New results on bifurcation for fractional-order octonion-valued neural networks involving delays.

This work chiefly explores fractional-order octonion-valued neural networks involving delays. We decompose the considered fractional-order delayed octonion-valued neural networks into equivalent real-valued systems via Cayley-Dickson construction. By virtue of Lipschitz condition, we prove that the solution of the considered fractional-order delayed octonion-valued neural networks exists and is unique. By constructing a fairish function, we confirm that the solution of the involved fractional-order delayed octonion-valued neural networks is bounded. Applying the stability theory and basic bifurcation knowledge of fractional order differential equations, we set up a sufficient condition remaining the stability behaviour and the appearance of Hopf bifurcation for the addressed fractional-order delayed octonion-valued neural networks. To illustrate the justifiability of the derived theoretical results clearly, we give the related simulation results to support these facts. Simultaneously, the bifurcation plots are also displayed. The established theoretical results in this work have important guiding significance in devising and improving neural networks.

Proximity Amplification-Enabled Electrochemical Analysis of Tumor-Associated Glycoprotein Biomarkers.

Glycoproteins produced and secreted from specific cells and tissues are associated with several diseases and emerge as typical biomarkers to provide useful information in cancer diagnosis considering their abnormal expression levels. In this work, we design a universal method to achieve the accurate and sensitive analysis of tumor-associated glycoprotein biomarkers based on both carbohydrate recognition and protein recognition at the same protein surface. The byproduct of dual recognition-induced proximity amplification, pyrophosphate, triggers the disassembly of methylene blue-encapsulated metal-organic frameworks, MB@ZIF-90. As a result, methylene blue molecules are released to arouse amplified electrochemical responses for glycoprotein analysis. Experimental results demonstrate the high-accuracy analysis of carcinoembryonic antigen, a typical glycoprotein biomarker in cancer diagnosis, in a linear range of 0.001-100 ng mL-1 with a low limit of detection of 0.419 pg mL-1. The method also displays satisfactory specificity and recoveries in complex serum samples and proves good versatility by adopting two other tumor-associated glycoprotein biomarkers, α-fetoprotein and mucin-1, as the targets. Therefore, this work provides a valuable tool for the analysis of glycoprotein biomarkers, which may be of great potential in early warning of malignant tumors in clinical applications.

Molecular Characterization of Exosomes for Subtype-Based Diagnosis of Breast Cancer.

Breast cancer is very heterogeneous and the most frequently diagnosed cancer worldwide, and precise therapy targeting specific subtypes may improve the survival rates of breast cancer patients. In this study, we designed a biomimetic vesicle by camouflaging catalytic DNA machinery with a breast cancer cell membrane, which enabled the molecular classification of circulating exosomes for subtype-based diagnosis through homotypic recognition. In addition, the vesicles specifically targeted and fused with breast cancer exosomes with phenotypic homology and manipulated the DNA machinery to amplify electrochemical signaling using exosomal RNA as an endogenous trigger. The biomimetic vesicles prepared with MCF-7 cancer cell-derived membranes were shown to recognize estrogen receptor-positive breast cancer exosomes and exhibited a low detection limit of 557 particles mL-1 with microRNA-375 used as the endogenous biomarker. Furthermore, the biomimetic vesicles prepared with MDA-MB-231 cancer cell-derived membranes displayed satisfactory performance in a homotypic analysis of triple-negative breast cancer exosomes with a potential therapeutic target, PD-L1 mRNA, used as the endogenous biomarker. Most importantly, cross-validation experiments confirmed the high accuracy and selectivity of this homotypic recognition-driven analysis for molecular subtyping of breast cancer. When applied to clinical samples of breast cancer patients, the vesicles demonstrated feasibility and reliability for evaluating the molecular features of cancer cell-derived exosomes and enabled stage-specific monitoring of breast cancer patients because the electrochemical signals showed a positive correlation with disease progression. Therefore, this work may provide new ideas for the precise diagnosis and personalized treatment of breast cancer patients throughout the whole disease process.

Preliminary Evaluation of Virtual Touch Tissue Imaging Quantification for Differential Diagnosis of Metastatic and Nonmetastatic Cervical Lymph Nodes.

