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Deriving rainfall thresholds is one of the most convenient and effective empirical methods for formulating landslide warnings. The previous rainfall threshold models only considered the threshold values for areas with landslide data. This study focuses on obtaining a threshold for each single landslide via the geostatistical interpolation of historical landslide–rainfall data. We collect the occurrence times and locations of landslides, along with the hourly rainfall data, for Dazhou. We integrate the short-term and long-term rainfall data preceding the landslide occurrences, categorizing them into four groups for analysis: 1 h–7 days (H1–7), 12 h–7 days (H12–D7), 24 h–7 days (H24–D7), and 72 h–7 days (H72–D7). Then, we construct a rainfall threshold distribution map based on the 2014–2020 data by means of Kriging interpolation. This process involves applying different splitting coefficients to distinguish the landslides triggered by short-term versus long-term rainfall. Subsequently, we validate these thresholds and splitting coefficients using the dataset for 2021. The results show that the best splitting coefficients for H1–D7, H12–D7, H24–D7, and H72–D7 are around 0.19, 0.52, 0.55, and 0.80, respectively. The accuracy of the predictions increases with the duration of the short-term rainfall, from 48% for H1–D7 to 67% for H72–D7. The performance of these threshold models indicates their potential for practical application in the sustainable development of geo-hazard prevention. Finally, we discuss the reliability and applicability of this method by considering various factors, including the influence of the interpolation techniques, data quality, weather forecast, and human activities. [ABSTRACT FROM AUTHOR]

Cancer vaccines hold great potential for clinical cancer treatment by eliciting T cell‐mediated immunity. However, the limited numbers of antigen‐presenting cells (APCs) at the injection sites, the insufficient tumor antigen phagocytosis by APCs, and the presence of a strong tumor immunosuppressive microenvironment severely compromise the efficacy of cancer vaccines. Trained innate immunity may promote tumor antigen‐specific adaptive immunity. Here, a personalized cancer vaccine is developed by engineering the inactivated probiotic Escherichia coli Nissle 1917 to load tumor antigens and β‐glucan, a trained immunity inducer. After subcutaneous injection, the cancer vaccine delivering model antigen OVA (BG/OVA@EcN) is highly accumulated and phagocytosed by macrophages at the injection sites to induce trained immunity. The trained macrophages may recruit dendritic cells (DCs) to facilitate BG/OVA@EcN phagocytosis and the subsequent DC maturation and T cell activation. In addition, BG/OVA@EcN remarkably enhances the circulating trained monocytes/macrophages, promoting differentiation into M1‐like macrophages in tumor tissues. BG/OVA@EcN generates strong prophylactic and therapeutic efficacy to inhibit tumor growth by inducing potent adaptive antitumor immunity and long‐term immune memory. Importantly, the cancer vaccine delivering autologous tumor antigens efficiently prevents postoperative tumor recurrence. This platform offers a facile translatable strategy to efficiently integrate trained immunity and adaptive immunity for personalized cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The durable response rate to immune checkpoint blockade such as anti-programmed cell death-1 (PD-1) antibody remains relatively low in hepatocellular carcinoma (HCC), mainly depending on an immunosuppressive microenvironment with limited number of CD8+ T cells, especially stem-like CD8+ T cells, in tumor tissues. Here we develop engineered microparticles (MPs) derived from alpha-fetoprotein (AFP)-overexpressing macrophages to load resiquimod (R848@M2pep-MPsAFP) for enhanced anti-PD-1 therapy in HCC. R848@M2pep-MPsAFP target and reprogram immunosuppressive M2-like tumor-associated macrophages (TAMs) into M1-like phenotype. Meanwhile, R848@M2pep-MPsAFP-reprogrammed TAMs act as antigen-presenting cells, not only presenting AFP antigen to activate CD8+ T cell-mediated antitumor immunity, but also providing an intra-tumoral niche to maintain and differentiate stem-like CD8+ T cells. Combination immunotherapy with anti-PD-1 antibody generates strong antitumor immune memory and induces abundant stem-like CD8+ T cell proliferation and differentiation to terminally exhausted CD8+ T cells for long-term immune surveillance in orthotopic and autochthonous HCC preclinical models in male mice. We also show that the R848-loaded engineered MPs derived from macrophages overexpressing a model antigen ovalbumin (OVA) can improve anti-PD-1 therapy in melanoma B16-OVA tumor-bearing mice. Our work presents a facile and generic strategy for personalized cancer immunotherapy to boost anti-PD-1 therapy. Tumor associated macrophages (TAMs) contribute to the immunosuppressive tumor microenvironment, including hepatocellular carcinoma (HCC). Here the authors show that macrophage-derived microparticles modified with a M2-like macrophage targeting peptide and loaded with the TLR7/8 agonist resiquimod reprogram TAMs from immunosuppressive to inflammatory, promoting anti-tumor immune responses in preclinical HCC models. [ABSTRACT FROM AUTHOR]

