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Compound 7–16 was designed and synthesized in our previous study and was identified as a more potential selective 5-HT2A receptor antagonist and inverse agonist for treating Parkinson's disease psychosis (PDP). Then, the metabolism, disposition, and excretion properties of 7–16 and its potential inhibition on transporters were investigated in this study to highlight advancements in the understanding of its therapeutic mechanisms. The results indicate that a total of 10 metabolites of 7–16/[14C]7–16 were identified and determined in five species of liver microsomes and in rats using UPLC-Q Exactive high-resolution mass spectrometry combined with radioanalysis. Metabolites formed in human liver microsomes could be covered by animal species. 7–16 is mainly metabolized through mono-oxidation (M470-2) and N-demethylation (M440), and the CYP3A4 isozyme was responsible for both metabolic reactions. Based on the excretion data in bile and urine, the absorption rate of 7–16 was at least 74.7%. 7–16 had weak inhibition on P-glycoprotein and no effect on the transport activity of OATP1B1, OATP1B3, OAT1, OAT3, and OCT2 transporters. The comprehensive pharmacokinetic properties indicate that 7–16 deserves further development as a new treatment drug for PDP. [ABSTRACT FROM AUTHOR]

Sleep disorders are the most widespread mental disorders after stroke and hurt survivors' functional prognosis, response to restoration, and quality of life. This review will address an overview of the progress of research on the biological mechanisms associated with stroke-complicating sleep disorders. Extensive research has investigated the negative impact of stroke on sleep. However, a bidirectional association between sleep disorders and stroke exists; while stroke elevates the risk of sleep disorders, these disorders also independently contribute as a risk factor for stroke. This review aims to elucidate the mechanisms of stroke-induced sleep disorders. Possible influences were examined, including functional changes in brain regions, cerebrovascular hemodynamics, neurological deficits, sleep ion regulation, neurotransmitters, and inflammation. The results provide valuable insights into the mechanisms of stroke complicating sleep disorders. [ABSTRACT FROM AUTHOR]

Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation. [ABSTRACT FROM AUTHOR]

With the increasing complexity of radar jamming threats, accurate and automatic jamming recognition is essential but remains challenging. Conventional algorithms often suffer from sharply decreased recognition accuracy under low jamming-to-noise ratios (JNR).Artificial intelligence-based jamming signal recognition is currently the main research directions for this issue. This paper proposes a new radar jamming recognition framework called Diff-SwinT. Firstly, the time-frequency representations of jamming signals are generated using Choi-Williams distribution. Then, a diffusion model with U-Net backbone is trained by adding Gaussian noise in the forward process and reconstructing in the reverse process, obtaining an inverse diffusion model with denoising capability. Next, Swin Transformer extracts hierarchical multi-scale features from the denoised time-frequency plots, and the features are fed into linear layers for classification. Experiments show that compared to using Swin Transformer, the proposed framework improves overall accuracy by 15% to 10% at JNR from −16 dB to −8 dB, demonstrating the efficacy of diffusion-based denoising in enhancing model robustness. Compared to VGG-based and feature-fusion-based recognition methods, the proposed framework has over 27% overall accuracy advantage under JNR from −16 dB to −8 dB. This integrated approach significantly enhances intelligent radar jamming recognition capability in complex environments. [ABSTRACT FROM AUTHOR]

