans, and numerous AA detection studies have been conducted. Most quantum dots (QDs)-based approaches depend on redox reactions involving AA, and they require the introduction of an intermediate (e.g., metal ions, OPD, TMB) or the assembly of fluorescent substances with nanosheets (such as MnO2) that can be degraded by AA. These methods are complex, unstable, and are susceptible to interferences. To address these problems, a core-shell fluorescence probe was developed for turn-on sensing of AA. The transition metal oxide shell FeOOH was generated around the surface of CuInZnS QDs to quench the fluorescence. In the presence of AA, the FeOOH shell was decomposed into Fe2+ and the fluorescence of QDs was recovered. Using a physical shell, the obtained nanocomposite realized direct AA detection, avoiding the effects of interfering substances caused by QDs exposure. Moreover, our probe showed great potential in point-of-care tests and was readily adapted for use as a smartphone-assisted paper sensor.
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High mortalities and highly variable results during the subsequent development of post-thaw larvae have been widely considered as key issues restricting the application of cryopreservation techniques to support genetic improvement programs and hatchery production in farmed marine bivalve species. To date, few studies have been undertaken to investigate the effects of cryodamage at the molecular level in bivalves. This study is the first to evaluate the effect of larval cryopreservation on the epigenetics of the resultant progenies of the Pacific oyster Crassostrea gigas. The results show that the level of DNA methylation was significantly (p < 0.05) higher and lower than that of the control when the trochophore larvae were revived and when they developed to D-stage larvae (day 1 post-fertilization), respectively, but the level returned to the control level from day 8 post-fertilization onwards. The expression of the epigenetic regulator genes DNMT3b, MeCP2, JmjCA, KDM2 and OSA changed significantly (p < 0.05) when the trochophore larvae were thawed, and then they reverted to the control levels at the D- and later larval developmental stages. However, the expression of other epigenetic regulator genes, namely, MBD2, DNMT1, CXXC1 and JmjD6, did not change at any post-thaw larval developmental stage. For the newly thawed trochophore larvae, the amount of methylated H3K4Me1 and H3K27Me1 significantly changed, and the expression of all Jumonji orthologs, except that of Jumonji5, significantly (p < 0.05) decreased. These epigenetic results agree with the data collected on larval performances (e.g., survival rate), suggesting that the effect period of the published cryopreservation technique on post-thaw larvae is short in C. gigas.
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Crassostrea , Animales , Crassostrea/genética , Larva/genética , Criopreservación/métodos , Epigénesis Genética , Metilación de ADNRESUMEN
Metaplastic breast cancer (MBC) is a rare disease, and there was rarely reported the treatment after recurrence and metastasis. Here, we report the treatment of an adult patient who suffered from MBC with lung, lymph nodes and left pleura metastasis after radical surgery. The next-generation sequencing result demonstrated that it had tumor mutational burden (TMB) of 12.0 Muts/Mb and microsatellite stability. The patient received sintilimab, an immune checkpoint inhibitor, plus chemotherapy and achieved partial response (PR). This is a report of a good outcome of metastatic MBC achieving 24 months of progression-free survival (PFS) and 39 months of overall survival (OS) with a combination therapy of immune checkpoint inhibitor and chemotherapy. Immuno-chemotherapy may have antitumor activity for relapse MBC. TMB may serve as a potential predictor associated with PD-1 inhibitors in MBC and help clinicians make an optimum treatment strategy.
