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AbstractCombined chemical-biological methods play an important role in ecological restoration. However, it is still unknown whether the addition of calcium peroxide (CaO2) can promote the growth of Pontederia cordata (P. cordata) and the improvement of water quality. Effects of different levels of added CaO2 (0, 0.2, 0.4, 0.6, 0.8, 1, and 2 kg/m2) on P. Cordata growth and water quality were investigated. CaO2 promoted germination and tillering and increased the leaf number (p

3-D building models are one of the most intuitive and widely used forms for understanding urban buildings. Generating 3-D building models based on a single off-nadir satellite image is an economical and rapid method, particularly valuable in large-scale 3-D reconstruction scenarios with limited time. In this article, we propose a novel pipeline for automatically reconstructing level of detail 1 (LoD1) 3-D building models based on a single off-nadir satellite remote sensing image. Our pipeline is built upon a multitask neural network called off-nadir building reconstruction network (ONBuildingNet), which extracts building roof polygons and offsets from the image. Using this information, the pipeline computes the building footprint polygons and heights, constructs LoD1 building models, and then extract textures from the off-nadir image. ONBuildingNet introduces our proposed cross-field auxiliary task and multiscale mask head to extract building roof polygons with accurate shapes. We have demonstrated through extensive experiments that our pipeline can automatically and rapidly construct LoD1 3-D urban building models. In addition, our proposed ONBuildingNet outperforms current state-of-the-art methods in extracting more shape accurate building roof polygons, thereby enhancing the accuracy of the final 3-D models produced by our pipeline. Experimental results demonstrate that our method for reconstructing 3-D models of urban building scenes has strong visualization effects, with an average height error of 3.3 m.

Understanding changes in the distribution and coverage of aquatic vegetation (AV) is of great significance for the restoration of lake ecosystems. In this study, the vegetation and bloom indices (VBI) algorithm were used to interpret submerged aquatic vegetation (SAV), floating/emergent aquatic vegetation (FEAV), and algal bloom (AB). The dynamics of AV and their influencing factors in Bao’ an Lake, in the middle reaches of the Yangtze River in China, were studied from 2000 to 2023. The results showed that (1) the VBI algorithm can accurately distinguish AV and AB of different life forms with an overall accuracy of 93% and a kappa coefficient of 0.86. (2) Macrophyte coverage decreases. AV grew vigorously in spring, and SAV was the dominant type within it, whereas AV coverage was low in summer, and SAV had no summer species for a long time. In 2000, the coverage of AV was the highest, reaching 64.5%, but a gradual decrease that followed in the coming years finally led to a coverage percentage of less than 5% by 2023. (3) The correlation between SAV coverage and total phosphorus (p < 0.01), total nitrogen (p < 0.05), and water depth/transparency (p < 0.05) in Bao’ an Lake were 0.23, 0.28, and 0.32, respectively. (4) The SAV species experienced three stages: richness (before 2003), monotonicity (2004–2020), and final disappearance (2021–present). This study shows that the coverage of AV in Bao’ an Lake is too low and the number of SAV species is one (2010–now). Therefore, it is necessary to implement measures to improve vegetation coverage and diversity.

Based on the BERTopic model, this study analyzes 15,744 scientific papers in the field of functional agriculture from 1995 to 2024 to uncover core themes and evolutionary trends in global functional agriculture, and particularly focuses on revealing the developmental trajectory in China. The results indicate that global functional agriculture research is characterized by diverse themes and intensive study, forming a multi-topic cross-network centered on plant chemical extraction and agricultural soil research, with a focus on food nutrition, human health, and environmental protection. By contrast, China’s functional agriculture research demonstrates a more focused and in-depth approach, concentrating on functional food development and agricultural environmental protection themes, with notable growth trends in areas such as selenium-enriched products and resistant starch. Combined with China’s agricultural development environment, this study makes the following suggestions for the development of functional agriculture in China: (1) Promoting interdisciplinary cooperation between functional agriculture and other technologies. (2) Developing agricultural products with Chinese characteristics and forming Chinese functional agricultural product brands. (3) Utilizing smart farming technology to boost functional agriculture.

AbstractUrban lakes play an important role in supporting the ecological environment and human society, yet increasing pollution poses a threat to water quality. Tangxun Lake, a typical Large urban lake in the middle reaches of the Yangtze River, has experienced cultural eutrophication in recent years; however, few studies have comprehensively examined the water quality of this lake. Therefore, we aimed to evaluate the water quality of the Tangxun Lake Basin using the Nemerow pollution index, principal component analysis (PCA), phytoplankton density and diversity, and the comprehensive trophic level index (TLI). Additionally, we analyzed the main influencing factors to provide a reference for the management of the aquatic environment of Tangxun Lake. The Nemerow pollution index evaluation showed that the annual degree of pollution in Tangxun Lake ranged from mild to heavy. The PCA results showed that the main pollution factors affecting water quality were total phosphorus (TP) and total nitrogen (TN). According to the results of TLI, the water in Tangxun Lake was moderately to severely eutrophic. Evaluation of algal cell density showed that Tangxun Lake was mesotrophic, and the phytoplankton diversity index showed that the eutrophication level was high. The degree of pollution in Tangxun Lake varied seasonally and was in the order of spring > winter > summer > autumn. The pollution in inner Tangxun Lake was relatively serious in spring, summer, and autumn, whereas that in outer Tangxun Lake was more serious in winter. This study provides a scientific basis for the comprehensive management of the ecological environment in the Tangxun Lake Basin.

IntroductionPhosphorus (P), which plays a vital role in plant growth, is continually added to soil to maximize biomass production, leading to excessive P accumulation and water eutrophication.ResultsIn this study, a pot experiment using a subtropical tobacco-growing soil fertilized with four P levels—no P, low P, medium P, and high P—was conducted and rhizosphere and bulk soils were analyzed.ResultsP addition significantly increased tobacco biomass production (except under low P input) and total soil P and available P content (P0.05). Moreover, a significant difference was found between rhizosphere soils with low (LR) and high (HR) P inputs (P0.05). Functional prediction revealed that P application significantly decreased the total P and N metabolism of microorganisms in rhizosphere soils (P

Abstract Background MicroRNA (miRNA) which can act as post-transcriptional regulators of mRNAs via base-pairing with complementary sequences within mRNAs is involved in processes of the complex interaction between immune system and tumors. In this research, we elucidated the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation and survival data. Results We conducted the analysis of differential miRNA/mRNA expression profile by GEO, TCGA and GTEx databases and the correlation between miRNA and targeted mRNA by miRTarBase and TarBase. Then we detected using qRT-PCR and validated the diagnostic value of miRNA-mRNA regulator pairs by the ROC, calibration curve and DCA. Phenotypic hallmarks of regulatory pairs including tumor-infiltrating lymphocytes, tumor microenvironment, tumor mutation burden, global methylation and gene mutation were also described. The expression levels of miRNAs and target mRNAs were detected in 80 paired colon tissue samples. Ultimately, we picked up two pivotal regulatory pairs (miR-139-5p/ STC1 and miR-20a-5p/ FGL2) and verified the diagnostic value of the complex model which is the combination of 4 signatures above-mentioned in 3 testing GEO datasets and an external validation cohort. Conclusions We found that 2 miRNAs by targeting 2 metastasis-related mRNAs were correlated with tumor-infiltrating macrophages, HRAS, and BRAF gene mutation status. Our results established the diagnostic model containing 2 miRNAs and their respective targeted mRNAs to distinguish CRCs and normal controls and displayed their complex roles in CRC pathogenesis especially tumor immunity.

