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Background: RNA methylation is a potential target for cancer therapy, while anoikis, a form of programmed cell death, is linked to cancer metastasis. However, the prognostic and immune significance of RNA methylation- and anoikis-related genes in colorectal cancer (CRC) remains unknown., Methods: Transcriptomic and clinicopathological data for CRC were obtained from TCGA and the GEO databases. A novel signature was constructed based on RNA methylation- and anoikis-related genes using univariate and multivariate Cox regression as well as LASSO Cox regression methods. CRC patients were stratified into low- and high-risk groups based on this signature. Differences in prognosis, immune infiltration, and drug sensitivity between two groups were analyzed. Finally, immunohistochemistry, western blot, and RT-qPCR were employed to validate the expression of the key gene SERPINE1 in CRC tissues and cells, as well as the effect of FTO on its expression., Results: We identified 79 differentially expressed RNA methylation-associated anoikis-related genes (RMRARGs) in both cancerous and normal tissues. A signature composed of 9 key genes (BID, FASN, PLK1, CDKN3, MYC, EPHA2, SERPINE1, CD36, PDK4) was established. Kaplan-Meier analysis revealed a poorer prognosis in the high-risk group. Compared to the other three published models, this signature demonstrated superior predictive performance based on the ROC curve analysis. Functional analyses highlighted differences in drug sensitivities and signaling pathways between risk groups. Furthermore, immune analysis results showed that risk score was associated with some immune cells and immune checkpoints. Immunohistochemistry showed high SERPINE1 expression in CRC tissues, with FTO expression positively correlated with SERPINE1. Furthermore, RT-qPCR and western blot indicated FTO knockdown markedly downregulated SERPINE1 levels., Conclusion: Our findings underscore the prognostic value of this signature in CRC patients and its utility in assessing immune status. Additionally, the m6A demethylase FTO regulates the expression of the anoikis-related gene SERPINE1., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of the Declaration of Helsinki, and was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Guangxi Medical University (No. 2022-KY-0055). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Photonic crystals (PC) play a key role in optical field modulation due to their unique photonic band gaps (PBGs). Anodic aluminum oxide (AAO) prepared by pulse anodization is a promising candidate for PC devices. In this research, an AAO-based PC with multi-band was fabricated on a single-slice & single-material film, which exhibits multi-band responses in the visible-to-near-infrared (vis-NIR) region. In other words, multiple PBGs present simultaneously at different wavelength ranges and can be precisely controlled by the experimental protocols. The deposition of a silver layer by a simple physical vapor deposition (PVD) method further modulates the refractive indices of the AAO-based PC, enabling the fabrication of well-distributed Bragg reflector (DBR) structures with tunable optical Tamm states (OTS). The prepared AAO-based PC can work as single-slice & single-material devices with excellent properties and broad application prospects in anti-counterfeiting and selective optical filtering.

Objective: Ulcerative colitis (UC) is a chronic inflammatory disorder challenging to diagnose clinically. We focused on identifying and validating SUMOylation-related signature genes in UC and their association with immune infiltration., Methods: Five eligible gene expression profiles were selected from the Gene Expression Omnibus (GEO) database and merged into a single dataset comprising 260 UC patients and 76 healthy controls (HC). Differentially expressed genes (DEGs) were identified, and these were intersected with SUMOylation-related genes to obtain differentially expressed SUMOylation-related genes (DESRGs). Next, we identify the signature genes and validate them through comprehensive analyses employing GO, KEGG, GSVA, Lasso-cox regression, ROC curves, and clustering analysis. The infiltrating immune cells were analyzed using the CIBERSORT algorithm and Pearson correlation analysis. Finally, in vitro and in vivo experiments validated the identified signature genes., Results: PALMD, THRB, MAGED1, PARP1, and SLC16A1 were identified. Next, an excellent predictive model for UC was established and distinct subgroups of patients associated with SUMOylation were identified. Moreover, the NF-κB signaling pathway likely plays a pivotal role in the regulation of SUMOylation in UC. Additionally, we validated that the alterations in PALMD, THRB, and MAGED1 expression in LPS-induced Caco-2 cells concurred with our bioinformatics findings, particularly demonstrating statistically significant differences in PALMD and THRB expression. Finally, in a DSS-induced mouse colitis model, we observed a significant upregulation of PALMD expression. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation., Conclusion: This study comprehensively elucidates the biological roles of SUMOylation-related genes in UC, identifying PALMD, MAGED1, THRB, PARP1, and SLC16A1 as signature genes that represent promising biomarkers for UC diagnosis and prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Relevant studies have demonstrated that plasma metabolites and immune cell characteristics are closely related to colorectal cancer (CRC). However, the causal relationship among these factors remains unclear, particularly regarding whether immune cell traits mediate the causal link between plasma metabolites and CRC. Methods: This study employed a two-step, two-sample Mendelian randomization (MR) using summary data from genome-wide association studies (GWAS) to assess causal associations between 1,400 plasma metabolites, 731 immune cell traits, and CRC. Additionally, it evaluated the mediating effect of immune cell traits and utilized single-cell RNA sequencing (scRNA-seq) to analyze immune cells infiltration in CRC, assess their metabolic functional changes and their interactions with CRC cells. Results: Univariable two-sample MR analysis revealed causal relationships between 49 plasma metabolites and CRC, as well as between 36 immune cell traits and CRC. Two-step MR analysis revealed that two plasma metabolites (Sphingomyelin (d18:1/22:1, d18:2/22:0, d16:1/24:1) and 16α-hydroxy-DHEA-3-sulfate) influence CRC through two immune cell traits (SSC-A on CD14+ monocyte and CD3 on CD28- CD8+ T cell). Among these, SSC-A on CD14+ monocyte exhibited the highest mediating effect proportion, at 11.723%. scRNA-seq analysis further confirmed the increased infiltration of CD28- CD8+ T cells and CD14+ monocytes in CRC, along with upregulated sphingolipid metabolism and steroid biosynthesis. These cells were also found to interact with CRC cells, contributing to tumor initiation and progression. Conclusion: This study provides new evidence for the causal relationship between plasma metabolites and CRC, and it identifies immune factors with potential mediating roles. These findings offer new insights for further exploration of the mechanisms underlying the development of CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Palladium nanosheets (Pd NSs) are widely used as electrocatalysts due to their high atomic utilization efficiency, and long-term stability. Here, the electronic structure modulation of the Pd NSs is realized by a femtosecond laser irradiation strategy. Experimental results indicate that laser irradiation induces the variation in the atomic structures and the macrostrain effects in the Pd NSs. The electronic structure of Pd NSs is modulated by laser irradiation through the balancing between Au-Pd charge transfer and the macros-strain effects. Finite element analysis (FEA) indicates that the lattice of the nanostructures undergoes fast heating and cooling during laser irradiation. The structural evolution mechanism is disclosed by a combined FEA and molecule dynamics (MD) simulation. These results coincide well with the experimental results. The L-AuPd NSs exhibit excellent mass activity and specific activity of 7.44 A mg-1 Pd and 18.70 mA cm -2 toward ethanol oxidation reaction (EOR), 4.3 and 4.4 times higher than the commercial Pd/C. The 2500-cycle accelerated durability (ADT) test confirms the outstanding catalytic stability of the L-AuPd NSs. Density functional theory (DFT) calculations reveal the catalytic mechanism. This unique strategy provides a new pathway to design the ultrathin nanosheet-based materials with excellent performance., (© 2024 Wiley‐VCH GmbH.)

