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Abstract Bladder cancer is one of the most frequent malignant tumors of the urinary system. The prevalence of bladder cancer among men and women is roughly 5:2, and both its incidence and death have been rising steadily over the past few years. At the moment, metastasis and recurrence of advanced bladder cancer—which are believed to be connected to the malfunction of multigene and multilevel cell signaling network—remain the leading causes of bladder cancer-related death. The therapeutic treatment of bladder cancer will be greatly aided by the elucidation of these mechanisms. New concepts for the treatment of bladder cancer have been made possible by the advancement of research technologies and a number of new treatment options, including immunotherapy and targeted therapy. In this paper, we will extensively review the development of the tumor microenvironment and the possible molecular mechanisms of bladder cancer.

A novel Na1−xKxTaO3 (x = 0, 0.025, 0.05, 0.075, 0.1, and 0.15) ceramic with high permittivity and high positive temperature coefficient was synthesized via the conventional solid-state method. All samples were determined to be pure phase orthorhombic NaTaO3 structure of space group Pmcn, and larger grain and lower porosity were observed after adding an appropriate amount of K+ ions. The Q × f value is majored by the packing fraction and grain size, while the value of τf is influenced by Ta–O bond valence. The Na0.95K0.05TaO3 ceramic possesses excellent dielectric properties of εr = 164.29, Q × f = 9091 GHz (f = 3.15 GHz), tanδ = 3.46×10–4, τf = +809.52 ppm/℃, sintered at 1550 ℃. Compared with NaTaO3 ceramics, the Na1−xKxTaO3 ceramics prepared in this study demonstrate higher dielectric constants and higher positive temperature coefficients, which are promising for device miniaturization and τf compensators.

ABSTRACT Blast disease caused by Magnaporthe oryzae threatens rice production worldwide, and chemical control is one of the main methods of its management. The high mutation rate of the M. oryzae genome results in drug resistance, which calls for novel fungicide targets. Fungal proteins that function during the infection process might be potential candidates, and Mps1 (M. oryzae mitogen-activated protein kinase 1) is such a protein that plays a critical role in appressorium penetration of the plant cell wall. Here, we report the structure-aided identification of a small-molecule inhibitor of Mps1. High-throughput screening was performed with Mps1 against a DNA-encoded compound library, and one compound, named A378-0, with the best performance was selected for further verification. A378-0 exhibits a higher binding affinity than the kinase cosubstrate ATP and can inhibit the enzyme activity of Mps1. Cocrystallization of A378-0 with Mps1 revealed that A378-0 binds to the catalytic pocket of Mps1, while the three ring-type substructures of A378-0 constitute a triangle that squeezes into the pocket. In planta assays showed that A378-0 could inhibit both the appressorium penetration and invasive growth but not the appressorium development of M. oryzae, which is consistent with the biological function of Mps1. Furthermore, A378-0 exhibits binding and activity inhibition abilities against Mpk1, the Mps1 ortholog of the soilborne fungal pathogen Fusarium oxysporum. Collectively, these results show that Mps1 as well as its orthologs can be regarded as fungicide targets, and A378-0 might be used as a hit compound for the development of a broad-spectrum fungicide. IMPORTANCE M. oryzae is the causal agent of rice blast, one of the most devastating diseases of cultivated rice. Chemical control is still the main strategy for its management, and the identification of novel fungicide targets is indispensable for overcoming existing problems such as drug resistance and food safety. With a combination of structural, biochemical, and in planta assays, our research shows that Mps1 may serve as a fungicide target and confirms that compound A378-0 binds to Mps1 and possesses bioactivity in inhibiting M. oryzae virulence. As fungal orthologs of Mps1 are conserved, A378-0 may serve as a hit for broad-spectrum fungicide development, as evidenced with Mpk1, the Mps1 ortholog of F. oxysporum. Additionally, A378-0 contains a novel chemical scaffold that has not been reported in approved kinase inhibitors, suggesting its potential to be considered the basis for the development of other kinase inhibitors.

Given that the pharmaceutical market has experienced severe market failures, it is necessary that we regulate pharmaceutical prices for many countries. Toward ensuring that pharmaceutical price regulation is efficient, this study investigated the antecedents that lead to an unreasonable pharmaceutical price. Based on 33 case-study countries, this study utilized QCA to analyze the conditional configuration of unreasonable pharmaceutical prices from the perspective of medical service provision. The results showed that the causes of unreasonable pharmaceutical prices are configured by medical service provision, especially cost compensation systems and payment mechanism. This study's conclusions contribute to the research on pharmaceutical price regulation and the institution of medical service provision.

