Mechanically Tough and Conductive Hydrogels Based on Gelatin and Z-Gln-Gly Generated by Microbial Transglutaminase.

Gelatin-based hydrogels with excellent mechanical properties and conductivities are desirable, but their fabrication is challenging. In this work, an innovative approach for the preparation of gelatin-based conductive hydrogels is presented that improves the mechanical and conductive properties of hydrogels by integrating Z-Gln-Gly into gelatin polymers via enzymatic crosslinking. In these hydrogels (Gel-TG-ZQG), dynamic π-π stacking interactions are created by the introduction of carbobenzoxy groups, which can increase the elasticity and toughness of the hydrogel and improve the conductivity sensitivity by forming effective electronic pathways. Moreover, the mechanical properties and conductivity of the obtained hydrogel can be controlled by tuning the molar ratio of Z-Gln-Gly to the primary amino groups in gelatin. The hydrogel with the optimal mechanical properties (Gel-TG-ZQG (0.25)) exhibits a high storage modulus, compressive strength, tensile strength, and elongation at break of 7.8 MPa at 10 °C, 0.15 MPa at 80% strain, 0.343 MPa, and 218.30%, respectively. The obtained Gel-TG-ZQG (0.25) strain sensor exhibits a short response/recovery time (260.37 ms/130.02 ms) and high sensitivity (0.138 kPa-1) in small pressure ranges (0-2.3 kPa). The Gel-TG-ZQG (0.25) hydrogel-based sensors can detect full-range human activities, such as swallowing, fist clenching, knee bending and finger pressing, with high sensitivity and stability, yielding highly reproducible and repeatable sensor responses. Additionally, the Gel-TG-ZQG hydrogels are noncytotoxic. All the results demonstrate that the Gel-TG-ZQG hydrogel has potential as a biosensor for wearable devices and health-monitoring systems.

Cascade Forest-Based Model for Prediction of RNA Velocity.

In recent years, single-cell RNA sequencing technology (scRNA-seq) has developed rapidly and has been widely used in biological and medical research, such as in expression heterogeneity and transcriptome dynamics of single cells. The investigation of RNA velocity is a new topic in the study of cellular dynamics using single-cell RNA sequencing data. It can recover directional dynamic information from single-cell transcriptomics by linking measurements to the underlying dynamics of gene expression. Predicting the RNA velocity vector of each cell based on its gene expression data and formulating RNA velocity prediction as a classification problem is a new research direction. In this paper, we develop a cascade forest model to predict RNA velocity. Compared with other popular ensemble classifiers, such as XGBoost, RandomForest, LightGBM, NGBoost, and TabNet, it performs better in predicting RNA velocity. This paper provides guidance for researchers in selecting and applying appropriate classification tools in their analytical work and suggests some possible directions for future improvement of classification tools.

The Preparation and Properties of Composite Hydrogels Based on Gelatin and (3-Aminopropyl) Trimethoxysilane Grafted Cellulose Nanocrystals Covalently Linked with Microbial Transglutaminase.

Mechanically enhanced gelatin-based composite hydrogels were developed in the presence of functionalized cellulose nanocrystals (CNCs) employing microbial transglutaminase (mTG) as a binding agent. In this work, the surfaces of CNCs were grafted with (3-Aminopropyl) trimethoxysilane with a NH2 functional group, and the success of CNCs' modification was verified by FTIR spectroscopy and XPS. The higher degree of modification in CNCs resulted in more covalent cross-linking and dispersibility within the gelatin matrix; thus, the as-prepared hydrogels showed significantly improved mechanical properties and thermo-stability, as revealed by dynamic rheological analysis, uniaxial compression tests and SEM. The biocompatibility of the obtained hydrogels was evaluated by the MTT method, and it was found that the grafted CNCs had no obvious inhibitory effect on cell proliferation. Hence, the mechanically enhanced gelatin-based hydrogels might have great potential in biomedical applications.

LGBMDF: A cascade forest framework with LightGBM for predicting drug-target interactions.

Prediction of drug-target interactions (DTIs) plays an important role in drug development. However, traditional laboratory methods to determine DTIs require a lot of time and capital costs. In recent years, many studies have shown that using machine learning methods to predict DTIs can speed up the drug development process and reduce capital costs. An excellent DTI prediction method should have both high prediction accuracy and low computational cost. In this study, we noticed that the previous research based on deep forests used XGBoost as the estimator in the cascade, we applied LightGBM instead of XGBoost to the cascade forest as the estimator, then the estimator group was determined experimentally as three LightGBMs and three ExtraTrees, this new model is called LGBMDF. We conducted 5-fold cross-validation on LGBMDF and other state-of-the-art methods using the same dataset, and compared their Sn, Sp, MCC, AUC and AUPR. Finally, we found that our method has better performance and faster calculation speed.

miR-34a-5p functions as a tumor suppressor in head and neck squamous cell cancer progression by targeting Flotillin-2.