OBJECTIVES: Virtual Touch tissue imaging quantification (VTIQ; Siemens Medical Solutions, Mountain View, CA) is useful for assessing tissue hardness. This study aimed to investigate the value of VTIQ in differential diagnosis of cervical lymph nodes. METHODS: We retrospectively analyzed conventional sonograms and VTIQ images of 85 pathologically confirmed patients with superficial lymph node lesions. Conventional sonography was first performed, with 2-dimensional images described. Then VTIQ shear wave velocity (SWV) values of superficial lymph nodes were measured. With pathologic diagnosis as the reference standard, a receiver operating characteristic curve was generated to evaluate VTIQ efficacy in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes. RESULTS: Of the 85 nodes, 44 and 41 were metastatic and nonmetastatic, respectively. The latter group included 24 and 17 hematologic/lymphatic system disease and reactive hyperplastic nodes, respectively. Shear wave velocity values of metastatic nodes were significantly higher than those of their nonmetastatic counterparts (P < .001). With an area under the curve (AUC) of 0.953 and SWV cutoff of 3.27 m/s, accuracy, sensitivity, and specificity were 89.4%, 88.6%, and 90.2%, respectively, for distinguishing metastatic and nonmetastatic nodes. An AUC of 0.943 and SWV cutoff of 3.23 m/s yielded accuracy, sensitivity, and specificity of 88.2%, 88.6%, and 87.5% for differentiating metastatic from hematologic/lymphatic system disease nodes. Finally, an AUC of 0.968 and SWV cutoff of 3.27 m/s yielded accuracy, sensitivity, and specificity of 90.2%, 88.6%, and 94.1% for differentiating metastatic from reactive hyperplastic nodes. CONCLUSIONS: Virtual Touch tissue imaging quantification is efficient in differential diagnosis of metastatic and nonmetastatic cervical lymph nodes.

Risk factors and nomogram to predict skip metastasis in papillary thyroid carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Skip metastases of PTCs are easily misdiagnosed before surgery, and it could lead to re-operation and affect the prognosis. Although there are a few studies about nomograms for predicting central lymph node metastases (CLNM) or lateral lymph node metastases (LLNM) of PTCs, there are few studies about nomograms for skip metastases. Based on the clinical and ultrasonographic characteristics of patients with PTCs, the aim of our study was to investigate the risk factors and establish a nomogram for predicting the risk of skip metastases in PTCs. Methods: This study enrolled 218 PTCs patients with lateral cervical lymph node metastases and their data were analyzed retrospectively. According to the postoperative pathological results, the patients were divided into skip-positive group and skip-negative group. In order to establish the nomogram, univariate and multivariate analyses were used to estimate risk factors of skip metastases. The receiver operating characteristic (ROC) curve, internal calibration plot and decision curve analysis (DCA) were used to evaluate the nomogram model's efficacy. Results: There were statistical differences between skip-positive group and skip-negative group in tumor location, the maximum diameter (D) and capsule invasion (P<0.05). No statistical differences were observed in sex, age, Hashimoto's thyroiditis, multifocality, anteroposterior diameter/transverse diameter (A/T) ratio, shape, margin, microcalcification, intra-nodular vascularity and preoperative serum thyroglobulin (Tg) (P≥0.05). The risk factors of skip metastases in PTCs were D ≤10 mm, location in the upper portion and capsule invasion. The area under the curve (AUC) of nomogram was 0.877, the accuracy was 85.32%, the sensitivity was 60.98%, and the specificity was 90.96%. The calibration curve and the Hosmer-Lemeshow goodness of fit test showed that the consistency between the nomogram and the actual observation was good. The DCA showed that most PTC patients might benefit from the predictive nomogram model. Conclusions: A nomogram for predicting skip metastases in PTCs may be useful in clinical diagnosis and treatment.

Ordered Labeling-Facilitated Electrochemical Assay of Alpha-Fetoprotein-L3 Ratio for Diagnosing Hepatocellular Carcinoma.

Serum alpha fetoprotein (AFP) is a "gold-standard" biomarker for the diagnosis of hepatocellular carcinoma (HCC). Available pieces of evidence suggest that the ratio of AFP-L3 isoform in the total AFP may provide more accurate prediction for the incidence of HCC. In this work, we design an electrochemical aptasensor for high-accuracy assay of AFP-L3 ratio based on differentiated labeling of AFP isoforms in an orderly fashion. Specifically, total AFP is first captured by an AFP aptamer-functionalized electrode and labeled with quantum dots-functionalized DNA probes via mild reduction. Then, AFP-L3 isoform that strongly binds to Lens culinaris agglutinin is labeled with silver nanoparticles after the exonuclease-catalyzed removal of DNA probes. By tracing the electrochemical responses of quantum dots and silver nanoparticles, respectively, the amounts of total AFP and AFP-L3 isoforms are determined and the AFP-L3 ratio is accordingly calculated to favor the accurate HCC diagnosis. Experimental results prove the high-accuracy assay of AFP-L3 ratio based on the AFP quantitation in a linear range of 0.0008-40 ng mL-1 and AFP-L3 quantitation in a linear range of 0.004-40 ng mL-1. The aptasensor also displays satisfactory specificity and good recoveries even in the complex serum samples. Therefore, the aptasensor may provide a valuable tool for the assay of the AFP-L3 ratio and have a great potential use in early warning of HCC for clinical application.

