•The biosensor had wide linear range (10aM∼100pM) and low detection limit (1.35aM).•The biosensor could realize accurate detection of miRNA-377 in human serum samples.•The biosensor amplified ...electrochemical signal by embedding MB into G-quadruplexes.•MXene-Au had high electrical conductivity and massive active sites for DNA capture.
MicroRNAs (miRNAs) are considered as potential biomarkers for early diagnosis and prognostic assessment of diabetic nephropathy. In this work, an electrochemical biosensor for ultrasensitive detection of miRNA-377 was constructed based on MXene-Au nanocomposites and G-quadruplex nano-amplification strategy. As a promising nanocarrier, taking advantage of leveraging synergistic effects between Au nanoparticles (AuNPs) and MXene nanosheet, MXene-Au nanocomposites exhibited excellent electronic conductivity and provided massive active sites for DNA capture probe immobilization by Au-S bonds. AuNPs modified with Guanine-rich sequence DNA detection probes were designed as signal amplification nano-labels. Specifically, by inducing the transition of Guanine-rich detection probes to G-quadruplex, the strong affinity interaction between methylene blue and G-quadruplex could not only reflect trace concentration information of miRNA-377, but also lead to the further enhancement of electrochemical signal (2.7-fold). As a result, this newly designed biosensor exhibited superior sensing performance with a wide linear range from 10 aM to 100 pM and the limit of detection was as low as 1.35 aM. Compared with biosensors based on other nanocomposites and reported miRNA-377 biosensors, the proposed sensing platform did not require any thermal cycling or reverse transcription process, meeting the miRNA sensing requirements of convenient, sensitive, specific and stable. Furthermore, the as-constructed biosensor also displayed good selectivity, which was applied to accurate detection of miRNA-377 in human serum samples with satisfactory sensitivity, suggesting the biosensor system has promising applications in biological researches and early clinical diagnosis for diabetic nephropathy.
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•PdCu/CB nanohybrid was synthesized in which PdCu nanoparticles were uniformly dispersed on the surface of CB.•The synergistic reaction of PdCu/CB enabled excellent electrocatalytic performance and ...high sensitivity of H2O2 biosensor.•This non-enzymatic electrochemical biosensor was successfully applied to monitor the H2O2 released from Raw 264.7 cells.
Hydrogen peroxide (H2O2) is a major metabolite of oxygen known as reactive oxygen species (ROS) in living organisms. Monitoring H2O2 released from living cells is of great significance as its concentration level is related to several diseases, which imposes stricter requirements on the sensitivity of detection technology. In this work, we have found that carbon black (CB) could preserve bimetallic PdCu alloy’s nanostructure, meanwhile improve the dispersion of nanoparticles, provided high conductivity and large specific surface area, thus the PdCu/CB nanohybrid exhibited enhanced electroanalytical performance of H2O2. Under the optimal conditions, the PdCu/CB nanohybrid modified electrode showed a low detection limit of 54 nM with a wide detection range from 0.4 μM to 5.0 mM. Finally, the application of PdCu/CB/GCE in real-time monitoring H2O2 released from Raw 264.7 cells was achieved, suggesting the PdCu/CB nanohybrid was the promising nanomaterial in monitoring physiological processes.
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•A miRNA electrochemical biosensor based on MXene nanocomposites was constructed.•The biosensor had wide linear range (1 fM ∼ 1 nM) and low detection limit (0.418 fM).•The outstanding ...performance of biosensor benefited from the excellent properties and large specific surface area of MXene.•The biosensor could realize accurate detection of miRNA-21 in both mouse and human urine samples.
The detection of microRNA is widely used in the early diagnosis of diseases such as cancer and acute kidney injury. In this work, we successfully constructed a label-free ultrasensitive biosensor for the instant detection of miRNA-21. The MXene-reduced graphene oxide (rGO)-Au was synthesized as electrode materials to immobilize DNA probes and MXene-AuPd was used as signal amplification materials. The highly sensitive biosensor had a wide range of linearity from 1 fM to 1 nM, and the limit of detection of as-fabricated biosensor was lower as 0.42 fM under optimized conditions. The biosensor also showed high specificity, outstanding stability and desirable reproducibility, which could also realize the accurate detection of miRNA-21 in real urine samples of both mouse and human with high sensitivity. The label-free electrochemical biosensor based on MXene nanocomposites is a promising candidate for potential applications on the early diagnosis of cancers and acute kidney injury.
Virtual radiographic simulation has been found educationally effective for students to practice their clinical examinations remotely or online. A free available virtual simulator-ImaSim has received ...particular attention for radiographic science education because of its portability, free of charge and no constrain of location and physical facility. However, it lacks evidence to validate this virtual simulation software to faithfully reproduce radiographs comparable to that taken from a real X-ray machine to date.
To evaluate image quality of the virtual radiographs produced by the ImaSim. Thus, the deployment of this radiographic simulation software for teaching and experimental studying of radiography can be justified.
