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Abstract Background Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating “Liushen Pill” and “Shenfu Decoction,” has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism. Methods In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague–Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated. Results In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism. Conclusions XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Abstract Background Reintroduction represents an effective strategy for the conservation of endangered wildlife, yet it might inadvertently impact the native ecosystems. This investigation assesses the impact of reintroducing endangered Przewalski's horses into the desert grassland ecosystem of the Kalamaili Nature Reserve (KNR), particularly its effect on the spatial distribution of ticks. In a 25 km2 core area of Przewalski's horse distribution, we set up 441 tick sampling sites across diverse habitats, including water sources, donkey trails, and grasslands, recording horse feces and characteristics to analyze the occurrence rate of ticks. Additionally, we gathered the data of 669 fresh feces of horses. To evaluate the spatial dynamics between these feces and ticks, we used methods such as Fixed Kernel Estimation (FKE), Moran’s I spatial autocorrelation index, and Generalized Linear Models (GLM). Results The dominant species of ticks collected in the core area were adult Hyalomma asiaticum (91.36%). Their occurrence rate was higher near donkey trails (65.99%) and water sources (55.81%), particularly in areas with the fresh feces of Przewalski's horses. The ticks’ three risk areas, as defined by FKE, showed significant overlap and positive correlation with the distribution of Przewalski's horses, with respective overlap rates being 90.25% in high risk, 33.79% in medium risk, and 23.09% in low risk areas. Moran's I analysis revealed a clustering trend of the fresh feces of Przewalski's horses in these areas. The GLM confirmed a positive correlation between the distribution of H. asiaticum and the presence of horse fresh feces, alongside a negative correlation with the proximity to water sources and donkey trails. Conclusions This study reveals the strong spatial correlation between Przewalski's horses and H. asiaticum in desert grasslands, underlining the need to consider interspecific interactions in wildlife reintroductions. The findings are crucial for shaping effective strategies of wildlife conservation and maintaining ecological balance.

Abstract The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

Abstract Background To investigate the clinical and immune characteristics of patients with primary Sjögren’s syndrome (pSS) who were negative for anti–Sjögren’s-syndrome-related antigen A antibodies (anti-SSA) and anti–Sjögren’s-syndrome-related antigen B antibodies (anti-SSB) in Chinese population. Methods A retrospective study were performed and 232 patients with pSS were analyzed. Patients positive for anti-SSA or/and anti-SSB were termed as seropositive pSS, and these negative for both anti-SSA and anti-SSB (non-antinuclear antibodies) as seronegative pSS. Clinical manifestations and laboratory findings were compared between the two groups. Results Among the 232 patients with pSS, 192 (82.8%) were seropositive pSS and 40 (17.2%) were seronegative pSS. Compared to seropositive pSS, seronegative pSS were older and with higher percentage of low disease activity (ESSDAI

Abstract Microdamage and its related inflammation contribute to the development of radiographic axial spondyloarthritis (r-axSpA). Inflammation and cell death in damaged tissues are associated with cell-free DNA (cfDNA) release. Here we investigated whether circulating cfDNA could be a potential biomarker for evaluating disease activity and treatment response in r-axSpA. Circulating cfDNA was detected in the discovery and validation cohort with 79 and 60 newly diagnosed r-axSpA patients respectively and 42 healthy controls using the Quant-iT PicoGreen dsDNA reagent and kit. As a result, cfDNA levels were significantly higher in r-axSpA patients compared with healthy controls in the discovery and validation cohort. Moreover, cfDNA levels were positively correlated with CRP, ASDAS-CRP and neutrophil counts. Additionally, non-steroid anti-inflammatory drugs (NSAIDs) combined with disease-modifying anti-rheumatic drugs or tumor necrosis factor inhibitors but not NSAIDs alone could reduce cfDNA levels. Moreover, a decrease of cfDNA levels after treatment was associated with an effective therapeutic response. Intriguingly, patients with higher levels of cfDNA at diagnosis responded better to combination therapy rather than NSAIDs. However, patients with lower levels of cfDNA displayed similar responses to combination or mono-NSAID treatment. In conclusion, circulating cfDNA levels showed a significant correlation with disease activity as well as treatment efficacy in patients with r-axSpA. Moreover, cfDNA at diagnosis might predict the response to different therapy. Consequently, cfDNA may serve as a useful biomarker of inflammation in r-axSpA.

In this article, we explore a cutting-edge concept known as class incremental learning (CIL) in novel category discovery for synthetic aperture radar (SAR) targets (CNTs). This innovative task involves the challenge of identifying categories within unlabeled datasets by utilizing a provided labeled dataset as reference. In contrast to the conventional category discover approaches, our method introduces novel categories without relying on old labeled classes and effectively mitigates the issue of catastrophic forgetting. Specifically, to reduce the bias of the established categories toward unknown ones, CNT extracts representational information via self-supervised learning, gleaned directly from the SAR data itself to facilitate generalization. To retain the model's competence in classifying previously acquired knowledge, we employ a dual strategy incorporating the rehearsal of base category feature prototypes and the application of knowledge distillation. Our methodology integrates multiview and pseudolabeling strategies. In addition, we introduce a novel approach that focuses on enhancing the discernibility of class spaces. This strategy primarily ensures distinct separation of the unlabeled classes from base class prototypes, and imposes stringent constraints on the internal relationships among individual samples and their corresponding perspectives. To the best of our knowledge, this is the first study on category discovery in the CIL scenario. The experimental results show that our method significantly improves the performance on SAR images compared to the previous optimal method, which indicates the effectiveness of our method.

Endangered Przewalski's horses have faced severe infections from Gasterophilus pecorum (Diptera, Gastrophilidae) in Xinjiang's Kalamaili Nature Reserve (KNR). This study examines G. pecorum's development and infection patterns in embryonic and larval stages, crucial for understanding horse botfly disease in desert grasslands. For the incubation of G. pecorum fertilized eggs, we established the six distinct temperature gradients: 16 °C, 20 °C, 24 °C, 28 °C, 30 °C, and 32 °C. Using the least squares method, we calculated the correlation between the developmental threshold temperature of the eggs and their cumulative effective temperature. Furthermore, we meticulously recorded the survival duration of the larvae across a spectrum of temperature gradients (−20 °C, −10 °C, 4 °C, 10 °C, 20 °C, and 30 °C) and under varying conditions (dark and light). This method allows us to analyze and interpret the impact of these environmental factors on larval survival durations. 1) The formula for predicting the embryonic development period of G. pecorum was N = (182.7 ± 12.03)/[T-(3.191 ± 1.48)], where the developmental threshold temperature was 3.191 ± 1.48 °C, and the effective accumulated temperature was 182.7 ± 12.03 d°C 2) The model describing the relationship between the embryonic development rate and temperature was: y = 0.0001x2+0.0007x+0.0378, demonstrating a positive correlation between the development rate and temperature (R-sq = 0.989, p

Abstract Background Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC. Methods We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth. Results NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%). Conclusions By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace

With the continual deployment of power-electronics-interfaced renewable energy resources, increasing privacy concerns due to deregulation of electricity markets, and the diversification of demand-side activities, traditional knowledge-based power system dynamic modeling methods are faced with unprecedented challenges. Data-driven modeling has been increasingly studied in recent years because of its lesser need for prior knowledge, higher capability of handling large-scale systems, and better adaptability to variations of system operating conditions. This paper discusses about the motivations and the generalized process of data-driven modeling, and provides a comprehensive overview of various state-of-the-art techniques and applications. It also comparatively presents the advantages and disadvantages of these methods and provides insight into outstanding challenges and possible research directions for the future.

