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Purpose. Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC. Methods. The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (125I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of 125I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (131I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis. Results. The binding ability of FITC- or 125I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of 125I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of 125I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of 125I-WT-pHLIP (3.76±0.37 vs. 2.87±0.60%ID/g, p=0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the 131I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (p=0.027), 131I (p=0.001), and saline (p

This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1β and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.

Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

The accurate detection and extraction of roads using remote sensing technology are crucial to the development of the transportation industry and intelligent perception tasks. Recently, in view of the advantages of CNNs in feature extraction, its related road extraction methods have been proposed successively. However, due to the limitation of kernel size, they perform less effectively at capturing long-range information and global context, which are crucial for road targets distributed over long distances and highly structured. To deal with this problem, a novel model named RoadFormer with a Swin Transformer as the backbone is developed in this paper. Firstly, to extract long-range information effectively, a Swin Transformer multi-scale encoder is adopted in our model. Secondly, to enhance the feature representation capability of the model, we design an innovative bottleneck module, in which the spatial and channel separable convolution is employed to obtain fine-grained and globe features, and then a dilated block is connected after the spatial convolution module to capture more integrated road structures. Finally, a lightweight decoder consisting of transposed convolution and skip connection generates the final extraction results. Extensive experimental results confirm the advantages of RoadFormer on the Deepglobe and Massachusetts datasets. The comparative results of visualization and quantification demonstrate that our model outperforms comparable methods.

The long-time retention issue of resistive random access memory (RRAM) brings a great challenge in the performance maintenance of large-scale RRAM-based computation-in-memory (CIM) systems. The periodic update is a feasible method to compensate for the accuracy loss caused by retention degradation, especially in demanding high-accuracy applications. In this paper, we propose a selective refresh strategy to reduce the updating cost by predicting the devices’ retention behavior. A convolutional neural network-based retention prediction framework is developed. The framework can determine whether an RRAM device has poor retention that needs to be updated according to its short-time relaxation behavior. By reprogramming these few selected devices, the method can recover the accuracy of the RRAM-based CIM system effectively. This work provides a valuable retention coping strategy with low time and energy costs and new insights for analyzing the physical connection between the relaxation and retention behavior of the RRAM device.

5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1β and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1β expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.

Benefiting from the advancement of deep neural networks (DNNs), detecting objects from drone-view images has achieved great success in recent years. It is a very challenging task to deploy such DNN-based detectors on drones in real-life applications due to their excessive computational costs and limited onboard computational resources. Large redundant computation exists because existing drone-view detectors infer all inputs with nearly identical computation. Detectors with less complexity can be sufficient for a large portion of inputs, which contain a small number of sparse distributed large-size objects. Therefore, a drone-view detector supporting input-aware inference, i.e., capable of dynamically adapting its architecture to different inputs, is highly desirable. In this work, we present a Dynamic Context Collection Network (DyCC-Net), which can perform input-aware inference by dynamically adapting its structure to inputs of different levels of complexities. DyCC-Net can significantly improve inference efficiency by skipping or executing a context collector conditioned on the complexity of the input images. Furthermore, since the weakly supervised learning strategy for computational resource allocation lacks of supervision, models may execute the computationally-expensive context collector even for easy images to minimize the detection loss. We present a Pseudo-label-based semi-supervised Learning strategy (Pseudo Learning), which uses automatically generated pseudo labels as supervision signals, to determine whether to perform context collector according to the input. Extensive experiment results on VisDrone2021 and UAVDT, show that our DyCC-Net can detect objects in drone-captured images efficiently. The proposed DyCC-Net reduces the inference time of state-of-the-art (SOTA) drone-view detectors by over 30 percent, and DyCC-Net outperforms them by 1.94% in AP75.

Breast milk is a perfect food for infants; however, the rate of exclusive breastfeeding is low. The relationship between exclusive breastfeeding practices and influencing factors is complex and remains unclear. This cross-sectional study was conducted in Changsha County, China, and 414 mothers were enrolled. An online questionnaire was used to collect data on general information, obstetrics and gynecology characteristics, the initial breastfeeding intention, breastfeeding practice, frequency of attending conventional breastfeeding programs before delivery, the status of breastfeeding self-efficacy, and the status of perceived social support. Structural equation modeling (SEM) was used to estimate the association between exclusive breastfeeding and potential risk factors of failing to practice exclusive breastfeeding for 6 months. The rate of exclusive breastfeeding for 6 months was 46.1%. The median and interquartile range of the scores for breastfeeding self-efficacy and perceived social support were 51.0 (18.0) and 68.0 (20.0), respectively. Factors that were statistically significant in the univariate analysis were included in the SEM and model fitness was acceptable based on the results. Exclusive breastfeeding for 6 months was directly associated with intention and self-efficacy, while it was indirectly associated with perceived social support and frequency of attending a breastfeeding program. The findings support the recommendation that comprehensive breastfeeding promotion strategies should be implemented to call on the intention and self-efficacy of breastfeeding mothers through various measures, such as education or providing medical and health services.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide. We aimed to identify potential genetic markers that could predict the prognosis of HNSCC. A total of 44 samples of GSE83519 from Gene Expression Omnibus (GEO) datasets and 546 samples of HNSCC from The Cancer Genome Atlas (TCGA) were adopted. The differently expressed genes (DEGs) of the samples were screened by GEO2R. We integrated the expression information of DEGs with clinical data from GES42743 using the weighted gene co-expression network analysis (WGCNA). A total of 17 hub genes were selected by the module membership (|MM| > 0.8), and the gene significance (|GS| > 0.3) was selected from the turquoise module. GOLM1 and FAM49B genes were chosen based on single-gene analysis results. Survival analysis showed that the higher expression of GOLM1 and FAM49B genes was correlated with a worse prognosis of HNSCC patients. Immunohistochemistry and multiplex immunofluorescence techniques verified that GOLM1 and FAM49B genes were highly expressed in HNSCC cells, and high expressions of GOLM1 were associated with the pathological grades of HNSCC. In conclusion, our study illustrated a new insight that GOLM1 and FAM49B genes might be used as potential biomarkers to determine the development of HNSCC, while GOLM1 and FAM49B have the possibility to be prognostic indicators for HNSCC.