A real medical X-ray examination machine is employed to scan three standard QC phantoms to produce radiographs for comparing to the corresponding virtual radiographs generated by ImaSim software. The high and low range of radiographic contrast and comprehensive contrast-detail performance are considered to characterize the radiographic quality of the virtual simulation software.
ImaSim software can generate radiographs with a contrast ranging from 30% to 0.8% and a spatial resolution as low as 0.6mm under the selected exposure setting condition. The characteristics of contrast and spatial resolution of virtual simulation generally agree with that of real medical X-ray examination machine.
ImaSim software can be used to simulate a radiographic imaging process to generate radiographs with contrast and detail detectability comparable to those produced by a real X-ray imaging machine. Therefore, it can be adopted as a flexible educational tool for proof of concept and experimental design in radiography.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Drug delivery nanoplatforms have been applied in bioimaging, medical diagnosis, drug delivery and medical therapy. However, insolubility, toxicity, instability, nonspecific targeting and short ...retention of many hydrophobic drugs limit their extensive applications. Herein, we have constructed a passive targeting and long retention therapeutic nanoplatform of core-shell gefitinib/poly (ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs). The Gef-PY NCs have good water-solubility, non-toxicity (correspond to 1/10 dosage of effective gefitinib (hydrochloride) (Gef·HCl) (normal drug administration and slow-release) and high stability (120 days, 80% drug retention at 4 or 25 °C). The core-shell Gef-PY NCs present unexpected kidney targeting and drug slow-release capacity (
ca.
72 h). The good water-solubility, non-toxicity and high stability of Gef-PY NCs effectively solve the bottleneck question that Gef-based therapy could be used only in intraperitoneal injection due to its insolubility and severe toxicity. Such excellent properties (
e.g.
, water-solubility, non-toxicity, high stability, kidney targeting and long retention) of Gef-PY NCs create their prominent anti-fibrosis capabilities, such as decreasing approximately 40% tubulointerstitial fibrosis area and 68% expression of collagen I within 7 days. This therapeutic efficacy is well-matched with that of 10 times the dosage of toxic Gef·HCl. It is very hopeful that Gef-PY NCs could realize clinical applications and such a strategy offers an effective route to design high-efficiency treatments for kidney- and tumor-related diseases.
A water-soluble, non-toxic, stable, passive kidney targeting, slow-released and long retentive therapeutic nanoplatform of core-shell gefitinib/poly(ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs) is designed and constructed.
This study aimed to create and verify a nomogram for preoperative prediction of Ki-67 expression in breast malignancy to assist in the development of personalized treatment strategies.
This ...retrospective study received approval from the institutional review board and included a cohort of 197 patients with breast malignancy who were admitted to our hospital. Ki-67 expression was divided into two groups based on a 14% threshold: low and high. A radiomics signature was built utilizing 1702 radiomics features based on an automated breast volume scanner intra- and peritumoral (10 mm) regions of interest. Using multivariate logistic regression, radiomics signature, and ultrasound (US) characteristics, the nomogram was developed. To evaluate the model's calibration, clinical application, and predictive ability, decision curve analysis (DCA), the calibration curve, and the receiver operating characteristic curve were used, respectively.
The final nomogram included three independent predictors: tumor size (P = .037), radiomics signature (P < .001), and US-reported lymph node status (P = .018). The nomogram exhibited satisfactory performance in the training cohort, demonstrating a specificity of 0.944, a sensitivity of 0.745, and an area under the curve (AUC) of 0.905. The validation cohort recorded a specificity of 0.909, a sensitivity of 0.727, and an AUC of 0.882. The DCA showed the nomogram's clinical utility, and the calibration curve revealed a high consistency among the expected and detected values.
The nomogram used in this investigation can accurately predict Ki-67 expression in people with malignant breast tumors, helping to develop personalized treatment approaches.
Regulated deficit irrigation (RDI) is an important means by which the water use efficiency (WUE) of peanut can be improved and facilitates the sustainable development of the peanut industry. However, ...most studies of RDI have only focused on single growth periods, which limits the water-saving potential. In this study, continuous regulated deficit irrigation (CRDI) was used to significantly improve the WUE of peanut through an experiment employing a split-plot design. Three levels of water deficit treatment, severe (H1/J1, 45% field capacity), moderate (H2/J2, 55% field capacity), and mild (H3/J3, 65% field capacity), were applied in the flower pegging stage (H) and the pod setting stage (J). Moderate CRDI (H2J2) stably improved the instantaneous water use efficiency of peanut leaves. Yield was not significantly decreased under the H2J2 treatment, and was only 4.47% lower than that of the H3J2 treatment, in which the yield was the highest. The highest WUE was observed in the H2J2 treatment (1.87 kg·m−3). The first time that the soil water content reached the lower limit in the pod setting stage, the proline content in the H1J1 treatment was 13.57 times higher than that in the H3J3, indicating that peanuts in the H1J1 treatment experienced substantial drought stress. The second time that the lower limit of soil water content was reached, the proline content in the H1J1 treatment was 7.14 times higher than that in the H3J3 treatment, indicating that the peanut drought resistance was improved by the drought-rehydration exercise at the flower pegging stage and drought stress was alleviated in the pod setting stage. We conclude that moderate CRDI is beneficial to peanut drought resistance for arid and semi-arid areas, and significantly promoted higher WUE.
