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Background: Pancreatic ductal adenocarcinoma (PDAC) is a fatal tumor with grave prognosis. Pyroptosis, a programmed cell death, is involved in tumorigenesis. However, a few studies have elucidated the functions of pyroptosis in PDAC. Methods: The mRNA expression profiles were downloaded from the TCGA and GEO databases. Univariate and LASSO Cox regression analyses were used to screen out differentially expressed genes (DEGs) and construct the pyroptosis-related genes (PRGs) risk model. The efficiency of model was examined by Kaplan–Meier curve, ROC curve, and nomogram. Univariate and multivariate Cox regression analyses were utilized to assess whether the risk model could be used as an independent prognostic factor. The biological function was analyzed by GO, KEGG, and GSEA enrichment analysis. qRT-PCR and immunohistochemical staining detected gene expression. Results: Totally 9 PRGs with differential expression were identified between normal and PDAC tissues. Then, according to PRGs, we filtered out three key DEGs and constructed the prognostic risk model. Kaplan–Meier curve, ROC curve, and nomogram indicated that the prognostic risk model had high survival prediction efficiency. Meanwhile, the risk model had also shown to be an independent prognostic factor. Further functional enrichment analysis showed that cell adhesion, PI3K–AKT signaling pathway, and dysregulated immune status may be associated with PDAC development. External validation of the model was carried out in the GEO cohort, and the results were similar to that in the TCGA cohort. Finally, the expression of three genes was verified by qRT-PCR and immunohistochemical staining. Conclusion: The prognostic risk model established in this study can give a good prediction of the prognosis of PDAC patients, which might provide insights into clinical treatments and prognostic prediction of PDAC. [ABSTRACT FROM AUTHOR]

Wearing a liquid cooling garment (LCG) that offers near-zone cooling improves the thermal comfort of pilots working in hot environments. Four LCG samples with different arrangements of tubes for distributing liquid were developed. Based on the analysis of the overall and local cooling efficiency of the four LCG samples using manikin tests, another novel LCG with a horizontal-vertical combined tube was proposed to achieve optimal cooling performance. Human trials were conducted to check the novel LCG for improving the thermal comfort of pilots in a hot indoor environment (40°C, 40% RH). The mean skin temperature of the subjects wearing the novel LCG was reduced by 1.9°C in the 120-minute-duration flying simulation work compared to the no-cooling scenario, and the greatest decrease in skin temperature (i.e., 5.7°C) was exhibited at the back waist. The thermal sensation at the upper body was improved to nearly neutral, and the heat stress level was reduced from moderate to slightly. The findings provide a guideline for designing personal LCG, thus benefiting the comfort and safety of pilots in hot cockpits. [ABSTRACT FROM AUTHOR]

High-fat exposure leads to impaired intestinal barrier function by disrupting the function of intestinal stem cells (ISCs); however, the exact mechanism of this phenomenon is still not known. We hypothesize that high concentrations of deoxycholic acid (DCA) in response to a high-fat diet (HFD) affect aryl hydrocarbon receptor (AHR) signalling in ISCs and the intestinal barrier. For this purpose, C57BL/6J mice feeding on a low-fat diet (LFD), an HFD, an HFD with the bile acid binder cholestyramine, and a LFD with the DCA were studied. We found that high-fat feeding induced an increase in faecal DCA concentrations. An HFD or DCA diet disrupted the differentiation function of ISCs by downregulating AHR signalling, which resulted in decreased goblet cells (GCs) and MUC2, and these changes were reversed by cholestyramine. In vitro experiments showed that DCA downregulated the differentiation function of ISCs, which was reversed by the AHR agonist 6-formylindolo [3,2-b]carbazole (FICZ). Mechanistically, DCA caused a reduction in indoleamine 2,3-dioxygenase 1 (IDO1) in Paneth cells, resulting in paracrine deficiency of the AHR ligand kynurenine in crypts. We demonstrated for the first time that DCA disrupts intestinal mucosal barrier function by interfering with AHR signalling in ISCs. Supplementation with AHR ligands may be a new therapeutic target for HFD-related impaired intestinal barrier function. [ABSTRACT FROM AUTHOR]

The thermo-physiological human simulator has been used in many regions for estimating thermal behavior of the locals. The applicability of the human simulator to populations from different regions is, however, questioned due to its lack of consideration for the ethnic diversities in thermoregulation. This study checked the potential of improving the applicability of the Newton human simulator, one of the most popular simulators, by correcting its local set point skin temperatures according to the target population (Chinese as an example). First, new set point skin temperatures were obtained by conducting tests with 101 Chinese under a thermal neutral condition. Then, simulator tests using the original and new set point skin temperatures were conducted separately for evaluating thermal responses of the Chinese under non-neutral conditions. The evaluated skin and core temperatures by the simulators were compared with those measured from the real human tests. It demonstrated that the evaluated skin temperatures are positively related with the set point skin temperatures of the simulator. Adjusting set point skin temperatures according to the Chinese improved the prediction performance of the local skin temperatures, with the root-mean-square-deviation being reduced for over 50% of the body segments. The proposed idea of correcting local set point skin temperatures would contribute to evaluating the thermal interaction between human body and its surroundings with a higher accuracy. [ABSTRACT FROM AUTHOR]