Abstract Purpose Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. Methods We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. Results The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. Conclusion EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

ABSTRACTThe occurrence and development of Parkinson’s disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1–3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [−12.98, −0.13], P

Summary: The multiple roles of TGR5 in the regulation of glucose metabolism, inflammation, and oxidative stress have drawn attention as therapeutic candidates for diabetes-related kidney disease. However, diabetes induces downregulation of renal TGR5 protein expression, and the regulatory mechanisms have not been clarified. Here, we identify that Smurf1, an E3 ubiquitin ligase, is a critical interactor of TGR5 and mediates the ubiquitination and proteasomal degradation of TGR5 under high glucose stimulation in glomerular mesangial cells. Genetic deficiency of Smurf1 restores TGR5 protein expression and attenuates renal injuries in diabetic mice. Mechanistically, Smurf1 interacts with the TGR5 ICL2 region by its HECT domain and induces K11/K48-linked polyubiquitination of TGR5 at K306 residue. Moreover, restoration of TGR5 protects db/db mice from diabetic nephropathy. These observations elucidate the critical role of Smurf1 in regulating TGR5 stability, suggesting that pharmacological targeting of the interaction between Smurf1 and TGR5 could serve as a promising therapeutic strategy against diabetic nephropathy.

The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.

Abstract Background Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30–40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. Methods IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. Discussion To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, ‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1

Abstract Background The dominant Gasterophilus species in the desert steppe (Xinjiang, China) Gasterophilus pecorum poses a serious threat to the reintroduced Przewalski’s horses. We investigated the distribution pattern of G. pecorum eggs in June 2017. Methods Two sampling methods, transect and grid, were used, and the results were analyzed via geostatistics by semivariance. The nest quadrat was used to determine the optimal quadrat size. Results Eggs were found in 99 quadrats (63.1%) and 187 clusters (1.5%) of Stipa caucasica on the steppe. The mean oviposition count of a cluster was 3.8 ± 1.6. Three-eggs is the mode of which females oviposit on each ovigerous S. caucasica (22.0%). Semivariogram analysis revealed that the distance of spatial dependence for eggs was 921 m, 1233 m and 1097 m for transect 1, transect 2 and grid methods, respectively, while spatial continuity was 62%, 77% and 57.0% for transect 1, transect 2 and grid, respectively. The eggs showed a patchy, aggregated distribution pattern. This suggested the spherical model is most applicable. The proportion of ovigerous S. caucasica was significantly correlated with the distance from water resources (r = − 0.382, p = 0). Conclusion Our findings indicated that diversification of G. pecorum oviposition was a new adaptative strategy for its survival in the desert steppe ecological niche. This made it more efficient at infecting hosts in the local environment. Areas surrounding water resources, especially around the drinking paths of equids (500 m radius surrounding the water), were concentrated epidemic areas. It is suggested that more attention to be paid to the ecological characteristics of G. pecorum in order to develop control measures that would reduce the infection risk for Przewalski’s horses.

BackgroundSpontaneous bacterial peritonitis (SBP) is a severe infection in cirrhotic patients that requires early diagnosis to improve the long-term outcome. Alterations in the gut microbiota have been shown to correlate with the development and progression of liver cirrhosis. However, the relationship between SBP and gut microbiota remains unknown.MethodsIn this study, we applied 16S rRNA pyrosequencing of feces to ascertain possible links between the gut microbiota and SBP. We recruited 30 SBP patients, 30 decompensated cirrhotic patients without SBP (NSBP) and 30 healthy controls. Metagenomic functional prediction of bacterial taxa was achieved using PICRUSt. ResultsThe composition of the gut microbiota in the SBP patients differed remarkably from that in the NSBP patients and healthy individuals. The microbial richness was significantly decreased, while the diversity was increased in the SBP patients. Thirty-four bacterial taxa containing 15 species, mainly pathogens such as Klebsiella pneumoniae, Serratia marcescens and Prevotella oris, were dominant in the SBP group, while 42 bacterial taxa containing 16 species, especially beneficial species such as Faecalibacterium prausnitzii, Methanobrevibacter smithii and Lactobacillus reuteri, were enriched in the NSBP group. Notably, we found that 18 gene functions of gut microbiota were different between SBP patients and NSBP patients, which were associated with energy metabolism and functional substance metabolism. Five optimal microbial markers were determined using a random forest model, and the combination of Lactobacillus reuteri, Rothia mucilaginosa, Serratia marcescens, Ruminococcus callidus and Neisseria mucosa achieved an area under the curve (AUC) value of 0.8383 to distinguish SBP from decompensated cirrhosis.ConclusionsWe described the obvious dysbiosis of gut microbiota in SBP patients and demonstrated the potential of microbial markers as noninvasive diagnostic tools for SBP at an early stage.

Renal tubulointerstitial fibrosis (TIF), characterized by epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells, is the typical pathological alteration in diabetic nephropathy. Gentiopicroside (GPS), a natural compound with anti-inflammatory activity, has been demonstrated to alleviate glomerulosclerosis, whereas whether GPS inhibits TIF via regulating inflammation remains unclear. In this study, diabetic db/db mice and high glucose (HG)-stimulated renal tubular epithelial cells (NRK-52E) were applied to explore the effects and mechanisms of GPS on TIF. The results in vivo showed that GPS effectively improves glycolipid metabolism disorder, renal dysfunction, and TIF. In particular, GPS treatment reversed the abnormal expressions of EMT marker proteins including elevated α-smooth muscle actin and vimentin and decreased E-cadherin in the kidney of db/db mice. Moreover, GPS treatment also inhibited protein expressions of angiotensinⅡ type 1 receptor (AT1R) and CK2α and the activation of the NF-κB pathway. Importantly, the aforementioned effects of GPS acted in vivo were further observed in vitro in HG-stimulated NRK-52E cells, which were independent of its effects on glucose and lipid-lowering activity but were reversed by AT1R over-expression. Together, our results indicate that GPS that directly inhibits the CK2/NF-κB inflammatory signaling pathway via AT1R may also contribute to the amelioration of TIF in diabetes.