IntroductionWith the advancement of new media, brand communication has been taken into consideration by lots of firms. Apparently, customer affection plays a significant role in brand communications, though few studies have determined how the twofold of information function works in this communication mechanism. Based on this research gap and practical background, this paper proposes a hybrid model of communication comprising the utilitarian and hedonic aspects.MethodsFor this study, 575 questionnaires were collected, followed by the structural equation modeling of the derived data to test the research model.ResultsThe results of statistical analysis show that the brand communication can be improved in terms of both utilitarian and hedonic aspects. Moreover, psychological contract and customer engagement play a chain mediation role in this mechanism.DiscussionThese findings contribute to the research of brand communication mechanism in digital era. Likewise, the findings offers several practical implications to the brand management.

Targeting some problems of the RRT_Connect path planning algorithm, such as average search and low efficiency, proposes an improved RRT_Connect algorithm that may optimize the searched nodes and parts of planned paths. Firstly, an improved RRT_Connect algorithm based on destination and searched node bias strategy is proposed. Secondly, an improved RRT_Connect algorithm is put forward for the optimization of the searched nodes and some planned paths to deal with the problem of low quality reflected in the improved RRT_Connect path planning algorithm, and the optimization for the cost of path planning by figuring out valid new nodes and parent nodes of adjacent nodes within a certain range. On this basis, the path planning algorithm is verified by simulation and actual experiments. It is shown by the experimental results that the improved RRT_Connect algorithm proposed in this paper can not only shorten the time and length of path planning but also decrease the number of search iterations and nodes.

Snf5 (sucrose nonfermenting) is a core component of the SWI/SNF complexes and regulates diverse cellular processes in model eukaryotes. In plant pathogenic fungi, its biological function and underlying mechanisms remain unexplored. In this study, we investigated the biological roles of MoSnf5 in plant infection and fungal development in the rice blast pathogen Magnaporthe oryzae. The gene deletion mutants of MoSNF5 exhibited slower vegetative hyphal growth, severe defects in conidiogenesis, and impaired virulence and galactose utilization capacities. Domain dissection assays showed that the Snf5 domain and the N- and C-termini of MoSnf5 were all required for its full functions. Co-immunoprecipitation and yeast two-hybrid assays showed that MoSnf5 physically interacts with four proteins, including a transcription initiation factor MoTaf14. Interestingly, the ∆MoTaf14 mutants showed similar phenotypes as the ∆Mosnf5 mutants on fungal virulence and development. Moreover, assays on GFP-MoAtg8 expression and localization showed that both the ∆Mosnf5 and ∆MoTaf14 mutants were defective in autophagy. Taken together, MoSnf5 regulates fungal virulence, growth, and conidiation, possibly through regulating galactose utilization and autophagy in M. oryzae.

Object detection is one of the most widespread applications for numerous Unmanned Aerial Vehicle (UAV) tasks. Due to the shooting angle and flying height of the UAV, compared with general scenarios, small objects account for a large proportion of aerial images, and common object detectors are not extremely effective in aerial images. Moreover, since the computing resources of UAV platforms are generally limited, the deployment of common detectors with a large number of parameters on UAV platforms is difficult. This paper proposes a lightweight object detector YOLO-UAVlite for aerial images. Firstly, the spatial attention module and coordinate attention module are modified and combined to form a novel Spatial-Coordinate Self-Attention (SCSA) module, which integrates spatial, location, and channel information to enhance object representation. On this basis, we construct a lightweight backbone, named SCSAshufflenet, which combines the Enhanced ShuffleNet (ES) network with the proposed SCSA module to improve feature extraction and reduce model size. Secondly, we propose an improved feature pyramid model, namely Slim-BiFPN, where we construct new lightweight convolutional blocks to reduce the information loss during the feature map fusion process while reducing the model weights. Finally, the localization loss function is modified to increase the bounding box regression rate while improving the localization accuracy. Extensive experiments conducted on the VisDrone-DET2021 dataset indicate that, compared with the YOLOv5-N baseline, the proposed YOLO-UAVlite reduces the number of parameters by 25.8% and achieves gains of 10.9% in mAP0.50. Compared with other lightweight detectors, both the mAP and the number of parameters are improved.