Using reclaimed asphalt pavement (RAP) has become an appealing development for economic and environmental benefits. One of the key issues when incorporating RAP materials is to ensure the performance of recycled binder blends. Despite extensive researches dealing with physical and chemical aspects, concerns about recycled materials combinations remain. This paper focuses on the kinetics of aging, cracking and healing process for blended binders with a novel hypothesis of mass-composite activation energies. Firstly, four blends were prepared with different ratios of virgin bitumen and laboratory-produced RAP binders. Then, Fourier-transform infrared spectroscopy was utilized to track the carbonyl formation in all samples initially and with aging, and aging activation energy (E acr) was computed in terms of Arrhenius equation. Thirdly, strain-controlled oscillatory measurements were conducted; moreover, representative energy change rates of dissipated pseudo strain energy and recoverable strain energy were obtained to determine the activation energy for cracking (E ac) and healing (E aH), respectively. Finally, hypotheses of mass-composite activation energies were validated with the test results. It shows that E acr of recycled binder blends are smaller than that of RAP binders, indicating a lower kinetic barrier to oxidation reaction for blended bituminous system. With the increase of RAP binder content, the blends exhibit a decrease in E ac and an increase in E aH , which reveals the adverse effect introduced by oxidation in cracking resistance and healing capability. Excitingly, the measured activation energies of recycled binder blends are consistent with the calculated mass-composite activation energies, which will hopefully provide support for performance estimation. [Display omitted] • Kinetics of aging, cracking and healing are studied on blended bituminous system. • Mass-composite rule of activation energy is established for recycled binder blends. • The proposed mass-composite activation energies are validated. [ABSTRACT FROM AUTHOR]

• A 'skin-electrically heated fabric-environment' heat transfer model was established. • Temperature and inner layer's thermal resistance affect T sk a more than other factors. • A prediction model for resultant skin temperature was developed. • The optimization design balances human thermal comfort and energy saving. A 3D heat transfer model was developed to optimize the design of electric heating garments (EHGs) towards human thermal comfort and energy efficiency. The model deals with the thermal interaction between human skin, a three-layer electrical heating fabric system, and cold environments, allowing analysis of the heating process and resultant skin temperature. Three heat transfer mechanisms, namely conduction, convection and radiation, were considered. The real-time and final skin temperatures from simulation and measurement exhibited a difference below 4%, demonstrating the efficiency of the model. A steady-state parametric study was conducted using the validated numerical model. Five parameters, such as heating temperature, thermal resistance of the inner and outer fabrics, wind speed, and environmental air temperature, were involved. The results indicate that the heating temperature and thermal resistance of the inner fabric have a more noticeable effect on the temperature of the skin surface below the heated area compared to the other three factors. Apart from the heating temperature, the other four factors have a greater impact on the skin temperature of non-heated regions than that of the heated region. Multiple linear regression analysis was performed to establish a relationship between skin temperature and the five factors. Based on this analysis, a prediction model for skin temperature was developed and subsequently used to determine relevant parameters for EHGs. A method for optimizing the design of electrically heated clothing is proposed, which can achieve the dual goals of human thermal comfort and energy efficiency. [ABSTRACT FROM AUTHOR]

Long-term high-fat diet (HFD) destroys the intestinal mucosal barrier by damaging intestinal stem cells (ISCs). A HFD can increase the concentration of intestinal deoxycholic acid (DCA) and decrease the secretion of interleukin-22 (IL-22), which plays an important role in the proliferation, repair and regeneration of ISCs. We hypothesized that increased level of intestinal DCA induced by a HFD leads to ISC dysfunction by reducing the IL-22 levels in intestinal tissues. In this study, 2 weeks of a DCA diet or a HFD damaged ileal ISC and its proliferation and differentiation, resulting in a decrease in Paneth cells and goblet cells. Importantly, 2 weeks of a DCA diet or a HFD also reduced ileal IL-22 concentration, accompanied by a decreased number of group 3 innate lymphoid cells in ileal mucosa, which produce IL-22 after intestinal injury. Concurrent feeding with bile acid binder cholestyramine prevented all these changes induced by a HFD. In addition, in vitro study further confirmed that exogenous IL-22 reversed the decline in the proliferation and differentiation of ileal ISCs induced by DCA stimulation. Collectively, these results revealed that the decrease in intestinal IL-22 induced by DCA may be a novel mechanism by which HFD damages ISCs. The administration of IL-22 or a bile acid binder may provide novel therapeutic targets for the metabolic syndrome caused by a HFD. [Display omitted] • Deoxycholic acid (DCA) elevated by high-fat feeding impaired the intestinal stem cells (ISCs). • DCA damaged group 3 innate lymphoid cells and reduced the IL-22 level in the ileum. • A bile acid binder cholestyramine restored the IL-22 levels and the functions of ISCs. • Exogenous IL-22 reversed DCA induced damage of ISC function. [ABSTRACT FROM AUTHOR]

