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In this study, we designed and developed a DOX nanodrug delivery system (PEG-GA@ZIF-8@DOX) using ZIF-8 as the carrier and glycyrrhetinic acid (GA) as the targeting ligand. We confirmed that DOX was loaded and PEG-GA was successfully modified on the surface of the nanoparticles. The in vitro release profile of the system was investigated at pH 5.0 and 7.4. The cellular uptake, in vitro cytotoxicity, and lysosomal escape characteristics were examined using HepG2 cells. We established an H22 tumor-bearing mouse model and evaluated the in vivo antitumor activity. The results showed that the system had a uniform nanomorphology. The drug loading capacity was 11.22 ± 0.87%. In acidic conditions (pH 5.0), the final release rate of DOX was 57.73%, while at pH 7.4, it was 25.12%. GA-mediated targeting facilitated the uptake of DOX by the HepG2 cells. PEG-GA@ZIF-8@DOX could escape from the lysosomes and release the drug in the cytoplasm, thus exerting its antitumor effect. When the in vivo efficacy was analyzed, we found that the tumor inhibition rate of PEG-GA@ZIF-8@DOX was 67.64%; it also alleviated the loss of the body weight of the treated mice. This drug delivery system significantly enhanced the antitumor effect of doxorubicin in vitro and in vivo, while mitigating its toxic side effects. [ABSTRACT FROM AUTHOR]

Surface suction provides an efficient way to delay boundary layer transitions. In order to verify the suction effects and determine the mechanism of suction control in transonic swept wing boundary layers, wind tunnel transition measurements in a hybrid laminar flow control (HLFC) wind tunnel model uses an infrared thermography technique in the Aircraft Research Association (ARA) 2.74 m × 2.44 m low turbulence level transonic wind tunnel. Based on the experimental data of stationary crossflow dominant transitions without and with surface suction in transonic swept wing boundary layers, in this paper, the effects on the receptivity and linear and nonlinear evolution of stationary crossflow vortices have been analyzed with the consideration of curvature. Theoretical analysis agreed with the experimental observations in regard to the transition delay caused by boundary layer suction near the leading-edge region. [ABSTRACT FROM AUTHOR]

Large-sized seven-degrees-of-freedom (7-DoF) hybrid spray-painting robots combine ample working space and high flexibility, making them lucrative for the spray painting of aircraft and rocket surfaces. However, their kinematic calibration is hindered by gravitational deformation, which problem is addressed in this study by introducing a rigid-flexible coupling error modeling method. The latter combines the finite element method (FEM) and stiffness matrix method to assess the spatial gravitational deformation of a hybrid robot, which is then introduced into a geometric error model to establish the rigid-flexible coupling error identification model. Given many redundant parameters in the identification model for 7-DoF robots, these parameters are classified and simplified using the nonlinear least-square regularization method for parameter identification. Combining the inverse solution of 7-DoF spray-painting robots with dynamic characteristics considered, an error compensation method for 7-DoF robots is proposed. The kinematic calibration test results strongly indicate that position errors are significantly reduced with gravity compensation taken into consideration, and error convergence speed increases, demonstrating that the kinematic calibration method is feasible and can effectively improve the accuracy of spray-painting robots. The mean errors in the X- and Y-directions are reduced by 20 and 17%, respectively, compared to the conventional method. The proposed method is instrumental in the accurate kinematic calibration of large-sized 7-DoF hybrid robots. [ABSTRACT FROM AUTHOR]