Aim: Patients with ischemic stroke (IS), transient ischemic attack (TIA), and/or peripheral artery disease (PAD) represent a population with an increased risk of coronary artery disease. Prognostic risk assessment to identify those with the highest risk that may benefit from more intensified treatment remains challenging. To explore the feasibility and capability of machine learning (ML) to predict long-term adverse cardiac-related prognosis in patients with IS, TIA, and/or PAD.Methods: We analyzed 636 consecutive patients with a history of IS, TIA, and/or PAD. All patients underwent a coronary CT angiography (CCTA) scan. Thirty-five clinical data and 34 CCTA metrics underwent automated feature selection for ML model boosting. The clinical outcome included all-cause mortality (ACM) and major adverse cardiac events (MACE) (ACM, unstable angina requiring hospitalization, non-fatal myocardial infarction (MI), and revascularization 90 days after the index CCTA).Results: During the follow-up of 3.9 ± 1.6 years, 21 patients had unstable angina requiring hospitalization, eight had a MI, 23 had revascularization and 13 deaths. ML demonstrated a significant higher area-under-curve compared with the modified Duke index (MDI), segment stenosis score (SSS), segment involvement score (SIS), and Framingham risk score (FRS) for the prediction of ACM (ML:0.92 vs. MDI:0.66, SSS:0.68, SIS:0.67, FRS:0.51, all P < 0.001) and MACE (ML:0.84 vs. MDI:0.82, SSS:0.76, SIS:0.73, FRS:0.53, all P < 0.05).Conclusion: Among the patients with IS, TIA, and/or PAD, ML demonstrated a better capability of predicting ACM and MCAE than clinical scores and CCTA metrics.

As the third most common malignancy and the second most deadly cancer, colorectal cancer (CRC) induces estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. The incidence of CRC is higher in highly developed countries, and it is increasing in middle- and low-income countries due to westernization. Moreover, a rising incidence of early-onset CRC is also emerging. The large number of CRC cases poses a growing global public health challenge. Raising awareness of CRC is important to promote healthy lifestyle choices, novel strategies for CRC management, and implementation of global screening programs, which are critical to reducing CRC morbidity and mortality in the future. CRC is a heterogeneous disease, and its subtype affiliation influences prognosis and therapeutic response. An accurate CRC subtype classification system is of great significance for basic research and clinical outcome. Here, we present the global epidemiology of CRC in 2020 and projections for 2040, review the major CRC subtypes to better understand CRC molecular basis, and summarize current risk factors, prevention, and screening strategies for CRC.

(1) Background: Research has shown that chronic inflammation can increase the risk of depression. The dietary inflammatory index (DII) is a novel measure of dietary inflammation, which has been used to investigate the relationship between diet and mental disorders in adults. However, little research has been conducted to establish an association between dietary inflammation (as measured by DII) and postpartum depression (PPD) in exclusively breastfeeding women. (2) Methods: In this cross-sectional study, 293 women who were exclusively breastfeeding for 6 months or less were enrolled. The DII scores were evaluated using semi-quantitative Food Frequency Questionnaires (FFQ), and the Edinburgh Postpartum Depression Scale (EPDS) was used to measure depression levels of breastfeeding mothers during the six months following delivery. The participants were classified by tertiles, and the possibility of DII being associated with PPD was assessed by binary regression analysis. (3) Results: The average DII score was 2.32 ± 1.08, which ranged from −1.66 to 4.19. The rate of depression was 60.1%. Adjusted for potential risk factors such as age, educational level, occupational level, number of babies, number of caregivers, social support level, and sleep quality, the results showed that the lowest DII score was associated with a lower risk of PPD than the highest score (OR tertile Q1 vs. 3 = 0.47, 95% CI: 0.24, 0.93, p = 0.030). (4) Conclusions: In exclusive breastfeeding women, the inflammatory potential of dietary intake seems to be related to depression. Interventions to improve diet quality might consider including a dietary component that aims to lower chronic systemic inflammation to prevent PPD. However, the relationship between DII and PPD among Chinese women remains to be demonstrated in a larger population.

This study aimed to investigate the relationship between anxiety, depression, and gut microbiota in elderly patients with FC. Methods: in this cross-sectional study, a total of 198 elderly participants (85 male and 113 female) aged over 60 years were recruited. The study was conducted in Changsha city, China. The participants completed an online questionnaire, including The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), The Patient Assessment of Symptoms (PAC-SYM), and The Patient Assessment of Quality of Life (PAC-QoL). We selected the 16S rDNA V3 + V4 region as the amplification region and sequenced the gut microbiota using the Illumina Novaseq PE250 high-throughput sequencing platform. Results: in total, 30.3% of patients with constipation had depression, while 21.3% had anxiety. The relative abundance of intestinal microbiota in the normal group was higher than that in the anxiety and depression group. According to LEfSe analysis, the relative abundance of g_Peptoniphilus and g_Geobacter in the people without depression and anxiety was higher. The relative abundance of g_Pseudoramibacter-Eubacterium and g_Candidatus-Solibacter in the depression group was lower, and the relative abundance of g_Bacteroides and g_Paraprevotella, g_Cc_115 in the anxiety group was higher. In addition, according to the correlation analysis, g_Aquicella and g_Limnohabitans were negatively correlated with constipation symptoms, anxiety, and depression. Conclusions: this study found that gut microbiota composition may be associated with a higher incidence of anxiety and depression in patients with FC, thus providing insight into the mechanisms that ameliorate mood disorders in patients with FC.