Various acoustic and mechanical wave components have been developed. Most of them focused on the control of energy flow. However, these waves are not only energy flow but also wave signals with a frequency dependence. In this Letter, we propose a mechanical wave switch (MWS) capable of controlling energy flow and output frequency simultaneously. It consists of a difference frequency generation (DFG) unit and a wave filter. The DFG unit consists of two mass blocks and a tension/compression asymmetrical bilinear spring, and the wave filter is a one-dimensional mass-spring lattice. Systematical calculations were carried out to identify the critical condition for the design of MWSs. Both numerical and experimental results demonstrate the capability of the proposed MWS to tune the energy flow and the output frequency of acoustic waves via a small amplitude control wave signal. The scale-independent MWS can be implemented at micro- and nanoscales. [ABSTRACT FROM AUTHOR]

• Acoustic emission could diagnose the fracture failure process of asphalt mixtures. • The wavelet coefficient of AE sequence is relevant to the damage evolution process. • The AE energy could stably reveal the fractal characteristic of AE process. • The waveform fractal dimension could identify the critical fracture condition. Dynamical diagnosis of damage evolution is essential to promote the pavement performance of asphalt materials and prolong their service life. As a non-destructive method, acoustic emission (AE) can be used to assess the degree of deformation or cracking of stressed materials by detecting the energy release from damage points. The objective of the study was to explore the continuous damage evolution behavior of asphalt mixtures by evaluating the variation characteristics of AE parameters and waveforms. Firstly, the three-point bending tests and AE tests were simultaneously conducted on asphalt mixture beams, and AE behaviors associated with the failure process were investigated. Secondly, considering the impact of material heterogeneity on AE transmission, wavelet transform was utilized to qualitatively determine the relationship between wavelet coefficient and damage degree of asphalt mixtures. Lastly, the fractal theory was applied to quantitatively explore the scale-invariance of AE process and the AE mutation of damage process. The results show that the accumulation of AE energy and AE count could reflect the dynamical failure process of asphalt mixtures under different loading rates. The effect of sampling frequency could be presented by time-scale characteristics of AE waveforms. The fracture characteristics of asphalt mixtures could be reflected by amplitude and energy distribution of cumulative AE energy and AE waveforms. The fractal result of AE energy is relatively stable in revealing the flexural failure characteristics of asphalt mixtures. The mutational rise of the waveform fractal dimension from the minimum value is related to the critical fracture condition of asphalt mixtures. [ABSTRACT FROM AUTHOR]