The safety and efficacy of tumor treatment are difficult problems to address. Recently, lysosomes have become an important target for tumor treatment because of their special environment and function. Nanoparticles have unique physicochemical properties which have great advantages in tumor research. Therefore, in recent years, researchers have designed various types of nanoparticles to treat tumors based on lysosomal function and environment. In this review, we summarize and analyze different perspectives of tumor treatment, including direct destruction of lysosomes or lysosomal escape, drug delivery by nanoparticles, response to endogenous or exogenous stimuli, and the targeting of tumor cells or other cells. We describe the advantages and disadvantages of these approaches as well as the developmental prospects in this field. We hope to provide new ideas for better tumor treatment. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs that are related to a number of complicated biological processes, and numerous studies have demonstrated that miRNAs are closely associated with many human diseases. In this study, we present a matrix decomposition and similarity-constrained matrix factorization (MDSCMF) to predict potential miRNA–disease associations. First of all, we utilized a matrix decomposition (MD) algorithm to get rid of outliers from the miRNA–disease association matrix. Then, miRNA similarity was determined by utilizing similarity kernel fusion (SKF) to integrate miRNA function similarity and Gaussian interaction profile (GIP) kernel similarity, and disease similarity was determined by utilizing SKF to integrate disease semantic similarity and GIP kernel similarity. Furthermore, we added L2 regularization terms and similarity constraint terms to non-negative matrix factorization to form a similarity-constrained matrix factorization (SCMF) algorithm, which was applied to make prediction. MDSCMF achieved AUC values of 0.9488, 0.9540, and 0.8672 based on fivefold cross-validation (5-CV), global leave-one-out cross-validation (global LOOCV), and local leave-one-out cross-validation (local LOOCV), respectively. Case studies on three common human diseases were also implemented to demonstrate the prediction ability of MDSCMF. All experimental results confirmed that MDSCMF was effective in predicting underlying associations between miRNAs and diseases. [ABSTRACT FROM AUTHOR]

Even dispersion is important for live sound reinforcement systems; however, it needs to be carefully designed when using a linear loudspeaker array. This is because the audience area is often large, while the loudspeakers are placed centrally in this case for convenience, and thus both the level and the frequency balance may not remain reasonably constant for all audiences. To solve this problem, the adaptive genetic algorithm is firstly introduced in the parameters optimization. Secondly, taking the radiation characteristics at different frequencies into account, a linear-phase non-uniform filter bank is proposed to decompose the broad frequency band into several sub-bands. The audio is re-synthesized with the optimized parameters in each frequency band for a linear loudspeaker array. To show the validity of the proposed method, the simulations and the experiments are conducted to demonstrate that the sound pressure level in the audience area is distributed within ± 1.33 dB, ranging from 200 Hz to 4000 Hz. [ABSTRACT FROM AUTHOR]

H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a new class of endogenous non-coding RNAs with covalent closed loop structure. Researchers have revealed that circRNAs play an important role in human diseases. As experimental identification of interactions between circRNA and disease is time-consuming and expensive, effective computational methods are an urgent need for predicting potential circRNA–disease associations. In this study, we proposed a novel computational method named GATNNCDA, which combines Graph Attention Network (GAT) and multi-layer neural network (NN) to infer disease-related circRNAs. Specially, GATNNCDA first integrates disease semantic similarity, circRNA functional similarity and the respective Gaussian Interaction Profile (GIP) kernel similarities. The integrated similarities are used as initial node features, and then GAT is applied for further feature extraction in the heterogeneous circRNA–disease graph. Finally, the NN-based classifier is introduced for prediction. The results of fivefold cross validation demonstrated that GATNNCDA achieved an average AUC of 0.9613 and AUPR of 0.9433 on the CircR2Disease dataset, and outperformed other state-of-the-art methods. In addition, case studies on breast cancer and hepatocellular carcinoma showed that 20 and 18 of the top 20 candidates were respectively confirmed in the validation datasets or published literature. Therefore, GATNNCDA is an effective and reliable tool for discovering circRNA–disease associations. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is currently spreading and mutating with increasing speed worldwide. Therefore, there is an urgent need for a simple, sensitive, and high-throughput (HTP) assay to quantify virus–host interactions in order to quickly evaluate the infectious ability of mutant viruses and to develop or validate virus-inhibiting drugs. Here, we developed an ultrasensitive bioluminescent biosensor to evaluate virus–cell interactions by quantifying the interaction between the SARS-CoV-2 receptor binding domain (RBD) and its cellular receptor angiotensin-converting enzyme 2 (ACE2) both in living cells and in vitro. We have successfully used this novel biosensor to analyze SARS-CoV-2 RBD mutants and evaluated candidate small molecules (SMs), antibodies, and peptides that may block RBD:ACE2 interaction. This simple, rapid, and HTP biosensor tool will significantly expedite the detection of viral mutants and the anti-COVID-19 drug discovery process. [ABSTRACT FROM AUTHOR]