Solid-solution MAX phase TiVAlC assisted with impurity for enhancing hydrogen storage performance of magnesium hydride.

Although MXene catalysts etched from precursor MAX have greatly improved the hydrogen storage performance of magnesium hydride (MgH2), the use of dangerous and polluting etchers (such as hydrofluoric acid) and the direct removal of potentially catalytically active A-layer substances (such as Al) present certain limitations. Here, solid-solution MAX phase TiVAlC catalyst without etching treatment has been directly introduced into MgH2 system to improve the hydrogen storage performance. The optimal MgH2-10 wt% TiVAlC can release about 6.00 wt% hydrogen at 300 °C within 378 s and absorb about 4.82 wt% hydrogen at 175 °C within 900 s. After 50 isothermal hydrogen ab/desorption cycles, the excellent cyclic stability and capacity retention (6.4 wt%, 99.6%) can be found for MgH2-10 wt% TiVAlC. The superb catalytic activity of TiVAlC catalyst can be explained by abundant electron transfer at external interfaces with MgH2/Mg, which can be further enhanced by impurity phase Ti3AlC2 due to strong H affinity brought from abundant electron transfer at internal interfaces (Ti3AlC2/TiVAlC). The influence of impurity phase which is common in MAX phase on the overall activity of catalysts has been firstly studied here, providing a unique method for designing composite catalyst to improve hydrogen storage performance of MgH2.

Diagnostic value of qualitative and quantitative parameters of contrast-enhanced ultrasound for differentiating differentiated thyroid carcinomas from benign nodules.

Objective: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) of qualitative and quantitative parameters for differentiating differentiated thyroid cancers from benign nodules. Method: A total of 290 thyroid nodules that were pathologically confirmed were enrolled in this study. The univariate analysis was performed for the clinical characteristics and CEUS qualitative and quantitative parameters of the inside and peripheral zone of nodules, including age, gender, nodule size, intensity of enhancement, homogeneity, wash-in and wash-out patterns, margin after CEUS, ring enhancement, peak intensity, sharpness, time to peak(TP), and area under the curve(AUC), and the meaningful indicators in the single-factor analysis were further included in multivariate logistic regression analysis. Results: Multivariate analysis showed that there were significant differences in age (p=0.031), nodule size (p<0.001), heterogeneous enhancement (p<0.001), hypo-enhancement (p=0.001), unclear margin after CEUS(p=0.007), inside peak (p<0.001), and outside sharpness(p<0.001) between benign and malignant nodules. However, there were no significant differences in gender, ring enhancement, wash-in, wash-out, outside TP, outside AUC between benign and malignant thyroid nodules (P>0.05, for all). Conclusion: CEUS might be useful in the differential diagnosis of differentiated thyroid cancers and benign nodules, which could provide a certain basis for clinical treatment.

Effects of miRNA-199a-5p on cell proliferation and apoptosis of uterine leiomyoma by targeting MED12.

BACKGROUND/AIMS: Uterine leiomyoma (ULM) is a kind of gene-involved benign tumor, which is located in the front of female reproductive tract. It is one of the most common reproductive tract tumors in women, which leads to abnormal menstruation, repeated pregnancy loss, and other serious gynecological diseases. Recently, microRNAs (miRNAs) have attracted much more attention in the process of exploring the molecular mechanisms of tumorigenesis. Furthermore, the deregulated miRNAs had been reported to play important roles in ULM pathology. METHODS: In this study, we assessed the expression level of microRNA-199a-5p (miR-199a-5p) in human ULM by quantitative polymerase chain reaction. After that cell counting kit 8, colony formation, 5-ethynyl-20-deoxyuridine, flow cytometry, and Western blot analyses were performed to investigate the effects of miR-199a-5p on ULM cell proliferation and apoptosis. RESULTS: We confirmed that miR-199a-5p was significantly downregulated in human ULM. The results of function analyses showed that miR-199a-5p inhibited cell proliferation and induced cell apoptosis in vitro. Bioinformatics tool showed oncogene MED12 was one of the target genes of miR-199a-5p, which mediated the effect of miR-199a-5p on the ULM. CONCLUSION: Our results showed that miR-199a-5p functioned as an antitumor factor in human ULM cells. These findings broaden the current findings on the function of miR-199a-5p into the ULM pathogenesis, and miR-199a-5p may serve as a prognosis and therapeutic target for the ULM and its related diseases.

miR-335-5p Inhibits Progression of Uterine Leiomyoma by Targeting ARGLU1.