Inspired by self-healing attributes, one of the key topics in the field of pavement engineering is changing the way that asphalt materials behave for prolonged service life and environmental savings. Extensive experimental approaches, models and technologies have been developed to characterize the evolution of healing influenced by internal and external factors. The purpose of this study is to explore the local kinetics of asphalt binders that energetically favor autonomous self-healing as well as its mechanism using free energy method. With consideration of driving forces including internal stress and interfacial forces of attraction (or surface energy) responsible for energy redistribution during the rest period, the healing of an asphalt binder was first modeled as a function of thermodynamic parameters. New healing indexes were then defined by the total free energy change for healing (Δ G H) and fast-rate response ratio (R H) of initial healing in duration to the total rest time. Thirdly, a fatigue-healing test was performed on #70 asphalt binder and SBS-modified asphalt binder to examine the potential and reactivity of healing affected by different damage levels. Finally, the effectiveness of proposed thermodynamic healing indexes in describing healing ability was discussed by considering their relations with properties measured by mechanical analysis. Results show that more negative Δ G H indicates a greater tendency to spontaneous healing while less negative Δ G H suggests a poor healing potential as crack propagates to a certain length. In contrast to #70 asphalt binder, SBS-modified asphalt binder exhibits a superior healing potential on a shorter crack length scale. R H gradually increases with the increase of crack length for both #70 asphalt binder and SBS-modified asphalt binder, implying limited mobility of molecules. By contrast with mechanistic healing indexes assessing properties before and after healing (i.e. the degree of healing), the thermodynamic healing indexes provide a new vision regarding healing potential, which reveals the true ability of a material to autonomously repair damaged areas. • Evolution of autonomous self-healing is characterized using free energy method. • Healing potential Δ G H is established and formulated for a damaged asphalt binder. • The initial healing characteristics R H are quantified at different damage levels. • Thermodynamic healing indexes could reveal the true healing ability of a material. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are widely observed in older adults and are closely associated with cognitive impairment. However, the underlying neuroimaging mechanisms of WMH-related cognitive dysfunction remain unknown. This study recruited 61 WMH individuals with mild cognitive impairment (WMH-MCI, n = 61), 48 WMH individuals with normal cognition (WMH-NC, n = 48) and 57 healthy control (HC, n = 57) in the final analyses. We constructed morphological networks by applying the Kullback-Leibler divergence to estimate interregional similarity in the distributions of regional gray matter volume. Based on morphological networks, graph theory was applied to explore topological properties, and their relationship to WMH-related cognitive impairment was assessed. There were no differences in small-worldness, global efficiency and local efficiency. The nodal local efficiency, degree centrality and betweenness centrality were altered mainly in the limbic network (LN) and default mode network (DMN). The rich-club analysis revealed that WMH-MCI subjects showed lower average strength of the feeder and local connections than HC (feeder connections: P = 0.034; local connections: P = 0.042). Altered morphological connectivity mediated the relationship between WMH and cognition, including language (total indirect effect: −0.010; 95 % CI: −0.024, −0.002) and executive (total indirect effect: −0.010; 95 % CI: −0.028, −0.002) function. The altered topological organization of morphological networks was mainly located in the DMN and LN and was associated with WMH-related cognitive impairment. The rich-club connection was relatively preserved, while the feeder and local connections declined. The results suggest that single-subject morphological networks may capture neurological dysfunction due to WMH and could be applied to the early imaging diagnostic protocol for WMH-related cognitive impairment. • The altered topological organization of morphological networks was mainly located in the DMN and LN. • The altered morphological connectivity mediated WMH-related cognitive impairment. • The rich-club connection was relatively preserved to delay cognitive decline. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) of assumed vascular origin are common in elderly individuals and are closely associated with cognitive decline. However, the underlying neural mechanisms of WMH-related cognitive impairment remain unclear. After strict screening, 59 healthy controls (HC, n = 59), 51 patients with WMH and normal cognition (WMH-NC, n = 51) and 68 patients with WMH and mild cognitive impairment (WMH-MCI, n = 68) were included in the final analyses. All individuals underwent multimodal magnetic resonance imaging (MRI) and cognitive evaluations. We investigated the neural mechanism underlying WMH-related cognitive impairment based on static and dynamic functional network connectivity (sFNC and dFNC) approaches. Finally, the support vector machine (SVM) method was performed to identify WMH-MCI individuals. The sFNC analysis indicated that functional connectivity within the visual network (VN) could mediate the impairment of information processing speed related to WMH (indirect effect: 0.24; 95% CI: 0.03, 0.88 and indirect effect: 0.05; 95% CI: 0.001, 0.14). WMH may regulate the dFNC between the higher-order cognitive network and other networks and enhance the dynamic variability between the left frontoparietal network (lFPN) and the VN to compensate for the decline in high-level cognitive functions. The SVM model achieved good prediction ability for WMH-MCI patients based on the above characteristic connectivity patterns. Our findings shed light on the dynamic regulation of brain network resources to maintain cognitive processing in individuals with WMH. Crucially, dynamic reorganization of brain networks could be regarded as a potential neuroimaging biomarker for identifying WMH-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Sugarcane is an economically important crop whose growth and carbon uptake play vital roles in the carbon cycle, food security, and global trade development. However, the response of the carbon uptake of sugarcane to climate variations and the influencing factors are still unclear. In this study, seven sugarcane plantation distribution maps during 2000 and 2018 in Guangxi, China, were generated using time series Landsat and Sentinel-2 imagery, and these maps were used to produce stable sugarcane sites by identifying pixels without land cover transformation. Time series gross primary production (GPP) and climate datasets were used to analyze the response of annual GPP to temperature, precipitation, and their interacting effects under different landforms (rugged ground and flat ground) and growing periods. The results showed a significantly positive correlation between annual GPP change and temperature variations. Extreme precipitation, including extreme drought and extreme wetness, caused the annual GPP to decrease sharply, except for extreme wetness in the early growing period. The decrease in annual GPP mainly appeared when extreme drought and hot conditions or extreme wet and cold conditions coexisted, ranging from −20.37% to −0.23%, while the increase in annual GPP especially appeared when non-extreme precipitation and high temperature co-occurred, ranging from 0.02% to 8.44%. In addition, the responses of sugarcane annual GPP change to extreme temperature and precipitation were significantly different between rugged and flat ground. Overall, this study indicated that spatiotemporal heterogeneities existed in the response of sugarcane carbon uptake to climate variations. In the future, effective measures should be adopted in sugarcane management and cultivation to reduce the negative effects of climate change on crop production. • Sugarcane's carbon uptake response discrepantly to heat and water stresses. • Impacts of climate variations on sugarcane GPP varied with growing stages. • Rugged grounds change the response of sugarcane GPP to extreme climates. [ABSTRACT FROM AUTHOR]

• Heat transfer from dressed human body was simulated using a validated CFD method. • Heat transfer distributes unevenly over human body covered with homogeneous air layer. • Considering only average value of the air gap thickness underestimates heat transfer. • Environmental air enters air layer through clothes openings and promote heat transfer. • Air speed decreases the threshold of air gap thickness for the onset of convection. With a great advantage of presenting physical phenomenon in a three-dimensional vision, the technology of computational fluid dynamics was utilized in the current study for simulating and revealing heat transfer in the air gap/layer between human body and clothing. Five clothing configurations including one with realistic heterogeneous air layer and four simplified ones with homogeneous air layers with air gap thickness (AGT) varying between 4 and 16.34 mm were built. All clothing configurations were simulated under environmental air speeds of 0.2–2.5 m/s. It was found the thermal plume, airflow through clothing openings and pathway at armhole have resulted in an uneven distribution of heat transfer underneath clothing, even for clothing with homogeneous air layers. Simply averaging AGT blurs the heterogeneity of heat transfer over the whole body. The threshold of AGT for arising free convection in the air gap is within 12–16.34 mm at the air speed of 0.2 m/s and 8–12 mm at 2.5 m/s, indicating a substantial influence of environmental airflow on thermal flow in the air gap. Besides, increase of air speed would enhance local heat exchange by entering the air gap through clothing openings, except at the arms, where the heat flux fluctuates due to the direction of airflow in sleeves changing from upwards to downwards. Results of the current study have offered a comprehensive insight into the heat transfer in the air gap and can contribute to improving the accuracy of analytical human – clothing – environment models in clothing thermal engineering. [ABSTRACT FROM AUTHOR]