Hexafluoropropylene Oxide Dimer Acid (HFPO-DA or GenX) is a pervasive perfluorinated compound with scant understood toxic effects. Toxicological studies on GenX have been conducted using animal models. To research deeper into the potential toxicity of GenX in humans and animals, we undertook a comprehensive analysis of transcriptome datasets across different species. A rank-in approach was utilized to merge different transcriptome datasets, and machine learning algorithms were employed to identify key genetic mechanisms common among various species and humans. We identified seven genes-TTR, ATP6V1B1, EPHX1, ITIH3, ATXN10, UBXN1, and HPX-as potential variables for classification of GenX-exposed samples, and the seven genes were verified in separate datasets of human, mouse, and rat samples. Bioinformatic analysis of the gene dataset further revealed that mitochondrial function and metabolic processes may be modulated by GenX through these key genes. Our findings provide insights into the underlying genetic mechanisms and toxicological impacts of GenX exposure across different species and offer valuable references for future studies using animal models to examine human exposure to GenX.

The preparation of electrocatalysts with high performance for the ethanol oxidation reaction is vital for the large-scale commercialization of direct ethanol fuel cells. Here, we successfully synthesized a high-performance electrocatalyst of a AuPd alloy with a decreased alloying degree via pulsed laser irradiation in liquids. As indicated by the experimental results, the photochemical effect-induced surficial deposition of Pd atoms, combined with the photothermal effect-induced interdiffusion of Au and Pd atoms, resulted in the formation of AuPd alloys with a decreased alloying degree. Structural characterization reveals that L-AuPd exhibits a lower degree of alloying compared to C-AuPd prepared via the conventional co-reduction method. This distinct structure endows L-AuPd with outstanding catalytic activity and stability in EOR, achieving mass and specific activities as high as 16.01 A mg Pd -1 and 20.69 mA cm -2 , 9.1 and 5.2 times than that of the commercial Pd/C respectively. Furthermore, L-AuPd retains 90.1% of its initial mass activity after 300 cycles. This work offers guidance for laser-assisted fabrication of efficient Pd-based catalysts in EOR.

The research of plant seeds has always been a focus of agricultural and forestry research, and seed identification is an indispensable part of it. With the continuous application of artificial intelligence technology in the field of agriculture, seed identification through computer vision can effectively promote the development of agricultural and forestry wisdom. Data is the foundation of computer vision, but there is a lack of suitable datasets in the agricultural field. In this paper, a seed dataset named LZUPSD is established. A device based on mobile phones and macro lenses was established to acquire images. The dataset contains 4496 images of 88 different seeds. This dataset can not only be used as data for training deep learning models in the computer field, but also provide important data support for agricultural and forestry research. As an important resource in this field, this dataset plays a positive role in modernizing agriculture and forestry., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is a complex disease characterized by a massive accumulation of lipids in the liver, with a continuous progression of simple steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is associated with obesity, insulin resistance, and metabolic syndrome; it is a severe public health risk and is currently the most common liver disease of the world. In addition to the fatty infiltration of the liver in non-alcoholic fatty liver disease patients, the field of liver transplantation faces similar obstacles. NAFLD and NASH primarily involve lipotoxicity, inflammation, oxidative stress, and insulin resistance. However, the precise mechanisms and treatments remain unclear. Therapeutic approaches encompass exercise, weight control, as well as treatments targeting antioxidants and anti-inflammatory pathways. The role of animal models in research has become crucial as a key tool to explore the molecular mechanisms and potential treatments for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Here, we summarized the current understanding of the pathogenesis of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis and discussed animal models commonly used in recent years., Competing Interests: None., (AJTR Copyright © 2024.)

Chemokines and their receptors play an important role in immune monitoring and immune defense during tumor growth and metastasis. However, their prognostic roles in pan-cancer have not been elucidated. In this work, we screened all chemokine receptors in pan-cancer and discovered X-C Motif Chemokine Receptor 1 ( XCR1 ) as a reliable immunological and prognostic biomarker in pan-cancer using bioinformation. The TCGA database served as the foundation for the primary research database analysis in this work. XCR1 was downregulated in tumors. Patients with reduced XCR1 showed worse prognoses and a concomitant decrease in immune cell infiltration (DCs and CD8 + T cells). According to a gene enrichment study, XCR1 enhanced immune system performance by promoting T-cell infiltration through the C-X-C Motif Chemokine Ligand 9 (CXCL9)- C-X-C Motif Chemokine Receptor 3 (CXCR3) axis. In addition, XCR1 is mainly expressed in infiltrated DCs and some malignant cells in tumor tissues. Our data revealed the important role of XCR1 in remodeling the tumor microenvironment and predicting the survival prognosis, which could also be used as a sensitive biomarker for tumor immunotherapy.

The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl 3 ) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl 3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc - axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl 3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y 3+ and its underlying mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Due to its complicated pathophysiology, propensity for metastasis, and poor prognosis, colon cancer is challenging to treat and must be managed with a combination of therapy. Using rolling circle transcription (RCT), this work created a nanosponge therapeutic medication system (AS1411@antimiR-21@Dox). Using the AS1411 aptamer, this approach accomplished targeted delivery to cancer cells. Furthermore, analysis of cell viability, cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) content, and mitochondrial membrane potential (MMP) levels revealed that functional nucleic acid nanosponge drug (FND) can kill cancer cells. Moreover, transcriptomics uncovered a putative mechanism for the FND anti-tumor effect. These pathways, which included mitotic metaphase and anaphase as well as the SMAC-mediated dissociation of the IAP: caspase complexes, were principally linked to the cell cycle and cell death. In conclusion, by triggering cell cycle arrest and apoptosis, the nano-synergistic therapeutic system allowed for the intelligent and effective targeted administration of RNA and chemotherapeutic medicines for colon cancer treatment. The system allowed for payload efficiency while being customizable, targeted, reliable, stable, and affordable., (© 2023. The Author(s).)