The plant architecture of higher plants is regulated through environmental and genetic factors, as well as phytohormones. Phytohormones play a critical role in regulating shoot branching. We determined the branching phenotype of D16 and N99-6, the content of strigolactones, the genetic expression level, and the interaction between auxin and strigolactones. We found that the branching development of the two soybean varieties under shading was significantly slower than that under normal light. The average branch length of N99-6 decreased by 40.9% after shading; however, the branch length of D16 was not significantly affected. Meanwhile, the branch formation rate in D16 was significantly higher than in N99-6. In addition, after shading treatment, the content of strigolactones in D16 and N99-6 axillary buds increased significantly, and the expression of phytochrome genes, PhyA and PhyB, showed opposite changes. However, strigolactone synthesis gene GmMAX4 and signal transduction gene GmMAX2 expression levels of D16 were lower than those of N99-6 after 24 h of shading. In addition, the application of strigolactone inhibitor TIS108 and auxin inhibitor NPA to soybean had no significant effect on the branch phenotype. The expression of the GmMAX2 gene was significantly up-regulated after the external application of the auxin analog, and the expression of auxin transporter gene GmPINI was significantly down-regulated after external application of the strigolactone analog under shade. In this study, we investigated the adverse effect of shade on soybean branching development, which may be due to the interaction of strigolactones with auxins. [ABSTRACT FROM AUTHOR]

The GRAPES (Global/Regional Assimilation and Prediction System) global medium-range ensemble forecast system (GRAPES_GFS) is a new generation numerical weather forecast model developed by the China Meteorological Administration (CMA). However, the forecasts of surface latent heat fluxes and surface air temperature have systematic biases, which affect the forecasts of atmospheric dynamics by modifying the lower boundary conditions and degrading the application of GRAPES_GFS since the 2 m air temperature is one of the key components of weather forecast products. Here, we add a soil resistance term to reduce soil evaporation, which ultimately reduces the positive forecast bias of the land surface latent heat flux. We also reduce the positive forecast bias of the ocean surface latent heat flux by considering the effect of salinity in the calculation of the ocean surface vapor pressure and by adjusting the parameterizations of roughness length for the exchanges in momentum, heat, and moisture between the ocean surface and atmosphere. Moreover, we modify the parameterization of the roughness length for the exchanges in heat and moisture between the land surface and atmosphere to reduce the cold bias of the nighttime 2 m air temperature forecast over areas with lower vegetation height. We also consider the supercooled soil water to reduce the warm forecast bias of the 2 m air temperature over northern China during winter. These modified parameterizations are incorporated into the GRAPES_GFS and show good performance based on a set of evaluation experiments. This paper highlights the importance of the representations of the land/ocean surface and boundary layer processes in the forecasting of surface heat fluxes and 2 m air temperature. [ABSTRACT FROM AUTHOR]

In this paper, through high-temperature tensile tests of 55NiCrMoV7 steel, high-temperature fracture behavior, microstructure evolution, and carbide distribution characteristics of both the thermal–mechanical coupling zone (fracture zone) and thermal stress zone (clamping zone) at different temperatures were studied. Intrinsic relationships between high-temperature fractures and carbide types, distribution and size were revealed, and evolution mechanisms of microstructure near cracks in 55NiCrMoV7 hot-working die steel during high-temperature deformation was clarified. Samples were stretched at different temperatures from 25 °C to 700 °C, and microscopic examinations were carried out using SEM and TEM. The results showed the following. With the increase in temperature, tensile strength and yield strength decreased, elongation and reduction of area increased, and fracture mode changed from brittle fracture to ductile fracture by transition temperature at about 400 °C. During high-temperature deformation, the grain dislocation density decreased and the tempered martensite decomposed, recovered, recrystallized, and then grain grew. M7C3 and M23C6 carbides precipitated and grew along the grain boundary, and a small amount of fine granular MC carbides was dispersed in the grain. The work done by the external force on the deformation zone would cause the temperature of it to be higher than the tensile temperature, which provides thermodynamic conditions for the redissolution of small carbides near the fracture zone and the grain growth of large carbides, resulting in a decrease in small carbides and increase in large carbides in thermal–mechanical coupling zones. [ABSTRACT FROM AUTHOR]