• Acoustic emission technique is used to monitor the fatigue process of asphalt mixtures. • The evolutionary feature of fatigue damage could be characterized by AE energy and RA-AF. • Different damage behaviors are identified by time and frequency characteristics of AE events. • A new AE index is proposed for assessing the damage state. Fatigue cracking of asphalt materials directly affects the performance and safety of asphalt pavements. It is necessary to identify the materials condition with acoustic emission (AE) as the real time monitoring technique. The objective of this study was to diagnose the damage behavior of asphalt mixtures from the time and frequency characteristics of AE signals. Firstly, the semi-circular bending (SCB) fatigue test and AE detection were conducted to explore the AE response of asphalt mixtures subjected to cyclic loads. Then, the Fast Fourier Transform (FFT) and Continuous Wavelet Transform (CWT) were applied to discuss the dominant frequency characteristics and time–frequency distribution of AE waveforms. Finally, an index (R BD), defined as the ratio of fractal dimension of AE waveforms decomposed by the Discrete Wavelet Transform (DWT), was proposed to evaluate the damage state of asphalt mixtures. The results show that AE energy rate exhibits distinct variation signatures at different damage stages. The average frequency (AF) and rise angle (RA) of AE signals reveal that the coupling effect of tensile and shear cracks promotes the deterioration of asphalt mixtures. Most of the dominant frequencies of AE events generated from cracks are concentrated within the range of 13 to 30 kHz. The discrepancies in the time–frequency distribution of AE events could effectively discriminate the types of damage sources. The proposed index R BD is sensitive to the change of damage state of asphalt mixtures, producing corresponding reductions. [ABSTRACT FROM AUTHOR]

l Incorporating origami into the armor design, breaking the traditional armor design concept. l Arc-armor can better protect the structures with curved surfaces. l Introducing origami can induce a stable and regular failure mode of the arc-scale. l The origami-based arc-scales have greatly improved the protection performance of the armor. l The second-level structure can further reduce the peak load of the scales under high-velocities for about 19.7%. Natural dermal armor has superior protective performance and flexibility for effectively protecting flexible objects. Limited by the complex microstructure of natural scales, the scales of common bionic armors are mostly solid flat scales, which will have a certain impact on the quality and protective performance of the armor, and they are not suitable for protecting flexible objects with a curved surface out of consideration for conformality and performance. Based on the Miura pattern with single-degree-of-freedom, this paper designs an arc-scale that can be conformal to the curved surface, and proposes an arc-armor inspired by fish scales. The experiments and numerical simulations have proved that the introduction of the origami structure design can induce a stable failure mode of the arc-scale. The origami-based arc-armor has the advantages of low peak load, long effective stroke, and small fluctuation, which greatly improves the protection performance of the armor. And based on the failure mode of the arc-scale, the second-level structure is proposed to further optimize the energy absorption characteristics of the arc-scale, which contributes to reducing the peak load of the scales under medium- and high-velocity impacts. Under high-velocity impact, the denser the distribution of cells inside the scales, the higher the energy absorption efficiency of the arc-scales, which provides certain guidance for the design and application of the arc-armor. We have obtained an arc-armor with excellent energy absorption characteristics that can be reverse-designed according to the target shape. And such structures can find a wide range application in the protection of flexible electronics, human bodies, and other flexible objects that require light weight and flexibility. [Display omitted] [ABSTRACT FROM AUTHOR]

The fractures in asphalt materials evolving from microcracks directly affect the performance of asphalt pavements. Acoustic Emission (AE) technique plays a crucial role in dynamically monitoring the internal structural changes of stressed materials. This study attempted to characterize the fracture mechanism of asphalt mixtures by identifying the characteristics of recoded AE data. Firstly, the three-point bending tests and AE tests were simultaneously conducted to investigate the damage evolution process of asphalt mixtures through the time characteristics of AE parameters. Secondly, the cusp catastrophe model based on AE energy rate was employed to explore the mutational characteristics of AE process and to evaluate the damage state of asphalt mixtures. Finally, the k-means method was applied to distinguish the patterns of AE signals associating with the specific damage behaviors of asphalt mixtures during the flexural failure process. The results show that abrupt change of AE energy rate and cumulative AE energy could reflect the evolutionary characteristics of damage in asphalt mixtures. The mutational analysis of AE energy rate reveals that the damage state of asphalt mixtures subjected to the continuous external forces would change between instability and stability, which could be served as a complementary approach for further understanding the periodic variation characteristics of damage evolution process based on cumulative AE energy. The k-means method could effectively classify the recorded AE signals of asphalt mixtures in three-point bending tests into three distinctive clusters. The potential mechanisms for the clustered signals corresponding to different damage behaviors of asphalt mixtures could be characterized by the parametric characteristics and the wavelet power spectrum of AE signals. [ABSTRACT FROM AUTHOR]