Classical J2 plasticity theory is the most popular continuum plasticity model. However, this plasticity theory is inapplicable for some metals due to the tension/compression asymmetry behavior. According to our previous study, the tension and compression mechanical response of laser-solid-formed Ti–6Al–4V alloy was significantly different in not only yield stress but also work hardening rate. In this study, effects of temperature and strain rate on the tension/compression asymmetry behavior of laser-solid-formed Ti-6Al-4V alloy were analyzed. Through mechanism discussion, different activations of slip systems and deformation twinning were considered to be the main causes of the tension/compression asymmetry. Finally, an improved constitutive model was developed, considering the synergistic effects of temperature, strain rate, and stress state on the plastic behavior of laser-solid-formed Ti–6Al–4V alloy. The calibrated model can accurately describe the temperature and strain rate dependences of the tension/compression asymmetry behavior. To verify the applicability of the developed constitutive model at different stress state, dynamic shear tests and finite element simulations were conducted at different temperatures. The improved constitutive model was shown to be able to predict the plastic behavior of laser-solid-formed Ti–6Al–4V alloy at different stress states over a wide range of temperatures and strain rates. [ABSTRACT FROM AUTHOR]

Ceratocystis fimbriata Ellis & Halsted is the pathogen causing black rot in sweet potatoes that can lead to flavor change and toxin release. This study detected the volatile organic compounds (VOCs) of C. fimbriata-infected sweet potatoes in the early stages using headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 55 VOCs were identified, including aldehydes, alcohols, esters, ketones, and others. The content of aldehydes and ketones showed a decreasing trend, while alcohols and esters showed an increasing trend. An increase in infection time elevated the content of malondialdehyde (MDA) and pyruvate, while the starch content decreased, the content of soluble protein initially increased, then decreased, and the activities of lipoxygenase (LOX), pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH), and phenylalanine ammonia-lyase (PAL) increased. The changes in VOCs were closely related to the content of MDA, starch, pyruvate, and the activities of LOX, PDC, ADH, and PAL. Sweet potatoes showed a good discrimination effect by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) from 0 to 72 h. Twenty-five differential VOCs could be used as early-stage characteristic compounds of C. fimbriata-infected sweet potatoes for early disease monitoring. [ABSTRACT FROM AUTHOR]

Sweetpotato is prone to disease caused by C. fimbriata without obvious lesions on the surface in the early period of infection. Therefore, it is necessary to explore the possibility of developing an efficient early disease detection method for sweetpotatoes that can be used before symptoms are observed. In this study, sweetpotatoes were inoculated with C. fimbriata and stored for different lengths of time. The total colony count was detected every 8 h; HS-SPME/GC–MS and E-nose were used simultaneously to detect volatile compounds. The results indicated that the growth of C. fimbriata entered the exponential phase at 48 h, resulting in significant differences in concentrations of volatile compounds in infected sweetpotatoes at different times, especially toxic ipomeamarone in ketones. The contents of volatile compounds were related to the responses of the sensors. E-nose was combined with multiple chemometrics methods to discriminate and predict infected sweetpotatoes at 0 h, 48 h, 64 h, and 72 h. Among the methods used, linear discriminant analysis (LDA) had the best discriminant effect, with sensitivity, specificity, precision, and accuracy scores of 100%. E-nose combined with K-nearest neighbours (KNN) achieved the best predictions for ipomeamarone contents and total colony counts. This study illustrates that E-nose is a feasible and promising technology for the early detection of C. fimbriata infection in sweetpotatoes during the asymptomatic period. [ABSTRACT FROM AUTHOR]