In this narrative review article, we discuss the role of sleep deprivation (SD) in memory processing in rodent models. Numerous studies have examined the effects of SD on memory, with the majority showing that sleep disorders negatively affect memory. Currently, a consensus has not been established on which damage mechanism is the most appropriate. This critical issue in the neuroscience of sleep remains largely unknown. This review article aims to elucidate the mechanisms that underlie the damaging effects of SD on memory. It also proposes a scientific solution that might explain some findings. We have chosen to summarize literature that is both representative and comprehensive, as well as innovative in its approach. We examined the effects of SD on memory, including synaptic plasticity, neuritis, oxidative stress, and neurotransmitters. Results provide valuable insights into the mechanisms by which SD impairs memory function. [ABSTRACT FROM AUTHOR]

The emergence of induced pluripotent stem cell (iPSC) technology has provided a new approach to regenerating decellularized trabecular meshwork (TM) in glaucoma. We have previously generated iPSC-derived TM (iPSC-TM) using a medium conditioned by TM cells and verified its function in tissue regeneration. Because of the heterogeneity of iPSCs and the isolated TM cells, iPSC-TM cells appear to be heterogeneous, which impedes our understanding of how the decellularized TM may be regenerated. Herein, we developed a protocol based on a magnetic-activated cell sorting (MACS) system or an immunopanning (IP) method for sorting integrin subunit alpha 6 (ITGA6)-positive iPSC-TM, an example of the iPSC-TM subpopulation. We first analyzed the purification efficiency of these two approaches by flow cytometry. In addition, we also determined cell viability by analyzing the morphologies of the purified cells. To conclude, the MACS-based purification could yield a higher ratio of ITGA6-positive iPSC-TM and maintain a relatively higher cell viability than the IP-based method, allowing for the preparation of any iPSC-TM subpopulation of interest and facilitating a better understanding of the regenerative mechanism of iPSC-based therapy. [ABSTRACT FROM AUTHOR]

PLK-1 (Polo-like kinase-1) plays an essential role in cytokinesis, and its aberrant expression is considered to be keenly associated with a wide range of cancers. It has been selected as an appealing target and small-molecule inhibitors have been developed and studied in clinical trials. Unfortunately, most have been declared as failures due to the poor therapeutic response and off-target toxicity. In the present study, a novel potent PLK-1 inhibitor, compound 7a, was designed and synthetized. 1H NMR, 13C NMR, 19F NMR and mass spectrum were comprehensively used for the compound characterization. The compound exhibited higher potency against PLK-1 kinase, HCT-116 and NCI-H2030 cell lines than the positive control. Molecular docking indicated that the binding mode that the ATP binding site of PLK-1 was occupied by the compound. Then, a UHPLC-MS/MS method was established and validated to explore the pharmacokinetic behavior of the drug candidate. The method had good selectivity, high sensitivity and wide linearity. The exposure increased linearly with the dose, but the oral bioavailability was not satisfactory enough. Then, the metabolism was studied using liver microsomes by UHPLC-Q-Orbitrap/HRMS. Our research first studied the pharmacokinetic metabolic characteristics of 7a and may serve as a novel lead compound for the development of PLK-1 inhibitors. [ABSTRACT FROM AUTHOR]

