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The efficacy of adeno-associated virus (AAV)-based gene therapy is dependent on effective viral transduction, which might be inhibited by preexisting immunity to AAV acquired from infection or maternal delivery. Anti-AAV neutralizing Abs (NAbs) titer is usually measured by in vitro assay and used for patient enroll; however, this assay could not evaluate NAbs' impacts on AAV pharmacology and potential harm in vivo. Here, we infused a mouse anti-AAV9 monoclonal antibody into Balb/C mice 2 h before receiving 1.2 × 1014 or 3 × 1013 vg/kg of rAAV9-coGAA by tail vein, a drug for our ongoing clinical trials for Pompe disease. The pharmacokinetics, pharmacodynamics, and cellular responses combined with in vitro NAb assay validated the different impacts of preexisting NAbs at different levels in vivo. Sustained GAA expression in the heart, liver, diaphragm, and quadriceps were observed. The presence of high-level NAb, a titer about 1:1000, accelerated vector clearance in blood and completely blocked transduction. The AAV-specific T cell responses tended to increase when the titer of NAb exceeded 1:200. A low-level NAbs, near 1:100, had no effect on transduction in the heart and liver as well as cellular responses, but decreased transduction in muscles slightly. Therefore, we propose to preclude patients with NAb titers > 1:100 from rAAV9-coGAA clinical trials. [ABSTRACT FROM AUTHOR]

Sialic acid (SA) is a kind of functional monosaccharide which exists widely in edible bird's nest (EBN), milk, meat, mucous membrane surface, etc. SA is an important functional component in promoting brain development, anti-oxidation, anti-inflammation, anti-virus, anti-tumor and immune regulation. The intestinal mucosa covers the microbial community that has a significant impact on health. In the gut, SA can also regulate gut microbiota and metabolites, participating in different biological functions. The structure, source and physiological functions of SA were reviewed in this paper. The biological functions of SA through regulating key signaling pathways and target genes were discussed. In summary, SA can modulate gut microbiota and metabolites, which affect gene expressions and exert its biological activities. It is helpful to provide scientific reference for the further investigation of SA in the functional foods. [ABSTRACT FROM AUTHOR]

Previous reports have shown that it is difficult to improve the methanol adsorption performance of nitrogen and oxygen groups due to their low polarity. Here, we first prepared porous carbon with a high specific surface area and large pore volume using benzimidazole as a carbon precursor and KOH as an activating agent. Then, we improved the surface polarity of the porous carbon by doping with Lithium (Li) to enhance the methanol adsorption performance. The results showed that the methanol adsorption capacity of Li-doped porous carbon reached 35.4 mmol g−1, which increased by 57% compared to undoped porous carbon. Molecular simulation results showed that Li doping not only improved the methanol adsorption performance at low pressure, but also at relatively high pressure. This is mainly because Li-modified porous carbon has higher surface polarity than nitrogen and oxygen-modified surfaces, which can generate stronger electrostatic interactions. Furthermore, through density functional theory (DFT) calculations, we determined the adsorption energy, adsorption distance, and charge transfer between Li atom and methanol. Our results demonstrate that Li doping enhances the adsorption energy, reduces the adsorption distance, and increases the charge transfer in porous carbon. The mechanism of methanol adsorption by Li groups was revealed through experimental and theoretical calculations, providing a theoretical basis for the design and preparation of methanol adsorbents. [ABSTRACT FROM AUTHOR]

To investigate the pollutant dispersion of a nuclear power plant, a field tracing experiment was carried out in neutral stratification weather with the main wind direction SSW. On this basis, a wind speed profile and turbulence intensity profile consistent with the site were created in the wind tunnel. Meanwhile, how to generate a wind field of neutral stratification in a wind tunnel was studied in detail. Finally, a 1:1000 nuclear power area model was made to conduct tracing experiments in the wind tunnel. The results show that when the horizontal and vertical distances of the spire are 300 mm and 500 mm, and the horizontal and vertical distances of the rough element are 250 mm and 500 mm. A wind speed profile with a wind profile index of 0.321 was generated in the wind tunnel (0.334 in the field test), and the wind tunnel tracer experiment had the same diffusion trend as the field, which verified the accuracy of the flow field. [ABSTRACT FROM AUTHOR]

