Search

Abstract The 2023 M7.8 and M7.5 earthquake doublet near Kahramanmaraş, Turkey, provides insight regarding how large earthquakes rupture complex faults. Here we determine the faults geometry using surface ruptures and Synthetic Aperture Radar measurements, and the rupture kinematics from the joint inversion of high-rate Global Navigation Satellite System (GNSS), strong-motion waveforms, and GNSS static displacement. The M7.8 event initiated on a splay fault and subsequently propagated along the main East Anatolian Fault with an average rupture velocity between 3.0 and 4.0 km/s. In contrast, the M7.5 event demonstrated a bilateral supershear rupture of about 5.0–6.0 km/s over an 80 km length. Despite varying strike and dip angles, the sub-faults involved in the mainshock are nearly optimally oriented relative to the local stress tensor. The second event ruptured a fault misaligned with respect to the regional stress, also hinting at the effect of local stress heterogeneity in addition to a possible free surface effect.

As the main form of digital trade, cross-border e-commerce plays an important role, allowing China to expand its opening-up and promote the optimal foreign trade structure. It also provides opportunities for Chinese enterprises to develop digital technology. From the perspective of the establishment of China's cross-border e-commerce comprehensive pilot zone (CBECPZ), this article uses the multi-period DID method to examine the effects of cross-border e-commerce on enterprise digital technology innovation based on listed companies in the Shanghai and Shenzhen stock markets from 2007 to 2020. The CBECPZ dramatically promotes enterprise digital technology innovation. The mechanism test shows that the CBECPZ promotes digital technology innovation by financing constraint alleviation, digital transformation, and producer service industry agglomeration. The heterogeneity test shows that the direct effect is more significant in the enterprises of large-scale, non-state-owned, with high ICT correlation and in areas with strong government resource allocation capabilities. The research findings have important reference value for how to utilize cross-border e-commerce to promote digital technology innovation, and they also provide directional references for other developing countries to develop cross-border e-commerce.

Abstract A M6.8 earthquake struck the High Atlas Mountains in Morocco on 8 September 2023, ending a 63‐year seismic silence. We herein attempt to clarify the seismogenic fault and explore the underlying mechanism for this seismic event based on multiple data sets. Utilizing probabilistic Bayesian inversion on interferometric radar data, we determine a seismogenic fault plane centered at a depth of 26 km, striking 251° and dipping 72°, closely aligned with the Tizi n’Test fault system. Given a hypocenter at the Moho depth, the joint inversion of radar and teleseismic data reveals that the rupture concentrates between depths of 12 and 36 km, offsetting the Mohorovičić discontinuity (Moho) at ∼32 km. Considering a strong link between magma activity and failure in lower crust, we propose that the triggering of the earthquake possibly was mantle upwelling that also supports the high topography.

Abstract As global temperature rises, the frequency of extreme climate events, e.g., severe droughts and floods, has increased significantly and caused severe damage over the past years. To this regard, precipitation efficiency, a crucial meteorological parameter, could provide valuable insights for a better understanding of the patterns and characteristics of these extreme events. In this study, taking Guangdong province as an exemplary region, we first obtained long-term and high-resolution historical records of precipitation efficiency by integrating the observations from a dense network of Global Navigation Satellite System (GNSS) stations with precipitation data, and then characterized the extreme drought and wetness through climate indices. We found a distinct seasonal trend in precipitation efficiency in Guangdong, with annual fluctuations ranging from 10 to 25%. Notably, precipitation efficiency is higher in proximity to the Pearl River Delta Plain and gradually decreases towards the east and west. The occurrence of anomalous peaks and valleys in precipitation efficiency generally corresponds to dry and wet conditions, respectively. A total of 9 extreme wet events and 6 dry events occurred from January 2007 to May 2022, with durations from 3 to 6 months. Our results also demonstrated that both wet and dry frequencies exhibit an increasing trend with the expansion of the time scale, and the frequency of extreme events near the Pearl River Delta Plain surpasses that of other regions. Furthermore, the propagation time from meteorological anomalies to agricultural and hydrological anomalies is about 3 months. The periodic characteristics of meteorological anomalies are identified as the primary driver for other anomalous periodic patterns. Our work unveils the long-term dynamic behavior of precipitation efficiency, as well as the characteristics of extreme drought and wetness events in the regions characterized by intricate land–atmosphere interactions.

Abstract Sepsis is a common acute and severe medical condition with a high mortality rate. Anoikis, an emerging form of cell death, plays a significant role in various diseases. However, the role of anoikis in sepsis remains poorly understood. Based on the datasets from Gene Expression Omnibus and anoikis-related genes from GeneCards, the differentially expressed anoikis-related genes (DEARGs) were identified. Based on hub genes of DEARGs, a novel prognostic risk model was constructed, and the pattern of immune infiltration was investigated by CIBERSORT algorithm. And small molecule compounds targeting anoikis in sepsis were analyzed using Autodock. Of 23 DEARGs, CXCL8, CFLAR, FASLG and TP53 were significantly associated with the prognosis of sepsis (P