Abstract Culture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC2000 prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC2010 cohort. Nasopharyngeal relative abundance values of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are associated with the same species in the hypopharyngeal cultures. A combined pathogen score of these bacteria’s abundance values is associated with persistent wheeze/asthma by age 7. No other taxa are associated. Compared to the hypopharyngeal aspirates from the COPSAC2010 cohort, the anaerobes Veillonella and Prevotella, which have previously been implicated in asthma development, are less commonly detected in the COPSAC2000 nasopharyngeal samples, but correlate with the pathogen score, hinting at latent community structures that bridge current and previous results. These findings have implications for future asthma prevention efforts.

Metasurfaces can realize the flexible manipulation of electromagnetic waves, which have the advantages of a low profile and low loss. In particular, the coding metasurface can flexibly manipulate electromagnetic waves through controllable sequence encoding of the coding units to achieve different functions. In this paper, a three-layer active coding metasurface is designed based on vanadium dioxide (VO2), which has an excellent phase transition. For the designed unit cell, the top patterned layer is composed of two split square resonant rings (SSRRs), whose gaps are in opposite directions, and each SSRR is composed of gold and VO2. When VO2 changes from the dielectric state to the metal state, the resonant mode changes from microstrip resonance to LC resonance, correspondingly. According to the Pancharatnam-Berry (P-B) phase, the designed metasurface can actively control terahertz circularly polarized waves in the near field. The metasurface can manipulate the order of the generated orbital angular momentum (OAM) beams: when the dielectric VO2 changes to metal VO2, the order l of the OAM beams generated by the metasurface changes from −1 to −2, and the purity of the generated OAM beams is relatively high. It is expected to have important application values in terahertz wireless communication, radar, and other fields.

Background: MicroRNA (miRNA) and mRNA levels in matching specimens were used to identify miRNA–mRNA interactions. We aimed to integrate transcriptome, immunophenotype, methylation, mutation, and survival data analyses to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer (BC) diagnosis. Methods: Based on the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interaction databases using Pearson's correlation analysis. We used real-time quantitative reverse transcription polymerase chain reaction to verify BC and benign disease samples, and logistic regression analysis was used to establish a diagnostic model based on miRNAs and target mRNAs. Receiver operating characteristic curve analysis was performed to test the ability to recognize the miRNA-mRNA pairs. Next, we investigated the complex interactions between miRNA-mRNA regulatory pairs and phenotypic hallmarks. Results: We identified 27 and 359 dysregulated miRNAs and mRNAs, respectively, based on the GEO and TCGA databases. Using Pearson's correlation analysis, 10 negative miRNA-mRNA regulatory pairs were identified after screening both databases, and the related miRNA and target mRNA levels were assessed in 40 BC tissues and 40 benign breast disease tissues. Two key regulatory pairs (miR-205-5p/High mobility group box 3 (HMGB3) and miR-96-5p/Forkhead Box O1 (FOXO1)) were selected to establish the diagnostic model. They also had utility in survival and clinical analyses. Conclusions: A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish between BC and benign breast diseases. These markers play essential roles in BC pathogenesis.

Hydraulic switching actuators are high-efficiency, fast response, and low-cost solutions for hydraulic control systems. One of the challenging problems is throttling losses during valve transitions. Previously, the authors proposed a zero-flowrate switching method to reduce the throttling energy loss of the switching valve, where a hydraulic resonator is applied to make the flowrates through the lines approaching zero before the valves are switched off. The major challenge of this approach is fast switching valves whose transition times are less than 2 ms. In this paper, an improved zero-flowrate switching method is presented. It utilizes the capacity with independent inlet/outlet ports to regulate flowrates through the lines. Models of capacity applied in a simple line with different pressure signals are developed to explore characteristics of the capacity, based on which a complete actuation system is developed. In the complete model, resistance and inductance are optimized to achieve the desired flowrate response. The improved zero-flowrate switching method reduces throttling energy losses by 99.945% compared to a hard switching system. The simulation results demonstrated that the improved zero-flowrate switching method performs as expected in the design condition. A capacity with proper volume is able to regulate flowrates through all the lines to zero, with the help of appropriate resistance and inductance. Compared to the previous zero-flowrate switching method, the novel strategy allows slower switching valves applied in hydraulic actuation systems and achieves better efficiency performance. This research paves a new avenue for reducing throttling energy losses and improves system efficiency in hydraulic switching actuators, as well as most of the hydraulic switch-mode circuits.

BackgroundChronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD.Materials and methodsWe screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed.ResultsA total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the “T cell receptor signaling pathway” and “positive regulation of NF-κB signaling pathway”, were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs.ConclusionIn summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.

The process of bone remodeling is connected with the regulated balance between bone cell populations (including bone-forming osteoblasts, bone-resorbing osteoclasts, and the osteocyte). And the mechanism of bone remodeling activity is related to the major pathway, receptor activator of nuclear factor kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) signaling axis. Recently, researchers have found a novel cytokine secreted by activated T cells, which is related to osteoclastogenesis in the absence of osteoblasts or RANKL, leading to bone destruction. They name it the secreted osteoclastogenic factor of activated T cells (SOFAT). SOFAT has been proven to play an essential role in bone remodeling, like mediating the bone resorption in rheumatoid arthritis (RA) and periodontitis. In this review, we outline the latest research concerning SOFAT and discuss the characteristics, location, and regulation of SOFAT. We also summarize the clinical progress of SOFAT and assume the future therapeutic target in some diseases related to bone remodeling.

AbstractEutrophication caused by nutrients and organic matter (OM) pollution is a common problem in the world. The contents of total nitrogen (TN), total phosphorus (TP) and OM in sediments were determined in four typical lakes in southeastern Hubei, China, in the spring of 2019, and their pollution status was evaluated by organic and comprehensive pollution indexes to identify pollution sources and provide specific directions for the pollution control in key areas of the lakes. We found the following: (1) Both nutrients and OM in Cihu Lake and Bao’an Lake were relatively high. Cihu Lake had the highest nutrient and OM in both surface and core sediments. TN, TP and OM in the surface sediments of Cihu Lake reached 700.9 mg/kg, 1668.8 mg/kg and 62.8 kg/g, respectively. The contents of nutrients and OM in Daye Lake and Liangzi Lake were relatively low. OM in these two lakes was significantly lower than that in the Cihu Lake (p 0.05). It indicated that the sources of nutrients and OM in sediments were not identical but were affected by many factors. However, the relationship between nutrients and OM was closer in core sediments. In the future, targeted measures should be taken to reduce sediment pollution based on specific pollution sources and pollution conditions in the four lakes, especially Cihu Lake.

Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.

Leucine-rich repeat-containing 8 A (LRRC8A) is an essential component of the volume-regulated anion channel (VRAC), which plays a vital role in cell proliferation, migration, apoptosis, and drug resistance. In this study, we investigated the effects of LRRC8A on oxaliplatin resistance in colon cancer cells. The cell viability was measured after oxaliplatin treatment with cell counting kit-8 (CCK8) assay. RNA sequencing was used to analyze the differentially expressed genes (DEGs) between HCT116 and oxaliplatin-resistant HCT116 cell line (R-Oxa) cells. CCK8 assay and apoptosis assay indicated that R-Oxa cells significantly promoted drug resistance to oxaliplatin compared with native HCT116 cells. R-Oxa cells, deprived of oxaliplatin treatment for over six months (R-Oxadep), maintained a similar resistant property as R-Oxa cells. The LRRC8A mRNA and protein expression were markedly increased in both R-Oxa and R-Oxadep cells. Regulation of LRRC8A expression affected the resistance to oxaliplatin in native HCT116 cells, but not R-Oxa cells. Furthermore, The transcriptional regulation of genes in the platinum drug resistance pathway may contribute to the maintenance of oxaliplatin resistance in colon cancer cells. In conclusion, we propose that LRRC8A promotes the acquisition rather than the maintenance of oxaliplatin resistance in colon cancer cells.

Abstract Purpose MicroRNA (miRNA) is a class of short non-coding RNA molecules that functions in RNA silencing and post-transcriptional regulation of gene expression. This study aims to identify critical miRNA-mRNA regulation pairs contributing to bladder cancer (BLCA) pathogenesis. Patients and methods MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. The tool of GEO2R and R packages were used to screen differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) and DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The miRNA-mRNA regulation pair were screened from the experimentally validated miRNA-target interactions databases (miRTarbase and TarBase). Twenty-eight pairs of BLCA tissues were used to further verify the screened DE-miRNAs and DE-mRNAs by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). The correlation analysis between the selected miRNA-mRNAs regulation pair and clinical, survival and tumor-related phenotypes was performed in this study. Results After miRTarBase, the analysis of 2 miRNA datasets, 6 mRNA datasets, and TCGA-BLCA dataset, a total of 13 miRNAs (5 downregulated and 8 upregulated in BLCA tissues) and 181 mRNAs (72 upregulated and 109 downregulated in BLCA tissues) were screened out. The pairs of miR-17-5p (upregulated in BLCA tissues) and TGFBR2 (downregulated in BLCA tissues) were verified in the external validation cohort (28 BLCA vs. 28 NC) using qRT-PCR. Areas under the ROC curve of the miRNA-mRNA regulation pair panel were 0.929 (95% CI: 0.885–0.972, p < 0.0001) in TCGA-BLCA and 0.767 (95% CI: 0.643–0.891, p = 0.001) in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing BLCA from normal controls. Correlation analysis showed that miR-17-5p and TGFBR2 correlated with tumor immunity. Conclusions The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of BLCA.

Abstract Background This study aims to examine the cross-sectional association between serum total bilirubin (STB) and type 2 diabetes (T2D) risk in the general population, and whether obesity could moderate this association. Methods We used data from the 1999–2018 National Health and Nutrition Examination Surveys (NHANES), including a total of 38,641 US adult participants who were 18 years or older. The STB was classified as the low, moderate, and high groups according to tertiles. Results We found that participants with lower STB had a significantly higher risk of T2D than those with moderate (OR = 0.81; 95% CI 0.74, 0.89; P

Salmonella is a zoonotic foodborne bacterial pathogen that can seriously harm health. Persistence of Salmonella and antibiotic resistance genes (ARGs) in different types of soil under flooding and natural conditions are rare explored. This study investigated the dynamic changes of the Salmonella, ARGs and bacterial communities in three types of soils applied with pig manure in lab scale. Abundance of the Salmonella Typhimurium in soils reduced to the detection limit varied from 40 to 180 days, most of the Salmonella did not survive in soil for more than 90 days. Flooding and soil texture (content of sand) promote the decline rate of Salmonella. No Salmonella was found have acquired resistance gene from the soil or manure after 90 days. 64 ARGs and 11 MGEs were quantified, abundance of these genes and risky ARGs both gradually decline along with the extension of time. Most of the extrinsic ARGs cannot colonize in soil, cellular protection and antibiotic deactivation were their main resistance mechanism. Multidrug resistance and efflux pump were the dominant class and mechanism of soil intrinsic ARGs. Flooding can affect the ARGs profiles by reducing the types of extrinsic ARGs invaded into soil and inhibit the proliferation of intrinsic genes. Soil sand content, soil moisture and nutrition concentrations had significant direct effect on the abundance or profile of ARGs. Soil bacterial community structures also changed along with the extension of time and affected by flooding. Network analyses between ARGs and bacteria taxa revealed that Actinobacteria and Myxococcia were the main hosts of intrinsic ARGs, some taxa may play a role in inhibiting extrinsic ARGs colonization in the soils. These findings unveil that saturate soil with water may play a positive role in reducing potential risk of Salmonella and ARGs in the farmland environment.

Introduction and objectives: Circular RNA (circRNA) has attracted extensive attention in studies related to the malignant progression of cancer, including hepatocellular carcinoma (HCC). Therefore, its molecular mechanism in HCC needs to be further explored. Materials and methods: The expression levels of circ_0008285, microRNA (miR)-384 and ribonucleotide reductase subunit M2 (RRM2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed using cell counting kit-8 assay and 5-ethynyl-2’-deoxyuridine assay, cell apoptosis was analyzed by flow cytometry, and cell migration and invasion were detected by transwell assay. Protein level was detected by western blot. The relationships between miR-384 and circ_0008285 or RRM2 were predicted by bioinformatics software and validated by dual luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Results: Circ_0008285 expression is elevated to HCC tissues and cell lines. Silencing of circ_0008285 inhibited the proliferation, migration and invasion of HCC cells but accelerated cell apoptosis in vitro and impeded HCC tumorigenesis in vivo. Mechanistically, circ_0008285 directly interacted with miR-384, and miR-384 silencing attenuated the effects of circ_0008285 interference on cell proliferation, migration, invasion, and apoptosis. RRM2 was a direct target of miR-384, and RRM2 overexpression reversed the effects of miR-384 overexpression on cell proliferation, migration, invasion, and apoptosis. In addition, circ_0008285 regulated RRM2 expression by sponging miR-384. Conclusion: In this study, circ_0008285 could promote the malignant biological behaviors of HCC cells through miR-384/RRM2 axis and has the potential to become a therapeutic target for HCC, providing a new idea for targeted therapy of HCC.