Over the past decade, stem cell- and tumor-derived organoids are the most promising models in developmental biology and disease modeling, respectively. The matrix is one of three main elements in the construction of an organoid and the most important module of its extracellular microenvironment. However, the source of the currently available commercial matrix, Matrigel, limits the application of organoids in clinical medicine. It is worth investigating whether the original decellularized extracellular matrix (dECM) can be exploited as the matrix of organoids and improving organoid construction are very important. In this review, tissue decellularization protocols and the characteristics of decellularization methods, the mechanical support and biological cues of extraccellular matrix (ECM), methods for construction of multifunctional dECM and responsive dECM hydrogel, and the potential applications of functional dECM are summarized. In addition, some expectations are provided for dECM as the matrix of organoids in clinical applications., (© 2023 Wiley-VCH GmbH.)

Gestational diabetes mellitus (GDM) is a common disease of pregnancy, but with very limited knowledge of its impact on human milk oligosaccharides (HMOs) in breast milk. This study aimed to explore the lactational changes in the concentration of HMOs in exclusively breastfeeding GDM mothers and the differences between GDM and healthy mothers. A total of 22 mothers (11 GDM mothers vs. 11 healthy mothers) and their offspring were enrolled in the study and the levels of 14 HMOs were measured in colostrum, transitional milk, and mature milk. Most of the HMOs showed a significant temporal trend with decreasing levels over lactation; however, there were some exceptions for 2'-Fucosyllactose (2'-FL), 3-Fucosyllactose (3-FL), Lacto-N-fucopentaose II (LNFP-II), and Lacto-N-fucopentaose III (LNFP-III). Lacto-N-neotetraose (LNnT) was significantly higher in GDM mothers in all time points and its concentrations in colostrum and transitional milk were correlated positively with the infant's weight-for-age Z-score at six months postnatal in the GDM group. Significant group differences were also found in LNFP-II, 3'-Sialyllactose (3'-SL), and Disialyllacto-N-tetraose (DSLNT) but not in all lactational periods. The role of differently expressed HMOs in GDM needs to be further explored by follow-up studies.

Improving the activity and stability of electrocatalysts for the hydrogen evolution reaction (HER) plays an essential role in the practical application of electrochemical water splitting under alkaline conditions. Here, trace Pd-doped Ru nanoparticles have been achieved using the pulsed laser ablation in liquid technology, which exhibit efficient HER catalytic performance. It is evidenced that the Pd doping amount is maintained at a trace level and increases nonlinearly with the concentration of the Pd precursor. Molecular dynamics simulations demonstrate that the trace doping of Pd is due to the slow thermal decomposition rate of the Pd precursor. This work improves the mechanistic explanation of the metal doping induced by liquid-phase laser ablation, which may promote the fabrication and application of advanced laser-based nanostructures.

The data incompleteness of aerosol optical depth (AOD) products and their lack of availability in highly urbanized areas limit their great potential of application in air quality research. In this study, we developed an ensemble machine-learning approach that integrated random forest-based Space Interpolation Model (SIM) and deep neural network-based Time Interpolation Model (TIM) to achieve high spatiotemporal resolution dataset of AOD. The spatial interpolation model first filled the spatial gaps in the Level-2 Himawari-8 hourly AOD product in 0.05° (∼5 km) spatial resolution, while the time interpolation model further improved the temporal resolution to 10 min on its basis. A full-coverage AOD dataset of Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD) and Pearl River Delta (PRD) in 2020 was obtained as a practical implementation. The validation against in-situ AOD observations from AERONET and SONET indicated that this new dataset was satisfactory (R = 0.80), and especially in spring and summer. Overall, our ensemble machine-learning model provided an effective scheme for reconstruction of AOD with high spatiotemporal resolution of 0.05° and 10 min, which may further advance the near-real-time monitoring of air-quality in urban areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Strain engineering of electrocatalysts provides an effective strategy to improve the intrinsic catalytic activity. Here, the defect-rich crystalline/amorphous Pd nanosheet aerogel with hybrid microstrain and lattice strain is synthesized by combining laser irradiation and phosphorus doping methods. The surface strain exhibited by the microstrain and lattice strain shifts the d-band center of the electrocatalyst, enhancing the adsorption of intermediates in the ethanol oxidation reaction and thus improving the catalytic performances. The measured mass activity, specific activity and C1-path selectivity of the Pd nanosheet aerogel are 4.48, 3.06, and 5.06 times higher than those of commercial Pd/C, respectively. These findings afford a new strategy for the preparation of highl activity and C1 pathway selective catalysts and provide insight into the catalytic mechanism of strain-rich heterojunction materials based on tunable surface strain values., (© 2022 Wiley-VCH GmbH.)

Background: The prevalence of malnutrition is unknown in patients with Hirschsprung disease. Undernutrition is associated with poor clinical outcomes. This study aims to describe the nutrition status among patients with Hirschsprung disease at admission., Methods: We retrospectively used data from children with Hirschsprung disease admitted to three pediatric surgery centers in China from January 2016 to December 2020. The weight-for-age z scores (WAZ), height-for-age z scores (HAZ), and body mass index-for-age z scores (BAZ) were calculated as the reference for nutrition risk according to the World Health Organization child growth standards. The nutrition status of enrolled children was described and nutrition risk in each clinical characteristic was compared. The association between nutrition status and clinical outcomes was analyzed using univariate and multivariate logistic regression., Results: A total of 624 patients were included in this study. The mean WAZ, HAZ, and BAZ of all patients was -0.64 ± 1.40, -0.45 ± 1.78, and -0.43 ± 1.50, respectively. Moderate to severe overall undernutrition was 16.3% (102/624). We found that WAZ and BAZ were significantly reduced with the length of aganglionic segments (P = 0.001). Children who had a definitive surgery at 3 years of age or older had significantly lower HAZ (P = 0.001). A multivariate regression model assessing postoperative Hirschsprung-associated enterocolitis showed that the WAZ was one of the independent risk factors (P = 0.001)., Conclusion: Undernutrition is prevalent among children with Hirschsprung disease. Nutrition assessment to identify individuals at risk of undernutrition for further intervention is necessary., (© 2022 The Authors. Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Introduction: Recurrent spontaneous abortion (RSA) is an important reproductive health issue with a serious adverse effect on patients and their families worldwide. The present study evaluated the association between mycoplasma infections and RSA in pregnant patients., Methodology: This case-control study included 107 patients with RSA (study group) and 89 normal pregnant women who had planned abortions (control group) between March 2019 and February 2021. Cervical swabs were assessed for the presence of Mycoplasma hominis and Ureaplasma urealyticum by Microtiter Plate Hybridization assay., Results: A total of 52 (48.6%) patients from the study group and 13 (14.6%) patients from control group were positive for mycoplasmas. The presence of M. hominis (29.9% vs. 9%; p = 0.024), U. urealyticum (18.7% vs. 5.6%; p = 0.015) and the co-infection of M. hominis/U. urealyticum (14% vs. 1%; p = 0.032) were significantly higher in the study group. Multivariate analysis revealed that pelvic pain (Odds Ratio [OR] = 3.42; 95% CI = 0.40-3.65; p = 0.015), dysuria (OR = 4.12; 95% CI = 1.59-8.23; p = 0.021), and urinary tract infection (OR = 3.97; 95% CI = 1.52-4.17; p = 0.032) were independent predictors of RSA., Conclusions: The high prevalence of M. hominis/U. urealyticum in this study reveals a significant association with RSA. Pelvic pain and Mycoplasma infections are independent predictors of RSA., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Jie Yu, Shanshan Yu, Liye Zhu, Xuan Sun, Boqi Lu, Jian Li, Yuecheng Hu, Peijun Li.)

