CircFNDC3B induced TIMP3 to suppress angiogenesis to inhibit CRC cell proliferation, migration and invasion by negatively targeting miR‐937‐5p. Also, circFNDC3B exosomes could repress CRC ...angiogenesis by decreasing VEGFR expression.
Circular RNA (circRNA) are single‐stranded RNA with covalently closed 3′ and 5′ ends, with many recognized to be involved in human diseases as gene regulators, typically by interacting with other RNA. CircFNDC3B is a circRNA formed by back‐splicing of exons 5 and 6 of the FNDC3B gene. CircFNDC3B was recently implicated in renal carcinoma, gastric and bladder cancer. However, the expression levels of circFNDC3B and its role in colorectal cancer (CRC) remain unclear. Expression of circFNDC3B and TIMP3 levels in CRC tissues and cell lines were found to be low, whereas microRNA (miR)‐937‐5p expression was high in CRC. MicroRNA‐937‐5p downregulated TIMP3, thereby promoting tumor cell proliferation, invasion, migration and angiogenesis. Moreover, CircFNDC3B was shown to bind to miR‐937‐5p. CircFNDC3B and circFNDC3B‐enriched exosomes inhibited tumorigenic, metastatic and angiogenic properties of CRC, and miR‐937‐5p overexpression or TIMP3 knockdown could reverse these effects. In vivo CRC tumor growth, angiogenesis and liver metastasis were suppressed by circFNDC3B overexpression, circFNDC3B‐enriched exosomes or miR‐937‐5p knockdown. In conclusion, our work reports a tumor‐suppressing role for the circFNDC3B–miR‐97‐5p–TIMP3 pathway and suggests that circFNDC3B‐enriched exosomes can inhibit angiogenesis and CRC progression.
Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging ...probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.
The construction of C−N bonds is a central tenet of modern synthetic chemistry as it widely exists in bioactive molecules, natural products, and functional materials. Visible‐light induced strategies ...can serve as particularly powerful tools for achieving C−N bond formation. This mini review summarizes the recent advancements in the transformation of C(sp3)−H bonds into C−N bonds via photocatalysis under metal catalyst‐free conditions. These reactions generally occur in the presence of abundant and clean visible‐light at ambient temperature without the use of metal catalysts, which undoubtedly represents a future trend in green and sustainable chemistry. The main achievements in this area from 2015 until the present are described according to the type of nitrogen sources and emphasis is placed on the working mechanisms.
miRNAs are regarded as molecular biomarkers and therapeutic targets for colorectal cancer (CRC), a series of miRNAs have been proven to involve into CRC carcinogenesis, invasion and metastasis. ...Aberrant miR-422a expression and its roles have been reported in some cancers. However, the function and underlying mechanism of miR-422a in the progression of CRC remain largely unknown.
Real-time PCR were used to quantify miR-422a expression in CRC tissues. Both vivo and vitro functional assays showed miR-422a inhibits CRC cell proliferation. Target prediction program (miRBase) and luciferase reporter assays were conducted to confirm the target genes AKT1 and MAPK1 of miR-422a. Specimens from 50 patients with CRC were analyzed for the correlation between the expression of miR-422a and the expression of the target genes AKT1 and MAPK1 by real-time PCR.
MiR-422a was down‑regulated in CRC tissues and cell lines. Ectopic expression of miR-422a inhibited cell proliferation and tumor growth ability; inhibition of endogenous miR-422a, by contrast, promoted cell proliferation and tumor growth ability of CRC cells. MiR-422a directly targets 3'-UTR of the AKT1 and MAPK1, down-regulation of miR-422a led to the activation of Raf/MEK/ERK and PI3K/AKT signaling pathways to promote cell proliferation in CRC. In addition, miR-422a expression was negatively correlated with the expressions of AKT1 and MAPK1 in CRC tissues.
miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.
For solving the large-scale linear least-squares problem, we propose a block version of the randomized extended Kaczmarz method, called the two-subspace randomized extended Kaczmarz method, which ...does not require any row or column paving. Theoretical analysis and numerical results show that the two-subspace randomized extended Kaczmarz method is much more efficient than the randomized extended Kaczmarz method. When the coefficient matrix is of full column rank, the two-subspace randomized extended Kaczmarz method can also outperform the randomized coordinate descent method. If the linear system is consistent, we remove one of the iteration sequences in the two-subspace randomized extended Kaczmarz method, which approximates the projection of the right-hand side vector onto the orthogonal complement space of the range space of the coefficient matrix, and obtain the generalized two-subspace randomized Kaczmarz method, which is actually a generalization of the two-subspace randomized Kaczmarz method without the assumptions of unit row norms and full column rank on the coefficient matrix. We give the upper bound for the convergence rate of the generalized two-subspace randomized Kaczmarz method which also leads to a better upper bound for the convergence rate of the two-subspace randomized Kaczmarz method.
Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN ...introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species' potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen's kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.
Our previous study showed that exogenous human mesenchymal stem cells (hMSCs) targeted established osteosarcoma and promoted its growth and pulmonary metastasis in vivo. As a follow‐up, the present ...study aimed to investigate how hMSCs would interact with Saos‐2 through autocrine/paracrine communication. The results showed that co‐injection of hMSCs with Saos‐2 into the proximal tibia of nude mice could promote tumor growth and progression. In vitro, the proliferation of Saos‐2 and hMSCs was promoted by each other’s conditioned medium, in which interleukin‐6 (IL‐6) played an important role. Osteogenic differentiation of hMSCs could be inhibited by conditioned medium of Saos‐2, in which IL‐6 was also involved. Furthermore, decreased IL‐6 secretion by hMSCs during its osteogenesis and increased IL‐6 secretion in response to conditioned medium of Saos‐2 were observed. Based on these data, we suggest that there was a positive feedback loop of IL‐6 in the interaction between hMSCs and Saos‐2. (Cancer Sci 2010; 101: 2554–2560)
The incorporation of multiple sensing elements to a single sensor has been proposed by our group as an improvement for the array sensing technique with retaining the high selectivity of traditional ...multi-sensor based sensor array but largely simplifying the analytical operation. How to select reasonable sensing elements to construct the sensor is the key to improve the analytical performance. Herein, we propose a concept to solve this issue, that is, using the components which test different properties of analytes to discriminate them from various aspects. As a proof-of-principle trial, a MOF based composite sensor was designed to analyze tetracycline type antibiotics. The porphyrin-containing main ligand, naphthyl auxiliary ligand and rhodamine B guest were installed to response to the redox property, adsorption affinity and absorption/exchanging capability of the analyte, respectively. Six tetracycline homologous were clearly identified by this sensor, and it also exhibited good quantification performance. This method was successfully applied to the analysis of practical milk sample.
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•A MOF based composite was designed as a tri-channel fluorescent sensor.•Three components of the sensor response to different analyte properties.•With this sensor, a single sensor based sensor array was developed.•It can identify six tetracycline homologous even with unknown concentrations.•This method was successfully applied to practical food analysis.
Quantum‐dot‐tagged reduced graphene oxide (QD‐rGO) nanocomposites (left) internalized into targeted tumor cells display bright fluorescence from the QDs (right); by absorbing NIR radiation incident ...on the rGO and converting it into heat, they also cause simultaneous cell death and fluorescence reduction (bottom). The nanocomposite is thus capable of tumor imaging, photothermal therapy and in situ monitoring of treatment in progress.
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