While a number of therapeutic advances have been made in recent years, the overall survival of patients with head and neck squamous cell cancer (HNSCC) remains poor. MicroRNAs (miRNAs) are key drivers of oncogenic progression, with miR-34a-5p downregulation having been observed in many different tumor types. Here, we assessed the link between miR-34a-5p and HNSCC progression and the mechanistic basis for this relationship. Levels of miR-34a-5p in HNSCC tumors and cell lines were assessed via qPCR, after which we explored the functional importance of this miRNA in this oncogenic setting. Through luciferase reporter assays, the ability of miR-34a-5p to regulate flotillin-2 (FLOT-2) was further clarified. Overall, these analyses revealed that HNSCC tumors and cells exhibited marked miR-34a-5p downregulation that was linked to the progression of this tumor type. At a functional level, miR-34a-5p constrained the proliferation, migratory/invasive activity, and epithelial-mesenchymal transition induction in HNSCC cells. At the mechanistic level, miR-34a-5p was found to suppress FLOT-2 expression and to activate the MEK/ERK1/2 pathway. Overall, these results suggest that miR-34a-5p can function as a tumor suppressor miRNA in HNSCC owing to its ability to target FLOT-2, highlighting the promise of targeting this regulatory axis to treat HNSCC.

Preparation and characterization of enzymatically cross-linked gelatin/cellulose nanocrystal composite hydrogels.

Gelatin is an attractive hydrogel material because of its excellent biocompatibility and non-cytotoxicity, but poor mechanical properties of gelatin-based hydrogels become a big obstacle that limits their wide-spread application. To solve it, in this work, gelatin/cellulose nanocrystal composite hydrogels (Gel-TG-CNCs) were prepared using microbial transglutaminase (mTG) as the crosslinking catalyst and cellulose nanocrystals (CNCs) as reinforcements. The physicochemical properties of the composite hydrogels were investigated by thermogravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The dynamic rheological measurement and uniaxial compression test were performed to study the effects of mTG and CNC contents on the storage modulus and breaking strength of the as-prepared Gel-TG-CNCs. Results showed that the addition of CNCs and mTG could significantly increase the storage modulus and breaking strength of gelatin-based hydrogels, especially when added simultaneously. The breaking strength of Gel-TG-CNCs (2%) at 25 °C can reach 1000 g which is 30 times greater than pure gelatin hydrogels. The biocompatibility of the composite hydrogels was also investigated by the MTT method with Hela cells, and the results demonstrated that the composite hydrogels maintained excellent biocompatibility. With a combination of good biocompatibility and mechanical properties, the as-prepared Gel-TG-CNCs showed potential application value in the biomedical field.

ADAR1 promotes the epithelial-to-mesenchymal transition and stem-like cell phenotype of oral cancer by facilitating oncogenic microRNA maturation.

BACKGROUND: Adenosine deaminases acting on RNA (ADARs) are involved in adenosine-to-inosine (A-to-I) editing and implicated in tumorigenesis and prognosis. Emerging evidence has indicated that ADAR1, an ADAR family member, participates in the regulation of various cancers; however, its biological function in oral squamous cell carcinoma (OSCC) remains unclear. This study aimed to determine the role of ADAR1 in OSCC progression. METHODS: ADAR1 expression in both normal tissues and carcinoma tissues and in OSCC cell lines was examined by real-time PCR and western blotting. Gain-of-function and loss-of-function approaches were used to examine the effect of ADAR1 on the migration, invasion, epithelial-mesenchymal transition (EMT) and stemness of OSCC. Furthermore, the relationship between ADAR1 and Dicer was determined by co-immunoprecipitation, and the expression of OSCC-associated oncogenic miRNAs was evaluated by real-time PCR. For in vivo experiments, a xenograft model where OSCC cells stably expressing ADAR1 were implanted was used to investigate the effect of ADAR1 on tumor growth and progression, and the expression of ADAR1, PCNA, SOX2 and POU5F1 was further detected by immunohistochemistry. The impact of ADAR1 expression on the survival status of OSCC patients was determined by survival analysis. RESULTS: ADAR1 was overexpressed in OSCC and significantly associated with poor patient survival. There was a positive correlation between ADAR1 and the migration, invasion, EMT and stemness of OSCC. Mechanistically, ADAR1 was physically associated with Dicer, and six OSCC-associated oncogenic miRNAs were increased in OSCC cells with ADAR1 overexpression. In the mouse xenograft model of OSCC, ADAR1 overexpression promoted tumor growth and progression. Moreover, ADAR1 was highly expressed in OSCC patients with low survival rates. CONCLUSIONS: Our findings demonstrated that ADAR1 may play a significant role in OSCC progression via combining with Dicer to regulate oncogenic miRNA maturation and further affect cell migration and invasion.

LC-MS/MS assay of ropinirole in rat biological matrices: elimination of lysoglycerophosphocholines-based matrix effect.