Premature infants are susceptible to many conditions that are inflammatory in nature. For this patient population, which is expecting the intrauterine environment, pathways necessary for fetal life and development may not have completed the transitions necessary for extrauterine life. In this study, responses to tumor necrosis factor-[alpha] were compared in human fetal and adult intestinal epithelial cell lines along with preweaned and postweaned mouse intestinal sections to identify a potential developmental difference that may explain the heightened inflammatory response of preterm infants. The nuclear factor-[kappa]B (NF-[kappa]B) pathway regulates a wide variety of genes involved in immune and inflammatory processes. We report that, compared with adult intestinal epithelial cells, immature intestinal epithelial cells have increased NF-[kappa]B activity associated with increased NF-[kappa]B-DNA binding and transcriptional activity. This increased activity appears due to inadequate inhibition of signaling leading to NF-[kappa]B activation since there is also increased phosphorylation, ubiquitination, and degradation of the inhibitor of NF-[kappa]B in conjunction with decreased baseline expression and delayed resynthesis of this inhibitor. Thus we demonstrate a potential mechanism for the heightened inflammatory response of immature intestinal epithelial cells. immature intestinal epithelium; inflammation; development; necrotizing enterocolitis doi:10.1152/ajpgi.00557.2006.

In this study, uniaxial compression experiments of K403 superalloy were conducted over temperature range of 298–1073 K and strain rate range of 0.1–5200/s. Temperature and strain rate effects on the flow stress were analysed. Double anomalous stress humps were noticed in the flow stress vs. temperature curves. The flow stress of the superalloy showed independence on strain rate over low strain rate range and an enormous increase with increasing strain rate over high strain rate range. Then, the effects of temperature and strain rate on the microstructure were observed and analysed. Due to the double-humped temperature dependence, the existing constitutive models were unable to accurately predict the plastic behaviour of K403 superalloy. Thus, a constitutive model was developed to describe the plastic behaviour of K403 superalloy. The model was able to capture the double-humped temperature dependence and anomalous strain rate dependence of plastic behaviour. It was shown that the plastic behaviour of the superalloy can be accurately predicted over a wide range of temperatures and strain rates. [ABSTRACT FROM AUTHOR]

Abstract Background Familial Alzheimer's disease-linked variants of presenilin (PSEN1 and PSEN2) contribute to the pathophysiology of disease by both gain-of-function and loss-of-function mechanisms. Deletions of PSEN1 and PSEN2 in the mouse forebrain result in a strong and progressive neurodegenerative phenotype which is characterized by both anatomical and behavioral changes. Results To better understand the molecular changes associated with these morphological and behavioral phenotypes, we performed a DNA microarray transcriptome profiling of the hippocampus and the frontal cortex of the PSEN1/PSEN2 double knock-out mice and littermate controls at five different ages ranging from 2–8 months. Our data suggest that combined deficiencies of PSEN1 and PSEN2 results in a progressive, age-dependent transcriptome signature related to neurodegeneration and neuroinflammation. While these events may progress differently in the hippocampus and frontal cortex, the most critical expression signatures are common across the two brain regions, and involve a strong upregulation of cathepsin and complement system transcripts. Conclusion The observed neuroinflammatory expression changes are likely to be causally linked to the neurodegenerative phenotype observed in mice with compound deletions of PSEN1 and PSEN2. Furthermore, our results suggest that the evaluation of inhibitors of PS/γ-secretase activity for treatment of Alzheimer's Disease must include close monitoring for signs of calpain-cathepsin system activation.