Objectives: To assess the association of road traffic noise exposure with Type 2 Diabetes (T2D) risk, and to explore the potential moderation effect of obesity.Methods: A total of 305,969 participants from the UK Biobank Cohort - an open access cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010 - were included in the study. A Cox proportional hazard model was fitted to assess the association between road traffic noise exposure and T2D.Results: A total of 19,303 participants were diagnosed with T2D during the 11.9-year median follow-up period. For every 10 dB increase in road traffic noise, there was a 4% increase in T2D risk (HR = 1.04, 95%CI: 1.01, 1.07). Besides, a significant positive interaction was observed between obesity and road traffic noise (P interaction

BackgroundHeart failure (HF) combined with hypertension is an extremely important cause of in-hospital mortality, especially for the intensive care unit (ICU) patients. However, under intense working pressure, the medical staff are easily overwhelmed by the large number of clinical signals generated in the ICU, which may lead to treatment delay, sub-optimal care, or even wrong clinical decisions. Individual risk stratification is an essential strategy for managing ICU patients with HF combined with hypertension. Artificial intelligence, especially machine learning (ML), can develop superior models to predict the prognosis of these patients. This study aimed to develop a machine learning method to predict the 28-day mortality for ICU patients with HF combined with hypertension.MethodsWe enrolled all critically ill patients with HF combined with hypertension in the Medical Information Mart for IntensiveCare Database-IV (MIMIC-IV, v.1.4) and the eICU Collaborative Research Database (eICU-CRD) from 2008 to 2019. Subsequently, MIMIC-IV was divided into training cohort and testing cohort in an 8:2 ratio, and eICU-CRD was designated as the external validation cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression with internal tenfold cross-validation was used for data dimension reduction and identifying the most valuable predictive features for 28-day mortality. Based on its accuracy and area under the curve (AUC), the best model in the validation cohort was selected. In addition, we utilized the Shapley Additive Explanations (SHAP) method to highlight the importance of model features, analyze the impact of individual features on model output, and visualize an individual’s Shapley values.ResultsA total of 3,458 and 6582 patients with HF combined with hypertension in MIMIC-IV and eICU-CRD were included. The patients, including 1,756 males, had a median (Q1, Q3) age of 75 (65, 84) years. After selection, 22 out of a total of 58 clinical parameters were extracted to develop the machine-learning models. Among four constructed models, the Neural Networks (NN) model performed the best predictive performance with an AUC of 0.764 and 0.674 in the test cohort and external validation cohort, respectively. In addition, a simplified model including seven variables was built based on NN, which also had good predictive performance (AUC: 0.741). Feature importance analysis showed that age, mechanical ventilation (MECHVENT), chloride, bun, anion gap, paraplegia, rdw (RDW), hyperlipidemia, peripheral capillary oxygen saturation (SpO2), respiratory rate, cerebrovascular disease, heart rate, white blood cell (WBC), international normalized ratio (INR), mean corpuscular hemoglobin concentration (MCHC), glucose, AIDS, mean corpuscular volume (MCV), N-terminal pro-brain natriuretic peptide (Npro. BNP), calcium, renal replacement therapy (RRT), and partial thromboplastin time (PTT) were the top 22 features of the NN model with the greatest impact. Finally, after hyperparameter optimization, SHAP plots were employed to make the NN-based model interpretable with an analytical description of how the constructed model visualizes the prediction of death.ConclusionWe developed a predictive model to predict the 28-day mortality for ICU patients with HF combined with hypertension, which proved superior to the traditional logistic regression analysis. The SHAP method enables machine learning models to be more interpretable, thereby helping clinicians to better understand the reasoning behind the outcome and assess in-hospital outcomes for critically ill patients.

In contrast to molecular changes associated with increased inflammatory responses, little is known about intracellular counter-regulatory mechanisms that control signaling cascades associated with functional responses of neutrophils. Active RHO GTPases are typically considered as effector proteins that elicit cellular responses. Strikingly, we show here that RHOH, although being constitutively GTP-bound, limits neutrophil degranulation and the formation of neutrophil extracellular traps (NETs). Mechanistically, RHOH is induced under inflammatory conditions and binds to non-muscle myosin heavy chain IIA (NMHC IIA) in activated neutrophils in order to inhibit the transport of mitochondria and granules along actin filaments, which is partially reverted upon disruption of the interaction with NMHC IIA by introducing a mutation in RhoH at lysine 34 (RhoHK34A). In parallel, RHOH inhibits actin polymerization presumably by modulating RAC1 activity. In vivo studies using Rhoh-/- mice, demonstrate an increased antibacterial defense capability against Escherichia coli (E. coli). Collectively, our data reveal a previously undefined role of RHOH as a molecular brake for actomyosin-mediated neutrophil effector functions, which represents an intracellular regulatory axis involved in controlling the strength of an antibacterial inflammatory response.

Abstract Background Arterial stiffness is an independent cardiovascular risk factor. However, the association between sodium/potassium intake and vascular stiffness was inconsistent. Therefore, a large community-based cross-sectional study was performed to try and achieve more definitive conclusion. Methods Urinary sodium, potassium, and creatinine levels were tested in spot urine samples during physical examinations of each recruited participant. The 24-h estimated urinary sodium excretion (eUNaE) and estimated urinary potassium excretion (eUKE) levels were determined using the Kawasaki formula (used as a surrogate for intake). Carotid intima-media thickness (IMT) and plaques were measured using ultrasound. Results In 13,523 subjects aged 18–80 years, the relationships between carotid plaques and IMT with eUNaE, eUKE and their ratios were analyzed. Overall, 30.2% of participants were diagnosed with carotid artery plaques. The ratio of estimated sodium vs. potassium excretion (Na/K ratio) of the individuals with carotid artery plaques was significantly higher than that of participants without plaque (2.14 ± 0.73 vs. 2.09 ± 0.61, P

Compared with the predecessor standards, versatile video coding (VVC) significantly improves compression efficiency by a quadtree with nested multi-type tree (QTMT) structure but at the expense of extremely high coding complexity.To reduce the coding complexity of VVC, a fast QTMT partition method was proposed based on deep learning.Firstly, an attention-asymmetric convolutional neural network was proposed to predict the probability of partition modes.Then, the fast decision of partition modes based on the threshold was proposed.Finally, the cost of coding performance and time was proposed to obtain the optimal threshold, and the threshold decision method was proposed.Experimental results at different levels show that the proposed method achieves an average time saving of 48.62%/52.93%/62.01% with the negligible BDBR of 1.05%/1.33%/2.38%.Such results demonstrate that the proposed method significantly outperforms other state-of-the-art methods.