• Acoustic emission could characterize the fatigue damage behavior of asphalt mixtures. • AE energy and amplitude b-value could reflect the stage features of damage evolution. • The distribution of AE event is related to the microstructure of mix and loading mode. • The Felicity ratio could measure the irreversibility of damage evolution. • The wavelet scalogram of AE waveforms could identify the damage mechanism. Understanding the fatigue damage mechanism of asphalt mixtures is essential to prolong the service life of asphalt pavements. Acoustic emission (AE) technique can effectively detect minor damage and evaluate material mechanical properties. The objective of this paper was to investigate the temporal-spatial variation of AE parameters associated with fatigue damage behavior of asphalt mixtures and characterize the irreversibility of damage evolution utilizing the Kaiser effect. Firstly, the semi-circular bending (SCB) tests with different rest time and AE tests were carried out simultaneously to discuss the AE characteristics of fatigue damage behavior of asphalt mixtures. Secondly, the spatial evolution of AE events was analyzed to correlate with the crack propagation path of asphalt mixtures. Finally, the Felicity ratio (R F) and wavelet scalogram were utilized to reveal the irreversible characteristics of the AE process of asphalt mixtures. The results show that the "blank area" in AE energy temporal, representing the intensity of AE activities in asphalt mixtures during the process of microcracks concentration, gradually disappears with the increase of rest time. The inflection point of the decline of AE amplitude b-value could be considered as a precursor to the rupture of asphalt mixtures. The spatial distribution of AE events from disorder to order reflects the influence of the microstructures of asphalt mixtures and loading mode on crack propagation. The change of R F could be divided into the three stages, corresponding to the deformation and compaction stage where 1 ≤ R F , microcracks initiation and concentration stage where 0.4 ≤ R F < 1, and macrocracks extension stage where R F < 0.4. The Kaiser effect mainly exists at the stage of deformation and compaction of asphalt mixtures. After the occurrence of macrocracks, the AE process would lose irreversible characteristics. The damage mechanisms related to the Kaiser effect and the Felicity effect could be identified by the energy distribution of AE waveforms. [ABSTRACT FROM AUTHOR]

• Acoustic emission could accurately detect damage sources of asphalt mixtures. • The AE signal has an effective propagation range due to signal attenuation. • The proposed denoising process could minimize the noise interference. • The enhanced TDOA method could improve the accuracy of the source localization. Fracture of asphalt materials has been a critical issue that affects the fatigue performance and service life of asphalt pavements. Acoustic emission (AE) technique, as a kind of non-destructive testing (NDT) method, can effectively detect minor damage in various materials. The objective of this paper was to propose a damage source localization method suitable for understanding the fracture behavior of asphalt mixtures by AE detection. Firstly, the pencil-lead-break (PLB) tests were conducted on asphalt mixture beams to explore the propagation characteristics of AE signals, and a reasonable layout scheme of AE sensors was determined for monitoring the AE process of asphalt mixtures. Secondly, the wavelet threshold denoising method was utilized to extract effective information from AE signals associated with the pencil-lead breaks on the surface of asphalt mixture beam by simultaneously considering the wavelet basis functions, decomposition levels and threshold rules. Finally, an effective time difference of arrival (TDOA) estimation method combining noise reduction, wavelet decomposition and cross-correlation processing was established to accurately locate the damage source of asphalt mixtures. The results show that there is less serious attenuation of amplitude and energy of AE parameters and frequency spectrum of AE waveforms within the range of 100 mm in asphalt mixtures. The larger signal-to-noise ratio (SNR) and the smaller root mean square error (RMSE) of denoised AE signals indicate that the threshold denoising method optimized by the Fruit Fly Optimization Algorithm (FOA) is more effective for AE detection of asphalt mixtures. The improved TDOA estimation method could obtain a minimum TDOA value, and the calculated locations of AE events are closer to the actual PLB points. [ABSTRACT FROM AUTHOR]

Long-term high-fat feeding (HF) induces intestinal mucosal barrier damage. However, the mechanism for this remains unclear. HF can elevate the intestinal and circulating bile acid (BA) levels, especially deoxycholic acid (DCA). We hypothesize that BAs elevated by HF regulate intestinal stem cell (ISC) function, which may contribute to mucosal barrier injury in the ileum of mice. In this study, we showed that 2 weeks of HF resulted in a shortening of intestinal villi and a decrease in the tight junction (TJ) protein occludin in the ileum of mice, accompanied by an increase in circulating BA levels. Importantly, 2 weeks of HF also reduced ileal ISCs and goblet cells and decreased the proliferation function of ISCs and their ability to differentiate into goblet cells. Endoplasmic reticulum (ER) stress was found to be involved in the process of ISC damage. All these alterations were reversed by cofeeding with the bile acid binder cholestyramine. In addition, the in vitro studies also confirmed a cytotoxic effect of DCA at a high concentration on ISCs and goblet cells. In conclusion, these data suggested that high levels of BAs induced by HF could impair ISC function by triggering ER stress, resulting in the disruption of the intestinal mucosal barrier. • High-fat feeding (HF) increases bile acids (BAs) and damages the intestinal mucosa. • HF reduces the number of small intestinal stem cells (ISCs) and decreases the differentiation of goblet cells from ISCs. • HF increases endoplasmic reticulum (ER) stress in the intestinal mucosa and ISCs. • BAs elevated by HF induce ER stress in ISCs and contribute to mucosal barrier damage in the ileum. [ABSTRACT FROM AUTHOR]