Aggressive driving behavior (ADB) is one of the main causes of traffic accidents. The accurate recognition of ADB is the premise to timely and effectively conduct warning or intervention to the driver. There are some disadvantages, such as high miss rate and low accuracy, in the previous data-driven recognition methods of ADB, which are caused by the problems such as the improper processing of the dataset with imbalanced class distribution and one single classifier utilized. Aiming to deal with these disadvantages, an ensemble learning-based recognition method of ADB is proposed in this paper. First, the majority class in the dataset is grouped employing the self-organizing map (SOM) and then are combined with the minority class to construct multiple class balance datasets. Second, three deep learning methods, including convolutional neural networks (CNN), long short-term memory (LSTM), and gated recurrent unit (GRU), are employed to build the base classifiers for the class balance datasets. Finally, the ensemble classifiers are combined by the base classifiers according to 10 different rules, and then trained and verified using a multi-source naturalistic driving dataset acquired by the integrated experiment vehicle. The results suggest that in terms of the recognition of ADB, the ensemble learning method proposed in this research achieves better performance in accuracy, recall, and F1-score than the aforementioned typical deep learning methods. Among the ensemble classifiers, the one based on the LSTM and the Product Rule has the optimal performance, and the other one based on the LSTM and the Sum Rule has the suboptimal performance. [ABSTRACT FROM AUTHOR]

Lane Utilization Ratio (LUR), affected by lane selection behavior directly, represents the traffic distribution on different lanes of road section for a single direction. The research on LUR, especially under Penetration Conditions of Connected and Automated Vehicles (PCCAV), is not comprehensive enough. Considering the difficulty in the conduction of real vehicle experiment and data collection under PPCAV, the lane selection model based on phase-field coupling and set pair logic, which considers the full-information of lanes, was used to carry out microscopic traffic simulation. From the analysis of microsimulation results, the basic relationships between Penetration of Connected and Automated Vehicles (PCAV), traffic volume, and Lane-Changing Times, also that between PCAV, traffic volume, and LUR in the basic section of the urban expressway were studied. Moreover, the influence of driving propensity on the effect of PCAVs was also studied. The research results could enrich the traffic flow theory and provide the theoretical basis for traffic management and control. [ABSTRACT FROM AUTHOR]

Multi-energy complementary systems (MCSs) are complex multilevel systems. In the process of system planning, many aspects—such as power planning, investment cost, and environmental impact—should be considered. However, different decision makers tend to have different levels of control objectives, and the multilevel problems of the system need to be solved effectively with comprehensive judgment. Therefore, based on the terminal MCS energy structure model, the optimization method of MCS planning and operation coordination, considering the influence of planning and operation in the system's life cycle, is studied in this paper. Consequently, the research on the collaborative optimization strategy of MCS construction and operation was carried out based on the bi-level multi-objective optimization theory in this paper. Considering the mutual restraint and correlation between system construction and operation in practical engineering, a bi-level optimization model for collaborative optimization of MCS construction and operation was constructed. To solve the model effectively, the existing non-dominated sorting genetic algorithm III (NSGA-III) was improved by the authors on the basis of previous research, which could enhance the global search ability and convergence speed of the algorithm. To effectively improve and strengthen the reliability of energy supply, and increase the comprehensive energy utilization of the system, the effects of carbon transaction cost and renewable energy penetration were considered in the optimization process. Based on an engineering example, the bi-level model was solved and analyzed. It should be noted that the optimization results of the model were verified to be applicable and effective by comparison with the single-level multi-objective programming optimization. The findings of this paper could provide theoretical reference and practical guidance for the planning and operation of MCSs, making them significant for social application. [ABSTRACT FROM AUTHOR]