Given the advantage of LoRaWAN private networks, multiple types of services have been implemented by users in one LoRaWAN system to realize various smart applications. With an increasing number of applications, LoRaWAN suffers from multi-service coexistence challenges due to limited channel resources, uncoordinated network configuration, and scalability issues. The most effective solution is establishing a reasonable resource allocation scheme. However, existing approaches are not applicable for LoRaWAN with multiple services with different criticalities. Therefore, we propose a priority-based resource allocation (PB-RA) scheme to coordinate multi-service networks. In this paper, LoRaWAN application services are classified into three main categories, including safety, control, and monitoring. Considering the different criticalities of these services, the proposed PB-RA scheme assigns spreading factors (SFs) to end devices on the basis of the highest priority parameter, which decreases the average packet loss rate (PLR) and improves throughput. Moreover, a harmonization index, namely HDex, based on IEEE 2668 standard is first defined to comprehensively and quantitively evaluate the coordination ability in terms of key quality of service (QoS) performance (i.e., PLR, latency and throughput). Furthermore, Genetic Algorithm (GA)-based optimization is formulated to obtain the optimal service criticality parameters which maximize the average HDex of the network and contribute to a larger capacity of end devices while maintaining the HDex threshold for each service. Simulations and experimental results show that the proposed PB-RA scheme can achieve the HDex score of 3 for each service type at 150 end devices, which improves the capacity by 50% compared to the conventional adaptive data rate (ADR) scheme. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most common malignancies, and the topoisomerase inhibitor irinotecan (CPT-11)-based chemotherapeutic regimen is currently the first-line treatment with impressive therapeutic efficacy. However, irinotecan has several clinically significant side effects, including diarrhea, which limit its clinical utility and efficacy in many patients. In an effort to discover better and improved pharmacotherapy against colorectal cancer, we synthesized a novel topoisomerase inhibitor, PCC0208037, examined its anti-tumor efficacy and related molecular mechanisms, and characterized its toxicity and pharmacokinetic profiles. PCC0208037 suppressed colorectal cancer cell (CRC) proliferation and increased cell cycle arrest, which may be related to its effects on up-regulating DNA damage response (DDR)-related molecules and apoptosis-related proteins. PCC0208037 demonstrated robust anti-tumor activity in vivo in a colorectal cancer cell xenograft model, which was comparable to or slightly better than CPT-11. In a preliminary toxicology study, PCC0208037 demonstrated much weaker tissue damage to colorectal tissue than CPT-11, and its impacts on food intake and body weight loss were more transient and recovered faster than CPT-11 in mice. This could be partially explained by the pharmacokinetic findings, which showed that PCC0208037 and its active metabolite, SN-38, were more accumulated in tumor tissue than in the intestine, as compared to CPT-11. Taken together, these results described a novel Topo I inhibitor with a comparative advantage over the standard treatment of colorectal cancer CPT-11 and could be a promising candidate compound for the treatment of colorectal cancer that warrants further investigation. [ABSTRACT FROM AUTHOR]

SMXL6,7,8 are important target proteins in strigolactone (SL) signal pathway, which negatively regulate the reception and response of SL signal, and play an important role in regulating plant branching. However, there is a relative lack of research on soybean SMXL gene family. In this study, 31 soybean SMXL genes were identified by phylogenetic analysis and divided into three groups. Based on the analysis of GmSMXL gene's structure and motif composition, it was found that the GmSMXL members in the same group were similar. The results of cis-element analysis showed that GmSMXL genes may regulate the growth and development of soybean by responding to hormones and environment. Based on the tissue specificity analysis and GR24 treatment, the results showed that four GmSMXLs in G1 group were predominantly expressed in stems, axillary buds and leaves and involved in SL signal pathway. Finally, under shading stress, the expression of four genes in G1 group was slightly different in different varieties, which may be the reason for the difference in branching ability of different varieties under shading stress. We have systematically studied the SMXL gene family in soybean, which may lay a foundation for the study of the function of GmSMXL gene in the future. [ABSTRACT FROM AUTHOR]

Organic photodetectors (OPDs) have aroused intensive attention for signal detection in industrial and scientific applications due to their advantages including low cost, mechanical flexibility, and large-area fabrication. As one of the most common organic light-emitting materials, 8-hydroxyquinolinato aluminum (Alq3) has an absorption wavelength edge of 460 nm. Here, through the introduction of Ag nanoparticles (Ag NPs), the spectral response range of the Alq3-based OPD was successfully extended to the near-infrared range. It was found that introducing Ag NPs can induce rich plasmonic resonances, generating plenty of hot electrons, which could be injected into Alq3 and then be collected. Moreover, as a by-product of introducing Ag NPs, the dark current was suppressed by around two orders of magnitude by forming a Schottky junction on the cathode side. These two effects in combination produced photoelectric signals with significant contrasts at wavelengths beyond the Alq3 absorption band. It was found that the OPD with Ag NPs can stably generate electric signals under illumination by pulsed 850 nm LED, while the output of the reference device included no signal. Our work contributes to the development of low-cost, broadband OPDs for applications in flexible electronics, bio-imaging sensors, etc. [ABSTRACT FROM AUTHOR]