High free sugar intake can lead to increased dental caries, obesity, and other health risks among adolescents. Studies have shown that family factors, especially parents, are one of the primary factors influencing adolescents’ sugar intake. This study aims to investigate the influence of adolescent parents’ free sugar intake, knowledge, attitude, and practice (KAP) on adolescents’ free sugar intake. A total of 1090 pairs of adolescents and their parents from 10 secondary schools in Changsha were enrolled in a cross-sectional study. Free sugar intakes of parents and adolescents were measured using the food frequency questionnaire (FFQ). The current status of parents’ knowledge, attitude, and practice in consuming free sugar was investigated using online and offline questionnaires. Parental free sugar intake was 11.55 (5.08, 21.95) g/d, and that of adolescents was 41.13 (19.06, 80.58) g/d. Parental free sugar intake, free sugar knowledge level, intake behavior, and guidance behavior were associated with adolescent free sugar intake. A superior level of parental free sugar knowledge (adjusted OR = 0.726, 95% CI: 0.557~0.946) was a protective factor for adolescent free sugar intake. Moderate and high levels of parental free sugar intake (adjusted OR = 1.706, 95% CI: 1.212~2.401; adjusted OR = 2.372, 95% CI: 1.492~3.773, respectively) were risk factors for free sugar intake in adolescents. Given the importance of parental influence on the adolescent free sugar intake, further limiting parental intake and increasing awareness of free sugars could play an active role in future interventions for adolescents’ free sugar intake.

(1) Introduction: Screen time may influence preschoolers’ food consumption. However, there is limited evidence regarding preschoolers, especially in China. The aim of this cross-sectional study was to investigate the association between screen time and the consumption of vegetables, fruits, snacks, and sugar sweetened beverages (SSBs). (2) Methods: Participants (1567 caregivers) were recruited from six kindergartens in Hunan, China. Caregivers completed the questionnaire, which included the food frequency questionnaire (FFQ) and questions regarding their children’s daily screen time. (3) Results: The mean screen time of preschoolers was 1.36 ± 1.26 h, and the proportion of children who spent more than one hour on screens was 54.3% in the overall sample. Children with longer screen time consumed vegetables and fruits less frequently, while having a higher consumption of snacks and SSBs. After adjustment of sociodemographic confounders, children’s eating behaviors and parental feeding practices, the association of screen time with vegetables and SSBs still remained significant. (4) Conclusions: Screen time exposure needs to be monitored in preschool children, which was negatively associated with their consumption of vegetables and fruits, whereas it was positively associated with snacks and SSBs. Future research should focus more on the impact of screen time on children’s unhealthy behaviors and dietary patterns.

The assembly quality of a complex product is the result of the combined effects of multiple manufacturing stages, including design, machining and assembly, and it is influenced by associated elements with complex coupling mechanisms. These elements generate and transmit assembly quality deviations during the assembly process which are difficult to analyze and express effectively. Current studies have focused on the analysis and optimization of the assembly surface errors of single or few components, while lacking attention to the impact of errors on the whole product. Therefore, in order to solve the above problem, an assembly quality deviation analysis (AQDA) model is constructed in this paper to analyze the deviation transfer process in the assembly process of complex products and to obtain the key features to optimize. Firstly, the assembly process information is extracted and the assembly quality network model is established on the basis of complex networks. Second, the Jacobian-Torsor (J-T) model is introduced to form a network edge weighting method suitable for the assembly process to objectively express the error propagation among product part features. Third, an error propagation model (EPM) is designed to simulate the error propagation and diffusion processes in the assembly network. Finally, the assembly process of an aero-engine fan rotor is used as an example for modeling and analysis. The results show that the proposed method can effectively identify the key assembly features in the assembly process of complex products and determine the key quality optimization points and monitoring points of the products, which can provide a decision basis for product quality optimization and control.

The understanding of the retention and endurance degradation behavior of different levels of filamentary analog RRAM is critical for the development of the neuromorphic computing. This paper investigates the conductance distribution of different levels during retention and endurance tests. The low conductance states and high conductance states change from the normal distribution at the beginning to asymmetric skewed distribution with baking time increasing. But intermediate states remain the normal distribution. A model is proposed to predict the conductance evolution of different levels. It is also found that endurance lifetime depends on the ratio and position of endurance window. The longer endurance lifetime is attributed to switching in a smaller high-C window. Physical mechanism of endurance degradation is discussed.

Big data analytics (BDA) is a systematic approach for analyzing and identifying different patterns, relations, and trends within a large volume of data. In this paper, we apply BDA to criminal data where exploratory data analysis is conducted for visualization and trends prediction. Several the state-of-the-art data mining and deep learning techniques are used. Following statistical analysis and visualization, some interesting facts and patterns are discovered from criminal data in San Francisco, Chicago, and Philadelphia. The predictive results show that the Prophet model and Keras stateful LSTM perform better than neural network models, where the optimal size of the training data is found to be three years. These promising outcomes will benefit for police departments and law enforcement organizations to better understand crime issues and provide insights that will enable them to track activities, predict the likelihood of incidents, effectively deploy resources and optimize the decision making process.

