To promote the accuracy of infrared monitoring of water-bearing rock stability, sandstone samples with varying moisture contents were subjected to infrared monitoring experiments under uniaxial ...compression. Additionally, the temporal-spatial variations of infrared radiation were analyzed. Furthermore, the infrared precursor information of water-bearing rock fracture was quantitatively discussed in light of the critical slowing down theory. The results reveal that the infrared radiation temperature of sandstone surface decreases as the moisture content rises. Variations of maximum infrared radiation temperature (MIRT) during loading on sandstone samples present distinct characteristics in different stages. As the moisture content rises, in the early stage, the trend of MIRT decrease weakens, and the effect of stress on MIRT variation is more obvious. In the plastic deformation stage, the MIRTs fluctuate earlier and more violently. When samples finally break, the MIRTs change suddenly in a reduced range. With the rise of moisture content, the variation trend of infrared image and MIRT gradually changes from falling-rising-abruptly changing to rising-being abnormal-abruptly changing. The MIRTs of sandstone samples with varying moisture contents present the characteristics of critical slowing down during loading; and the sample with a higher moisture content exhibits more notable precursor characteristics. In addition, the variance index is more sensitive to macro-fractures than the autocorrelation coefficient and can provide more accurate precursor information for the fracture and instability monitoring of water-bearing rock.
To evaluate the effects of fructose diphosphate (FDP) on routine coagulation tests in vitro, we added FDP into the mixed normal plasma to obtain the final concentration of 0, 1, 2, 3, 4, 5, 6, 10, ...15, 20, 25, 30 and 35 mg/mL of drug. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen (FBG) and thrombin time (TT) of samples were analyzed with blood coagulation analyzers from four different manufacturers(Sysmex, Stago, SEKISUI and Werfen) and their corresponding reagents, respectively. Before the experiment, we also observed whether there were significant differences in coagulation test results of different lots of reagents produced by each manufacturer. At the same time as the four routine clotting tests, the Sysmex blood coagulation analyzer and its proprietary analysis software were used to detect the change of maximum platelet aggregation rate in platelet-rich plasma after adding FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL). The results of PT, aPTT and TT showed a FDP (0-35 mg/mL) concentration-dependent increase and a FBG concentration-dependent decrease. The degree of change (increase or decrease) varied depending on the assay system, with PT and aPTT being more affected by the Sysmex blood coagulation testing instrument reagent system and less affected by CEKISUI, TT less affected by CEKISUI and more affected by Stago, and FBG less affected by Stago and more affected by Sysmex. The results of PT, aPTT and TT were statistically positively correlated with their FDP concentrations, while FBG was negatively correlated. The correlation coefficients between FDP and the coagulation testing systems of Sysmex, Stago, Werfen and SEKISUI were 0.975, 0.988, 0.967, 0.986 for PT, and 0.993, 0.989, 0.990 and 0.962 for aPTT, 0.994, 0.960, 0.977 and 0.982 for TT, - 0.990, - 0.983, - 0.989 and - 0.954 for FBG, respectively. Different concentrations of FDP (0, 1, 2, 3, 4, 5 and 6 mg/mL) had different effects on the maximum aggregation rate of platelet induced by the agonists of adenosine diphosphate (ADP, 5 µmol/L), arachidonic acid (Ara, 1 mmol/L), collagen (Col, 2.5 µg/mL) and epinephrine (Epi,10 µmol/L), but the overall downward trend was consistent, that is, with the increase of FDP concentration, the platelet aggregation rate decreased significantly. Our experimental study demonstrated a possible effect of FDP on the assays of coagulation and Platelet aggregation, which may arise because the drug interferes with the coagulation and platelet aggregation detection system, or it may affect our in vivo coagulation system and Platelet aggregation function, the real mechanism of which remains to be further verified and studied.