Valve switching is one of the most important power losses in digital hydraulics. In this paper, a dynamic Zero-Flowrate-Switching (ZFS) control method is developed for hydraulic/pneumatic systems. The proposed control strategy is to actively reduce the flowrate passing through the valve to zero before switching off the valve. To realize it, an accessory line, in which a RLC oscillator is applied to generate a sinusoidal flowrate, is allocated parallel to the main control line for flowrate regulation. The pressure, with high frequency and small amplitude wave outputs from a regular piston pump, is used to drive the RLC oscillator. To evaluate the performance of this strategy, mathematical models for switching power loss and pressure pulses are developed and characteristic analysis is conducted. The results show that the energy loss of the system when applying the dynamic ZFS controller is reduced to 16% compared to that of a normal hydraulic system without a dynamic ZFS controller; moreover, pressure pulses in a dynamic ZFS system are much more minor than those in a Hard-Switching system.

Organic manure application is crucial for the maintenance and improvement of soil fertility. However, it inevitably results in increased paddy CH4 emissions, restricting the use of organic manure in the rice fields. In the present study, two kinds of manures, rapidly composted manure (RCM) and non-composted manure (NCM), were investigated through a 19-week greenhouse experiment, during which the dynamics of CH4 emission, soil parameters (DOC, acetate, NH4+, NO3−, and SO42−), and communities of methanogens and methanotrophs were simultaneously measured. The results showed that NCM significantly enhanced CH4 emission, while RCM decreased CH4 emission by 65.03%; there was no significant difference with the manure-free treatment. In order to well understand the methanogenic process, the seasonal CH4 flux was divided into two periods, namely Stage 1 (before drainage) and Stage 2 (after drainage), on the basis of CH4 emission intensity. The different CH4 production abilities among the three treatments could contribute to the varied CH4 emissions at Stage 1. The much higher soil DOC concentrations were observed in the manure-amended soils (NCM- and RCM-treatments), which could correspondingly lead to the relative higher CH4 emissions compared to the control during Stage 1. Furthermore, the increased methanogenic abundance and the shifted methanogenic archaeal community characterized by the functionally stimulated growth of Methanosarcina genus were observed in the NCM-treated soils, which could consequently result in a higher CH4 emission from the NCM treatment relative to the RCM treatment. As for Stage 2, apart from the significant decrease in soil DOC, the increased contents of soil NO3− and SO42−, especially with the RCM-treated soils, were also detected following the drainage, which might retard CH4 production. The lower CH4 emission at Stage 2 could also be attributed to the vigorous aerobic CH4 oxidations, especially in the RCM-treated soils. As a support, the amount of methanotrophs revealed an increasing trend during the late rice growth period, as did the predominance of the methylotrophy of Methylophilaceae species, which showed robust co-occurrence with methanotrophs, inferring interspecies cooperation in methane oxidation.

BackgroundPancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC.MethodsPatients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort (n = 4,586) and validation cohort (n = 1,966). Data of patients in 2016–2018 (n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA).ResultsAge, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715–0.735) and 0.711 (95%CI: 0.695–0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778–0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS.ConclusionsA web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients.

Bladder cancer is a common malignancy of the urinary system, which occurs mostly in elderly men, and the incidence is increasing year by year. To analyze the status quo and related factors of discharge readiness of patients with bilateral ureteral stoma after radical cystectomy, a retrospective, noncomparative was performed. 544 patients with bilateral ureteral stoma after radical cystectomy in our hospital from December 2018 to December 2020 were selected. The self-designed questionnaire, discharge readiness scale (RHDS) and discharge guidance quality scale (QDTS) were used to investigate the general data, and multiple linear regression was used to analyze the related influencing factors. The total score of RHDS was (72.57 ± 18.56) and the total score of QDTS was (105.63 ± 24.18); the total score of RHDS was positively correlated with the total score of QDTS (r = 0.882, p = 0.000); the results of multiple linear regression showed that age, discharge direction and care mode were the main factors influencing the discharge readiness of patients (p

Purpose: MicroRNA (miRNA) binds to target mRNA and inhibit post-transcriptional gene expression. It plays an essential role in regulating gene expression, cell cycle, and biological development. This study aims to identify potential miRNA-mRNA regulatory networks that contribute to the pathogenesis of lung squamous cell carcinoma (LUSC).Patients and Methods: MiRNA microarray and RNA-Seq datasets were obtained from the gene expression omnibus (GEO) databases, the cancer genome atlas (TCGA), miRcancer, and dbDEMC. The GEO2R tool, “limma” and “DEseq” R packages were used to perform differential expression analysis. Gene enrichment analysis was conducted using the DAVID, DIANA, and Hiplot tools. The miRNA-mRNA regulatory networks were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUSC tissues by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) were conducted to evaluate the diagnostic value. Clinical, survival and phenotypic analysis of miRNA-mRNA regulatory networks were further explored.Results: We screened 5 miRNA and 10 mRNA expression datasets from GEO and identified 7 DE-miRNAs and 270 DE-mRNAs. After databases screening and correlation analysis, four pairs of miRNA-mRNA regulatory networks were screened out. The miRNA-mRNA network of miR-205-5p (up) and PTPRM (down) was validated in 30 pairs of LUSC tissues. MiR-205-5p and PTPRM have good diagnostic efficacy and are expressed differently in different clinical features and are related to tumor immunity.Conclusion: The research identified a potential miRNA-mRNA regulatory network, providing a new way to explore the genesis and development of LUSC.

Liver cancer: Common anesthetic can accelerate tumor progression Researchers warn against using the anesthetic dexmedetomidine (DEX) in liver cancer patients after indications that it promotes tumor growth. Concerns have been raised that certain anesthetics, including DEX, can accelerate the progression of cancerous tumors, but the precise effects of DEX on liver cancer tumors are unclear. Most liver cancers develop in patients who already have fibrosis, a build-up of scarred tissue in the liver. This tissue accumulation stems from the activation of hepatic stellate cells (HSCs) during liver damage. Using human cancer cell lines and mouse models, Aimin Li and Xue Ning at the Southern Medical University, Guangzhou, China and co-workers demonstrated that DEX interacts with HSCs via a receptor protein on their cell surface, further enhancing activation levels. Activated HSCs in turn secrete factors that accelerate tumor growth and invasion.

Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs.

We reported on an efficient RNA imaging strategy based on a CRISPR-Cas and Tat peptide with a fluorescent RNA aptamer (TRAP-tag). Using modified CRISPR-Cas RNA hairpin binding proteins fused with a Tat peptide array that recruits modified RNA aptamers, this simple and sensitive strategy is capable of visualizing endogenous RNA in cells with high precision and efficiency. In addition, the modular design of the CRISPR-TRAP-tag facilitates the substitution of sgRNAs, RNA hairpin binding proteins, and aptamers in order to optimize imaging quality and live cell affinity. With CRISPR-TRAP-tag, exogenous GCN4, endogenous mRNA MUC4, and lncRNA SatIII were distinctly visualized in single live cells.