The aim of the present study is to examine the effect of group-play intervention on executive function (EF) in preschoolers. This group-play intervention was integrated as moderate to vigorous physical activity and cognitively loaded exercise to promote EF in preschoolers. An 8-week group-play MVPA intervention program, consisting of a series of outdoor physical and cognitively loaded games, was designed to improve preschoolers’ EF. This intervention program was implemented in group-play form, and conducted by teachers who received standardized training before the intervention. Two classes of second grade preschoolers (N = 62) were randomly allocated to experimental (n = 30, Mage = 4.16, SD = 0.29) and control (n = 32, Mage = 4.7, SD = 0.43) groups. The intervention group received the intervention three times a week, while the control group exercised as usual in preschool. Before, in the middle of, and after the intervention, 10-m running, standing broad jump, throwing, body flexion, balance beam, and skip jump were assessed as tests of motor skills. In addition, three components of EF were measured separately before, in the middle of, and after the intervention: inhibitory control was assessed by using the silly sound Stroop task, working memory was tested using the empty house task, and shifting was assessed using the dimensional change card sorting task. Although both groups showed an increasing trend in terms of motor skills and EF during the intervention, the increasing amounts of the intervention group were significantly higher than the control group. The findings of the present study suggested that group-play intervention has positive effects on aspects of EF in addition to motor skills in preschoolers.

Containerized microservices have been widely deployed in the industry. Meanwhile, security issues also arise. Many security enhancement mechanisms for containerized microservices require predefined rules and policies. However, it is challenging when it comes to thousands of microservices and a massive amount of real-time unstructured data. Hence, automatic policy generation becomes indispensable. In this paper, we focus on the automatic solution for the security problem: irregular traffic detection for RPCs.We propose Informer, a two-phase machine learning framework to track the traffic of each RPC and automatically report anomalous points. We first identify RPC chain patterns using density-based clustering techniques and build a graph for each critical pattern. Next, we solve the irregular RPC traffic detection problem as a prediction problem for attributed graphs with time series by leveraging spatial-temporal graph convolution networks. Since the framework builds multiple models and makes individual predictions for each RPC chain pattern, it can be efficiently updated upon legitimate changes in any graphs.In evaluations, we applied Informer to a dataset containing more than 7 billion lines of raw RPC logs sampled from a large Kubernetes system for two weeks. We provide two case studies of detected real-world threats. As a result, our framework found fine-grained RPC chain patterns and accurately captured the anomalies in a dynamic and complicated microservice production scenario, which demonstrates the effectiveness of Informer. Furthermore, we extensively evaluated the risk of adversarial attacks for our prediction model under different reality constraints and showed that the model is robust to such attacks in most real-world scenarios.

Abstract Background The departure of the mature larvae of the horse stomach bot fly from the host indicates the beginning of a new infection period. Gasterophilus pecorum is the dominant bot fly species in the desert steppe of the Kalamaili Nature Reserve (KNR) of northwest China as a result of its particular biological characteristics. The population dynamics of G. pecorum were studied to elucidate the population development of this species in the arid desert steppe. Methods Larvae in the freshly excreted feces of tracked Przewalski’s horses (Equus przewalskii) were collected and recorded. The larval pupation experiments were carried out under natural conditions. Results There was a positive correlation between the survival rate and the number of larvae expelled (r = 0.630, p

Reconstruction-based and prediction-based approaches are widely used for video anomaly detection (VAD) in smart city surveillance applications. However, neither of these approaches can effectively utilize the rich contextual information that exists in videos, which makes it difficult to accurately perceive anomalous activities. In this paper, we exploit the idea of a training model based on the “Cloze Test” strategy in natural language processing (NLP) and introduce a novel unsupervised learning framework to encode both motion and appearance information at an object level. Specifically, to store the normal modes of video activity reconstructions, we first design an optical stream memory network with skip connections. Secondly, we build a space–time cube (STC) for use as the basic processing unit of the model and erase a patch in the STC to form the frame to be reconstructed. This enables a so-called ”incomplete event (IE)” to be completed. On this basis, a conditional autoencoder is utilized to capture the high correspondence between optical flow and STC. The model predicts erased patches in IEs based on the context of the front and back frames. Finally, we employ a generating adversarial network (GAN)-based training method to improve the performance of VAD. By distinguishing the predicted erased optical flow and erased video frame, the anomaly detection results are shown to be more reliable with our proposed method which can help reconstruct the original video in IE. Comparative experiments conducted on the benchmark UCSD Ped2, CUHK Avenue, and ShanghaiTech datasets demonstrate AUROC scores reaching 97.7%, 89.7%, and 75.8%, respectively.

Abstract Background When infected with Mycobacterium tuberculosis, only a small proportion of the population will develop active TB, and the role of host genetic factors in different TB infection status was not fully understood. Methods Forty-three patients with active tuberculosis and 49 with latent tuberculosis were enrolled in the prospective cohort. Expressing levels of 27 candidate mRNAs, which were previously demonstrated to differentially expressed in latent and active TB, were measured by dual color reverse transcription multiplex ligation dependent probe amplification assay (dcRT-MLPA). Using expression levels of these mRNAs as quantitative traits, associations between expression abundance and genome-wild single nucleotide polymorphisms (SNPs) were calculated. Finally, identified candidate SNPs were further assessed for their associations with TB infection status in a validation cohort with 313 Chinese Han cases. Results We identified 9 differentially expressed mRNAs including il7r, il4, il8, tnfrsf1b, pgm5, ccl19, il2ra, marco and fpr1 in the prospective cohort. Through expression quantitative trait loci mapping, we screened out 8 SNPs associated with these mRNAs. Then, CG genotype of the SNP rs62292160 was finally verified to be significantly associated with higher transcription levels of IL4 in LTBI than in TB patients. Conclusion We reported that the SNP rs62292160 in Chinese Han population may link to higher expression of il4 in latent tuberculosis. Our findings provided a new genetic variation locus for further exploration of the mechanisms of TB and a possible target for TB genetic susceptibility studies, which might aid the clinical decision to precision treatment of TB.