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OBJECTIVES: To investigate the predictive significance of dynamic changes in the neutrophil to lymphocyte ratio (NLR) and platelet counts (PLTs) in patients with advanced gastric cancer (GC) during chemotherapy. METHODS: A total of 259 advanced GC patients receiving chemotherapy were enrolled and grouped by high or low NLR with a cut value of 2.5 and PLT with cut value of 300×109/L. The Kaplan-Meier survival model and the Log-rank test were carried out to determine the comparison on the overall survival differences. Cox regression analysis was employed to carry out both univariate and multivariate regression studies, aiming to explore potential prognostic factors acting independently. RESULTS: Higher pre-chemotherapy NLR exhibited an association with metastasis and advanced grade of Borrmann type, and higher NLR of pre- or post-chemotherapy GC patients was related with Borrmann type grade. Moreover, higher PLT counts are associated with advanced grades of Borrmann type. Interestingly, patients with lower post-chemotherapy NLR or decreasing NLR hold better overall response rate and disease control rate than those with higher NLR or increasing NLR. Furthermore, patients with high post-chemotherapy NLR alone or higher post-chemotherapy NLR plus higher post-chemotherapy PLT. CONCLUSION: Our study suggested that high post-chemotherapy NLR and post-chemotherapy PLT might be adverse prognostic markers in advanced GC patients undergoing chemotherapy.
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Neutrófilos , Neoplasias Gástricas , Humanos , Pronóstico , Recuento de Plaquetas , Plaquetas/patología , Estimación de Kaplan-Meier , Linfocitos/patologíaRESUMEN
Background: Traditional Chinese medicine (TCM) effectively improves the survival rate and quality of life of primary liver cancer patients, but high-level evidence is lacking. Patients and methods: Patients were selected from 5 tertiary hospitals in Henan Province, China. Two thousand sixty-seven patients with primary liver cancer were included in the study. The electronic medical records (EMRs) of the patients were collected. Patients who received adjunctive TCM treatment and underwent treatment cumulative time for more than 1 month were classified as the TCM intervention cohort. Patients who did not receive adjunctive TCM treatment or underwent treatment cumulative time for less than 1 month were classified as the non-TCM intervention cohort. The main outcome indicators were the survival rate and overall survival time. The propensity score inverse probability weighting method was used to balance the differences between the groups. Results: The primary cohort comprised 2,067 patients, including 462 patients who received adjunctive TCM treatment and 1,605 patients who did not receive adjunctive TCM treatment. The results of the KaplanâMeier survival curve indicated that the survival rate and median survival time of the exposure group before and after propensity score weighting were greater than those of the control group (p < 0.0001). Univariate Cox regression analysis after propensity score weighting showed that adjunctive TCM treatment was an independent protective factor for survival [regression coefficient = -0.215, hazard ratio (HR) = 0.8066, 95% confidence interval (CI) (0.6609-0.9844)]. Conclusion: Adjuvant treatment with TCM has a protective effect on the prognosis of patients with primary liver cancer; it can reduce the mortality and prolong the survival time.
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The precious medicinal plant, Amomum tsao-ko Crevost et Lemarié, is the nectariferous plant from which the rare Amomum tsao-ko Crevost et Lemarié honey (ATH) is produced. Presently, chemical markers for authentication of this honey are not available due to the lack of data on its chemical composition. Here, we analyzed the volatile components and their odor activity values (OAVs), which revealed that the unique aroma was mildly flowery and fruity, accompanied by subtle sweet and fresh undertones. Since non-volatile chemicals are more reliable markers for routine authentication, we used a metabolomic approach combined with NMR-based identification to find and confirm a suitable compound to unambiguously distinguish ATH from other honeys. Isorhamnetin 3-O-neohesperidoside ranged from 3.62 to 9.38 mg/kg in ATH and was absent in the other tested honeys. In sum, the study uncovered unique chemical characteristics of ATH that will be helpful to control its quality.