Most reported wearable electronic devices lack self-healing chemistry and flexible function to maintain stable energy output while irreversible damages and complex deformations. In this work, we report a dual-dynamic network electrolyte synthesized by micellar elastomers introduced into strong hydrogel matrix. The gel electrolyte is fabricated by physically cross-linking the borax-polyvinyl alcohol (B-PVA) network as tough matrix and poly (ethylene oxide) (PEO)-poly (propylene oxide) (PPO)-poly (ethylene oxide) (Pluronic) to frame elastic network, followed by immersion in potassium chloride solution. Under the action of dynamic borate ester bond and multi-network hydrogen bond, the as-prepared electrolyte exhibits high stretchability (1535%) and good self-healing efficiency. Based on the electrolyte, we assemble the interfacial compatible micro-supercapacitor (MSC) by multi-walled carbon nanotubes (MWCNT) interdigital electrode printed on cellulosic paper by direct ink writing (DIW) technique. Thanks to the large specific area and compressive deformation resistance of cellulosic paper, the MSC with tightly interfacial contact achieves high volumetric capacitance of 801.9 mF cm−3 at the current density of 20 μA cm−2. In the absence of stimulation of the external environment, the self-healing MSC demonstrates an ideal capacity retention (90.43%) after five physical damaged/healing cycles. Our research provides a clean and effective strategy to construct wearable MSC. [ABSTRACT FROM AUTHOR]

AISI M2 steel was smelted in a 150 kg medium-frequency induction furnace and cast to form round billets with a cross-section diameter of 100 mm via a vertical continuous caster and sand mold. The secondary dendrite arm spacing (λ2), cooling rates, permeability and size and distribution of grains and network carbides of the two billets were studied. The results show that the continuous casting process can effectively decrease the λ2 value, permeability and size of the grains and carbides and improve the distribution of the grains and carbides during solidification. The λ2 values of the billets cast with a sand mold and continuous caster are 37.34 μm and 21.14 μm, respectively, and the cooling rate is 3.6 K·s−1 and 12.0 K·s−1, respectively. The area fractions of carbides at the center of the billets cast with the sand mold and continuous caster are 0.24 and 0.16, respectively, and increase by 27.7% and 25.4%, respectively, compared with their average values. The average grain size of billets cast with the sand mold and continuous caster is 69.4 μm and 50.5 μm, respectively. Compared with the sand mold billet, the grain size at the center of the continuous casting billet is reduced by 25.5%. The relationship between the grain size and cooling rate is presented in this paper. [ABSTRACT FROM AUTHOR]

As the first in a new class of non-opioid drugs, ω-Conotoxin MVIIA was approved for the management of severe chronic pains in patients who are unresponsive to opioid therapy. Unfortunately, clinical application of MVIIA is severely limited due to its poor ability to penetrate the blood-brain barrier (BBB), reaching the central nervous system (CNS). In the present study, we have attempted to increase MVIIA's ability to cross the BBB via a fusion protein strategy. Our results showed that when the TAT-transducing domain was fused to the MVIIA C-terminal with a linker of varied numbers of glycine, the MVIIA-TAT fusion peptide exhibited remarkable ability to cross the bio-membranes. Most importantly, both intravenous and intranasal administrations of MVIIA-TAT in vivo showed therapeutic efficacy of analgesia. Compared to the analgesic effects of intracerebral administration of the nascent MVIIA, these systemic administrations of MVIIA-TAT require higher doses, but have much prolonged effects. Taken together, our results showed that TAT conjugation of MVIIA not only enables its peripheral administration, but also maintains its analgesic efficiency with a prolonged effective time window. Intranasal administration also rendered the MVIIA-TAT advantages of easy applications with potentially reduced side effects. Our results may present an alternative strategy to improve the CNS accessibility for neural active peptides. [ABSTRACT FROM AUTHOR]