Hot-electron photodetectors (HEPDs) are triggering a strong surge of interest in applications of image sensors and optics communication, since they can realize photoelectric responses when the incident photon energy is lower than the bandwidth of the semiconductor. In traditional HEPD systems, the metal layers are dressed with regular gratings, which can only excite plasmonic resonance over a narrow bandwidth, limiting the hot-electron photoelectric effect. To break this limitation, hybrid plasmonic nanostructures should be applied in HEPDs. Here, we propose a TiO2 based HEPD device incorporated with a hybrid plasmonic nanostructure, which consists of Au nanoparticles (Au NPs) and a conformal transparent Au film. With the assistance of the plasmonic resonances excited in this hybrid nanostructure, the spectrum of the photocurrent response is significantly broadened from the UV band to the visible and near-infrared (NIR) ranges. It is demonstrated that at the wavelengths of 660 nm and 850 nm, the photocurrent in the hybrid HEPD device is enhanced by 610% and 960%, respectively, compared with the counterparts without the addition of Au NPs. This work promotes the development of high performances HEPDs, offering an alternative strategy for realizing photodetection and image sensing in the NIR range. [ABSTRACT FROM AUTHOR]

The article responds to comments made on the authors' paper about the gender differences in the effect of sleeping, eating behavior, and stress on body mass index and dietary risk.

Background: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. Methods: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. Results: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as "other"). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. Conclusions: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful. [ABSTRACT FROM AUTHOR]

Lithium sulfur (Li-S) batteries stand out among many new batteries for their high energy density. However, the intermediate charge–discharge product dissolves easily into the electrolyte to produce a shuttle effect, which is a key factor limiting the rapid development of Li-S batteries. Among the various materials used to solve the challenges related to pure sulfur cathodes, biomass derived carbon materials are getting wider research attention. In this work, we report on the fabrication of cathode materials for Li-S batteries based on composites of sulfur and biomass-derived porous ramie carbon (RC), which are coated with multiwalled carbon nanotubes (MWCNTs). RC can not only adsorb polysulfide in its pores, but also provide conductive channels. At the same time, the MWCNTs coating further reduces the dissolution of polysulfides into the electrolyte and weakens the shuttle effect. The sulfur loading rate of RC is 66.3 wt.%. As a result, the initial discharge capacity of the battery is 1325.6 mAh·g−1 at 0.1 C long cycle, and it can still maintain 812.5 mAh·g−1 after 500 cycles. This work proposes an effective double protection strategy for the development of advanced Li-S batteries. [ABSTRACT FROM AUTHOR]

High-quality, all-inorganic CsPbBr3/Cs4PbBr6 composite perovskite nanocrystals (NCs) were obtained with all-solution-processing at room temperature, and a photodetector (PD) with high detectivity was realized based on CsPbBr3/Cs4PbBr6 NCs. The detectivity (D*) of the proposed PD is 4.24 × 1012 Jones under 532 nm illumination, which is among the highest levels for PDs based on all-inorganic perovskite NCs. In addition, a high linear dynamic range (LDR) of 115 dB under 1 V bias was also realized. Furthermore, the underlying mechanism for the enhanced performance of the proposed PD was discussed. Our work might promote the preparation of high-performance PDs based on dual-phase all-inorganic perovskite nanocrystals. [ABSTRACT FROM AUTHOR]