The present research was designed to evaluate the protective effects and underlying mechanisms of different ratios of linoleic acid (LA) and α-linolenic acid (ALA), two essential polyunsaturated fatty acids (PUFAs) fatty acids, on atopic dermatitis (AD)-like skin lesions induced by 2, 4-dinitrofluorobenzene (DNFB). The dorsal flank and ear pinnas of mice were sensitized and challenged with DNFB for four weeks in order to establish AD model. Simultaneously, the mice were orally administered different ratios of LA/ALA (v/v; 4:1 or 1:1), or dexamethasone (Dex; 0.1 mg/kg). Results showed that different LA/ALA ratios, especially a ratio of 4:1 treatment, could effectively ameliorate DNFB-induced skin lesions, ear edema, scratching behavior and skin inflammation, as reflected by the reduced inflammatory blood cells, IgE serum levels, and skin levels of the pro-inflammatory lipid mediators, including PGE2 and LTB4. These findings were further confirmed by skin pathological examination. Moreover, LA/ALA administration markedly suppressed the proliferation and infiltration of T cells, the production of T helper cell type 1 (Th1), Th2 and Th17 cytokines in dorsal skin and serum of DNFB-treated mice. Western blotting and immunohistochemistry staining revealed that LA/ALA downregulated the protein expressions of JAK2 and STAT4, and thus reducing the synthesis of type Th1 cytokine IFN-γ. Taken together, these results suggest that optimal nutrition ratio of LA/ALA has beneficial effects on AD-like symptoms, which provide theoretical basis for its therapeutic potential in the clinical prevention and treatment of AD.

Directing at various problems of the traditional Q-Learning algorithm, such as heavy repetition and disequilibrium of explorations, the reinforcement-exploration strategy was used to replace the decayed ε-greedy strategy in the traditional Q-Learning algorithm, and thus a novel self-adaptive reinforcement-exploration Q-Learning (SARE-Q) algorithm was proposed. First, the concept of behavior utility trace was introduced in the proposed algorithm, and the probability for each action to be chosen was adjusted according to the behavior utility trace, so as to improve the efficiency of exploration. Second, the attenuation process of exploration factor ε was designed into two phases, where the first phase centered on the exploration and the second one transited the focus from the exploration into utilization, and the exploration rate was dynamically adjusted according to the success rate. Finally, by establishing a list of state access times, the exploration factor of the current state is adaptively adjusted according to the number of times the state is accessed. The symmetric grid map environment was established via OpenAI Gym platform to carry out the symmetrical simulation experiments on the Q-Learning algorithm, self-adaptive Q-Learning (SA-Q) algorithm and SARE-Q algorithm. The experimental results show that the proposed algorithm has obvious advantages over the first two algorithms in the average number of turning times, average inside success rate, and number of times with the shortest planned route.

In recent years, with the rise of global diabetes, a growing number of subjects are suffering from pain and infections caused by the invasive nature of mainstream commercial glucose meters. Non-invasive blood glucose monitoring technology has become an international research topic and a new method which could bring relief to a vast number of patients. This paper reviews the research progress and major challenges of non-invasive blood glucose detection technology in recent years, and divides it into three categories: optics, microwave and electrochemistry, based on the detection principle. The technology covers medical, materials, optics, electromagnetic wave, chemistry, biology, computational science and other related fields. The advantages and limitations of non-invasive and invasive technologies as well as electrochemistry and optics in non-invasives are compared horizontally in this paper. In addition, the current research achievements and limitations of non-invasive electrochemical glucose sensing systems in continuous monitoring, point-of-care and clinical settings are highlighted, so as to discuss the development tendency in future research. With the rapid development of wearable technology and transdermal biosensors, non-invasive blood glucose monitoring will become more efficient, affordable, robust, and more competitive on the market.

Irinotecan (CPT-11), a water-soluble derivative of camptothecin, belongs to the class of DNA topoisomerase I inhibitors and has been approved worldwide for the treatment of advanced colorectal cancer, lung cancer, and malignant lymphoma. Although CPT-11-based chemotherapy is widely used, severe gastrointestinal (GI) toxicity, especially late-onset diarrhea, is a common adverse reaction, limiting clinical application of the drug. The incidence of grade 3 or 4 diarrhea is high, with 20–40% of CPT-11-treated patients experiencing this adverse effect. High-dose loperamide and octreotide are generally recommended for treatment of CPT-11-induced diarrhea. However, in clinical practice, loperamide is associated with a significant failure rate and the beneficial effects of octreotide are controversial. An accumulating number of recent studies have suggested that medicinal herbs and their derived phytocompounds may be effective complementary treatments for CPT-11-induced diarrhea. In this mini-review, we briefly summarize currently available literatures regarding the formulae and herbs/natural products used as adjuvants in animal and clinical studies for the treatment of diarrhea caused by CPT-11.