Detecting objects from images captured by Unmanned Aerial Vehicles (UAVs) is a highly demanding task. It is also considered a very challenging task due to the typically cluttered background and diverse dimensions of the foreground targets, especially small object areas that contain only very limited information. Multi-scale representation learning presents a remarkable approach to recognizing small objects. However, this strategy ignores the combination of the sub-parts in an object and also suffers from the background interference in the feature fusion process. To this end, we propose a Fine-grained Target Focusing Network (FiFoNet) which can effectively select a combination of multi-scale features for an object and block background interference, which further revitalizes the differentiability of the multi-scale feature representation. Furthermore, we propose a Global–Local Context Collector (GLCC) to extract global and local contextual information and enhance low-quality representations of small objects. We evaluate the performance of the proposed FiFoNet on the challenging task of object detection in UAV images. A comparison of the experiment results on three datasets, namely VisDrone2019, UAVDT, and our VisDrone_Foggy, demonstrates the effectiveness of FiFoNet, which outperforms the ten baseline and state-of-the-art models with remarkable performance improvements. When deployed on an edge device NVIDIA JETSON XAVIER NX, our FiFoNet only takes about 80 milliseconds to process an drone-captured image.

Infrared and visible image fusion is to combine the information of thermal radiation and detailed texture from the two images into one informative fused image. Recently, deep learning methods have been widely applied in this task; however, those methods usually fuse multiple extracted features with the same fusion strategy, which ignores the differences in the representation of these features, resulting in the loss of information in the fusion process. To address this issue, we propose a novel method named multi-modal feature self-adaptive transformer (MFST) to preserve more significant information about the source images. Firstly, multi-modal features are extracted from the input images by a convolutional neural network (CNN). Then, these features are fused by the focal transformer blocks that can be trained through an adaptive fusion strategy according to the characteristics of different features. Finally, the fused features and saliency information of the infrared image are considered to obtain the fused image. The proposed fusion framework is evaluated on TNO, LLVIP, and FLIR datasets with various scenes. Experimental results demonstrate that our method outperforms several state-of-the-art methods in terms of subjective and objective evaluation.

Open and high-temporal- and spatial-resolution global land use/land cover (LULC) mapping data form the foundation of global change research and cross-scale land management planning. However, the consistency and reliability of the use of multisource LULC datasets in specific regions need to be quantitatively assessed. In this study, we selected the Indochina Peninsula as the research area; considered four datasets: LSV10, GLC_FCS30, ESRI10, and Globeland30; and analyzed them from four dimensions: the similarity of composition type, the degree of category confusion, spatial consistency, and data accuracy. The results show that: (1) the land composition descriptions of the different datasets are consistent. The study area is dominated by forest and cropland, supplemented by grassland, shrubland, and other land types. (2) The correlation coefficient between datasets is between 0.905 and 0.972; the spatial consistency of datasets is good; and the high-consistency area accounts for 77.87% of the total. (3) The overall accuracy of LSV10 is the highest (83.25%), and that of GLC_FCS30 is the lowest (72.27%). The accuracy of cropland, forest, water area, and built-up land is generally high (above 85%); the accuracy of grassland, shrubland, and bare land is low (below 60%). Therefore, researchers must conduct validation for specific regions and specific land types before using the above datasets. Our findings provide a basis for selecting LULC datasets in related research on the Indochina Peninsula and a reference method for assessing the reliability of multisource LULC datasets in other regions.

Neural epidermal growth factor-like 1 protein (Nell-1) is first studied because of its association with human craniosynostosis. Nell-1 has been used to accelerate the process of fracture healing because of the osteoinductive ability in recent years. However, the role of Nell-1 during the process of osteointegration is unknown. Here we show that activation of Nell-1 in the BMSC sheet promotes osseointegration in vivo and in vitro. We found that overexpression of Nell-1 improved osteogenic differentiation and enhanced matrix mineralization of BMSCs through increasing expression of Runx2 and Osterix. Activation of Nell-1 up-regulated the expression ratio of OPG/RANKL, which might have a negative influence on osteoclast differentiation. Furthermore, we obtained BMSC sheet-implant complexes transfected with lentivirus overexpressing and interfering Nell-1 in in vivo study, and confirmed that overexpression of Nell-1 promoted new bone formation around the implant and increased the bone-implant contacting area percentage. Our results demonstrate that activation of Nell-1 improves implant osteointegration by regulating Runx2/Osterix axis and shows the potential of BMSC sheet-implant complexes in gene therapy.

Abstract Functional probes are a leading contender for the recognition and manipulation of nervous behavior and are characterized by substantial scientific and technological potential. Despite the recent development of functional neural probes, a flexible biocompatible probe unit that allows for long‐term simultaneous stimulation and signaling is still an important task. Here, a category of flexible tiny multimaterial fiber probes (90%), and effectively minimizes the impedance (by up to one order of magnitude) of the probe. This ability allows to realize long‐term (at least 10 weeks) simultaneous optical stimulation and neural recording at the single‐cell level in behaving mice with signal‐to‐noise ratio (SNR = 30 dB) that is more than 6 times that of the benchmark probe such as an all‐polymer fiber.