A polarized micropulse lidar (P-MPL) employing a pulsed laser at 532 nm was developed by the Institute of Oceanographic Instrumentation, Qilu University of Technology (Shandong Academy of Sciences). The optomechanical structure, technical parameters, detection principle, overlap factor calculation method, and inversion methods of the atmospheric boundary layer (ABL) depth and depolarization ratio (DR) were introduced. Continuous observations using the P-MPL were carried out at Xi'an Meteorological Bureau, and the observation data were analyzed. In this study, we gleaned much information on aerosols and clouds, including the temporal and spatial variation of aerosols and clouds, aerosol extinction coefficient, DR, and the structure of ABL were obtained by the P-MPL. The variation of aerosols and clouds before and after a short rainfall was analyzed by combining time-height-indication (THI) of range corrected signal (RCS) and DR was obtained by the P-MPL with profiles of potential temperature (PT) and relative humidity (RH) detected by GTS1 Digital Radiosonde. Then, the characteristics of tropopause cirrus cloud were discussed using the data of DR, PT, and RH. Finally, a haze process from January 1st to January 5th was studied by using aerosol extinction coefficients obtained by the P-MPL, PT, and RH profiles measured by GTS1 Digital Radiosonde and the time-varying of PM2.5 and PM10 observed by ambient air quality monitor. The source of the haze was simulated by using the NOAA HYSPLIT Trajectory Model. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic worsened financial stress for higher education students in the U.S. Financial stress is associated with poor dietary behaviors; however, factors that might influence this relationship are not well characterized. The present cross-sectional study investigated the associations between financial stress and dietary intake and dietary risk scores among higher education students (undergraduate and graduate students) in the U.S. and examined whether poor sleep quality and short sleep duration mediated the relationship between financial stress and dietary risk score. Validated tools were used to assess financial stress, sleep quality, sleep duration, dietary intake, and dietary risk. A total of 1280 students from three large U.S. universities completed the study. Results indicated that higher financial stress was associated with lower vegetable, fruit, fiber, and calcium intake, higher added sugar intake from sugar sweetened beverages, and higher dietary risk score. Further, the positive relationship between financial stress and dietary risk score was completely mediated by poor sleep quality among students who reported poor sleep quality and by short sleep duration among students who slept less than 7 h per night. These findings suggest that students might benefit from both financial management training and sleep education services to reduce undesirable dietary behaviors. [ABSTRACT FROM AUTHOR]

Campylobacter jejuni is an important foodborne pathogen causing campylobacteriosis. It can infect humans through the consumption of contaminated chicken products or via the direct handling of animals. Diallyl trisulfide (DATS) is a trisulfide compound from garlic extracts that has a potential antimicrobial effect on foodborne pathogens. This study investigated the antimicrobial activity of DATS on C. jejuni by evaluating the minimal inhibitory concentrations (MICs) of C. jejuni 81-168, and fourteen C. jejuni isolates from chicken carcasses. Thirteen of 14 C. jejuni isolates and 81-176 had MICs ≤ 32 μg/mL, while one isolate had MIC of 64 μg/mL. Scanning electron microscopy (SEM) analysis showed the disruption and shrink of C. jejuni bacterial cell membrane after the DATS treatment. A time-killing analysis further showed that DATS had a dose-dependent in vitro antimicrobial effect on C. jejuni during the 24 h treatment period. In addition, DATS also showed an antimicrobial effect in chicken through the decrease of C. jejuni colony count by 1.5 log CFU/g (cloacal sample) during the seven-day DATS treatment period. The transcriptional analysis of C. jejuni with 16 μg/mL (0.5× MIC) showed 210 differentially expression genes (DEGs), which were mainly related to the metabolism, bacterial membrane transporter system and the secretion system. Fourteen ABC transporter-related genes responsible for bacterial cell homeostasis and oxidative stress were downregulated, indicating that DATS could decrease the bacterial ability to against environmental stress. We further constructed five ABC transporter deletion mutants according to the RNA-seq analysis, and all five mutants proved less tolerant to the DATS treatment compared to the wild type by MIC test. This study elucidated the antimicrobial activity of DATS on C. jejuni and suggested that DATS could be used as a potential antimicrobial compound in the feed and food industry. [ABSTRACT FROM AUTHOR]