Background and Study Aims: The ability to predict severe acute pancreatitis (SAP) at an early stage is crucial for reducing the associated complications and mortality. In this study, we compared the ratio of red cell distribution width to albumin (RDW-to-ALB) using predictive scoring systems, such as the Ranson score, BISAP, and MCTSI, to develop a simple and accurate method of predicting SAP., Patients and Methods: We included 212 patients with mild acute pancreatitis (MAP) and 89 with SAP between January 2013 and December 2018. The differences in the general characteristics and biochemical analysis as well as the various predictive scores were compared between the two groups. We evaluated the sensitivity and specificity between the RDW-to-ALB ratio, RDW, ALB, and multiple predictive scores in patients with early acute pancreatitis (AP) by using the receiver operating characteristic (ROC) curve., Results: The RDW-to-ALB ratio (%) of patients with SAP was higher than that of patients with MAP (0.43 ± 0.08 vs. 0.32 ± 0.04, p < 0.001). Patients with SAP had higher Ranson, BISAP, and MCTSI scores than those with MAP. The ROC curve revealed that, when the RDW-to-ALB ratio (%) was >0.36, the sensitivity and specificity of the predicted SAP were 80.0% and 80.7%, respectively. Further statistical analysis found that the RDW-to-ALB ratio and Ranson, BISAP, and MCTSI scores were consistent in predicting SAP effectiveness (P > 0.05)., Conclusions: The RDW-to-ALB ratio has a promising predictive power for SAP, and its effectiveness is comparable with those of Ranson, BISAP, and MCTSI scores., Competing Interests: Conflict of interest statement All authors declare to have no conflicts of interest directly or indirectly related to the manuscript contents., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

In recent years, China has been facing severe ozone (O 3 ) pollution, which poses a remarkable threat to human health. Most estimation methods only provide ozone products at a relatively coarse resolution, such as 5 km, but high-resolution ozone data are essential for ozone pollution prevention and control. To this end, we proposed a new framework for estimating ozone concentrations at 300 m resolution in China based on Landsat 8 infrared (IR) bands and meteorological data using a deep forest (DF) model. DF combines the excellent performance of tree integration with the expressive power of hierarchical distributed representations of neural networks. The accuracy and mapping results of DF are considerably better than some widely used machine learning methods (generalized regression neural regression network and random forest). The sample-based cross-validation (CV), station-based CV, time-based CV, and extrapolation validation show that the estimations of DF are in high agreement with the station observations with determination coefficient values of 0.938, 0.926, 0.687, and 0.660, respectively. The proposed method was used to analyze the spatial and temporal ozone variations at fine scales in three typical Chinese cities (Beijing, Wuhan and Guangzhou), where the mean ozone concentrations during the polluted season are consistent with the land use and urban heat island distribution. The rationality of ozone estimates was verified, and the advantages of high-resolution mapping was demonstrated by comparing the monitoring data from municipal controlling stations in Beijing, 10 km ozone products, and satellite images. Our product can represent spatial details and locate local pollution sources, such as temples. The proposed method has important implications for the fine-scale monitoring of ozone pollution., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Reducing the loose-layer-to-dense-layer ratio in PEO coatings on aluminum and its alloys is the key to improving their corrosion resistance and expanding their applications in the aerospace industry and other fields. In this paper, we describe the discharge evolution during the PEO process in exhaustive detail and report the appearance of a novel "chain-like" discharge for the first time. We investigated the microstructure and composition of PEO coatings using a scanning electron microscope (SEM) equipped with an energy-dispersive spectrometer (EDS) and an X-ray diffractometer (XRD). The results reflected that the coating composition changed from amorphous Al 2 O 3 to crystalline γ-Al 2 O 3 and α-Al 2 O 3 phases with the evolution of the plasma spark discharge state. We evaluated the electrochemical behavior of the coatings using a potentiodynamic polarization curve and electrochemical impedance spectroscopy (EIS) in 3.5 wt.% NaCl solution. Under "chain-like" discharge, the i corr of the coating on Al was 8.564 × 10 -9 A∙cm -2 , which was five orders of magnitude lower than that of the sample without the PEO coating. Moreover, we evaluated the adhesion strength of the coatings at different stages using a pull-off test. The adhesion strength of the PEO coatings at stage V reached 70 MPa. Furthermore, the high content of α-Al 2 O 3 increased the hardness of the coating to 2000 HV. Therefore, the "chain-like" discharge promoted the formation of a single dense layer with 2.8% porosity and that demonstrated excellent properties. We also propose a mechanism to explain the influence of the plasma spark discharge state on the microstructure and composition of the PEO coatings.