Spasmolytic polypeptide-expressing metaplasia (SPEM) is an important risk factor for the occurrence of gastric cancer. It may be driven by a chronic inflammatory environment in which macrophage is involved. Studies have shown that intestinal metaplasia may originate from SPEM, and bile acid-induced chronic inflammation plays an important role in the process of intestinal metaplasia. However, whether bile acids are involved in the development of SPEM and the specific mechanism are unclear. Meanwhile, macrophages are known to be involved in inflammation regulation by releasing various factors, including exosomes. In this study, we hypothesized that the exosomes released from macrophages stimulated by deoxycholic acid participated in the development of SPME. In vivo, mice were gavaged with deoxycholic acid for 4 weeks, and gastric tissues were harvested. In vitro, deoxycholic acid-induced macrophage-derived exosomes were isolated by ultracentrifugation and cocultured with the gastric organoids of mice. Immunofluorescence staining and quantitative real-time PCR were used to analyze markers of macrophages and SPEM. In vivo, after 4 weeks of deoxycholic acid intragastric administration, macrophage markers (F4/80) and SPEM markers (TFF2 and GSII lectin) were increased in from treated mice compared with those from normal control mice. In vitro, macrophage-derived exosomes labeled with PKH67 were internalized by gastric organoids. Deoxycholic acid-induced macrophage-derived exosomes increased the expression of SPEM markers (TFF2 and GSII lectin) in gastric organoids compared to exosomes derived from macrophages without deoxycholic acid stimulation. Macrophage-derived exosomes may be a novel mechanism by which deoxycholic acid promotes SPEM. • Deoxycholic acid promoted the development of spasmolytic polypeptide-expressing metaplasia in the stomach of mouse. • Macrophage-derived exosomes were internalized by gastric organoid from mouse. • Exosomes promoted the development of spasmolytic polypeptide-expressing metaplasia in gastric organoids. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells 2 (TREM2) is an important member of the immunoglobulin family of inflammatory stimulating receptors and is involved in a number of pathophysiological processes. The present study aimed to investigate the role of TREM2 in neurotoxicity induced by high cholesterol levels in SH-SY5Y cells and explore the potential mechanism. SH-SY5Y cells were routinely cultured and stimulated with a range of cholesterol concentrations. Cell viability was assessed using an MTT assay, morphological changes were observed, and the cell cycle distribution was measured using flow cytometry. Lipid deposition was measured by Oil red O staining, and the mRNA and protein expression levels of SRBEP-1 and SRBEP-2 were detected by quantitative PCR and western blotting, respectively. Moreover, the protein expression levels of BDNF, Copine-6, TREM1, TREM2, and key molecules of the Wnt signaling pathways were detected by western blotting. Finally, TREM2 was overexpressed to investigate its potential role in high cholesterol-induced neurotoxicity. The results showed that cell viability was significantly decreased in SH-SY5Y cells stimulated with cholesterol (0.1~100 µM) in a dose- and time-dependent manner. Stimulation with 100 µM cholesterol for 24 h resulted in morphological injuries, increased the proportion of SH-SY5Y cells at G0/G1, the degree of lipid accumulation, and the protein expression levels of sterol regulatory element binding protein (SREBP)1 and SREBP2, markedly decreased the protein expression levels of BDNF, Copine-6, and TREM2, and the p-β-catenin/β-catenin ratio, and increased the expression levels of nesfatin-1, TREM1 and the p-GSK3β/GSK3β ratio. Furthermore, the imbalanced expression of BDNF, Copine-6, nesfatin-1, and p-GSK3β induced by high cholesterol levels was reversed after overexpression of TREM2. These results suggest that a high concentration of cholesterol could induce cell injury and lipid deposition in SH-SY5Y cells and that the underlying mechanism may be associated with imbalanced TREM2 expression. [ABSTRACT FROM AUTHOR]

• The DIC method-based fracture energy could evaluate the crack resistance of CRAEM. • AE test could comprehensively characterize the fracture evolution process of CRAEM. • The AE fractal dimension is closely related to the macrocracks formation of CRAEM. • The complete fracture of CRAEM could be forecast by the change of AE b-value. Cracking damage have great influence on the service life of cold recycled asphalt emulsion mixtures (CRAEM). As non-destructive methods, digital image correlation (DIC) and acoustic emission (AE) techniques can diagnose and visualize various distresses efficiently. The objective of this research was to explore and characterize the fracture behaviors of CRAEM with DIC and AE. Firstly, the semi-circular bending (SCB) tests, accompanied with DIC and AE monitoring were conducted on CRAEM with different cement contents. Secondly, the fracture energy examined by DIC as well as the tracked cracking path were analyzed to correlate with the fracture characteristics of CRAEM. Then, the variation of AE parameters (i.e., AE energy, AE amplitude) were investigated to identify the damage stages of SCB specimens. Finally, the box-counting dimension and the AE b-value were established based on cumulative AE energy and AE amplitude separately to quantitatively assess the transition of damage state. The results indicate that the cement content would significantly affect the cracking resistance performance of CRAEM, and CRAEM with a moderate content could have the benefits of more alternative energy release paths in the process of crack initiation and propagation. The fracture failure process of CRAEM could be divided into four stages through the simultaneous mutations of cumulative AE energy and AE amplitude. The difference of fracture surface morphologies of CRAEM with different cement contents obtained by the digital microscope could provide a reliable explanation for the fracture behaviors of the whole damage evolution process of CRAEM. The transition of the value of box-counting dimension from the maximum to the minimum could reflect the formation of macrocracks of CRAEM. The inflection point of the AE b-value curve arriving at the minimum value could be regarded as a precursor information to predict the complete fracture of CRAEM. [ABSTRACT FROM AUTHOR]