Semantic segmentation of remote sensing (RS) images, which is a fundamental research topic, classifies each pixel in an image. It plays an essential role in many downstream RS areas, such as land-cover mapping, road extraction, traffic monitoring, and so on. Recently, although deep-learning-based methods have shown their dominance in automatic semantic segmentation of RS imagery, the performance of these existing methods has relied heavily on large amounts of high-quality training data, which are usually hard to obtain in practice. Moreover, human-in-the-loop semantic segmentation of RS imagery cannot be completely replaced by automatic segmentation models, since automatic models are prone to error in some complex scenarios. To address these issues, in this paper, we propose an improved, smart, and interactive segmentation model, DRE-Net, for RS images. The proposed model facilitates humans’ performance of segmentation by simply clicking a mouse. Firstly, a dynamic radius-encoding (DRE) algorithm is designed to distinguish the purpose of each click, such as a click for the selection of a segmentation outline or for fine-tuning. Secondly, we propose an incremental training strategy to cause the proposed model not only to converge quickly, but also to obtain refined segmentation results. Finally, we conducted comprehensive experiments on the Potsdam and Vaihingen datasets and achieved 9.75% and 7.03% improvements in NoC95 compared to the state-of-the-art results, respectively. In addition, our DRE-Net can improve the convergence and generalization of a network with a fast inference speed.

Background: Male urethral stricture is a disease with a high incidence rate. With social-economic development in the developing countries, the trend of etiology and treatment of male urethral stricture changed was speculated.Methods: The clinical data of the male patients with urethral stricture from 2000 to 2019 were analyzed. The subjects were divided into Group A (2000–2009) and Group B (2010–2019) according to treatment time. The pooled analysis of the data extracted from pieces of literature was also performed.Results: About 540 patients were included in the present study, including 235 patients in Group A and 305 patients in Group B. In recent 10 years, trauma has still been the main cause of urethral stricture. Iatrogenic injury, especially transurethral operation, increases significantly, while male urethral stricture secondary to radiotherapy and infection decrease. Urethroplasty increases and the reoperation rate decreases in treating simple urethral stricture, and flap urethroplasty also increases in treating complex urethral stricture. The results of a pooled analysis of data from 11 centers in Mainland China are partially consistent with it. Complications, such as urethral fistula, false canal, ejaculation disorder, and penile curvature, decrease significantly.Conclusions: The main causes of urethral stricture in the recent 10 years are still trauma and iatrogenic injuries, and the etiology of urethral stricture is related to socioeconomic development. With the increase of intracavitary minimally invasive treatment and flap urethroplasty, the curative effect is increasing, while iatrogenic urethral stricture cannot be ignored.

ObjectiveTo evaluate the feasibility and effectivity of deep learning (DL) plus three-dimensional (3D) printing in the management of giant sporadic renal angiomyolipoma (RAML).MethodsThe medical records of patients with giant (>15 cm) RAML were retrospectively reviewed from January 2011 to December 2020. 3D visualized and printed kidney models were performed by DL algorithms and 3D printing technology, respectively. Patient demographics and intra- and postoperative outcomes were compared between those with 3D-assisted surgery (3D group) or routine ones (control group).ResultsAmong 372 sporadic RAML patients, 31 with giant ones were eligible for analysis. The median age was 40.6 (18–70) years old, and the median tumor size was 18.2 (15–28) cm. Seventeen of 31 (54.8%) had a surgical kidney removal. Overall, 11 underwent 3D-assisted surgeries and 20 underwent routine ones. A significant higher success rate of partial nephrectomy (PN) was noted in the 3D group (72.7% vs. 30.0%). Patients in the 3D group presented a lower reduction in renal function but experienced a longer operation time, a greater estimated blood loss, and a higher postoperative morbidity. Subgroup analysis was conducted between patients undergoing PN with or without 3D assistance. Despite no significant difference, patients with 3D-assisted PN had a slightly larger tumor size and higher nephrectomy score, possibly contributing to a relatively higher rate of complications. However, 3D-assisted PN lead to a shorter warm ischemia time and a lower renal function loss without significant difference. Another subgroup analysis between patients under 3D-assisted PN or 3D-assisted RN showed no statistically significant difference. However, the nearness of tumor to the second branch of renal artery was relatively shorter in 3D-assisted PN subgroup than that in 3D-assisted RN subgroup, and the difference between them was close to significant.Conclusions3D visualized and printed kidney models appear to be additional tools to assist operational management and avoid a high rate of kidney removal for giant sporadic RAMLs.

Zinc oxide nanoparticles (ZnO NPs) have been increasingly and widely utilized in various fields, such as agriculture, food and cosmetics. However, various levels of adverse impacts of ZnO NPs on the ecological environment and public health have been associated with each stage of their production, use and disposal. ZnO NPs can be ingested by pregnant women and transferred to developing embryos/foetus through the placental barrier, however, the potential toxicity of ZnO NPs to embryonic and foetal development is largely unclear. In this study, we discovered that ZnO NPs exposure caused growth proportional failure of neural tube closure in mouse and chicken embryos and a simultaneous increase in apoptosis in the developing neural tubes of chicken embryos, which was verified in an in vitro experiment using the SH-SY5Y cell line. Furthermore, removal of free Zn2+ ions with EDTA or inhibition of Zn2+ ion absorption by CaCl2 partially alleviated the neurotoxicity induced by ZnO NPs, implying that ZnO NPs-induced developmental neurotoxicity is probably due to both ZnO NPs and the Zn2+ ions released from ZnO NPs. In addition, we found that ZnO NPs exposure caused endoplasmic reticulum stress-mediated apoptosis driven mainly by an increase in intracellular calcium (Ca2+) concentrations, rather than by the activation of three membrane protein receptors (ATF6, IRE-1 and PERK). Thus, Ca2+ imbalance-mediated apoptosis in the context of ZnO NPs exposure may lead to cellular dysfunctions in developing neural precursors, such as, abnormalities involved in neural tube closure, ultimately leading to neural tube defects (NTDs) during embryogenesis. In sum, our results revealed that ZnO NPs exposure greatly increases the risk of failure of neural tube closure through endoplasmic reticulum stress-mediated neural cell death in the developing embryos, which may further lead to the NTD in fetal stage, including failure of neural tube closure.