The development and utilization of low-carbon energy systems has become a hot topic of energy research in the international community. The construction of a multi-energy complementary distributed energy system (MCDES) is researched in this paper. Based on the multi-objective optimization theory, the planning optimization of an MCDES is studied, and a three-dimensional objective-optimization model is constructed by considering the constraints of the objective function and decision variables. Aiming at the optimization problem of building terminals for the MCDES studied in the paper, two genetic optimization algorithms—Non-Dominated Sorting Genetic Algorithm II (NSGA-II) and Non-Dominated Sorting Genetic Algorithm III (NSGA-III)—are used for calculation based on an example analysis. The constraint conditions of practical problems were added to the existing algorithms. Combined with the comparison of the solution quality and the optimal compromise solution of the two algorithms, a multi-decision method is proposed to obtain the optimal solution based on the Pareto optimal frontier of the two algorithms. Finally, the optimal decision scheme of the example is determined and the effectiveness and reliability of the optimization model are verified. Under the application of the MCDES optimization model studied in this paper, the iteration speed and hypervolume index of NSGA-III are found to be better than those of NSGA-II. The values of the life cycle cost and life cycle carbon emission objectives after the optimization of NSGA-III are indicated as 2% and 14% lower, respectively, than those of NSGA-II. The primary energy efficiency of NSGA-III is shown to be 20% higher than that of NSGA-II. According to the optimal decision, the energy operation strategies of the example MCDES with each typical day in the four seasons indicate that good integrated energy application and low-carbon operation performance are shown during the four-seasons operation process. The consumption of renewable energy is significant, which effectively reduces the application of high-grade energy. Thus, the theoretical guidance and engineering application reference are provided for MCDES design planning and operation optimization. [ABSTRACT FROM AUTHOR]

The performance of pollutant removals, tetracycline (TC) and norfloxacin (NOR) removals, membrane fouling mitigation and the microbial community of three Anoxic/Oxic membrane bioreactors (AO-MBRs), including a moving bed biofilm MBR (MBRa), a fixed biofilm MBR (MBRb) and an AO-MBR (MBRc) for control, were compared in treating antibiotic-containing synthetic mariculture wastewater. The results showed that MBRb had the best effect on antibiotic removal and membrane fouling mitigation compared to the other two bioreactors. The maximum removal rate of TC reached 91.65% and the maximum removal rate of NOR reached 45.46% in MBRb. The addition of antibiotics had little effect on the removal of chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N)—both maintained more than 90% removal rate during the entire operation. High-throughput sequencing demonstrated that TC and NOR resulted in a significant decrease in the microbial diversity and the microbial richness MBRs. Flavobacteriia, Firmicutes and Azoarcus, regarded as drug-resistant bacteria, might play a crucial part in the removal of antibiotics. In addition, the dynamics of microbial community had a great change, which included the accumulation of resistant microorganisms and the gradual reduction or disappearance of other microorganisms under antibiotic pressure. The research provides an insight into the antibiotic-containing mariculture wastewater treatment and has certain reference value. [ABSTRACT FROM AUTHOR]

Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways. [ABSTRACT FROM AUTHOR]

Chinese jujube (Ziziphus jujuba), a medicinal and edible plant, is widely consumed in Asian countries owing to the remarkable health activities of its fruits. To facilitate selection of the suitable processing method for jujube fruits, in this study their contents of triterpenic acids, nucleosides, nucleobases and saccharides after drying and steaming treatment were determined using ultra-high performance liquid chromatography and high performance liquid chromatography coupled with evaporative light scattering detector methods. The results showed that except for sucrose, the content levels of most analytes were increasing in the jujube fruits during drying treatment at 45 °C. The levels of cyclic nucleotides such as adenosine 3',5'-cyclic monophosphate and guanosine 3',5'-cyclic monophosphate, were significantly decreased after the fruits were steamed. Therefore, owing to the bioactivities of these components for human health, the dried fruits would be the better choice as medicinal material or functional food, and dried jujube fruit should not be further steamed.