Structural analysis and new zircon U/Pb geochronology were performed in the Cuonadong Dome in order to test the hypothesis that the top‐to‐North deformation in the North Himalayan Gneiss Domes (NHGD) has been correlated with deformation along the South Tibetan detachment system (STDS). Structural analysis suggests that the X‐axes of sheath folds at the different flanks of the dome are consistent, and show average a trend and plunge of 350° and 18°. Many shear sense indicators are recorded in the ductile shear zone during the top‐to‐north deformation, including the augen structure, σ‐type and δ‐type rotating porphyroclast, S–C fabric and pressure shadow structure. The development of the sheath folds first provide a direct‐field structural evidence that represents a deeper ductile manifestation of the STDS, and further suggests that the top‐to‐north deformation in the NHGD have been correlated with deformation along the STDS. The emplacement of the synkinematic granites at ca. 32 Ma exposed at the core of the sheath folds is also interpreted as the initiation of slip along the STDS. [ABSTRACT FROM AUTHOR]

Objective. To analyze the development of cardio-oncology, summarize the research achievements, and provide proposals for its future research. Methods. The web of science database was used to search for "cardio-oncology" and "oncocardiology" related articles from the beginning of the database (1970) to April 5, 2019. Excel 2016 and Cytoscape were used to analyze the trend of cardio-oncology research. Results. A total of 356 articles were obtained. The number of articles has grown rapidly in recent years. Cardiac injury caused by tumor therapy was a research hotspot (n = 107). Researchers paid more attention to the prevention and treatment of cardiotoxicity (n = 54). Experimental researches were a small part of all studies (n = 72), mainly focusing on the study of cancer drugs' cardiac injury, test indicators of cardiotoxicity, and preventive drugs. The United States (n = 156.25), Italy (n = 48.5), and Canada (n = 23.5) published the most articles, making a great contribution to the development of cardio-oncology. Conclusions. Cardio-oncology has been developing rapidly and receiving a large amount of research efforts in recent years. Most articles on cardio-oncology were published by the authors from the United States (44%) and Italy (17%), while other countries need to pay more attention to cardio-oncology. As an independent discipline, cardio-oncology is certainly in need of significant progress, but it has formed a basic framework, which has obtained many leading theories and meaningful achievements in diagnostic criteria, diagnostic methods, prevention and treatment, mechanism research, and influencing factor. Cardiac injury of tumor drugs has always been a research hotspot in this discipline, and there is still a lot of research space. The research about detection methods of cardiotoxicity and preventive drugs is gradually increasing. Basic research lags behind, and many mechanisms are still unclear. [ABSTRACT FROM AUTHOR]

Abstract: In‐syringe solid‐phase extraction is a promising sample pretreatment method for the on‐site sampling of water samples because of its outstanding advantages of portability, simple operation, short extraction time, and low cost. In this work, a novel in‐syringe solid‐phase extraction device using metal–organic frameworks as the adsorbent was fabricated for the on‐site sampling of polycyclic aromatic hydrocarbons from environmental waters. Trace polycyclic aromatic hydrocarbons were effectively extracted through the self‐made device followed by gas chromatography with mass spectrometry analysis. Owing to the excellent adsorption performance of metal–organic frameworks, the analytes could be completely adsorbed during one adsorption cycle, thus effectively shortening the extraction time. Moreover, the adsorbed analytes could remain stable on the device for at least 7 days, revealing the potential of the self‐made device for on‐site sampling of degradable compounds in remote regions. The limit of detection ranged from 0.20 to 1.9 ng/L under the optimum conditions. Satisfactory recoveries varying from 84.4 to 104.5% and relative standard deviations below 9.7% were obtained in real samples analysis. The results of this study promote the application of metal–organic frameworks in sample preparation and demonstrate the great potential of in‐syringe solid‐phase extraction for the on‐site sampling of trace contaminants in environmental waters. [ABSTRACT FROM AUTHOR]