This study aimed to investigate the prevalence of excessive daytime sleepiness (EDS) and explore the association between free sugars intake and EDS. In this cross-sectional study, a total of 1517 middle school students (808 boys and 707 girls) aged 12~14 years were recruited. The study was conducted in Changsha city, China. Adolescents completed an online questionnaire, including the Epworth Sleepiness Scale (ESS), sleep characteristics, a 12-item Food Frequency Questionnaire (FFQ), and other self-reported information. The ESS score ≥ ten was defined as EDS. The anthropometric indices, including height, weight, and waist circumference, were measured and recorded by uniformly trained assistants. Statistical analyses included the Chi-square test and binary logistic regression model. The mean ESS score and free sugars consumption were 6.8 ± 3.9 points and 53.1 ± 44.7 g/d, respectively. The prevalence of EDS among adolescents was 22.5%, and more girls than boys had EDS (26.1% vs. 19.4%, p < 0.05). An exceeded free sugars intake was positively associated with EDS, with the adjusted Odds Ratio (OR) with its 95% Confident Interval (95% CI) of 1.366 (1.060~1.761, p < 0.05). EDS and excessive consumption of free sugars are commonly found among Chinese adolescents. Further studies are needed to confirm whether free sugars restriction can be meaningful to improve daytime drowsiness in those with EDS.

Parental perception of children’s weight may influence parents’ feeding practices, and in turn, child dietary intake and weight status; however, there is limited evidence generated for preschoolers. The aim of this cross-sectional study was to investigate associations between Chinese parents’ perceptions of child weight, feeding practices and preschoolers’ dietary patterns. Participants (1616 parent-child pairs) were recruited from six kindergartens in Hunan, China. Parents’ misperception, concern, and dissatisfaction on child weight were collected through a self-administered caregiver questionnaire. Parental feeding practices and children’s dietary intake were, respectively, assessed using the Child Feeding Questionnaire and a Food Frequency Questionnaire. Linear regression models were applied to analyze associations between parental weight perceptions, feeding practices, and preschooler’s dietary patterns. Associations between parents’ weight perceptions and dietary patterns were significant only among underweight children. Regardless of child weight status, parental weight underestimation and preference for a heavier child were positively associated with pressure-to-eat. Parental weight concern was positively associated with restriction in normal weight child, but this was not found in other weight groups. In conclusion, Parents’ misperception, concern, and dissatisfaction about child weight are associated with parents’ feeding practices and may influence preschoolers’ dietary quality, but the relationships vary by children’s actual weight status.

There is a lack of evidence to show prevalence of laryngopharyngeal reflux (LPR) and the association between LPR and dietary factors. Adolescents consume the most amount of free sugars among the Chinese population. We conducted this study to investigate the prevalence of LPR in Chinese adolescents and explore the association between free sugars consumption and LPR. A cross-sectional study was conducted on 1517 middle school students in Hunan, China. An online questionnaire was applied to collect data on the condition of LPR, consumption of free sugars and other self-reported covariates. Height, weight and waist circumference were collected by anthropometric measurements. Logistic regression was applied to assess the association between LPR and free sugars consumption. The mean and standard deviation of free sugars consumption was 53.14 ± 44.75 (g/d). The prevalence of LPR was 8.11%. A positive association was observed between LPR and higher free sugars consumption after adjusted multiple covariates, with adjusted odds ratio (95% confident interval) of 1.656 (1.125–2.438). The prevalence of LPR among Chinese adolescents was high. Further analytic studies with strict design are required to test the association between LPR and free sugar consumption. Systematic strategies and policies should to be developed to reduce the intake of free sugars in order to prevent LPR.

School gardening activities (SGA) combined with physical activities (PA) may improve childhood dietary intake and prevent overweight and obesity. This study aims to evaluate the effect of SGA combined with PA on children’s dietary intake and anthropometric outcomes. We searched studies containing randomized controlled trials up to January 2021 in Web of Science, PubMed, Cochrane Library, and the EBSCO database on this topic for children aged 7 to 12 years. Fourteen studies met the requirements for meta-analysis (n = 9187). We found that SGA has no obvious effect on improving children’s BMI (WMD = −0.49; p = 0.085; I2 = 86.3%), BMI z-score (WMD = −0.12; p = 0.235; I2 = 63.0%), and WC (WMD = −0.98; p = 0.05; I2 = 72.9%). SGA can effectively improve children’s FVs (WMD = 0.59, p = 0.003, I2 = 95.3%). SGA combined with PA can significantly increase children’s FVs but cannot greatly improve weight status. Although more studies on this topic are needed to prove the effectiveness of this method, the results of our review show that both SGA and SGA combined with PA has a modest but positive impact of reducing BMI and WC outcomes but can significantly increase children’s FVs.

Healthy diet is essential to type 2 diabetes mellitus (T2DM) prevention for women with previous gestational diabetes mellitus (GDM). To evaluate the effect of a lifestyle intervention program on diet quality for rural women who were previously diagnosed with GDM, we conducted a randomized controlled study in two counties located in south-central China. A total of 404 eligible women were allocated into an intervention group and control group. Participants in the intervention group received 6-month lifestyle intervention including six group seminars and eight telephone consultations. Dietary data were collected at baseline and 18 months via a 24 h dietary recall, and dietary quality was measured by two indicators, Chinese Healthy Eating Score (CHEI) and Minimum Dietary Diversity for Women (MDD-W). Baseline CHEI scores (54.4 vs. 53.5, p = 0.305) and the proportions of participants who met MDD-W (73.8% vs. 74.5%, p = 0.904) were comparable between the two groups. The intervention group achieved a higher CHEI score (62.2 vs. 58.9, p = 0.001) and higher MDD-W proportion (90.6% vs. 81.2%, p = 0.023) at 18 months. Lifestyle intervention was associated with the change of CHEI (p = 0.049) but not with MDD-W (p = 0.212). In conclusion, compared with usual care, lifestyle intervention resulted in greater improvement of dietary quality among rural women with previous GDM.