The pharmacokinetics, tissue distribution, and elimination of enrofloxacin (ENR) and its metabolite ciprofloxacin (CIP) were investigated to the crucian carp (Carassius auratus gibelio) after single (20 mg/kg b. w.) and multiple oral administration (20 mg/kg b.w. one time daily for 5 days) at 28°C. The concentrations of ENR and CIP in the plasma and tested tissues (muscle/skin, liver, and kidney) were detected simultaneously by high-performance liquid chromatography (HPLC), and the pharmacokinetic data were analyzed with a non-compartmental model using WinNonLin 6.1 PK software (Pharsight Corporation, Mountain View, CA, USA). The pharmacokinetic characteristics of ENR in crucian carp exhibited slow absorption, wide tissue distribution, and long elimination half-life. In the single-dose group, the peak concentrations (Cmax) of ENR in the plasma, muscle/skin, liver, and kidney were 8.93 μg/mL, 13.9 μg/g, 31.2 μg/g, and 27.3 μg/g, respectively, observed at 3 h, 6 h, 1 h, and 3 h after dosing. The elimination half-lives (T1/2λz) of ENR in plasma, muscle/skin, liver, and kidney were calculated to be 67.4, 82.8, 94.4, and 114 h, respectively. In the multiple-dose group, the Cmax of ENR in the plasma, muscle/skin, liver, and kidney were 18.4 μg/mL, 26.8 μg/g, 82.8 μg/g, and 74.5 μg/g, respectively, achieved at 3 h, 6 h, 1 h, and 1 h after the last dose. The T1/2λz of ENR in the plasma, muscle/skin, liver, and kidney were calculated to be 76.4 h, 91.5 h, 114 h, and 148 h, respectively. During the multiple-dose administration, significant accumulations of ENR and CIP were observed in the plasma and tissues of crucian carp, possibly due to their long elimination half-lives. In both dose groups, the AUC0−∞ for both ENR and CIP followed the order of liver > kidney > muscle/skin > plasma. The finding suggested that the liver may play an important role in the metabolism of ENR. According to the calculated PK/PD indices of Cmax/minimum inhibitory concentrations (MIC) and AUC24h/MIC, the multiple-dose regimen would be highly effective against pathogenic bacteria with a MIC value of ≤ 1.84 μg/ml. Depletion studies indicated that a withdrawal period of at least 29 or 32 days was necessary to guarantee food security after single or multiple oral gavage administration at 28°C.

Diabetic nephropathy (DN) is quickly becoming the largest cause of end-stage renal disease (ESRD) in diabetic patients, as well as a major source of morbidity and mortality. Our previous studies indicated that the activation of Nrf2/ARE pathway via Connexin43 (Cx43) considerably contribute to the prevention of oxidative stress in the procession of DN. Fraxin (Fr), the main active glycoside of Fraxinus rhynchophylla Hance, has been demonstrated to possess many potential pharmacological activities. Whereas, whether Fr could alleviate renal fibrosis through regulating Cx43 and consequently facilitating the activation of Nrf2/ARE pathway needs further investigation. The in vitro results showed that: 1) Fr increased the expression of antioxidant enzymes including SOD1 and HO-1 to inhibit high glucose (HG)-induced fibronectin (FN) and inflammatory cell adhesion molecule (ICAM-1) overexpression; 2) Fr exerted antioxidant effect through activating the Nrf2/ARE pathway; 3) Fr significantly up-regulated the expression of Cx43 in HG-induced glomerular mesangial cells (GMCs), while the knock down of Cx43 largely impaired the activation of Nrf2/ARE pathway induced by Fr; 4) Fr promoted the activation of Nrf2/ARE pathway via regulating the interaction between Cx43 and AKT. Moreover, in accordance with the results in vitro, elevated levels of Cx43, phosphorylated-AKT, Nrf2 and downstream antioxidant enzymes related to Nrf2 were observed in the kidneys of Fr-treated group compared with model group. Importantly, Fr significantly improved renal dysfunction pathological changes of renal fibrosis in diabetic db/db mice. Collectively, Fr could increase the Cx43-AKT-Nrf2/ARE pathway activation to postpone the diabetic renal fibrosis and the up-regulation of Cx43 is probably a novel mechanism in this process.

Through in-depth analysis of the typical international wireless sensor network experimental system, the current design generally lacks the real-time diagnosis of the health state of the fault node and the experimental platform, the management and control mechanism to minimize the interference of the experimental task, and the highly integrated and friendly experimental entrance, which will have an obvious distortion impact on the experimental results. In view of the above shortcomings, on the basis of fully absorbing the design advantages in this research field, this paper studies and designs a high fidelity WSN experimental system, which covers the elements of open source, heterogeneity, analysis visualization, and experimental repeatability and innovates the mechanisms of real-time diagnosis, hierarchical parallel control, and TDMA to collect a large amount of experimental data. In order to support a variety of applications based on IEEE802.15.4 band, a high-fidelity and user-friendly experimental platform software and hardware system with 15 clusters and 130 heterogeneous nodes is studied and designed, which can simulate outdoor mesh networks with more than 6 hops. This paper is designed and implemented on Linux open-source platform. The whole system has low cost and can be replicated. The design results have good reference and application value for the research and design of wireless sensor network experimental system.

The cold start of fuel cells limits their wide application. Since the water produced by fuel cells takes up more space when it freezes, it may affect the internal structure of the stack, causing collapse and densification of the pores inside the catalytic layer. This paper mainly analyzes the influence of different startup strategies on the stack cold start, focusing on the change in the stack temperature and the ice volume fraction of the catalytic layer. When designing a startup strategy, it is important to focus not only on the optimization of the startup time, but also on the principle of minimizing the damage to the stack. A lumped parameter cold-start model was constructed, which was experimentally verified to have a maximum error of 8.9%. On this basis, a model predictive control (MPC) algorithm was used to control the starting current. The MPC cold-start strategy reached the freezing point at 17 s when the startup temperature was −10 °C, which is faster than other startup strategies. Additionally, the time to ice production was controlled to about 20 s. Compared with the potentiostatic strategy and maximum power strategy, MPC is optimal and still has great potential for further optimization.

A simple, sensitive, and simultaneous method was established and validated for the active clinical components of teicoplanin and ramoplanin in environmental water by LC-MS/MS coupled with cascade elution. Moreover, a cascade elution method, which was rapid, solvent-less, and high-extraction efficient was successfully proposed to realize the extraction and purification of seven targets in one step. Under optimized conditions, the method showed excellent linearity with the correlation coefficient (R2) ≥0.998 in the range of 1.0–100.0 ng L−1. Low matrix effects and good recoveries which ranged from 86 to 114% were reached with RSDs lower than 3.0% for most targets. The limits of detection and limit of quantification were 0.1–1.3 and 0.3–4.0 ng L−1, respectively. This method was successfully applied for the determination of teicoplanin and ramoplanin in water samples from the Pearl River and the South China Sea. TA2-2,3 was quantified in only one sample with the concentration of 8.0 ng L−1.