In order to study the effect of water on the electromagnetic radiation (EMR) signals released during rock deformation and fracturing, uniaxial compression experiments were performed on sandstone ...samples with different water contents. During the experiments, the EMR signals were acquired. Furthermore, the time-frequency characteristics of the signals were analyzed, and their generation mechanism and the effect of water were discussed in depth. The results show that the EMR energy released decreases gradually with the increase of water content, and the EMR energy and water content can be linked by a binomial equation. For sandstone with higher water content, the precursor characteristics of EMR released in the fracturing process are more obvious. With the increase of water content, the proportion of signals in the low frequency band grows gradually, while that of signals in high frequency band falls gradually. Water reduces the macroscopic mechanical strength and fracture mechanical characteristics of sandstone, which weakens the EMR signals produced by piezoelectric effect and charge separation. Besides, with respect to the microscopic fracturing mode, the sandstone with higher water content is more likely to undergo inter-granular fracturing, which may be an important microscopic reason for the weakening of EMR of water-bearing sandstone. An EMR-based damage evolution model of water-bearing sandstone was preliminarily established, and the model helps to calculate the stress state of water-bearing rock.
•The time-frequency characteristics of EMR of sandstone with different water content during loading were studied.•The causes of EMR reduction of water-bearing sandstone were studied.•A damage evolution model of water-bearing sandstone based on EMR was established.
A numerical model of internal solitary waves in continuously stratified fluids is developed by introducing a density transport equation to the three-dimensional Navier–Stokes equation and adopting ...the fully nonlinear models of the Dubreil-Jacotin-Long equation to obtain the initial field of the ISW. The corresponding turbulence model has also been modified to ensure that it considers the variable density field. Comparisons between numerical simulation results and experimental results show that the total resistance, the nondimensional pressure coefficient, and the nondimensional friction coefficient for the standard submarine model proposed by the Defense Advanced Research Projects Agency under different flow field conditions are highly consistent with the experimental results. The model established is used to numerically analyse the forces and moments of the standard submarine model encountering ISWs at different submergence depths. The influence of the rotation centre position on the moment is discussed, and the position range of the optimal rotation centre is proposed.
The damage of integrated epithelial epithelium is a key pathogenic factor and closely associated with the recurrence of ulcerative colitis (UC). Here, we reported that vanillic acid (VA) exerted ...potent therapeutic effects on DSS-induced colitis by restoring intestinal epithelium homeostasis via the inhibition of ferroptosis. By the CETSA assay and DARTS assay, we identified carbonic anhydrase IX (CAIX, CA9) as the direct target of VA. The binding of VA to CA9 causes insulin-induced gene-2 (INSIG2) to interact with stromal interaction molecule 1 (STIM1), rather than SREBP cleavage-activating protein (SCAP), leading to the translocation of SCAP-SREBP1 from the endoplasmic reticulum (ER) to the Golgi apparatus for cleavage into mature SREBP1. The activation of SREBP1 induced by VA then significantly facilitated the transcription of stearoyl-CoA desaturase 1 (SCD1) to exert an inhibitory effect on ferroptosis. By inhibiting the excessive death of intestinal epithelial cells caused by ferroptosis, VA effectively preserved the integrity of intestinal barrier and prevented the progression of unresolved inflammation. In conclusion, our study demonstrated that VA could alleviate colitis by restoring intestinal epithelium homeostasis through CA9/STIM1-mediated inhibition of ferroptosis, providing a promising therapeutic candidate for UC.
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•VA alleviates colitis by restoring intestinal epithelium homeostasis via inhibiting ferroptosis.•CA9 is identified as the direct target of VA.•VA promotes the binding of CA9 to STIM1, leading to the activation of SCAP/SREBP1 complex.•Inhibition of ferroptosis by VA is dependent on CA9-SREBP1/SCD1 axis.