Cell-specific aptamers are a promising emerging player in the field of disease therapy. This paper reviews the multidimensional research progress made in terms of their classification, modification, and application. Based on the target location of cell-specific aptamers, it is defined and classified cell-specific aptamers into three groups including aptamers for cell surface markers, aptamers for intracellular components, and aptamers for extracellular components. Moreover, the modification methods of aptamers to achieve improved stability and affinity are concluded. In addition, recent advances in the application of cell-specific aptamers are discussed, mainly focusing on the increasing research attraction of cell state improving helpers and cell recruitment mediators in the improvement of cellular microenvironments to achieve successful disease therapy. This review also highlights 11 types of clinical aptamer drugs. Finally, the challenges and future directions of potential clinical applications are presented. In summary, we believe that cell-specific aptamers are promising drugs in disease therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We conduct the first 4D-Var inversion of NH 3 accounting for NH 3 bi-directional flux, using CrIS satellite NH 3 observations over Europe in 2016. We find posterior NH 3 emissions peak more in springtime than prior emissions at continental to national scales, and annually they are generally smaller than the prior emissions over central Europe, but larger over most of the rest of Europe. Annual posterior anthropogenic NH 3 emissions for 25 European Union members (EU25) are 25% higher than the prior emissions and very close (<2% difference) to other inventories. Our posterior annual anthropogenic emissions for EU25, the UK, the Netherlands, and Switzerland are generally 10%-20% smaller than when treating NH 3 fluxes as uni-directional emissions, while the monthly regional difference can be up to 34% (Switzerland in July). Compared to monthly mean in-situ observations, our posterior NH 3 emissions from both schemes generally improve the magnitude and seasonality of simulated surface NH 3 and bulk NH x wet deposition throughout most of Europe, whereas evaluation against hourly measurements at a background site shows the bi-directional scheme better captures observed diurnal variability of surface NH 3 . This contrast highlights the need for accurately simulating diurnal variability of NH 3 in assimilation of sun-synchronous observations and also the potential value of future geostationary satellite observations. Overall, our top-down ammonia emissions can help to examine the effectiveness of air pollution control policies to facilitate future air pollution management, as well as helping us understand the uncertainty in top-down NH 3 emissions estimates associated with treatment of NH 3 surface exchange., (© 2022. The Authors.)

Introduction: miRNA-derivative clinical nucleotide drugs (mdCNDs) effectively treat several diseases, with numerous undergoing clinical trials. In early-stage trials in disease therapeutics, such as malignant pleural mesothelioma and hepatic virus C infection, mdCND's therapeutic potency is undeniably good for effectiveness and safety., Areas Covered: Fifteen mdCNDs undergoing clinical trials are introduced in this review. MiRNA modifications methods have been summarized, including phosphorothioate, cholesterol, locked nucleic acid, 2'-O-methyl, N,N-diethyl-4-(4-nitronaphthalen1-ylazo)-phenylamine modifications, and many more. Moreover, delivery systems, including self-assembled, inorganic ions nanoparticles, exosomes, and lipid-based nanosystems for mdCNDs targeted delivery, are presented. Among that, EnGeneIC, N-Acetylgalactosamine, liposomal nanoparticles, and cholesterol-conjugated for mdCNDs delivery are currently undergoing clinical trials. The pH, light, temperature, redox-responsive, enzyme, and specific-substance modes to trigger the release of miRNAs to target sites on-demand and the prospects of mdCNDs are discussed in this review., Expert Opinion: mdNCDs are one type of promising clinical drugs, however, it is still in the infancy. During the development process, it is imperative to advance in modifying miRNAs, especially at the 5'-end, to enhance targetability and stability against nucleases, develop a stimuli-responsive mode to control the release of mdCNDs to tissue cell-type-specific sites.

Exosomes are regarded as a promising biomarker for the noninvasive diagnosis and treatment of diseases. The value of exosomes for medical research has promoted the search for a fast, efficient, and sensitive detection method. This study reported a sandwich-based evanescent wave fluorescent biosensor (S-EWFB) for exosome detection. A two-step strategy was implemented to take advantages of the simple binding of fluorescent probes with exosomes via the hydrophobic interaction between the cholesteryl and phospholipid bilayer membrane, as well as real-time detection on an evanescent wave liquid-solid interface based on CD63 aptamer-specific capture to form an exosome@fluorescence probe/aptamer sandwich structure. The one-to-many connection between exosomes and signal molecules and the aptamer-modified evanescent wave optical fiber detection platform reduced the detection limit of exosomes to 7.66 particles/mL, with a linear range of 47.5-4.75 × 10 6 particles/mL. The entire detection process was simple, rapid, and real-time and lasted about 1 h while requiring no separation and purification. Additionally, this platform showed excellent surface regeneration capability and exhibited good performance during the analysis of tumor and non-tumor-derived exosomes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Gold (Au) can be used as an ideal metal electrocatalyst for ethanol and glucose oxidation reactions due to its high performance-to-cost ratio. In this paper, the Au aerogel with high-index facets was synthesized by using the laser ablation in liquid technology, which can improve the electrocatalytic activity of Au. The as-prepared Au aerogel showed excellent mass activity and specific activity toward ethanol oxidation reaction, which are 4.6 times and 2.1 times higher than Au/C, respectively. The 3D porous nature and rich defect of the Au aerogel provide more active sites. In addition, the high-index facets with under-coordinated atoms enhance the adsorption of ethanol and glucose molecules, thus improving the intrinsic catalytic activity of Au aerogel. The effect of high-index facets has also been investigated by density functional theory calculations. Furthermore, the Au aerogels also show good electrocatalytic activity and stability toward glucose oxidation reaction. These results are conducive to promote the practical application of Au in electrocatalysis., (© 2022 IOP Publishing Ltd.)

CircRNA is a type of covalently closed circular RNA molecule that serves as a potential biomarker for the disease early diagnosis and clinical researches. To achieve living cell imaging of specific circRNA, we developed a novel graphene oxide (GO)-based catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) signal dual amplification system (GO-CHA-HCR, abbreviated GO-AR) for circ-Foxo3 imaging in living cells. The developed system consists of four types of designed hairpin DNA HP1, HP2, H1, and fluorophore-labeled H2, which are absorbed on the GO nanosheets surface leading to fluorescence quenching. In the presence of circ-Foxo3, the CHA cycle was initiated to form a hybrid chain with split fragments, which triggered the HCR cycle to generate dsDNA nanowires that were then released from GO. This process recovered the quenched fluorescence, realizing two-stage signal amplification. The GO-AR system effectively improved the signal-to-noise ratio compared to the traditional GO-CHA and GO-HCR detection system. The detection limit of circ-Foxo3 was as low as 15 pM with excellent sensitivity and selectivity. In addition, the enzyme-free sensing system was successfully applied in living cell circRNA imaging and serum circRNA detection, indicating its high potential in clinical diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ochratoxin A (OTA) is one of the mycotoxins, which widely pollutes food systems and seriously threatens human health. OTA's target organ is the kidney. Exosome, as one of the extracellular vesicles, could be secreted by all kinds of cells. It contains different proteins, nucleic acid, and lipid, which are decided by their donor cells and could be uptake by the recipient cells, release their contents, and affect the recipient cell's life activity. In this study, a 24 h-treatment with 5 μM OTA was found to significantly reduce the cell viability of HEK293 cells and meanwhile to provide a sufficient quantity of exosomes, thus this concentration and time were selected for subsequent experiments. In addition, exosomes extracted by ultracentrifugation had higher purity, fewer impurities, and uniform morphology than that by the ExoQuick-TC kit. Furthermore, these exosomes increased ROS levels and decreased mitochondrial membrane potential in HEK293 cells. By RNA-seq, the cytotoxicity mechanisms induced by OTA-treated HEK293 cell-derived exosomes (EXO-OTA) and OTA were mainly the metabolism of proteins and the cell cycle respectively. Also, it proved that exosomes deliver partial OTA-induced cytotoxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Epicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro., (© 2021. The Author(s).)