The task of drug-target interaction (DTI) prediction plays important roles in drug development. The experimental methods in DTIs are time-consuming, expensive and challenging. To solve these problems, machine learning-based methods are introduced, which are restricted by effective feature extraction and negative sampling. In this work, features with electrotopological state (E-state) fingerprints for drugs and amphiphilic pseudo amino acid composition (APAAC) for target proteins are tested. E-state fingerprints are extracted based on both molecular electronic and topological features with the same metric. APAAC is an extension of amino acid composition (AAC), which is calculated based on hydrophilic and hydrophobic characters to construct sequence order information. Using the combination of these feature pairs, the prediction model is established by support vector machines. In order to enhance the effectiveness of features, a distance-based negative sampling is proposed to obtain reliable negative samples. It is shown that the prediction results of area under curve for Receiver Operating Characteristic (AUC) are above 98.5% for all the three datasets in this work. The comparison of state-of-the-art methods demonstrates the effectiveness and efficiency of proposed method, which will be helpful for further drug development. [ABSTRACT FROM AUTHOR]

Scab, frogeye spot, and cedar rust are three common types of apple leaf diseases, and the rapid diagnosis and accurate identification of them play an important role in the development of apple production. In this work, an improved model based on VGG16 is proposed to identify apple leaf diseases, in which the global average poling layer is used to replace the fully connected layer to reduce the parameters and a batch normalization layer is added to improve the convergence speed. A transfer learning strategy is used to avoid a long training time. The experimental results show that the overall accuracy of apple leaf classification based on the proposed model can reach 99.01%. Compared with the classical VGG16, the model parameters are reduced by 89%, the recognition accuracy is improved by 6.3%, and the training time is reduced to 0.56% of that of the original model. Therefore, the deep convolutional neural network model proposed in this work provides a better solution for the identification of apple leaf diseases with higher accuracy and a faster convergence speed. [ABSTRACT FROM AUTHOR]

The study of protein-protein interaction is of great biological significance, and the prediction of protein-protein interaction sites can promote the understanding of cell biological activity and will be helpful for drug development. However, uneven distribution between interaction and non-interaction sites is common because only a small number of protein interactions have been confirmed by experimental techniques, which greatly affects the predictive capability of computational methods. In this work, two imbalanced data processing strategies based on XGBoost algorithm were proposed to re-balance the original dataset from inherent relationship between positive and negative samples for the prediction of protein-protein interaction sites. Herein, a feature extraction method was applied to represent the protein interaction sites based on evolutionary conservatism of proteins, and the influence of overlapping regions of positive and negative samples was considered in prediction performance. Our method showed good prediction performance, such as prediction accuracy of 0.807 and MCC of 0.614, on an original dataset with 10,455 surface residues but only 2297 interface residues. Experimental results demonstrated the effectiveness of our XGBoost-based method. [ABSTRACT FROM AUTHOR]

Large scale Atomic/Molecular dynamic Parallel Simulator (LAMMPS) molecular dynamics simulation software was used to simulate the copper and aluminum atom diffusion and changes of interface during heating and cooling process of copper and aluminum composite panels. The structures of the interface were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), and transmission electron microscope (TEM), and the mechanical properties were also tested. The simulation results show that the diffusion rate of copper atom is higher than that of aluminum atom, and that the CuAl2 radial distribution function of the interface at 300 K is consistent with that of pure CuAl2 at room temperature. At 930 K, t = 50 ps Cu atoms spread at a distance of approximately four Al lattice constants around the Al layer, and Al atoms spread to about half a lattice constant distance to the Cu layer. The experimental results show that the thickness of the interface in copper–aluminum composite plate is about 1 μm, and only one kind of CuAl2 with tetragonal phase structure is generated in the interface, which corresponds with the result of molecular dynamics simulation. [ABSTRACT FROM AUTHOR]