AIM: To adequately support PK evaluation of ropinirole in rats following intranasal administration, it was desirable to determine ropinirole concentrations in rat plasma, brain homogenate and microdialysate. Results & methodology: A robust LC-MS/MS method has been developed for the determination of ropinirole in biological samples. Liquid-liquid extraction using ethyl acetate eliminated matrix effect due to significantly reduced levels of lysoglycerophosphocholines. The assay was fully validated with dynamic ranges of 0.01-20 ng/ml for plasma and brain homogenate samples and 0.1-200 ng/ml for microdialysate samples. CONCLUSION: The proposed method was accurate and precise for the quantification of ropinirole in biological samples and was successfully applied to a microdialysis study of ropinirole in rats.

A Gold Nanoparticle Platform for the Delivery of Functional TGF-ß1 siRNA Into Cancer Cells.

Nanoparticles, especially gold nanoparticles (AuNPs), have been shown to be an efficient carrier to deliver small RNAs into cancer cells. In this study, we used cysteamine-functionalized AuNPs to effectively deliver TGF-ß1 siRNA into hepatoma HepG2 cells in vitro and in vivo. We found that, compared with AuNPs-mediated NC siRNA (AuNP-siNC), AuNPs-delivered TGF-ß1 siRNA (AuNP-siTGFß1) efficiently decreased the level of TGF-ß1, increased cell apoptosis, and significantly inhibited the proliferation of recipient tumour cells. Systemic administration of the AuNP-siTGFß1 complexes into human HepG2 xenografted mice likewise reduced TGF-ß1 expression and downstream TGF-ß1 signalling. Functionally, AuNP-siTGFß1 strongly inhibited tumour growth and improved the survival rate of tumour-bearing mice compared with the control groups. In conclusion, our results demonstrate that the siRNA delivery system with AuNP described here appears to be a highly effective method to deliver RNAi therapeutics into tumour cells for oncotherapy.

Screening of stabilizers for LC-MS/MS analysis of clevidipine and its primary metabolite in dog whole blood.

BACKGROUND: Clevidipine is an ester-containing antihypertensive agent that undergoes rapid hydrolysis in blood. A reliable stabilizer cocktail containing citric acid and ascorbic acid was established and the LC-MS/MS method was validated for simultaneous determination of clevidipine and its major metabolite in beagle dog whole blood. RESULTS: The stabilizer could nearly completely inhibit the esterase activity. Both analytes were extracted from whole blood by toluene and detected by MS/MS in positive ESI mode. The linearity range was 0.1-100.0 ng/ml for clevidipine and 1.0-1000.0 ng/ml for the primary metabolite. CONCLUSION: The stabilizer cocktail was able to effectively suppress the activity of esterase in blood. The method was successfully applied to a PK study of clevidipine in beagle dogs.

Finite-time master-slave synchronization and parameter identification for uncertain Lurie systems.

This paper investigates the finite-time master-slave synchronization and parameter identification problem for uncertain Lurie systems based on the finite-time stability theory and the adaptive control method. The finite-time master-slave synchronization means that the state of a slave system follows with that of a master system in finite time, which is more reasonable than the asymptotical synchronization in applications. The uncertainties include the unknown parameters and noise disturbances. An adaptive controller and update laws which ensures the synchronization and parameter identification to be realized in finite time are constructed. Finally, two numerical examples are given to show the effectiveness of the proposed method.

Robust master-slave synchronization for general uncertain delayed dynamical model based on adaptive control scheme.

In this paper, the robust exponential synchronization problem for a class of uncertain delayed master-slave dynamical system is investigated by using the adaptive control method. Different from some existing master-slave models, the considered master-slave system includes bounded unmodeled dynamics. In order to compensate the effect of unmodeled dynamics and effectively achieve synchronization, a novel adaptive controller with simple updated laws is proposed. Moreover, the results are given in terms of LMIs, which can be easily solved by LMI Toolbox in Matlab. A numerical example is given to illustrate the effectiveness of the method.

Hybrid impulsive control for closed quantum systems.

The state transfer problem of a class of nonideal quantum systems is investigated. It is known that traditional Lyapunov methods may fail to guarantee convergence for the nonideal case. Hence, a hybrid impulsive control is proposed to accomplish a more accurate convergence. In particular, the largest invariant sets are explicitly characterized, and the convergence of quantum impulsive control systems is analyzed accordingly. Numerical simulation is also presented to demonstrate the improvement of the control performance.

A Lie algebraic condition for exponential stability of discrete hybrid systems and application to hybrid synchronization.

A Lie algebraic condition for global exponential stability of linear discrete switched impulsive systems is presented in this paper. By considering a Lie algebra generated by all subsystem matrices and impulsive matrices, when not all of these matrices are Schur stable, we derive new criteria for global exponential stability of linear discrete switched impulsive systems. Moreover, simple sufficient conditions in terms of Lie algebra are established for the synchronization of nonlinear discrete systems using a hybrid switching and impulsive control. As an application, discrete chaotic system's synchronization is investigated by the proposed method.