Metabolic syndrome (MetS) is a set of complex, chronic inflammatory conditions that are characterized by central obesity and associated with an increased risk of cardiovascular diseases. In recent years, microRNAs (miRNAs) have become an important type of endocrine factors, which play crucial roles in maintaining energy balance and metabolic homeostasis. However, its unfavorable properties such as easy degradation in blood and off-target effect are still a barrier for clinical application. Nanosystem based delivery possess strong protection, high bioavailability and control release rate, which is beneficial for success of gene therapy. This review first describes the current progress and advances on miRNAs associated with MetS, then provides a summary of the therapeutic potential and targets of miRNAs in metabolic organs. Next, it discusses recent advances in the functionalized development of classic delivery systems (exosomes, liposomes and polymers), including their structures, properties, functions and applications. Furthermore, this work briefly discusses the intelligent strategies used in emerging novel delivery systems (selenium nanoparticles, DNA origami, microneedles and magnetosomes). Finally, challenges and future directions in this field are discussed provide a comprehensive overview of the future development of targeted miRNAs delivery for MetS treatment. With these contributions, it is expected to address and accelerate the development of effective NA delivery systems for the treatment of MetS.

Mycotoxins contaminate all types of food and feed, threatening human and animal health through food chain accumulation, producing various toxic effects. Increasing attention is being focused on the molecular mechanism of mycotoxin-induced toxicity in all kinds of in vivo and in vitro models. Epigenetic alterations, including DNA methylation, non-coding RNAs (ncRNAs), and protein post-translational modifications (PTMs), were identified as being involved in various types of mycotoxin-induced toxicity. In this review, the emphasis was on summarizing the epigenetic alterations induced by mycotoxin, including aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone (ZEA), fumonisin B1 (FB1), and deoxynivalenol (DON). This review summarized and analyzed the roles of DNA methylation, ncRNAs, and protein PTMs after mycotoxin exposure based on recently published papers. Moreover, the main research methods and their deficiencies were determined, while some remedial suggestions are proposed. In summary, this review helps to understand better the epigenetic alterations induced by the non-genotoxic effects of mycotoxin., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nucleic acid-based hydrogels that integrate intrinsic biological properties of nucleic acids and mechanical behavior of their advanced assemblies are appealing bioanalysis and biomedical studies for the development of new-generation smart biomaterials. It is inseparable from development and incorporation of novel structural and functional units. This review highlights different functional units of nucleic acids, polymers, and novel nanomaterials in the order of structures, properties, and functions, and their assembly strategies for the fabrication of nucleic acid-based hydrogels. Also, recent advances in the design of multifunctional and stimuli-responsive nucleic acid-based hydrogels in bioanalysis and biomedical science are discussed, focusing on the applications of customized hydrogels for emerging directions, including 3D cell cultivation and 3D bioprinting. Finally, the key challenge and future perspectives are outlined., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Adoptive natural killer (NK) cell transfer has been demonstrated to be a promising immunotherapy approach against malignancies, but requires the administration of sufficient activated cells for treatment effectiveness. However, the paucity of clinical-grade to support the for large-scale cell expansion limits its feasibility. Here we developed a feeder-based NK cell expansion approach that utilizes OX40L armed NK-92 cell with secreting neoleukin-2/15 (Neo-2/15), a hyper-stable mimetic with a high affinity to IL-2Rβγ. The novel feeder cells (NK92-Neo2/15-OX40L) induced the expansion of NK cells with a 2180-fold expansion (median; 5 donors; range, 1767 to 2719) after 21 days of co-culture without added cytokines. These cells were highly cytotoxic against Raji cells and against several solid tumors in vivo . Mechanistically, NK92-Neo2/15-OX40L induced OX40 and OX40L expression on expanded NK cells and promoted the OX40-OX40L positive feedback loop, thus boosting NK cell function. Our data provided a novel NK cell expansion mechanism and insights into OX40-OX40L axis regulation of NK cell expansion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Sun, Qian, Zhu, Ta, Wang, Zheng, Guo and Liu.)

Functional nucleic acid (FNA) nanotechnology is an interdisciplinary field between nucleic acid biochemistry and nanotechnology that focuses on the study of interactions between FNAs and nanomaterials and explores the particular advantages and applications of FNA nanomaterials. With the goal of building the next-generation biomaterials that combine the advantages of FNAs and nanomaterials, the interactions between FNAs and nanomaterials as well as FNA self-assembly technologies have established themselves as hot research areas, where the target recognition, response, and self-assembly ability, combined with the plasmon properties, stability, stimuli-response, and delivery potential of various nanomaterials can give rise to a variety of novel fascinating applications. As research on the structural and functional group features of FNAs and nanomaterials rapidly develops, many laboratories have reported numerous methods to construct FNA nanomaterials. In this Review, we first introduce some widely used FNAs and nanomaterials along with their classification, structure, and application features. Then we discuss the most successful methods employing FNAs and nanomaterials as elements for creating advanced FNA nanomaterials. Finally, we review the extensive applications of FNA nanomaterials in bioimaging, biosensing, biomedicine, and other important fields, with their own advantages and drawbacks, and provide our perspective about the issues and developing trends in FNA nanotechnology., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Fine particulate matter (PM 2.5 ) has attracted extensive attention because of its baneful influence on human health and the environment. However, the sparse distribution of PM 2.5 measuring stations limits its application to public utility and scientific research, which can be remedied by satellite observations. Therefore, we developed a Geo-intelligent long short-term network (Geoi-LSTM) to estimate hourly ground-level PM 2.5 concentrations in 2017 in Wuhan Urban Agglomeration (WUA). We conducted contrast experiments to verify the effectiveness of our model and explored the optimal modeling strategy. It turned out that Geoi-LSTM with TOA reflectance, meteorological conditions, and NDVI as inputs performs best. The station-based cross-validation R 2 , root mean squared error and mean absolute error are 0.82, 15.44 μg/m 3 , 10.63 μg/m 3 , respectively. Based on model results, we revealed spatiotemporal characteristics of PM 2.5 in WUA. Generally speaking, during the day, PM 2.5 concentration remained stable at a relatively high level in the morning and decreased continuously in the afternoon. While during the year, PM 2.5 concentrations were highest in winter, lowest in summer, and in-between in spring and autumn. Combined with meteorological conditions, we further analyzed the whole process of a PM 2.5 pollution event. Finally, we discussed the loss in removing clouds-covered pixels and compared our model with several popular models. Overall, our results can reflect hourly PM 2.5 concentrations seamlessly and accurately with a spatial resolution of 5 km, which benefits PM 2.5 exposure evaluations and policy regulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aflatoxin B1 (AFB1) is widely distributed in nature and is confirmed to be the most toxic of all the aflatoxins, whose predominant metabolism site is the liver. As a well-studied and vital mode of epigenetic modifications, aberrant methylation of the promoters in eukaryotic cells may cause the silence of essential genes, affecting their related transcriptional pathways and ultimately leading to the development of disease and cancers. This study investigated the mechanisms of AFB1-induced hepatotoxicity in S phase-arrested L02 cells using single-cell RNA-seq and single-cell reduced representation bisulfite sequencing (RRBS). AFB1 induced apoptosis and cell cycle S phase arrest, reduced mitochondrial membrane potential (ΔΨm), and increased reactive oxygen species (ROS) generation, as well as the DNA methylation level. Hepatotoxicity mechanism patterns induced by AFB1 in S phase-arrested L02 cells were revealed by combining single-cell RNA-seq with single-cell RRBS analysis, in which DNA methylation played a role via regulating the gonadotropin-releasing hormone receptor pathway, the Wnt signaling pathway, and the TGF-beta signaling pathway. Moreover, a novel strategy for precision toxicology exploration was obtained, including the selection of target cells, multi-group non-directional sequencing, and pathway analysis.