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Amomum , Miel , Cromatografía de Gases y Espectrometría de Masas , Cromatografía Liquida , Especias , Espectrometría de Masas en TándemRESUMEN
This study aimed to examine the hsa-miR-497-3p effect and mechanism on the behavior of triple-negative breast cancer (TNBC) cells. We evaluated the expression of Hsa-miR-497-3p in tissue samples obtained from patients diagnosed with TNBC or luminal breast cancer (BrCa), utilizing the quantitative fluorescence polymerase chain reaction (PCR) method. We transfected hsa-miR-497-3p mimics and NC into MDA-MB-231 cells, whilehsa-miR-497-3p inhibitor and NC into TNBC cells, respectively. To examine the impact of hsa-miR-497-3p expression level on TNBC cell proliferation, invasion, and migration, we employed MTT, clone formation, Transwell, and wound healing assays. We utilized both q-PCR and western blot to validate the role of hsa-miR-497-3p in the epithelial-mesenchymal transition (EMT) of TNBC cells. To confirm the targeting relationship between hsa-miR-497-3p and ZEB1, we performed luciferase assays, q-PCR, and western blot analysis. We found that the hsa-miR-497-3p expression was down-regulated in both TNBC tissues and cell lines in comparison to luminal BrCa tissues and cell lines. Furthermore, hsa-miR-497-3p overexpression hindered the cell function of TNBC cells MDA-MB-231, while downregulating the mRNA and protein expression of vimentin and N-cadherin, while simultaneously upregulating E-cadherin expression. Our results demonstrate that hsa-miR-497-3p regulates EMT in TNBC cells through ZEB1 targeting, as evidenced by the modulation of the expression of vimentin, N-cadherin, and E-cadherin via ZEB1 inhibition. Overall, our study suggests that hsa-miR-497-3p inhibits the proliferation and invasion of TNBC cells through the modulation of EMT via ZEB1 targeting.
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MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Transición Epitelial-Mesenquimal/genética , Neoplasias de la Mama Triple Negativas/genética , Vimentina/genética , MicroARNs/genética , Proliferación Celular/genética , Cadherinas/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genéticaRESUMEN
Here, we describe highly efficient intramolecular hydroarylations mediated by Re2O7/HReO4. Styrene derivatives of different electronic properties have been activated to effect a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures. This method is characterized by mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy. The potential synthetic application of this methodology was exemplified by the efficient total synthesis of an isoCA-4 analogue.
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PURPOSE: Colorectal cancer (CRC) is the third most common cancer in the world. The purpose of this study was to investigate the role of TNNT2 in the proliferation, migration and invasion of CRC cells and its expression in CRC tissues to better understand the regulatory role of TNNT2 in CRC. METHODS: Western blotting (WB) and qPCR were used to detect the expression of TNNT2 in colorectal cancer tissues and paracancerous tissues. CCK-8, colony formation, Transwell and other experiments were used to clarify the role of TNNT2 in the proliferation, migration and invasion of colorectal cancer cells. Changes in TNNT2, EGFR and HER2 mRNA transcription levels were detected by SYBR Real-Time PCR assay, and the effects of TNNT2 overexpression or knockdown on the expression of EGFR, HER2 and EMT-related proteins in CRC cells were determined by WB. TNNT2 and EGFR intreaction was carried out in HCT116 cells by coimmunoprecipitation experiments. RESULTS: The protein and mRNA expression level of TNNT2 in CRC tissues were higher than those in paracancerous tissues. The CCK-8 results suggested that overexpression of TNNT2 significantly promoted the proliferation of HCT116 and RKO cells, and TNNT2 konckdown gets the opposite result; and the colony formation results were the same as tthose of CCK-8 assay. Transwell invasion and migration experiments showed that overexpression of TNNT2 promoted the migration and invasion of HCT116 and PKO cells, and TNNT2 konckdown suppressed the migration and invasion of the these cells. The SYBR Green I real-time PCR method revealed that them RNA levels of TNNT2, EGFR and HER2 in the TNNT2 overexpression group were higher than those in RKO cells. WB showed that overexpressing TNNT2 increased the expression of EGFR and HER2 in HCT16 and RKO cells,decreased the expression of EMT marker E-cadherin, and increased the expression of Vimentin and N-cadherin. Konckdown of TNNT2 decreased the expression of EGFR and HER2, increased the expression of E-cadherin, and decreased the expression of Vimentin and N-cadherin in HCT16 and RKO cells. The immunocoprecipitation experiment showed that there was an interaction between EGFR and TNNT2. CONCLUSION: TNNT2 can promote the proliferation, invasion and metastasis of colorectal cancer cells. There is an interaction between TNNT2 and EGFR protein. TNNT2 can upregulate EGFR and HER2-related proteins in colorectal cancer cells and promote the occurrence of EMT. Therefore, TNNT2 can promote the invasion and metastasis of CRC cells through the EGFR/HER2/EMT signal axis, suggesting that TNNT2 is a potential target of CRC treatment.