Combined cooling, heating and power (CCHP) micro-grids have the advantage of high energy efficiency, and can be integrated with renewable energies and demand response programs (DRPs). With the deepening of electricity market (EM) reforms, how to carry out operation optimization under EM circumstances will become a key problem for CCHP micro-grid development. This paper proposed a stochastic-CVaR (conditional value at risk) optimization model for CCHP micro-grid operation with consideration of EM participation, wind power accommodation and multiple DRPs. Specifically, based on the stochastic scenarios for EM clearing prices and wind power outputs uncertainties, the stochastic optimization method was applied to ensure the realization of operational cost minimization and wind power accommodation; the CVaR method was implemented to control the potential risk of operational cost increase. Moreover, by introducing multiple DRPs, the electrical, thermal and cooling loads can be transformed as flexible sources for CCHP micro-grid operation. Simulations were performed to show the following outcomes: (1) by applying the proposed stochastic-CVaR approach and considering multiple DRPs, CCHP micro-grid operation can reach better performance in terms of cost minimization, risk control and wind power accommodation etc.; (2) higher energy utilization efficiency can be achieved by coordinately optimizing EM power biddings; etc.

All-day atmospheric water vapor content measurements determined by Raman lidar and a sunphotometer were combined to investigate the all-day variation characteristics in the water vapor distribution in Xi’an, China (34.233°N, 108.911°E). To enhance the daytime lidar performance, the wavelet threshold de-noising method is used to filter out the strong solar background light, and effective denoised results are demonstrated with the following optimization: wavelet sym6, the improved threshold function, and the improved threshold selection. The denoised system signal-to-noise ratio (SNR) for the water vapor daytime measurement is validated, with an enhancement of ~3.4 times up to a height of 3 km compared to that of the original signal. The time series of the atmospheric water vapor mixing ratio profiles and the obtained precipitable water vapor (PWV) measured by Raman lidar are used to reveal the temporal and spatial variations in water vapor, and the comparisons with the total column water vapor content (TCWV) measured by a sunphotometer validate the daytime variation trend of the water vapor. All-day continuous observations clearly present a consistent variation trend in the water vapor between the sunphotometer and Raman lidar measurements. The correlation analysis between TCWV and PWV at the layers below 850 hPa and below 700 hPa yields a good positive correlation coefficient (>0.75), indicating that PWV determination in the bottom layer by Raman lidar can directly reflect the variations in the total water vapor content. Moreover, different diurnal variation trends in water vapor are also observed, that is, a downward trend from the afternoon to the night, or a tendency of being high in the morning and afternoon and low at noon, demonstrating the high temporal-spatial variation characteristics of water vapor and close correlation with weather changes. The results reflected and validated that the diurnal variation in water vapor is complicated and can be an indicator of the weather to a certain extent.

To evaluate the potential of Raman lidar observations for measuring precipitable water vapor (PWV), PWV variations and distribution characteristics were investigated in Xi’an (34.233°N, 108.911°E), and its comparisons with meteorological parameters were also analysed. Comparisons of lidar PWV with radiosonde PWV verified the ability and accuracy of using Raman lidars for PWV measurements. The diurnal and monthly variation trends in PWV in different layers are first discussed via the statistical analysis of lidar data from November 2013 to July 2016; different proportions of PWV were found in different layers, and the PWV in each layer presented a slight diurnal change trend and consistent seasonal variation, which was relatively rich in summer, less so in spring and autumn, and relatively deficient in winter. Furthermore, correlation analyses between lidar PWV and meteorological parameters are explored. Water vapor pressure and surface temperature revealed the same inter-seasonal oscillation of PWV, with a correlation coefficient of ~0.90. However, incomplete synchronization was found between PWV and relative humidity and precipitation parameters. Higher humidity appeared in the late summer and the beginning of autumn of each year, which was also the case for precipitation and precipitation efficiency. In addition, atmospheric water vapor density profiles and the obtained PWV by Raman lidar are discussed employing a rainfall case, and a comprehensive analysis with meteorological parameters is undertaken. The intensifying characteristics of vertical change in water vapor and the accumulation of PWV in the lower troposphere can be captured by lidar before the onset of rainfall. In contrast to the obvious diurnal change trend, such meteorological parameters as relative humidity, water vapor pressure, and dew-point temperature difference are accompanied with stable trends with a change rate of close to 0 in the rainfall processes; they also show high correlated variations with lidar PWV. Thus, with the advantage of lidar detection, investigation of water vapor profiles and PWV by Raman lidar, and the comprehensive correlation analyses with synchronic meteorological parameters can prove to be good indications of rainfall.