Aflatoxin B1 (AFB1) is a known carcinogen found in contaminated food and designated by the World Health Organization as a class I carcinogenic substance. AFB1 presents with carcinogenicity, teratogenicity, and mutagenicity, and the liver is the human organ most susceptible to AFB1. Zinc (Zn), which is one of the essential nutrient elements that could protect the cells from biological toxins, heavy metals, hydrogen peroxide, metal chelators and radiation, is assessed in this study for its potential to alleviate AFB1-induced cytotoxicity. Samples were divided into three groups, namely CK, AFB1, and AFB1+Zn. Protein expressions were analyzed by two-way electrophoresis combined with flight mass spectrometry, with 41 differentially expressed proteins identified in the results, mainly related to oxidative stress, cell apoptosis, DNA damage, and energy metabolism. Zn was found to regulate the expression of peroxidases (peroxiredoxin-1, peroxiredoxin-5, peroxiredoxin-6) to relieve AFB1-induced oxidative stress. Moreover, Zn could decrease the expression of pro-apoptotic genes (cleaved-caspase-3, caspase-9, and Bax) and increase the expression of anti-apoptotic genes (Bcl-2 and Bcl-xl) to alleviate the cell apoptosis induced by AFB1. In addition, AFB1 reduced intracellular ATP levels, whereas Zn supplementation boosted ATP levels and maintained homeostasis and a steady state of cellular energy metabolism by modulating AMPK-ACC phosphorylation levels, while many zinc finger proteins changed after AFB1 treatment. These results, therefore, indicate that Zn could alleviate AFB1-induced cytotoxicity by changing the expressions of zinc finger proteins in liver hepatocellular carcinoma (HepG2 cells)., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

In this work, a duplex-specific nuclease (DSN)-resistant triplex-helix DNA nanoswitch was designed for assays of single-base differentiation of the let-7a family in lung cancer cells. Initially, although a 10-bp duplex stem in the nanoswitch was cleaved to pieces, a 10-bp triplex stem was resistant to DSN. Consequently, a triple-stranded DNA structure resistant to DSN was obtained. The pH-dependent formation of the triplex structure then produced the pH-related nanoswitch/miRNA hybrid, and the metastable nanoswitch generated an obvious signal increase at pH 6.8. Surprisingly, the pH condition at 6.8 for the best nanoswitch/miRNA hybrid is consistent with the optimal DSN catalysis, which paves the way for a first-rank DSN signal amplification (DSNSA) strategy for the single-base selective capacity of the homologous let-7a family with a limit of detection of 0.26 pM. The cyclic strategy based on the DSN-mediated triplex-helix DNA nanoswitch was verified in lung cancer cell samples and exhibited better discriminatory ability without user-unfriendly nucleotide modification or extra probe-mediated assistance, showing excellent potential for application in biomedical sensing and clinical diagnosis. Graphical abstract Based on the discovery that a triple-helix DNA nanoswitch is resistant to DSN and that the nanoswitch/miRNA hybridization was pH-related, pH at 6.8, which is suitable for the optimal nanoswitch/miRNA hybrid and DSN catalysis, reinforced the DSNSA strategy for the single-base selective capacity of the homologous let-7a family with a limit of detection of 0.26 pM.

Precision toxicology evaluates the toxicity of certain substances by isolating a small group of cells with a typical phenotype of interest followed by a single cell sequencing-based analysis. In this in vitro attempt, ochratoxin A (OTA), a typical mycotoxin and food contaminant, is found to induce G0/G1 phase cell cycle arrest in human renal proximal tubular HKC cells at a concentration of 20 μM after a 24h-treatment. A small number of G0/G1 phase HKC cells are evaluated in both the presence and absence of OTA. These cells are sorted with a flow cytometer and subjected to mRNA and DNA methylation sequencing using Smart-Seq2 and single-cell reduced-representation bisulfite sequencing (scRRBS) technology, respectively. Integrated analysis of the transcriptome and methylome profiles reveals that OTA causes abnormal expression of the essential genes that regulate G1/S phase transition, act as signal transductors in G1 DNA damage checkpoints, and associate with the anaphase-promoting complex/cyclosome. The alteration of their DNA methylation status is a significant underlying epigenetic mechanism. Furthermore, Notch signaling and Ras/MAPK/CREB pathways are found to be suppressed by OTA. This attempt at precision toxicology paves the way for a deeper understanding of OTA toxicity and provides an innovative strategy to researchers in the toxicology and pharmacology field.