Studies have demonstrated that miR-335-5p exhibits an essential role in the progress of multiple tumors, including thyroid cancer, pancreatic cancer, and non-small-cell lung cancer. However, the possible expression, the detailed role, and the underlying mechanisms of miR-335-5p in uterine leiomyoma (UL) still remained unclear. Therefore, the present study was designed to investigate the mechanism and function of miR-335-5p in UL. In our study, microRNA-335-5p (miR-335-5p) is significantly downregulated in UL tissues and UL cell lines, especially in HCC1688 and SK-UT-1 cells. Functionally, overexpression of miR-335-5p notably inhibits the viability of UL cell lines by CCK-8 assay. Besides, upregulation of miR-335-5p inhibits proliferation of UL cell lines by colony formation assay and decreases the protein levels of PCNA and Ki-67 detected by western blot assay. In addition, overexpression of miR-335-5p induces UL cell cycle arrest at G1 phase. Upregulation of miR-335-5p decreases the levels of Cyclin A1, Cyclin B1, and Cyclin D2 and upregulates the expression of p27 protein. Additionally, upregulation of miR-335-5p promotes the apoptosis of UL cell lines, increases the protein levels of Bax, Cleaved caspase-3, and Cleaved caspase-9, and decreases the protein expression of Bcl-2. Moreover, Arginine and Glutamate-Rich protein 1 (ARGLU1) is predicted as a target of miR-335-5p by ENCORI and miRDB and confirmed by dual-luciferase reporter assay. ARGLU1 is negatively associated with miR-335-5p. Furthermore, overexpression of ARGLU1 partly restores the effects of miR-335-5p mimic on the viability, proliferation, cell cycle, and apoptosis of UL cell lines. To conclude, miR-335-5p may play a repressive role in UL by targeting ARGLU1 and serve as a potential therapeutic target for the treatment of UL.

Supra Hydrolytic Catalysis of Ni3 Fe/rGO for Hydrogen Generation.

Light metal hydrolysis for hydrogen supply is well suited for portable hydrogen fuel cells. The addition of catalysts can substantially aid Mg hydrolysis. However, there is a lack of clear catalytic mechanism to guide the design of efficient catalysts. In this work, the essential role of nanosized catalyst (Ni3 Fe/rGO) in activating micro-sized Mg with ultra-rapid hydrolysis process is investigated for the first time. Here, an unprecedented content of 0.2 wt% Ni3 Fe/rGO added Mg can release 812.4 mL g-1 hydrogen in just 60 s at 30 °C. Notably, an impressive performance with a hydrogen yield of 826.4 mL g-1 at 0 °C in only 30 s is achieved by the Mg-2 wt% Ni3 Fe/rGO, extending the temperature range for practical applications of hydrolysis. Moreover, the four catalysts (Ni3 Fe/rGO, Ni3 Fe, Ni/rGO, Fe/rGO) are designed to reveal the influence of composition, particle size, and dispersion on catalytic behavior. Theoretical studies corroborate that the addition of Ni3 Fe/rGO accelerates the electron transfer and coupling processes and further provides a lower energy barrier diffusion path for hydrogen. Thus, a mechanism concerning the catalyst as migration relay is proposed. This work offers guidelines designing high-performance catalysts especially for activating the hydrolysis of micro-sized light weight metals.

Recent advances in cell membrane camouflage-based biosensing application.

Cell membrane, a semi-permeable membrane composed of phospholipid bilayers, is a natural barrier to prevent extracellular substances from freely entering the cell. Cell membrane with selective permeability and fluidity ensures the relative stability of the intracellular environment and enables various biochemical reactions to smoothly operate in an orderly manner. Inspired by the natural composition and transport process, various cell membranes and synthetic bionic films as the mimics of cell membranes have emerged as appealing camouflage materials for biosensing applications. The membranes are devoted to surface modification and substance delivery, and realize the detection or in situ analysis of multiple biomarkers, such as glucose, nucleic acids, virus, and circulating tumor cells. In this review, we summarize the recent advances in cell membrane camouflage-based biosensing applications, mainly focusing on the use of the membranes extracted from natural cells (e.g., blood cells and cancer cells) as well as biomimetic membranes. Materials and surfaces camouflaged with cell membranes are shown to have superior stability and biocompatibility as well as intrinsic properties of original cells, which greatly facilitate their use in biosensing. In specific, camouflage with blood cell membranes bestows low immunogenicity and prolonged blood circulation time, camouflage with cancer cell membranes provides homologous targeting ability, and camouflage with biomimetic membranes endows considerable plasticity for functionalization. Further research is expected to focus on the deeper understanding of cell-specific properties of membranes and the exploration of hybrid membranes, which might provide new development opportunities for cell membrane camouflage-based biosensing application.