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BACKGROUND: Immunocheckpoint inhibitor(ICI) is a major breakthrough in tumor treatment. It can activate the patient's own immune system and play an anti-tumor role, but not all patients can benefit from it. At present, there is still a lack of effective biomarkers to guide clinical application. The systemic immune inflammation(SII) index reflects the systemic inflammatory state and immune state of patients. Prognostic nutrition index(PNI) can be used to evaluate immune status of patients. Therefore, SII and PNI indexes may have some value in predicting the efficacy and prognosis of immunotherapy, but there is still a lack of relevant research. The purpose of our study was to explore the influence of SII and PNI index on the efficacy and prognosis of immunotherapy. METHODS: A total of 1935 patients treated with ICIs treatment in the Fourth Hospital of Hebei Medical University from November 2016 to October 2021 were retrospectively collected. 435 patients who met the inclusion criteria and did not meet the exclusion criteria. The imaging data, blood results of each patient were collected within 1 week before ICIs treatment. The neutrophil lymphocyte ratio(NLR), platelet lymphocyte ratio(PLR), monocyte lymphocyte ratio(MLR), PNI,systemic inflammatory response index(SIRI),neutrophil-eosinophil ratio(NER) was calculated. The patients were followed up by in-patient, out-patient reexamination and telephone contact, and the efficacy evaluation and survival status were recorded. The deadline of follow-up: January 2021. SPSS-24.0 software was employed for statistical analysis. RESULTS: Among the 435 patients receiving ICI treatment, 61,236 and 138 patients were evaluated respectively as partial response (PR), stable disease (SD) and progressive disease (PD). The overall response rate(ORR) and disease control rate (DCR) of this cohort were 14.0% and 68.3%, respectively. Median progression-free survival (mPFS) is 4.0 months, The overall survival (mOS) of this cohort is 6.8 months. Multivariate analysis showed that SIRI(Hazard Ratio, HR = 1.304, P = 0.014), PNI (HR = 0.771, P = 0.019), prealbumin (PAB) (HR = 0.596, P = 0.001), and PNI(HR = 0.657, P = 0.008) were independent risk factors for PFS and OS, respectively. CONCLUSIONS: Patients with high SIRI value and low PNI value before ICI treatment have shorter PFS. Patients with higher PNI value have better prognosis. Therefore, hematological indicators may become predictors of immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Inflamación , Neutrófilos/patologíaRESUMEN
AIM: The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) administration. METHODS: A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly. RESULTS: The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs 10.9 months, P=0.023) and (median PFS: 14.0 vs 10.1 months, P=0.001). CONCLUSION: This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.