Myocardial infarction is the major cause of death in cardiovascular disease. In vitro and in vivo models are used to find the exercise mode which has the most significant effect on myocardial irisin/FNDC5 expression and illuminate the cardioprotective role and mechanisms of exercise-activated myocardial irisin/FNDC5-PINK1/Parkin-mediated mitophagy in myocardial infarction. The results indicated that expression of irisin/FNDC5 in myocardium could be up-regulated by different types of exercise and skeletal muscle electrical stimulation, which then promotes mitophagy and improves cardiac function and the effect of resistance exercise. Resistance exercise can improve cardiac function by activating the irisin/FNDC5-PINK1/Parkin-LC3/P62 pathway, regulating mitophagy and inhibiting oxidative stress. OPA1 may play an important role in the improvement of cardiac function and mitophagy pathway in myocardial infarction mice by irisin-mediated resistance exercise. Resistance exercise is expected to become an effective therapeutic way to promote myocardial infarction rehabilitation.

Neural circuits underlying innate fear are only partially understood. Huanget al. identify a subset of retinal ganglion cells that project to both the dorsal raphe nucleus and the superior colliculus, and show that these RGCs mediate looming-evoked defensive behaviours in mice.

An amendment to this paper has been published and can be accessed via the original article.

The effects of ionizing radiation on the reproductive system have always been a matter of great interest. Both artificial and naturally occurring ionizing radiation can directly or indirectly affect the reproductive system via the introduction of DNA single-strand and double-strand breaks, the excitation of water molecules, and the generation of free radicals. In order to quantitatively investigate the effects of ionizing radiation on reproductive function, 60 Co γ irradiation was applied on a model organism, Caenorhabditis elegans (C. elegans) . The egg-laying and embryo-hatching activities were observed for the parent (F0) and the first 2 progeny (F1 and F2) generations. The incidence rate of ovipositor malformation was also recorded. Acridine orange was used to detect the number of apoptotic germ cells. With the above metrics, the effects of 60 Co γ irradiation on the reproductive function of C. elegans were systematically evaluated. The results showed that the postirradiation egg-laying and embryo-hatching activities of the F0 generation were increasingly suppressed by increasing doses of 60 Co γ irradiation. Those of the F1 generation showed a trend toward recovery although also suppressed by the radiation to the F0 generation compared with the control. Those activities were restored to normal or near-normal levels for the F2 generation. The incidence rate of ovipositor malformation was greatly increased by 60 Co γ irradiation according to radiation doses. Gamma irradiation by 60 Co also substantially induced germ cell apoptosis, and the apoptosis rate increased with increasing radiation doses. Therefore, 60 Co γ irradiation affects the reproductive function of C. elegans . The suppression on its reproductive function increases with increasing radiation doses. The reproductive functions of progeny generations are also affected and weakened.

(1) Background: Whether early supplementation of probiotics to improve intestinal flora can effectively prevent eczema remains a controversial issue. We aimed to investigate the effect of a mixed strain of Lactobacillus and Bifidobacterium on eczema in infants under three years old at present; (2) Methods: We searched the databases of PubMed, Web of Science, and Cochrane Library, as well as National Knowledge Infrastructure (CNKI), WeiPu (VIP), and WanFang Data (WanFang) for randomized controlled trials (RCTs) of probiotics in the prevention of eczema in infants without language restriction. The main outcome was eczema incidence, while adverse events during the intervention constituted the secondary outcome. The random-/fixed-effects model was utilized to calculate the combined relative risk (RR) and 95% confidence interval (CI). The methodological quality of the study was evaluated using the Cochrane “bias risk” tool. According to the initial intervention time, subgroup analysis was carried out, follow-up time, family history, etc.; (3) Results: Nine articles were selected (2093 infants). The Lactobacillus and Bifidobacterium mixed strain could prevent eczema in infants under three years of age compared to the placebo (RR = 0.60; I2 = 67%; p < 0.001). Subgroup analysis revealed that the mixture of two probiotic strains had preventive effects on both infants with positive (RR = 0.53; I2 = 52%; p < 0.001) and negative (RR = 0.69; I2 = 62%; p = 0.02) family history; The follow-up time for ≤12 months (RR = 0.65; I2 = 12%; p = 0.01) and 12–24 months (RR = 0.60; I2 = 79%; p = 0.003), daily dose of probiotics ≤ 1 × 109 and > 1 × 109 colony forming units all can be effective (p < 0.01); Compared with the intervention of infants alone (RR = 0.63; I2 = 63%; p = 0.29), the effect of probiotics mixture at the beginning of pregnancy was more significant (RR = 0.59; I2 = 71%; p < 0.001); Except for the mixture of Lactobacillus rhamnosusGG (LGG) and Bifidobacterium longum (B. longum) (p = 0.18), other subgroups of intervention group can play a preventive effect (p < 0.05); (4) Conclusions: The mixed strain of Lactobacillus and Bifidobacterium can effectively reduce the incidence of eczema in infants under three years old. However, further research is needed to fully understand the exact mechanism of their effect on infant eczema.