Diabetes nephropathy (DN) is the most common microvascular complications of diabetes, as hyperglycemia induces mesangial cell (MC) proliferation and inflammation and subsequently contributes to the development of renal fibrosis. Sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate receptor 2 (S1P2) signaling pathway could activate AP-1 and NF-κB, which played a key regulatory role in the pathological progression of DN. This study investigates whether resveratrol (RSV) plays a regulatory role by SphK1/S1P2 pathway in MCs proliferation and inflammation under high glucose condition. Herein, we found that RSV inhibited MCs proliferation and attenuated high glucose (HG)-induced FN, TGF-β1, ICAM-1, iNOS, SphK1 and S1P2 expression and inhibited SphK1 activity andS1P production, which was also in accordance with MCs transfected with wild-type SphK1WT plasmid. Furthermore, RSV remarkably reduced AP-1 and NF-κB activation. Overall, these results indicated that RSV could be a potential and valuable resource of natural compounds for DN treatment via SphK1/S1P2 pathway.

In this letter, we propose an indoor visible light positioning technique that combines deep neural network based on the Bayesian Regularization (BR-DNN) with sparse diagonal training data set. Unlike other neural networks, which require a large number of training data points to locate accurately, we realize the high precision positioning with only 20 training points in a 1.8 m × 1.8 m × 2.1 m location area. Furthermore, we test a new optimization method of training data set, which is the diagonal set. To verify our ideas, we experimentally demonstrate three different training data acquisition methods that contain the common choice of training points (even set), arbitrary selection (arbitrary set), and diagonal selection (diagonal set). Experimental results show that the average localization accuracy optimized by the BR-DNN is 3.40 cm with the diagonal set, while the average localization accuracy is 4.35 cm for the arbitrary set and 4.58 cm for the even set. In addition, the training time and positioning time are only 11.25 and 8.66 ms due to a significant reduction of the sparse training data. All of the aforementioned experimental results show that the algorithm and training data optimization we proposed provide a new solution for real-time and high-accuracy positioning with the neural network.

Owing to different positioning methods in indoor locations that require base stations, the positioning accuracy cannot be guaranteed, and the cost of reconstructing the base station becomes high. In this paper, a positioning method based on a two-dimensional code with feature graphs using the advantage of scale-invariant feature transform (SIFT) is proposed, where the reconstruction cost of the scene is minimized, and the SIFT matching accuracy is improved with iteration of the transformation matrix. The experimental results demonstrated the positioning error is within 1.2 cm for a room with the dimension of 7 m × 6 m × 2.8 m. Compared with the previously published results under the similar conditions, our proposed scheme has the advantage of low-cost and high-precision system.

A light-emitting diode (LED) can be modulated in visible light positioning systems so that it acts as a transmitter with a unique ID. However, we must be able to support unique IDs for many different LEDs, and LEDs sometimes also need to transmit other information. Therefore, it is necessary to increase the length of an LED ID. However, long codes are prone to contain excessive continuous strings of 0s or 1s, which is not conductive to correct ID identification. The Manchester code is usually used to eliminate this phenomenon, but its encoding efficiency is low. Furthermore, the Manchester code has no error-correction function. In this paper, we present a new method for encoding a long LED ID. We apply an exclusive OR (XOR) operation to the code using an appropriate mask so that no long continuous strings of 0s or 1s appear in the XOR result. Then the LED transmits the XOR result and the mask serial number. The ID of the LED is obtained by decoding. Compared with the Manchester code, the mask XOR code approach is more efficient. When a 34-bit ID is divided into two blocks, the encoding efficiency of the mask XOR code is 33% higher than that of the Manchester code. Compared with the Manchester code, when the information transmitted by an LED is encoded with the same ID length, the mask XOR code can additionally incorporate an error correction function to reduce the bit error rate. Adding an artificial baffle to the above methods results in a 5% error rate in the Manchester code, but the mask XOR code has no code errors.

Urban rivers represent a unique ecosystem in which pollution occurs regularly, altering the biogeochemical characteristics of waterbodies and sediments. However, little is presently known about the spatiotemporal patterns of planktonic and sediment bacterial community diversities and compositions in urban rivers. Herein, Illumina MiSeq high-throughput sequencing was performed to reveal the spatiotemporal dynamics of bacterial populations in Liangtan River, a heavily polluted urban river in Chongqing City (China). The results showed the richness and diversity of sediment bacteria were significantly higher than those of planktonic bacteria, whereas a strong overlap (46.7%) in OTUs was identified between water and sediment samples. Bacterial community composition remarkably differed in waters and sediments. Planktonic bacterial communities were dominated by Proteobacteria, Bacteroidetes, Cyanobacteria and Actinobacteria, while sediment bacterial communities mainly included Proteobacteria, Actinobacteria, Chloroflexi and Bacteroidetes. Additionally, several taxonomic groups of potential bacterial pathogens showed an increasing trend in water and sediment samples from residential and industrial areas (RI). Variation partition analysis (VPA) indicated that temperature and nutrient were identified as the main drivers determining the planktonic and sediment bacterial assemblages. These results highlight that bacterial communities in the polluted urban river exhibit spatiotemporal variation due to the combined influence of environmental factors associated with sewage discharge and hydropower dams.

Oxidative stress is the main factor responsible for the induction of diabetic renal fibrosis. Thus, improving the state of oxidative stress can effectively prevent the further deterioration of diabetic nephropathy (DN). Previous research has shown that formononetin (FMN), a flavonoid with significant antioxidant activity and Sirt1 activation effect, can improve diabetic renal fibrosis. However, the exact mechanisms underlying the effect of FMN on diabetic renal fibrosis have yet to be elucidated. In this study, we carried out in vivo experiments in a db/db (diabetic) mouse model and demonstrated that FMN activated the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway and improved oxidative stress by increasing levels of sirtuin-1 (Sirt1) protein level in renal tissue. We also found that this process reversed the up-regulation of fibronectin (FN) and intercellular adhesion molecule 1 (ICAM-1) and led to an improvement in renal insufficiency. In vitro results further showed that FMN significantly reversed the upregulation of FN and ICAM-1 in glomerular mesangial cells (GMCs) exposed to high glucose. FMN also promoted the expression of Nrf2 and widened its nuclear distribution. Thus, our data indicated that FMN inhibited hyperglycemia-induced superoxide overproduction by activating the Nrf2/ARE signaling pathway. We also found that FMN up-regulated the expression of Sirt1 and that Sirt1 deficiency could block the activation of the Nrf2/ARE signaling pathway in GMCs induced by high glucose. Finally, we found that Sirt1 deficiency could reverse the down-regulation of FN and ICAM-1 induced by FMN. Collectively, our data demonstrated that FMN up-regulated the expression of Sirt1 to activate the Nrf2/ARE signaling pathway, improved oxidative stress in DN to prevent the progression of renal fibrosis. Therefore, FMN probably represents an efficient therapeutic option of patients with DN.