•Moderate continuous regulated deficit irrigation (H2J2) improved the peanut WUE without reducing peanut yield.•Moderate continuous regulated deficit irrigation improved the peanut drought resistance by drought-rehydration exercise.•After drought resistance exercise, moderate continuous regulated deficit irrigation greatly increased IWUE during the pod setting stage.
Bisphenol A (BPA) and fluoroquinolone antibiotics (FQs) have been detected frequently in aquatic environments. Studies have shown that high levels of BPA and FQs exposure have adverse effects on ...chondrogenesis in young terrestrial vertebrates. However, little is known about their combined toxicity to bone metabolism. Here, we evaluated the single and combined effects of BPA and norfloxacin (NOR, a typical species of FQs) at an environmentally relevant level (1 μg/L) on early skeletal development in zebrafish. We found that both individual and combined BPA and NOR exposure resulted in poor embryo quality and decreased calcium-phosphorus ratio. The malformation increased after exposure to BPA and NOR, and craniofacial cartilage ossification was delayed. At the molecular level, the transcriptions of genes related to ossification were down-regulated significantly, and the lysine oxidase activity decreased. Hence, we infer that an environmentally relevant concentration of BPA and NOR have adverse effects on early skeletal development in fish. In addition, combined exposure to BPA and NOR seems to have an antagonistic effect on early skeletal development.
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•Both individual exposure and combined exposure to BPA and NOR can affect embryonic development.•BPA and NOR exposure induced skeletal development disorders.•Combined exposure to BPA and NOR seems to have an antagonistic effect on early skeletal development.
Artesunate (ART), a water-soluble derivative of artemisinin, has been reported to exert antineoplastic effects via diverse mechanisms in various types of cancer. Therefore, understanding the ...underlying mechanism of action of ART in distinct cancer types is indispensable to optimizing the therapeutic application of ART for different types of cancer. The present study aimed to investigate the cellular and molecular mechanisms responsible for the antineoplastic effects of ART in diffuse large B cell lymphoma (DLBCL) cells. Cell proliferation was measured using Cell Counting Kit-8 and colony formation assays. The levels of apoptosis and cell cycle distribution were investigated using flow cytometry. In addition, western blotting was used to analyze the expression levels of ART-induced apoptosis-, autophagy- and ferroptosis-related proteins. Monodansylcadaverine staining was performed to determine the levels of autophagy. Moreover, malondialdehyde and reactive oxygen species assays were used to determine the levels of ferroptosis. The results of the present study revealed that ART inhibited proliferation, and induced apoptosis, cell cycle arrest, autophagy and ferroptosis in DLBCL cells. Pharmacological inhibition of autophagy and ferroptosis alleviated the increased levels of apoptosis induced by ART. Notably, ART was found to exert its effects via inhibition of STAT3 activation. The genetic knockdown of STAT3 enhanced ART-induced autophagy and ferroptosis, and concomitantly upregulated the expression levels of apoptosis- and cell cycle-related proteins. In conclusion, the findings of the current study suggested that ART may induce apoptosis and cell cycle arrest to inhibit cell proliferation, and regulate autophagy and ferroptosis via impairing the STAT3 signaling pathway in DLBCL cells.
•Artesunate induces apoptosis, cell cycle arrest, autophagy and ferroptosis in DLBCL cells•Inhibition of autophagy alleviates Artesunate-induced apoptosis in DLBCL cells•Ferroptosis Inducer exerts synergistic effect with Artesunate in DLBCL cells•Artesunate induces autophagy and ferroptosis in DLBCL cells by impairing STAT3 signaling
In recent years, the popularity of IoT (Internet of Things) applications and services has brought great convenience to people's lives, but ubiquitous IoT has also brought many security problems. ...Among them, advanced persistent threat (APT) is one of the most representative attacks, and its continuous outbreak has brought unprecedented security challenges for the large-scale deployment of the IoT. However, important research on analyzing the attribution of APT malware samples is still relatively few. Therefore, we propose a classification method for attribution organizations with APT malware in IoT using machine learning. It aims to mark the real attacking organization entities to better identify APT attack activity and protect the security of IoT. This method performs feature representation and feature selection based on APT behavior data obtained from devices in the Internet of Things and selects the features with a high degree of differentiation among organizations. Then, it trains a multiclass model named SMOTE-RF that can better deal with imbalance and multiclassification problems. Our experiments on real dynamic behavior data are combined to verify the effectiveness of the method proposed in this paper for attribution analysis of APT malware samples and achieve good performance. Our method could identify the organization behind complex APT attacks in IoT devices and services.
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