Cholesterol overloading and bile acid metabolic disorders play an important role in the onset of cholesterol gallstone (CGS). Short-chain fatty acids (SCFAs) can regulate bile acid metabolism by modulating the gut microbiota. However, the role and mechanism by which sodium butyrate (NaB) targets bile acids to attenuate CGS are still unknown. In this study, continuous administration of 12 mg/day for 8 weeks was decreased the incidence of gallstones induced by lithogenic diet (LD) from 100% to 25%. NaB modulated SCFAs and improved the gut microbiota. The remodeling of the gut microbiota changed the bile acid compositions and decreased cecal tauro-α-muricholic acid (T-α-MCA) and tauro-β-muricholic acid (T-β-MCA) which are effective farnesoid X receptor (FXR) antagonists. The quantitative real-time PCR examination showed that NaB significantly increased levels of ileal Fxr, fibroblast growth factor-15 (Fgf-15) and small heterodimer partner (Shp) mRNA and subsequently inhibited bile acid synthesis. In addition, NaB enhanced bile acid excretion by increasing the levels of hepatic multidrug resistance protein 2 (Mdr2) and bile salt export pump (Bsep) mRNA, and it enhanced bile acid reabsorption in the intestine by increasing the levels of ileal bile acid transporter (Ibat) mRNA. In addition, NaB reduced the absorption of cholesterol in the intestine and inhibited the excretion of cholesterol in the liver, which reduced the cholesterol concentration in serum and bile. Furthermore, the protective effects of NaB administration were abolished by FXR antagonists. Taken together, our results suggest that NaB mitigates CGS by modulating the gut microbiota to regulate the FXR-FGF-15/SHP signaling pathway. [ABSTRACT FROM AUTHOR]

Ag nanoparticles embedded in soda-lime silicate glass were fabricated by ion-exchange and subsequently annealing method. Z-scan technique, femtosecond time-resolved optical Kerr effect (OKE) technique and femtosecond pump-probe experiment were used to investigate the effects of laser wavelength and laser pulse duration as well as annealing temperature on the third-order optical nonlinearity and ultrafast dynamics of the composites. It was found that the third-order susceptibility of Ag nanoparticles composite glass measured by 400 nm pulse source is larger than that measured by 800 nm pulse source due to an enhancement effect of local field near surface plasmon resonance of Ag nanoparticles in silicate glass. The third-order optical nonlinearity measured by ns laser source is about two orders of magnitude larger than that measured from fs pulse. The annealing temperature has an important effect on the third-order optical nonlinearity and ultrafast dynamics of the composites. Third-order nonlinear susceptibility up to 10-10 esu and fast relaxation process up to 0.2 ps have been obtained in Ag nanoparticles doped glass. [ABSTRACT FROM AUTHOR]

The crosstalk between macrophages and gastric epithelial cells has emerged as a player in chronic inflammation during intestinal metaplasia. However, the role of bile acid on this modulation remains to be studied. We hypothesized that deoxycholic acid-induced macrophages secreted exosomes to mediate intercellular communication and promoted intestinal metaplasia in human gastric epithelial cells (GES-1 cells). Macrophage-derived exosomes (M-Exos) and deoxycholic acid-induced macrophage-derived exosomes (D-Exos) were isolated by ultracentrifugation. EdU staining and CCK-8 assay were utilized to evaluate the effects of exosomes on the proliferation of GES-1 cells. Intestinal metaplasia was assessed by the expression of caudal-related homeobox transcription factor 2 (CDX2) at both mRNA and protein level. MicroRNA sequencing revealed the microRNA (miRNA) expression profiles of M-Exos and D-Exos. The role of a specific miRNA and mRNA was analyzed by using miRNA mimics, miRNA inhibitors and siRNAs. D-Exos promoted the expression of CDX2 and suppressed the proliferation of GES-1 cells, compared to M-Exos. The miRNA profiles and quantitative real-time PCR examination showed D-Exos enriched a higher level of hsa-miR-30a-5p than M-Exos. Overexpressed has-miR-30a-5p increased CDX2 expression and inhibited the proliferation in GES-1 cells via targeted Forkhead Box D1 (FOXD1), a potential regulatory factor in the process of intestinal metaplasia. D-Exos may promote intestinal metaplasia and suppress proliferation of GES-1 cells via hsa-miR-30a-5p targeting FOXD1, which may be involved in the action mechanism of bile acid on gastric mucosa. [ABSTRACT FROM AUTHOR]