The present study aimed to delineate the characteristics of empathy and mental health in preschool teachers and to examine the role of empathy in preschool teachers’ mental health. The sample in this study consisted of 4348 preschool teachers, who were divided into four groups according to their years of teaching experience (less than 2, 2–5, 5–10, and more than 10 years). The Chinese version of the Symptom Checklist 90 was used to measure the mental health symptoms of the participants, and the Chinese version of the interpersonal reactivity index was employed to assess various aspects of the participants’ empathy. The results indicated that most symptoms increased as teaching experience increased, independent of the effect of age. The study also found that the four dimensions of empathy showed different trends across the four teaching experience groups: fantasy remained stable, empathic concerns and perspective taking showed decreasing trends, and personal distress showed an increasing trend. Moreover, the present research found a relatively complex relationship between empathy and mental health in preschool teachers: whereas fantasy and personal distress positively predicted mental health symptoms in preschool teachers, perspective taking and empathic concern negatively correlated with most of the symptoms. It seems that empathy contains both risk and protective factors for individuals’ mental health, and these factors are affected by years of teaching experience.

Nowadays, voice control becomes a popular application that allows people to communicate with their devicesmore conveniently. Amazon Echo, designed around Alexa, is capable of controlling devices, e.g., smart lights, etc. Moreover, with the help of IFTTT (if-this-then-that) service, Amazon Echo’s skill set gets improved significantly. However, people who are enjoying these conveniences may not take security into account. Hence, it becomes important to carefully scrutinize the Echo’s voice control attack surface and the corresponding impacts. In this paper, we proposed MUTAE (Manipulating Users’ Trust on Amazon Echo) attack to remotely compromise Echo’s voice control interface. We also conducted security analysis and performed taxonomy based on different consequences considering the level of trust that users have placed on Echo. Finally, we also proposed mitigation techniques that protect Echo from MUTAE attack.

Aims: With the specific pharmacological activities including anti-inflammation, anti-oxidant and hypoglycemic effects, Naringin may possess the potential to ameliorate diabetic nephropathy (DN). The purpose of this study was to investigate the anti-DN effect of Naringin and the molecular mechanism by which Naringin ameliorates diabetic renal fibrosis. Methods: The effects of Naringin on fibronectin (FN) and intercellular adhesion molecule (ICAM-1) as well as the MAPK signaling pathways were detected in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-cultured glomerular mesangial cells (GMCs) respectively. Results: Naringin significantly alleviated the renal fibrosis injury and suppressed the expression of FN and ICAM-1, with down-regulating the phosphorylation of ERK1/2 and JNK and inhibiting the activation of the downstream activating protein (AP-1). There were no meaningful difference between Naringin and the MAPK specific inhibitors. Conclusion: Inhibiting the ERK1/2 and JNK MAPK signaling pathways is probably a novel mechanism by which Naringin alleviates experimental diabetic renal fibrosis.

Background: The micro-RNA miR-30b-3p has been reported to play a crucial role in several cancers. However, the biological function of miR-30b-3p in hepatocellular carcinoma (HCC) is still unknown.Methods: RT-qPCR was employed to determine the expression of miR-30b-3p in HCC tissues and cells. The MTT assay, colony formation assay, and cell migration and invasion assay were employed to evaluate the role of miR-30b-3p in HCC cells. A dual-luciferase reporter assay was employed to verify the target of miR-30b-3p. Western blotting was employed to determine the expression of key molecular signal transducers along TRIM27-PI3K/Akt axis.Results: Expression of miR-30b-3p was markedly decreased in HCC tissues and cells and positively correlated with higher overall survival. Moreover, miR-30b-3p overexpression significantly repressed cell viability, proliferation, migration, and invasion of HCC cells in vitro. Notably, we demonstrated that miR-30b-3p directly bound to the 3′-untranslated region of tripartite motif containing 27 (TRIM27) mRNA by downregulating the expression of TRIM27, which was demonstrated to be negatively correlated with miR-30b-3p expression. TRIM27 was demonstrated to have an oncogenic role in HCC cells by enhancing cell viability, proliferation, migration, and invasion. Finally, the miR-30-3p-TRIM27-PI3K/Akt axis was shown to play a crucial role in HCC cells in vitro.Conclusion: Our results indicated that miR-30-3p might act as a new biomarker for the future diagnosis and treatment HCC.

Abstract Background Gasterophilus species are widely distributed around the world. The larvae of these flies parasitize the digestive tract of equids and cause damage, hindering horse breeding and protection of endangered species. However, study of the genetic structure of geographically distinct Gasterophilus populations is lacking. Here, we analyzed the genetic diversity of Gasterophilus pecorum, G. intestinalis, G. nasalis and G. nigricornis from three typical grasslands (meadow, desert and alpine steppes) in China as compared to published sequences from Italy, Poland and China (Daqing and Yili), based on the mitochondrial cytochrome c oxidase cox1 and cox2 gene sequences. Results Haplotype diversity and nucleotide diversity of mitochondrial genes was generally high in all Gasterophilus populations. Due to the unique natural climatic conditions of the alpine steppe, there were high levels of genetic differentiation among different geographical populations of G. pecorum and G. nasalis, indicating that environmental variations influenced population genetic structure. Frequent exchanges between meadow and desert steppe Gasterophilus species resulted in low genetic differentiation. The highest exchange rates were found among G. intestinalis populations. Genetic differentiation was only observed on a large geographical scale, which was confirmed by analyzing population genetic structure. Three species, G. pecorum, G. intestinalis and G. nasalis, from meadow steppe showed a high emigration rate, indicating that the direction of Gasterophilus dispersal in China was from east to west. Conclusions Our results show that the four Gasterophilus species have a high level of genetic diversity and different degrees of genetic differentiation and gene flow among different populations of the same species, reflecting their potential to adapt to the environment and the environmental impact on genetic structure. Knowledge of the genetic structure, population history, and migration will help understand the occurrence and prevalence of gasterophilosis and provide a basis for controlling the local spread of Gasterophilus spp.