East and south coastal China is made up of a cluster of six developed provinces whose CO2 emissions account for one third of the total CO2 emissions in China. As such, it is meaningful to predict carbon emissions in this region to assess whether China can achieve emission reduction targets. This paper employed STIRPAT to analyze the factors impacting the carbon emissions of this area from 2000 to 2015, including population (POP), urbanization (UR), GDP per capita (GDP), energy intensity (EI), and industrial structure (IS). The results showed that GDP was mainly responsible for increasing carbon emissions while EI played a significant role in reducing it. Considering the importance of GDP, EI, and IS obtained from regression analysis, basic, highest-rate, middle, and advanced scenarios were set to predict carbon emissions according to different change rates. In the basic scenario, carbon intensity was reduced by 48.5% in 2020 compared to 2005, which was slightly higher than the national target of 40–45%, and was reduced by 59.7% in 2030, which was close to a 60–65% reduction. Nevertheless, in the advanced scenario, carbon intensity was reduced by 51.7% in 2020 and 69.1% in 2030 compared to 2005, which were higher than the national targets. Therefore, improving energy efficiency, optimizing energy structure, and adjusting industrial structure were suggested to be major strategies for carbon intensity mitigation. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the most common malignancies, and the topoisomerase inhibitor irinotecan (CPT-11)-based chemotherapeutic regimen is currently the first-line treatment with impressive therapeutic efficacy. However, irinotecan has several clinically significant side effects, including diarrhea, which limit its clinical utility and efficacy in many patients. In an effort to discover better and improved pharmacotherapy against colorectal cancer, we synthesized a novel topoisomerase inhibitor, PCC0208037, examined its anti-tumor efficacy and related molecular mechanisms, and characterized its toxicity and pharmacokinetic profiles. PCC0208037 suppressed colorectal cancer cell (CRC) proliferation and increased cell cycle arrest, which may be related to its effects on up-regulating DNA damage response (DDR)-related molecules and apoptosis-related proteins. PCC0208037 demonstrated robust anti-tumor activity in vivo in a colorectal cancer cell xenograft model, which was comparable to or slightly better than CPT-11. In a preliminary toxicology study, PCC0208037 demonstrated much weaker tissue damage to colorectal tissue than CPT-11, and its impacts on food intake and body weight loss were more transient and recovered faster than CPT-11 in mice. This could be partially explained by the pharmacokinetic findings, which showed that PCC0208037 and its active metabolite, SN-38, were more accumulated in tumor tissue than in the intestine, as compared to CPT-11. Taken together, these results described a novel Topo I inhibitor with a comparative advantage over the standard treatment of colorectal cancer CPT-11 and could be a promising candidate compound for the treatment of colorectal cancer that warrants further investigation.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study. Eligible students filled out an online survey comprised of validated tools for assessing sleep quality and duration, dietary risk, alcohol misuse and physical activity between late April and the end of May 2020. Health behaviors were fairly consistent across countries, and all countries reported poor sleep quality. However, during the survey period, the COVID-19 pandemic influenced the health behaviors of students in European countries and the USA more negatively than Asian countries, which could be attributed to the differences in pandemic time course and caseloads. Students who experienced a decline in sleep quality during the COVID-19 pandemic had higher dietary risk scores than students who did not experience a change in sleep quality ( p = 0.001). Improved sleep quality was associated with less sitting time ( p = 0.010). Addressing sleep issues among higher education students is a pressing concern, especially during stressful events. These results support the importance of making education and behavior-based sleep programming available for higher education students in order to benefit students' overall health.

Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG) was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT) and aspirate aminotransferase (AST). Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg). More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC) of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood-brain barrier, but had less hepatotoxicity.