This study aims to explore the association between restrained eating, body image, and dietary intake among Chinese college students. This cross-sectional study included 1301 college students at two universities in Hunan Province. Electronic questionnaires were used to collect information including students’ demographic characteristics, restrained eating, perception of body weight, body satisfaction, and dietary intake. Anthropometric measurements were collected to calculate body mass index (BMI). The prevalence of high restrained eating was 52.8%. Students who were dissatisfied with their bodies or overestimated their body weight showed a higher tendency toward high restrained eating (p < 0.05). Students with high restrained eating tended to eat fruits and eggs more frequently, while the frequency of eating domestic animals and poultry, sugar-sweetened beverages, and fast food were the opposite. Moreover, high restrained eating was a risk factor for low dietary diversity (odds ratio (OR) = 1.384, 95% confidence interval: 1.002~1.912). The high incidence of restrained eating among Chinese college students and its energy-restricted diets that may lead to possible health implications require attention. Further studies are needed to investigate the characteristics of college students’ restrained eating to tailor appropriate interventions for forming positive body images and promoting healthy eating behaviors, thus, improving dietary quality.

To understand the co-evolution in yield-related traits with the breeding, selection, and introduction of genotypes for increased grain yield, field experiments were carried out at two sites in the western area of the Loess Plateau in China that differed in hydrothermal conditions. Sixteen genotypes of spring wheat introduced and grown over the past 120 years were compared in terms of their yield and yield-related traits. As the grain yield increased, the spike number per unit area and the grain number per spike increased linearly, but the 1000-kernel weight was not correlated with grain yield. In the more recent genotypes, anthesis was initiated significantly earlier, although the length of the period from anthesis to maturity remained unchanged. Water use and the Effective Use of Water (EUW) for aboveground biomass before anthesis and the contribution of pre-anthesis aboveground biomass to grain yield all decreased as grain yield increased. Soil water content at anthesis was negatively correlated with aboveground biomass at anthesis, but positively correlated with grain yield. Conclusively, breeding in spring wheat over the past century has increased the yield of new genotypes by (1) increasing the number of grains per unit area; (2) shortening the period of vegetative growth; (3) decreasing EUW and the soil water use before anthesis; thereby (4) retaining more soil water and increasing biomass accumulation after anthesis. Future spring wheat breeding for this dryland region should determine whether the time for grain filling from anthesis to maturity can be extended to enable greater use of environmental resources and higher yields.

This study aims to estimate the free sugars intake, identify the primary food sources of free sugars, and explore the relationship between free sugars intake and dental caries among Chinese adolescents. This cross-sectional study included 1517 middle-school students aged 12–14 years in Changsha city, China. Adolescents completed a 12-item Food Frequency Questionnaire (FFQ) and oral health assessment. The students’ dental caries experience was available as DMFT score (number of decayed, missing, and filled permanent teeth). Statistical analyses included the Mann–Whitney test, Kruskal–Wallis test, Chi-square test, and binary logistic regression model. The average intake of free sugars was 53.1 g/d in adolescents, and 43.2% of the students consumed more than 50 g of free sugars daily. The primary contributor to free sugars was sugar-sweetened beverages (SSBs). Age, boarders, and high family income were risk factors for excessive free sugars intake (p < 0.05), and increased free sugars intake was a risk factor for dental caries (odds ratio, OR = 1.446, 95% confidence interval: 1.138–1.839). Both the free sugars intake and dental caries prevalence in Chinese adolescents were high. Targeted interventions are urgently needed to address the excessive consumption of free sugars and improve Chinese adolescents’ oral health.

This study aims to explore associations between emotional eating, depression and laryngopharyngeal reflux among college students in Hunan Province. Methods: This cross-sectional study was conducted among 1301 students at two universities in Hunan. Electronic questionnaires were used to collect information about the students’ emotional eating, depressive symptoms, laryngopharyngeal reflux and sociodemographic characteristics. Anthropometric measurements were collected to obtain body mass index (BMI). Results: High emotional eating was reported by 52.7% of students. The prevalence of depressive symptoms was 18.6% and that of laryngopharyngeal reflux symptoms 8.1%. Both emotional eating and depressive symptoms were associated with laryngopharyngeal reflux symptoms (AOR = 3.822, 95% CI 2.126–6.871 vs. AOR = 4.093, 95% CI 2.516–6.661). Conclusion: The prevalence of emotional eating and depressive symptoms among Chinese college students should be pay more attention in the future. Emotional eating and depressive symptoms were positively associated with laryngopharyngeal symptoms. The characteristics of emotional eating require further study so that effective interventions to promote laryngopharyngeal health among college students may be formulated.

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptor family, attract wide attention as promising therapeutic targets for the treatment of multiple diseases, and their target selective ligands were also intensively developed for pharmacological agents such as the approved drugs fibrates and thiazolidinediones (TZDs). Despite their potent pharmacological activities, PPARs are reported to be involved in agent- and pollutant-induced multiple organ toxicity or protective effects against toxicity. A better understanding of the protective and the detrimental role of PPARs will help to preserve efficacy of the PPAR modulators but diminish adverse effects. The present review summarizes and critiques current findings related to PPAR-mediated types of toxicity and protective effects against toxicity for a systematic understanding of PPARs in toxicology and applied pharmacology.