Abstract Our previous studies have shown adenosine A2A R activation markedly promotes the expression of cystatin F (CF) and exacerbates the white matter lesions induced by hypoxic brain injuries. Thus, we hypothesized that CF was probably involved in neuroinflammation of activated microglia induced by A2A R activation. We transfected the BV2 cells with a CF shRNA vector and examined the production of pro-inflammatory cytokines in hypoxic-BV2 cells in which A2A R was activated or inactivated to confirm this hypothesis. Additionally, we also investigated the probable signaling pathways involved in modulation of A2A R activation on CF expression in hypoxia-activated BV2 cells. Activation of A2A R promoted CF expression, which was significantly increased after the low glucose and hypoxia treatments in BV2 cells. CF gene knockdown markedly inhibited the increase in the expression of pro-inflammatory cytokines induced by A2A R activation in hypoxic-BV2 cells. Furthermore, the increased expression of the CF induced by A2A R activation was remarkably inhibited in hypoxic-BV2 cells administrated with the PKA inhibitor H-89 and the PKC inhibitor staurosporine. Hence, these results indicate that hypoxia BV2 cells highly express CF, which is involved in A2A R activation-mediated neuroinflammation via the PKA/CREB and PKC/CREB or ERK1/2 signaling pathways.

Objectives: The serological antibody detection tests offer several advantages for the rapid diagnosis of tuberculosis (TB). The Mycobacterium tuberculosis-specific antibody responses associated with different stages of TB infection remain to be investigated. Methods: The Pathozyme-Myco IgG (Myco G), Pathozyme TB Complex Plus (TB Complex), IBL M. tuberculosis IgG ELISA (IBL), Anda Biologicals TB IgG (Anda-TB), and T-SPOT.TB (T-SPOT) tests were performed for 133 active TB patients (ATB group), 131 controls (CON group), and 95 subjects with latent TB infection (LTBI group). Results: The four serological tests all showed relatively low sensitivity in the ATB group but high specificity in the LTBI and CON groups. The antibody levels of the four serological tests were significantly higher in the ATB group than in the LTBI group. The same trend was observed between the LTBI and CON groups. The four serological tests demonstrated potential diagnostic value in discriminating ATB from LTBI. A combination of the Anda-TB and TB Complex tests exhibited the best diagnostic potential in discriminating ATB from LTBI, with a sensitivity of 89.4% and a specificity of 94.7%. Further, the diagnostic value of Anda-TB and TB Complex were validated in a prospective cohort including 106 patients with suspected ATB. Combined with the T-SPOT test, the tests showed a sensitivity of 87.2% and a specificity of 92.5% for discriminating ATB patients from all ATB suspected cases in the validation group. Conclusions: The antibody responses of the serological tests all showed significant differences between the ATB and LTBI groups. A combination of Anda-TB and the TB Complex test demonstrated high diagnostic potential in discriminating ATB from LTBI and may be an additional diagnostic tool in the diagnosis of M. tuberculosis infection. Keywords: Tuberculosis, Latent infection, Serodiagnosis

Citrus fruit detection can provide technical support for fine management and yield determination of citrus orchards. Accurate detection of citrus fruits in mountain orchards is challenging because of leaf occlusion and citrus fruit mutual occlusion of different fruits. This paper presents a citrus detection task that combines UAV data collection, AI embedded device, and target detection algorithm. The system used a small unmanned aerial vehicle equipped with a camera to take full-scale pictures of citrus trees; at the same time, we extended the state-of-the-art model target detection algorithm, added the attention mechanism and adaptive fusion feature method, improved the model’s performance; to facilitate the deployment of the model, we used the pruning method to reduce the amount of model calculation and parameters. The improved target detection algorithm is ported to the edge computing end to detect the data collected by the unmanned aerial vehicle. The experiment was performed on the self-made citrus dataset, the detection accuracy was 93.32%, and the processing speed at the edge computing device was 180 ms/frame. This method is suitable for citrus detection tasks in the mountainous orchard environment, and it can help fruit growers to estimate their yield.

Recently, several positioning systems based on visible light communications (VLC) have been proposed, and most of them are based on received signal strength (RSS) because of its simplicity and high accuracy. In order to improve the accuracy further, a differential detection-based positioning algorithm is proposed. It can reduce positioning instability caused by light intensity fluctuation and the area outside the light-emitting diode (LED) cell can also be positioned. Experimental results show that the proposed method can improve the positioning accuracy from 10.0 to 4.0 cm and reduce the standard deviation from 9.0 to 2.5 cm. Meanwhile, the positioning accuracy outside the cell can reach 10.0 cm or less.

Context: Withaferin A (WFA) exhibits diverse pharmaceutical applications on human diseases, including rheumatoid arthritis, cancers and microbial infection. Objective: We evaluated the neuroprotective role of WFA using a mouse model of spinal cord injury (SCI). Materials and methods: BALB/c mice were administrated 10 mg/kg of WFA. Gene expression was measured by real-time PCR, western blot and immunohistochemistry. Cell morphology and apoptosis were determined by H&E staining and TUNEL assay. Motor function was evaluated by the BBB functional scale for continuous 7 weeks. Results: WFA significantly improved neurobehavioural function and alleviated histological alteration of spinal cord tissues in traumatized mice. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) significantly increased in WFA-treated mice. Meanwhile, the expression of Nogo-A and RhoA remarkably decreased in the presence of WFA. Furthermore, the apoptotic cell death was attenuated in mice treated with WFA (31.48 ± 2.50% vs. 50.08 ± 2.08%) accompanied by decreased bax and increased bcl-2. In addition, WFA decreased the expression of pro-inflammatory mediators such as IL-1β (11.20 ± 1.96 ng/mL vs. 17.59 ± 1.42 ng/mL) and TNF-α (57.38 ± 3.57 pg/mL vs. 95.06 ± 9.13 pg/mL). The anti-inflammatory cytokines including TGF-β1 (14.32 ± 1.04 pg/mL vs. 9.37 ± 1.17 pg/mL) and IL-10 (116.80 ± 6.91 pg/mL vs. 72.33 ± 9.35 pg/mL) were elevated after WFA administration. Discussion and conclusion: This study demonstrated that WFA has a neuroprotective role by inhibition of apoptosis and inflammation after SCI in mice.

Our previous study proved that paeonol (Pae) could lower blood glucose levels of diabetic mice. There are also a few reports of its potential use for diabetes treatment. However, the role of Pae in regulating glucose and lipid metabolism in diabetes remains largely unknown. Considering the critical role of serine/threonine kinase B (Akt) in glucose and lipid metabolism, we explored whether Pae could improve glucose and lipid metabolism disorders via Akt. Here, we found that Pae attenuated fasting blood glucose, glycosylated serum protein, serum cholesterol and triglyceride (TG), hepatic glycogen, cholesterol and TG in diabetic mice. Moreover, Pae enhanced glucokinase (GCK) and low-density lipoprotein receptor (LDLR) protein expressions, and increased the phosphorylation of Akt. In insulin-resistant HepG2 cells, Pae increased glucose uptake and decreased lipid accumulation. What’s more, Pae elevated LDLR and GCK expressions as well as Akt phosphorylation, which was consistent with the in vivo results. Knockdown and inhibition experiments of Akt revealed that Pae regulated LDLR and GCK expressions through activation of Akt. Finally, molecular docking assay indicated the steady hydrogen bond was formed between Pae and Akt2. Experiments above suggested that Pae ameliorated glucose and lipid metabolism disorders and the underlying mechanism was closely related to the activation of Akt.