Microbial inoculation is a promising strategy to improve crop yields and reduce the use of chemical fertilizers, thereby creating environment-friendly agriculture. In this study, the long-term (5 years) effects of a phosphate-solubilizing bacterium Burkholderia cepacia ISOP5, a purple non-sulfur bacterium Rhodopseudomonas palustris ISP-1, and a mixed inoculation of these two bacteria (MB) on peanut yield, soil microbial community structure, and microbial metabolic functions were evaluated in a field experiment. After 5 years of inoculation, total peanut yield with B. cepacia ISOP5, R. palustris ISP-1, and MB treatments increased by 8.1%, 12.5%, and 19.5%, respectively. The treatments also significantly promoted the absorption of N and increased the protein content in peanut seeds. Nutrient content also increased to some extent in the bacteria-inoculum-treated soil. However, bacterial community diversity and richness were not significantly affected by bacterial inoculums, and only minor changes occurred in the bacterial community composition. Functional prediction revealed that bacterial inoculums reduced the relative abundance of those genes associated with P uptake and transport as well as increased the abundance of genes associated with inorganic P solubilization and organic P mineralization. Bacterial inoculums also increased the total relative abundance of genes associated with N metabolism. In addition to developing sustainable and eco-friendly agricultural practice, crop inoculation with B. cepacia ISOP5 and R. palustris ISP-1 would improve soil fertility, enhance microbial metabolic activity, and increase crop yield.

Abstract Background Colon cancer is one of the three common malignant tumors, with lower 5 years survival rate. Akt is an important therapeutic target, while SC66 is a novel allosteric AKT inhibitor, which enhances the therapeutic effect in several types of cancer. However, the molecular mechanisms of targeting AKT by SC66 during colon cancer therapy are not well understood. Methods The biological role of GSK-3β in colon cancer growth suppression induced by SC66 was detected in vitro and in vivo. Hoechst 33342 and crystal violet staining were used to determine whether targeting AKT affected apoptosis and cell proliferation. The CCK8 assay was utilized to analyze cell viability. The expression levels of Akt, GSK-3β, Bax, Bcl-xL, p53 and PUMA were measured by immune blotting. Xenograft mouse model was established to study the antitumor effect of SC66 in vivo. Results Our results show that SC66 induced significantly colon cancer cell apoptosis, accompanied with Akt inactivation. After AKT inhibition, activated GSK-3β interacted with Bax directly, leading to Bax oligomerization and activation. Knocking down GSK-3β abrogated SC66-triggered Bax activation and apoptosis, which was enhanced by over-expressed GSK-3β. In addition, the expression level of Bcl-xL was down-regulated while p53 had no function during SC66-induced apoptosis. Furthermore, colon cancer growth was suppressed by SC66 therapy in vivo. Conclusion Taken together, these data indicated that the novel small molecule AKT inhibitor SC66 shows visible antitumor effects via the AKT/GSK-3β/Bax axis in vitro and in vivo. Our results provide a rational basis for the development of targeting-GSK-3β, which may serve as a potential biomarker and yield meaningful benefits for colon cancer patients in the future.

The development of hard, multi-layer coatings is an effective strategy to enhance the wear resistance of cutting tools and so extend their service life. In the present study, a sandwich structured TiN/g-TiSiN/TiSiN film (where a graded (g-) TiSiN layer with an increasing Si content from 0 to 10 at% was inserted as a transitional layer between the TiN layer and the TiSiN layer with a fixed silicon content of 10 at%) was prepared on to a M42 tool steel substrate. Its mechanical properties were compared to both a dual-layered TiN/g-TiSiN film and a monolithic TiN film. Nanoindentation testing, assisted by focused-ion-beam (FIB) microscopy, was employed to evaluate contact-induced deformation and the mode of fracture of these films. Indented regions created on samples by a 5 μm radius indenter were examined by transmission electron microscopy (TEM). Finite element analysis was used to model the stress distributions within these films and predict the regions where crack initiation and growth may occur. The deformation of the monolithic TiN film was found to be predominantly accommodated by shear sliding along columnar grain boundaries, leading to a lower resistance to deformation. For the bilayer TiN/g-TiSiN film, the g-TiSiN layer hindered the propagation of columnar cracks, however, this bilayer film exhibited a stress concentration together with radial cracks at the bottom of the film. Compared with the former two films, the sandwich-structured film that contained the graded TiSiN interlayer exhibited the highest resistance to contact damage. This is because the graded TiSiN interlayer altered the stress distribution in the film and lowered the overall stress concentration level. Keywords: TiSiN graded interlayer, Deformation mechanism, Nanoindentation, Finite element method

Road networks play a fundamental role in our daily life. It is of importance to extract the road structure in a timely and precise manner with the rapid evolution of urban road structure. Recently, road network extraction using deep learning has become an effective and popular method. The main shortcoming of the road extraction using deep learning methods lies in the fact that there is a need for a large amount of training datasets. Additionally, the datasets need to be elaborately annotated, which is usually labor-intensive and time-consuming; thus, lots of weak annotations (such as the centerline from OpenStreetMap) have accumulated over the past a few decades. To make full use of the weak annotations, we propose a novel semi-weakly supervised method based on adversarial learning to extract road networks from remote sensing imagery. Our method uses a small set of pixel-wise annotated data and a large amount of weakly annotated data for training. The experimental results show that the proposed approach can achieve a maintained performance compared with the methods that use a large number of full pixel-wise annotations while using less fully annotated data.

Animal manure is a reservoir of antibiotic resistance genes (ARGs), and direct application of the manure will lead to spread of ARGs in farmland. Here, we explored the impacts of chicken manure and heat-treated chicken manure on the patterns of soil resistome after 3 years’ application, with mushroom residues set as the plant-derived organic manure treatment. A total of 262 ARG subtypes were detected in chicken manure using high-throughput qPCR, and heat treatment can effectively remove 50 types of ARGs. Although ARG subtypes and abundance were both higher in chicken manure, there was no significant difference in the ARG profiles and total ARG abundance among three manure-treated soils. Soil bacteria community compositions were significantly different among manure-treated soils, but they were not significantly correlated with soil ARG profiles. Fast expectation–maximization microbial source tracking (FEAST) was used for quantifying the contributions of the potential sources to microbial taxa and ARGs in manure-fertilized soil. Results revealed that only 0.2% of the chicken manure-derived bacterial communities survived in soil, and intrinsic ARGs were the largest contributor of soil ARGs (95.8–99.7%); ARGs from chicken manure only contributed 0.4%. The total ARG abundance in the heat-treated chicken manure-amended soils was similar to that in the mushroom residue-treated soils, while it was 1.41 times higher in chicken manure-treated soils. Thus, heat treatment of chicken manure may efficiently reduce ARGs introduced into soil and decrease the risk of dissemination of ARGs.