Calcium plays a central role in regulating signal transduction pathways. Calcineurin B-like proteins (CBLs), which harbor a crucial region consisting of EF hands that capture Ca2+, interact in a specific manner with CBL-interacting protein kinases (CIPKs). This two gene families or their interacting-complex widely respond to various environment stimuli and development processes. The genome-wide annotation and specific expression patterns of CBLs and CIPKs, however, in grapevine remain unclear. In the present study, eight CBL and 20 CIPK genes were identified in grapevine genome, and divided into four and five subfamilies, respectively, based on phylogenetic analysis, and validated by gene structure and the distribution of conserved protein motifs. Four (50%) out of eight VvCBLs and eight (40%) out of 20 VvCIPKs were found to be derived from tandem duplication, and five (25%) out of 20 VvCIPKs were derived from segmental duplication, indicating that the expansion of grapevine CBL and CIPK gene families were mainly contributed by gene duplication, and all duplication events between VvCIPK genes only detected in intron poor clade. Estimating of synonymous and non-synonymous substitution rates of both gene families suggested that VvCBL genes seems more conserved than VvCIPK genes, and were derived by positive selection pressure, whereas VvCIPK genes were mainly derived by purifying selection pressure. Expressional analyses of VvCBL and VvCIPK genes based on microarray and qRT-PCR data performed diverse expression patterns of VvCBLs and VvCIPKs in response to both various abiotic stimuli and at different development stages. Furthermore, the co-expression analysis of grapevine CBLs and CIPKs suggested that CBL-CIPK complex seems to be more responsive to abiotic stimuli than during different development stages. VvCBLs may play an important and special role in regulating low temperature stress. The protein interaction analysis suggested divergent mechanisms might exist between Arabidopsis and grapevine. Our results will facilitate the future functional characterization of individual VvCBLs and VvCIPKs.

Crushing of rock particles is a phenomenon commonly encountered in geotechnical engineering practice. It is however difficult to study the crushing of rock particles using classical theory because the physical structure of the particles is complex and irregular. This paper aims at evaluating fractal and morphological characteristics of single rock particle. A large number of particle crushing tests are conducted on single rock particle. The force-displacement curves and the particle size distributions (PSD) of crushed particles are analysed based on particle crushing tests. Particle shape plays an important role in both the micro- and macroscale responses of a granular assembly. The PSD of an assortment of rocks are analysed by fractal methods, and the fractal dimension is obtained. A theoretical formula for particle crushing strength is derived, utilising the fractal model, and a simple method is proposed for predicting the probability of particle survival based on the Weibull statistics. Based on a few physical assumptions, simple equations are derived for determining particle crushing energy. The results of applying these equations are tested against the actual experimental data and prove to be very consistent. Fractal theory is therefore applicable for analysis of particle crushing.

BACKGROUND: Cardiac sympathetic nerve sprouting and the dysregulation of β-adrenergic receptor (β-AR) play a critical role in the deterioration of cardiac function after myocardial infarction (MI). Growing evidence indicates that exercise provides protection against MI. The aims of this study were to investigate whether aerobic exercise following MI could inhibit sympathetic nerve sprouting and restore the balance of β3-AR/β1-AR. METHODS: Male Sprague-Dawley rats were divided into three groups: sham-operated control group (SC), MI group (MI), and MI with aerobic exercise group (ME). The rats in ME group were assigned to 8 weeks of exercise protocol (16 m/min, 50 min/d, 5 d/wk). The expression of nerve growth factor (NGF), the sympathetic nerve marker-tyrosine hydroxylase (TH), the nerve sprouting marker-growth associated protein 43 (GAP43), and β1- and β2-AR expression in the peri-infarct area of the left ventricle (LV) were measured by Western blot and immunohistochemistry, while β3-AR expression was determined by Western blot and immunofluorescence. Endothelial nitric oxide synthase (NOS2), phospho-NOS2 (p-NOS2), and neuronal nitric oxide synthase (NOS1) were measured by Western blot. RESULTS: MI increased LV end-diastolic pressure (LVEDP), and decreased LV systolic pressure (LVSP). Compared with the MI group, aerobic exercise significantly decreased LVEDP and increased LVSP. The protein expression of TH, GAP43 and NGF was significantly increased after MI, which was normalized by exercise. Compared with the SC group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were elevated in the MI group, and the protein expression of β3-AR and NOS1 increased after MI. Compared with the MI group, the ratios of β2-AR/β1-AR and β3-AR/β1-AR were normalized in the ME group, while the protein expression of β3-AR and NOS1 significantly increased, and NOS2 was activated by exercise. CONCLUSIONS: Aerobic exercise inhibits cardiac sympathetic nerve sprouting, restores β3-AR/β1-AR balance and increases β3-AR expression through the activation of NOS2 and NOS1 after myocardial infarction.

BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. METHODS: We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and HMGB1, the TLRs (TLR1-TLR11), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b in the rat renal tissues of the various age groups. RESULTS: We found that during kidney aging, the HSP70 and HMGB1 expression levels were significantly increased, and the expression levels of TLR1, 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b were significantly upregulated. CONCLUSIONS: These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors.

Hypoxia and interactions with bone marrow (BM) stromal cells have emerged as essential components of the leukemic BM microenvironment in promoting leukemia cell survival and chemoresistance. High levels of transforming growth factor beta 1 (TGFβ1) produced by BM stromal cells in the BM niche regulate cell proliferation, survival, and apoptosis, depending on the cellular context. Exogenous TGFβ1 induced accumulation of acute myeloid leukemia (AML) cells in a quiescent G0 state, which was further facilitated by the co-culture with BM-derived mesenchymal stem cells (MSCs). In turn, TGFβ-neutralizing antibody 1D11 abrogated rhTGFβ1 induced cell cycle arrest. Blocking TGFβ with 1D11 further enhanced cytarabine (Ara-C)-induced apoptosis of AML cells in hypoxic and in normoxic conditions. Additional constituents of BM niche, the stroma-secreted chemokine CXCL12 and its receptor CXCR4 play crucial roles in cell migration and stroma/leukemia cell interactions. Treatment with 1D11 combined with CXCR4 antagonist plerixafor and Ara-C decreased leukemia burden and prolonged survival in an in vivo leukemia model. These results indicate that blockade of TGFβ by 1D11 and abrogation of CXCL12/CXCR4 signaling may enhance the efficacy of chemotherapy against AML cells in the hypoxic BM microenvironment.