An indoor positioning method based on metameric white light sources and subpixels on a color image sensor is proposed in this paper. Metameric white light sources are obtained by merging multiple-color light-emitting diode (LED) chips with different intensity ratios. The output intensity ratios of subpixels on color image sensor at the receiver are employed to identify the respective metameric white light sources. Proof of concept experiments demonstrates that the average error of 2-D indoor positioning is 1.50 cm and 3-D indoor positioning is 3.58 cm. The indoor positioning system with the proposed method is cost effective and convenient because image sensors in nowadays available mobile devices can be utilized.

The self-oriented and other-oriented empathy dimensions may have different relationships with playfulness. However, a scarcity of research exists on the association between empathy and playfulness. The present research contained two studies. Parents of 386 preschoolers (M[subscript age] = 4.89, SD[subscript age] = 0.79) attended Study 1, and teachers of 369 preschoolers (M[subscript age] = 4.16, SD[subscript age] = 0.83) attended Study 2. The parents and teachers completed the Chinese versions of the Children's Playfulness Scale (CPS-C) and the Chinese Empathy Questionnaire (EmQue-C). The results of these two studies revealed the pattern of associations between empathy and playfulness: while the self-oriented empathy dimension (i.e. emotion contagion) negatively predicted preschoolers' playfulness, the two other-oriented empathy dimensions (attention to others' distress and prosocial behaviour) positively predicted playfulness. Moreover, gender moderated the association between empathy and playfulness. These findings enhanced our understanding of the social and emotional traits of playful children.

Research on tree-type irrigation pipe networks is an important component of agricultural water-saving projects. The optimal design of tree-type irrigation pipe networks is a key aspect regarding the profitability of irrigated agriculture. Meanwhile, swarm intelligence optimization algorithms have good computational ability and can be applied to solve many optimization problems in agricultural engineering. To identify the lowest investment cost for a pipe network, this study defined the concept of an upper water node to ensure the connectivity of tree-type irrigation pipe networks, and therefore, improve the pipe network planning model without using preliminary network connection diagrams. In addition, this study proposed an improved chicken swarm optimization algorithm (Improved Chicken Swarm Optimization using Adaptive Search and Variation, ICSO-ASV), which was applied to solve 12 test functions of different dimensions. The test results show that, compared to the traditional chicken swarm algorithm and other algorithms in the control group, the ICSO-ASV algorithm could effectively improve the global search capability. Finally, the ICSO-ASV algorithm was used to plan and design 15-node and 40-node pipe networks. The calculation results show that the average investment costs of the two pipe networks generated by the ICSO-ASV algorithm were 42.20% and 31.09% lower than those generated by the traditional chicken swarm algorithm, which further verified the feasibility of applying ICSO-ASV to design tree-type irrigation pipe networks. Thus, the design method proposed in this study can solve the optimal problems of tree-type irrigation pipe networks with varying topologies. The optimal solutions can be generated automatically using the ICSO-ASV algorithm if essential parameters of the pipe network planning model are provided.

Riverbanks vary considerably in anti-scourability and consequently take various profiles. By using an isosceles trapezoid as the generalized form of river channel cross-sections and then incorporating the effects of bank angle into the variational analytical approach developed by Huang and Nanson (2000), this study presents a detailed theoretical investigation of the self-adjustment of alluvial channel forms. It is demonstrated that when alluvial channel flow achieves stable equilibrium, a significant decrease in riverbank steepness leads to a slight decrease in maximum sediment (bedload) discharge, and yet results in a significant increase in optimal channel width and a considerable decrease in optimal channel depth. The hydraulic geometry relations, theoretically derived for bank steepness to vary across a wide range, show that among the multivariant controls, the roles of bed sediment size, channel roughness, flow discharge and sediment (bedload) discharge are independent of bank steepness. While the effects of bank steepness illustrated in the theoretically derived hydraulic geometry relations are highly consistent with the results of threshold theory and previous empirical studies, limitations on using bank angle to reflect the anti-scourability of natural riverbanks are also highlighted.

Mun River is the largest tributary of the Mekong River in Thailand and provides abundant water resources not only for an important agricultural area in Thailand but also for the lower Mekong River. To understand how the runoff of Mun River responds to climate change and human activities in recent decades, this study performed a detailed examination of the characteristics of runoff variation based on measurements at two hydrological gauging stations on the main stem of Mun River during 1980−2018. Using the Mann-Kendall test, Morlet wavelet transform and Double Cumulative Curve methods, this study identifies that the variation of annual runoff of Mun River encountered an abruption in 1999/2000, with an increased trend taking place since then. Furthermore, a detailed assessment of the effects of the variations in rainfall, temperature, evaporation, and land use types extracted from remote sensing images at the basin scale reveals that a significant reduction in forest area and slight reductions in evaporation and farmland area taking place since 1999 can lead to an increase in the runoff of Mun River, while the dramatic increase in garden area since 1999 tends to make the runoff decrease.

The current study aimed to investigate differences in theory of mind between left-behind children and non-left-behind children in rural China and to examine the potential protective role of general reasoning ability in left-behind children’s theory of mind. Participants included 213 children aged 7.10–13.67 years (111 boys and 102 girls, M = 10.51 years, SD = 1.33), 101 of whom were left behind in rural areas by one or both migrating parents for at least 6 months. The Strange Stories task, a second-order false belief task, and a faux pas task were used to measure children’s theory of mind, and Sessions B and C in Raven’s Standard Progressive Matrices were used to test children’s general reasoning ability. The results showed that left-behind children scored lower on both the faux pas task and Strange Stories task. Additionally, on second-order false belief understanding, left-behind boys performed worse than non-left-behind boys, while left-behind girls scored higher than non-left behind girls. Moreover, children’s general reasoning ability moderated the relationship between parental migrant status and children’s faux pas understanding: For children with high levels of general reasoning ability, left-behind children performed similarly to non-left-behind children, while for children with low levels of general reasoning ability, left-behind children scored lower than non-left-behind children, indicating that general reasoning ability buffered the negative effect of being left behind on children’s theory of mind development. The implications of these findings for training directed at left-behind children are discussed.