To alleviate the cavitation damage of metallic engineering components in hydrodynamic systems operating in marine environments, a NbN nanoceramic coating was synthesized on to a Ti-6Al-4V substrate via a double cathode glow discharge technique. The microstructure of the coating consisted of a ~13 μm thick deposition layer of a hexagonal δ′-NbN phase and a diffusion layer ~2 μm in thickness composed of face-centered cubic (fcc) B1-NaCl–structured (Ti,Nb)N. The NbN coating not only exhibited higher values of H/E and H2/E than those measured from NbN coatings deposited by other techniques, but also possessed good adhesion to the substrate. The cavitation erosion resistance of the NbN coating in a 3.5 wt% NaCl solution was investigated using an ultrasonic cavitation-induced apparatus combined with a range of electrochemical test methods. Potentiodynamic polarization measurements demonstrated that the NbN coated specimens demonstrated both a higher corrosion potential (Ecorr) and lower corrosion current density (icorr) than the uncoated substrate. Mott-Schottky analysis, combined with the point defect model (PDM), revealed that, for a given cavitation time, the donor density (ND) of the passive film on the NbN coating was reduced by 1 ~ 2 orders of magnitude relative to the uncoated Ti-6Al-4V, and the diffusivity of the point defects (D0) in the passive film grown on the NbN coating was nearly one order of magnitude lower than that on the uncoated substrate. In order to better understand the experimental observations obtained from Mott-Schottky analysis and double-charge layer capacitance measurements, first-principles density-functional theory was employed to calculate the energy of vacancy formation and the adsorption energy for chloride ions for the passive films present on both the NbN coating and bare Ti-6Al-4V.

Due to the low hydration rate of high-volume fly ash (HVFA) concrete at early age, the temperature gradient between the concrete core and surfaces could be effectively reduced. However, the low hydration rate results in a lack of hydration degree for early-age HVFA concrete. Thus, during curing, compared to the strength of ordinary Portland cement (OPC), a subsequent lower one of HVFA concrete leads to a more sensitive response to inner stresses induced by thermal and moisture loads. Based on ABAQUS, in this paper, user subroutines in the temperature and moisture fields were developed, with regard to the hydration degree, for simulation of the temperature and moisture influences on concrete. Additionally, the Double Power Law (DPL) model was used to depict early-age deformations of concrete in the mechanical field. Combined with the extended finite element method (XFEM), another subroutine for early-age cracking analysis in the mechanical field was then developed. Together with aforementioned subroutines, a thermo-hygro-mechanical model is derived. For evaluation of early-age cracking initiation and propagation of a pier composed of HVFA concrete, the model was implemented with XFEM. The obtained results show that (1) temperature and restraints are the main causes of cracking; (2) moisture loss affects surface cracks on structures at early age; and (3) although the temperature difference between the core and surfaces is not much obvious due to the reduced rate of heat dissipation from hydration, cracking of early-age HVFA concrete is still likely to happen for its low early strength. Thus, timely curing is critical to prevent early cracking.

The radioprotective effect of amitriptyline, an inhibitor of acid sphingomyelinase (ASMase), on radiation-induced impairment of hippocampal neurogenesis, loss of interneuron, and animal weight changes was investigated in BALB/c mice by immunostaining of biomarkers for cell division (Ki67), immature neurons (doublecortin or DCX), and interneurons (parvalbumin or PV) in the dentate gyrus (DG) of hippocampus. The results indicated that preirradiation (with 10 mg/kg, 2 times per day, for 7 consecutive days) or postirradiation (with 10 mg/kg, 2 times per day, for 14 consecutive days) treatment (pretreatment or posttreatment) with intraperitoneal injection of amitriptyline prevented the loss of newly generated neurons, proliferating cells, and interneurons in the subgranular zone of the DG. At the molecular level, pretreatment or posttreatment inhibited the expression of sphingomyelin phosphodiesterase 1 ( SMPD1 ) gene which codes for ASMase. The pretreatment for 7 days also prevented radiation-induced weight loss from 2 to 3 weeks, but not within 1 week after irradiation. On the other hand, the posttreatment with amitriptyline for 14 days could improve animal weight gain from 4 to 6 weeks after irradiation. The present study suggests that amitriptyline may be a promising candidate radio-neuroprotective drug to improve radiation-induced impairment of hippocampal neurogenesis and relevant neurological and neuropsychological disorders.

Non-viral vectors are important for transfection but can be limited in the uptake, protection and release of ssDNA. Here, the authors report on the design of metal-organic-framework vectors with precisely controlled pore geometry and demonstrate the vector in the transfection of immune cells.

Onboard observation task planning plays an essential role in satellite autonomy, which has attracted considerable attention from researchers in recent years. Most of the existing studies solve the satellite onboard observation task planning problem (SOOTP) by searching algorithms. However, the limited computing resources and the changes of onboard condition present a new challenge for these methods. In this paper, we develop a sequential decision-making model and propose a deep learning-based planning method to solve the SOOTP. Instead of generating a short-term or long-term plan in advance, the sequential decisionmaking model enables the satellite to decide the observation task to execute in real-time. In the deep learning-based planning method, a long short-term memory-based encoding network is designed to extract the features and a classification network is used to make such a decision. In the experiment, we compared our method with the gated recurrent unit network and other three searching algorithms based on five scenarios. The experimental results show that our method can solve problems with 90.3%-93.7% accuracy, 2.19%-3.95% profit gap, and 0.004-0.006 s response time per task, which confirms its feasibility.

The NLRP3 inflammasome is central to a variety of inflammatory diseases, but how it is regulated to prevent excessive inflammation is not clear. Here the authors show that NLRP3 activation causes SHP2 translocation to the mitochondria to interact with and dephosphorylate ANT1, thus stabilizing the mitochondria and preventing release of proinflammatory mitochondrial DNA and ROS.

CCAAT/enhancer-binding homologous protein (CHOP), a transcriptional regulator induced by endoplasmic reticulum stress (ER stress) is a pivotal factor in the ER stress-mediated apoptosis pathway. Previous studies have shown that CHOP is involved in the formation of fibrosis in a variety of tissues and is associated with alternative macrophage activation. The role of CHOP in the pathologic effects of liver fibrosis in schistosomiasis has not been reported, and underlying mechanisms remain unclear. This study is aimed at understanding the effect of CHOP on liver fibrosis induced by Schistosoma japonicum (S. japonicum) in vivo and clarifying its mechanism. C57BL/6 mice were infected with cercariae of S. japonicum through the abdominal skin. The liver fibrosis was examined. The level of IL-13 was observed. The expressions of CHOP, Krüppel-like factor 4 (KLF4), signal transducer and activator of transcription 6 (STAT6), phosphorylation STAT6, interleukin-13 receptor alpha 1 (IL-13Rα1), and interleukin-4 receptor alpha (IL-4Rα) were analysed. The eosinophilic granuloma and collagen deposition were found around the eggs in mice infected for 6 and 10 weeks. IL-13 in plasma and IL-13Rα1 and IL-4Rα in liver tissue were significantly increased. The phosphorylated STAT6 was enhanced while Krüppel-like factor 4 (KLF4) was decreased in liver tissue. The expression of CHOP and colocalization of CHOP and CD206 were increased. Overall, these results suggest that CHOP plays a critical role in hepatic fibrosis induced by S. japonicum, likely through promoting alternative activation of macrophages.