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Quantum dots (QDs) have become promising electrochemiluminescence (ECL) emitters with high quantum yield and size-tunable luminescence. However, most QDs generate strong ECL emission at the cathode, developing anodic ECL-emitting QDs with excellent performance is challenging. In this work, low-toxic quaternary AgInZnS QDs synthesized by a one-step aqueous phase method were used as novel anodic ECL emitters. AgInZnS QDs exhibited strong and stable ECL emission and a low excitation potential, which could avoid the side reaction of oxygen evolution. Furthermore, AgInZnS QDs displayed high ECL efficiency (ΦECL) of 5.84, taking the ΦECL of Ru(bpy)32+/tripropylamine (TPrA) ECL system as 1. Compared to AgInS2 QDs without Zn doping and traditional anode luminescent CdTe QDs, the ECL intensity of AgInZnS QDs was 1.62 times and 3.64 times higher than that of AgInS2 QDs and CdTe QDs, respectively. As a proof-of-concept, we further designed an "on-off-on" ECL biosensor for detecting microRNA-141 based on a dual isothermal enzyme-free strand displacement reaction (SDR), which not only to achieve the cyclic amplification of the target and ECL signal, but also to construct a switch of the biosensor. The ECL biosensor had a wide linear range from 100 aM to 10 nM with a low detection limit of 33.3 aM. Together, the constructed ECL sensing platform is a promising tool for rapid and accurate diagnosis of clinical diseases.
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Técnicas Biosensibles , Compuestos de Cadmio , Puntos Cuánticos , Técnicas Biosensibles/métodos , Telurio , Mediciones Luminiscentes/métodos , Electrodos , Técnicas Electroquímicas/métodosRESUMEN
Anaplastic lymphoma kinase (ALK) rearrangements have been reported in 3-7% of non-small-cell lung cancers (NSCLC). ALK has been reported to be fused with a variety of genes in NSCLC. Significant clinical activity was achieved by ALK inhibitors in patients with NSCLC harbouring ALK translocations. We reported on a 48-year-old male Chinese patient with advanced lung adenocarcinoma harboring a novel ALK-LIMS1 who showed no response to crizotinib. The tissue was assayed by immunohistochemistry (IHC) for ALK and showed diffuse expression of ALK. Next-generation sequencing (NGS) was performed on the peripheral blood and tissue. The previous tumor tissue showed diffuse expression of ALK. Tissue and the later peripheral blood revealed a ALK- LIMS1 fusion. The patient failed to benefit from crizotinib (250 mg, twice a day), with a progression-free survival of two months. We identified a new ALK-LIMS1 fusion from an advanced lung adenocarcinoma which was primary resistant to crizotinib. Our case suggested that the coexistence of mutations and the non-dominant clone, as well as the rearrangement of ALK fusion, did not result in expressed ALK kinase domain that might lead to no response to ALK-TKIs.
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China has a long history of pig breeding and a number of local breeds. The Songliao Black pig, bred in China in 2009, shows high variation in backfat thickness and therefore is well-suited to fat deposition research. Fat deposition is a complex trait, and the underlying regulatory factors are not fully characterized. In this study, the molecular basis of fat deposition traits was evaluated by comparisons between three individuals with extremely high-backfat thickness and three with extremely low-backfat thickness selected from 53 gilts. Subcutaneous adipose tissues of the back were collected for strand-specific library RNA sequencing (RNA-seq) and small RNA-seq. We identified 13 184 mRNAs, 2046 long non-coding (lnc)RNAs, and 494 micro (mi)RNAs by high-throughput sequencing. Furthermore, we detected 150 differentially expressed mRNAs, 66 differentially expressed lncRNAs, and eight differentially expressed miRNAs. A functional enrichment analysis indicated that these genes are involved in multiple fat metabolism-related pathways, including positive regulation of fat cell differentiation, and fat digestion and absorption. We used various algorithms (miRanda, TargetScan, and RNAhybrid) to predict targeting relationships and constructed a competing endogenous RNA network containing seven lncRNAs, three miRNAs, and six mRNAs. All these genes were differentially expressed between the extremely high and low backfat thickness groups or enriched in pathways related to fat metabolism. Our results provide insight into the regulatory mechanisms by which non-coding RNAs and their target genes influence backfat deposition in pigs. Furthermore, our newly constructed competing endogenous RNA (lncRNA-miRNA-mRNA) network provides a basis for further exploration of fat deposition traits and non-coding RNA functions.