BACKGROUND Ginkgo biloba extract (EGb761), a standard extract of the Chinese traditional medicine Ginkgo biloba, plays an anti-tumor role in various cancers. However, whether EGb761 is involved in the invasion and metastasis of gastric cancer remains unclear. MATERIAL AND METHODS In the current study, cell viability assay, Western blotting, wound-healing assay, Transwell invasion assay, and orthotopic transplantation model were performed to explore the effects of EGb761 on gastric cancer. RESULTS In vitro, the results showed that EGb761 suppressed the proliferation of gastric cancer cells in a dose-dependent manner. Furthermore, the migration and invasiveness were weakened and the protein levels of p-ERK1/2, NF-kappaB P65, NF-kappaB p-P65, and MMP2 were decreased by EGb761 or U0126 (an inhibitor of ERK signaling pathway) exposure in gastric cancer cells. Moreover, the combined treatment with EGb761 and U0126 significantly inhibited ERK, NF-kappaB signaling pathway, and the expression of MMP2 than those of single drug. In vivo, EGb761 inhibited the tumor growth and hepatic metastasis of gastric cancer in the mouse model. Results of immunohistochemistry indicated that the expression of ERK1/2, NF-kappaB P65 and MMP2 were decreased by EGb761 in the tumor tissues. CONCLUSIONS EGb761 plays a vital role in the suppression of metastasis and ERK/NF-kappaB signaling pathway in gastric cancer.

Two plasma electrolytic oxidation (PEO) coatings were fabricated on LD7 aluminum alloy in oxalate and dihydrogen phosphate electrolytes. The phase composition, morphology and corrosion resistant of the two PEO coatings were analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and electrochemical test. Both PEO coatings presented three-layer structure, i.e., a porous outer layer, a relative dense intermediate layer with nano-size micro-pores and an inner nanoscale barrier layer at the coating/substrate interface. It was found that the porosity of the coating in oxalate electrolyte was lower than that in dihydrogen phosphate electrolyte. The small quantity of the nanosize micro-pores might be attributed to the appearance of "soft spark" in oxalate electrolyte, whereas the large number of micro-pores and cracks should be related to intensive micro-discharges in dihydrogen phosphate electrolyte during PEO process. The compact coating with nano-size micropores in oxalate electrolyte provided better protection than that in dihydrogen phosphate electrolyte from corrosion.

Ochratoxin A (OTA) is a secondary metabolite of fungi such as Aspergillus ochraceus, A. niger and A. carbonarius, Penicillium verrucosum, and various other Penicillium, Petromyces, and Neopetromyces species. Various foods can be contaminated with OTA, potentially causing several toxic effects such as nephrotoxicity, hepatotoxicity and neurotoxicity. Typically, OTA is excreted by organic anion transporters (OATs). There is no research indicating organic cation transporters (OCTs) are involved in OTA nephrotoxicity. In our study, NRK-52E cells and rats were treated with OTA. OTA changed the expression of OCT1, OCT2 and OCT3 in NRK-52E cells and rat kidneys. TEA alleviated OTA-induced cell death, apoptosis, and DNA damage, and increased ROS. The OCT2 knockout cell line was constructed by the CRISPR/Cas 9 system. OCT2 knockout did not change the gene expression of OCT1, OAT1 and OAT3. OCT2 knockout alleviated the increase of Caspase 3 and CDK1 induced by OTA, leading to a reduction of apoptosis. In addition, OCT2 overexpression increased cell toxicity and expression of Caspase 3. In short, our findings indicate that OCT2 knockout possibly mitigate OTA-induced apoptosis by preventing the increase of Caspase 3 and CDK1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mitochondrial pyruvate carrier 1 (MPC1) is a component of the MPC1/MPC2 heterodimer that facilitates the transport of pyruvate into mitochondria. Pyruvate plays a central role in carbohydrate, fatty, and amino acid catabolism. The present study examined epididymal white adipose tissue (eWAT) and intrascapular brown adipose tissue (iBAT) from MPC1 ±  mice following 24 weeks of feeding, which indicated low energy accumulation as evidenced by low body and eWAT weight and adipocyte volume. To characterize molecular changes in energy metabolism, we analyzed the transcriptomes of the adipose tissues using RNA-Sequencing (RNA-Seq). The results showed that the fatty acid oxidation pathway was activated and several genes involved in this pathway were upregulated. Furthermore, qPCR and western blotting indicated that numerous genes and proteins that participate in lipolysis were also upregulated. Based on these findings, we propose that the energy deficiency caused by reduced MPC1 activity can be alleviated by activating the lipolytic pathway., Competing Interests: The authors declare there are no competing interests.

Ground and satellite observations show that air pollution regulations in the United States (US) have resulted in substantial reductions in emissions and corresponding improvements in air quality over the last several decades. However, large uncertainties remain in evaluating how recent regulations affect different emission sectors and pollutant trends. Here we show a significant slowdown in decreasing US emissions of nitrogen oxides (NO x ) and carbon monoxide (CO) for 2011-2015 using satellite and surface measurements. This observed slowdown in emission reductions is significantly different from the trend expected using US Environmental Protection Agency (EPA) bottom-up inventories and impedes compliance with local and federal agency air-quality goals. We find that the difference between observations and EPA's NO x emission estimates could be explained by: ( i ) growing relative contributions of industrial, area, and off-road sources, ( ii ) decreasing relative contributions of on-road gasoline, and ( iii ) slower than expected decreases in on-road diesel emissions., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Aflatoxin B1 (AFB1) is widely distributed in nature, especially in a variety of food commodities. It is confirmed to be the most toxic of all the aflatoxins. The toxicity of AFB1 has been well investigated, and it may result in severe health problems including carcinogenesis, mutagenesis, growth retardation, and immune suppression. Epigenetic modifications including DNA methylation, histone modifications and regulation of non-coding RNA play an important role in AFB1-induced disease and carcinogenesis. To better understand the evidence for AFB1-induced epigenetic alterations and the potential mechanisms of the toxicity of AFB1, we conducted a review of published studies of AFB1-induced epigenetic alterations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this review, we introduce a new concept, precision toxicology: the mode of action of chemical- or drug-induced toxicity can be sensitively and specifically investigated by isolating a small group of cells or even a single cell with typical phenotype of interest followed by a single cell sequencing-based analysis. Precision toxicology can contribute to the better detection of subtle intracellular changes in response to exogenous substrates, and thus help researchers find solutions to control or relieve the toxicological effects that are serious threats to human health. We give examples for single cell isolation and recommend laser capture microdissection for in vivo studies and flow cytometric sorting for in vitro studies. In addition, we introduce the procedures for single cell sequencing and describe the expected application of these techniques to toxicological evaluations and mechanism exploration, which we believe will become a trend in toxicology.

We present a dual-isothermal cascade strategy assisted by a lateral flow peptide nucleic acid biosensor for point-of-care detection of urinary microRNAs without a temperature protocol and complex instruments. The proposed assay is expected to be of great promise for bladder cancer diagnosis and point-of-care diagnostics.