Entity alignment is an important task in knowledge fusion, which aims to link entities that have the same real-world identity in two knowledge graphs. However, in the process of constructing a ...knowledge graph, some noise may inevitably be introduced, which must affect the results of the entity alignment tasks. The triple confidence calculation can quantify the correctness of the triples to reduce the impact of the noise on entity alignment. Therefore, we designed a method to calculate the confidence of the triples and applied it to the knowledge representation learning phase of entity alignment. The method calculates the triple confidence based on the pairing rates of the three angles between the entities and relations. Specifically, the method uses the pairing rates of the three angles as features, which are then fed into a feedforward neural network for training to obtain the triple confidence. Moreover, we introduced the triple confidence into the knowledge representation learning methods to improve their performance in entity alignment. For the graph neural network-based method GCN, we considered entity confidence when calculating the adjacency matrix, and for the translation-based method TransE, we proposed a strategy to dynamically adjust the margin value in the loss function based on confidence. These two methods were then applied to the entity alignment, and the experimental results demonstrate that compared with the knowledge representation learning methods without integrating confidence, the confidence-based knowledge representation learning methods achieved excellent performance in the entity alignment task.
A large number of electromagnetic radiation (EMR) signals are released during loading failure of rock mass, and these signals which contain complex and abundant fracture information can provides ...precursor of rock mass instability. In order to investigate the effect of water on the EMR characteristics of fractured sandstone, a uniaxial compression experiment was performed on the dried and saturated sandstone samples with prefabricated parallel double cracks. The EMR signals during loading failure of rock samples were acquired and their mechanical properties and EMR signal characteristics were analyzed. Besides, the precursor of rock sample instability was extracted based on the critical slowing down theory. The experimental results show that compared with the dried rock sample, the saturated rock sample has lower compressive strength, starts to crack earlier, and exhibits a more complicated failure mode. During the loading failure of rock samples, their EMR signals respond well to the fracturing and damage. The cumulative number of pulses of saturated rock sample grows uniformly, while that of dried rock sample show a “gentle-violent” rising mode. Moreover, the cumulative number of pulses of dried rock sample is greater than that of saturated rock sample. Water reduces the crack initiation stress level, and the saturated rock sample is the first to experience a sudden jump of EMR pulse. With the increase of the loading stress, the dominant frequency of EMR gradually transitions from low frequency to high frequency. Compared with dried rock samples, saturated rock samples have a lower proportion of high-frequency signals. Since the dominant mechanism of EMR varies with the change of failure stage, water first promotes the EMR signals of rock samples in the early stage of loading; then, it weakens the EMR signals in the middle and late stages of loading. Based on the critical slowing down theory, the EMR pulse signals were analyzed, which conduces to the extraction of potential precursor of rock sample failure and instability. Compared with dried rock samples, the precursory characteristic of saturated rock sample is more obvious. The research results provide some guidance for the stability of water-bearing fractured rock mass and the monitoring and early warning of related geological hazards.
In order to study the mechanics and acoustic emission (AE) characteristics of fractured rock under water-rock interaction, dried and saturated sandstone samples with prefabricated double parallel ...cracks were prepared. Then, uniaxial compression experiments were performed to obtain their AE signals and crack propagation images. The results show that water reduces the strength and fracture toughness of fractured sandstone and enhances plasticity. After saturation, the samples start to crack earlier; the cracks grow slowly; the failure mode is transformed from shear failure along the prefabricated cracks to combined shear and tensile failure; more secondary cracks are produced. The saturated samples release less elastic energy and weaker AE signals in the whole failure process. However, their AE precursor information is more obvious and advanced, and their AE sources are more widely distributed. Compared with dry specimens, the AE frequencies of saturated specimens in the early stage of loading are distributed in a lower frequency domain. Besides, the saturated samples release less complex AE signals which are dominated by small-scale signals with weaker multi-fractal characteristics. After discussion and analysis, it is pointed out that this may be because water makes rock prone to inter-granular fracture rather than trans-granular fracture. The water lubrication also may reduce the amplitude of middle-frequency band signals produced by the friction on the fracture surface. Multi-fractal parameters can provide more abundant precursory information for rock fracture. This is of great significance to the stability of water-bearing fractured rock mass and its monitoring, and is conducive to the safe exploitation of deep energy.
Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial ...influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown.
The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms.
We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM.
Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease.
The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading ...indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.
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•FXR is a crucial therapeutic target for the management of NAFLD.•Dyslipidemia and pruritus remain major challenges in the development of FXR agonists.•Intestinal FXR antagonists represent a promising strategy for NAFLD therapy.