A finite-fault earthquake slip model can characterize the kinematics of rupture, which is essential for earthquake mechanism studies and seismic hazard assessments. The finite-fault model of an earthquake can be inverted from a wide range of geodetic measurements and seismic recordings. The linear least squares method minimizes misfits between observations and forward modeling and is a common approach in finite-fault inversion problems. This method may not yield the most plausible finite-fault model and has four main limitations. First, total parameter spaces are challenging to explore, and non-Gaussian parameter uncertainties cannot be evaluated. Second, to improve the stability of the fault slip inversion, fault slip smoothing operators (regularization techniques) are usually applied; however, determining the strength of smoothing a fault slip distribution is subjective. Third, the fault geometry needs to be predetermined, and different fault geometry settings can result in varying inversion results. Fourth, it is difficult to account for uncertainties in forward modeling because of imprecise Earth velocity models. In contrast, Bayesian inversion determines the probability density distribution of the model parameters, providing a globally optimized solution to all model parameters and characterizing trade-offs between pairs of model parameters. Therefore, the Bayesian approach effectively overcomes the problems encountered in linear inversion. With the rapid improvement in computer technology, Bayesian inversion has become highly developed, especially in the past decade. This review reports the results of recent Bayesian finite-fault inversion studies and explains the theory and methodology of Bayesian finite-fault inversion.

Abstract Fault geometry is an essential component for understanding earthquake genesis and dynamic rupture propagation. Here we employed space-based geodetic observations and geological survey, adopting a fully Bayesian approach, to probabilistically estimate the fault geometry of the 2021 Mw7.4 Maduo earthquake. The fault is predominantly characterized by strike-slip motions with three main geometry irregularities, reflecting the segmented pattern of the earthquake rupture. On the west side of the epicenter, the fault exhibits north-dipping angles (75–81°), whereas on the east side, it shows sub-vertical angles (82–87°). For the southeast branch, geodetic inversion reveals an overall shallow-dipping (44 ± 5°) faulting, yet further segmentation of the branch in the model and analysis of aftershock mechnism indicate that the dip of the branch faults may vary between vertical and shallow angles. This finding warrants confirmation through future underground observation data.These results suggest that strike-slip faulting could occur on unsuitably orientated planes during any seismic event.

Background: Obesity is a globally increasing health problem that impacts multiple organ systems and a potentially modifiable risk factor for many diseases. Obesity has a significant impact on lung function and is strongly linked to the pathophysiology that contributes to lung diseases. On the other hand, reports have emerged that obesity is associated with a better prognosis than for normal weight individuals in some lung diseases, including pneumonia, acute lung injury/acute respiratory distress syndrome, chronic obstructive pulmonary disease, and lung cancer. The lesser mortality and better prognosis in patients with obesity is known as obesity paradox. While obesity paradox is both recognized and disputed in epidemiological studies, recent research has suggested possible mechanisms. Summary: In this review, we attempted to explain and summarize these factors and mechanisms, including immune response, pulmonary fibrosis, lung function, microbiota, fat and muscle reserves, which are significantly altered by obesity and may contribute to the obesity paradox in lung diseases. We also discuss contrary literature that attributes the “obesity paradox” to confounding. Key Messages: The review will illustrate the possible role of obesity in the prognosis or course of lung diseases, leading to a better understanding of the obesity paradox and provide hints for further basic and clinical research in lung diseases.

Objectives. To evaluate the relationship between the plasma miR-223 expression level and clopidogrel resistance in acute coronary syndrome (ACS) patients. Methods. We performed a search for publications using online databases including PubMed, EMBASE, Cochrane Library, and Chinese Databases (CNKI database, Weipu database, and Wanfang database) from the inception of the databases to June 18, 2023, to identify studies reporting the relationship between the plasma miR-223 level and clopidogrel resistance in ACS patients. Two researchers independently searched and screened to ensure the consistency of the results and assess the quality of the included studies according to the Newcastle-Ottawa scale. A fixed-effects model was used for pooling data with STATA 14.0. Results. Four articles including 399 Chinese ACS patients were eligible for the meta-analysis. Low plasma miR-223 levels were independently correlated with clopidogrel resistance in Chinese ACS patients (OR 0.58, 95% CI: 0.33–1.04). Conclusion. Lower plasma miR-223 levels are associated with clopidogrel resistance in Chinese ACS patients, suggesting that miR-223 may be a potential diagnostic biomarker of clopidogrel resistance.

The interaction between platelets and vascular endothelial cells plays a pivotal role in the pathophysiology of acute ischemic stroke (AIS), especially in atherosclerosis formation. However, the underlying mechanism is not entirely clear. The aim of this study was to elucidate the role of platelets-derived miRNA in the development of atherosclerosis and AIS. We evaluated the miRNA expression profiles of serum microvesicles (MV) in five AIS patients and five healthy controls using RNA-seq, and then measured the levels of selected platelets derived miRNAs by qRT-PCR. miR-200a-3p expression in the serum MV and platelets had increased to 1.41 (p < 0.05) and 3.29 times (p < 0.001), respectively, in AIS patients compared with healthy controls, and was modified by severity of AIS. We transferred Cy5-miR-200a-3p into platelets, collected and identified platelets-derived MV (PMVs). Then, the gene expression of p38 MAPK/c-Jun pathway was analyzed using both miR-200a-3p gain- and loss-of-function experiments and PMVs coincubation with HUVEC. The results showed that activated platelets remotely modulated endothelins 1 (ET-1) and vascular endothelial growth factor A (VEGFA) levels in HUVEC through the release of miR-200a-3p-containing PMVs via targeting MAPK14. The results of ROC analyses showed that combination of platelet miR-200a-3p, serum ET-1 and VEGFA levels had an AUC of 0.817, a sensitivity of 70%, and a specificity of 89%. Our results presented new evidence that activated platelets could remotely modulate ET-1 and VEGFA expression in HUVEC via releasing miR-200a-3p-enriched PMVs, which provides a potential miRNA-based predictive biomarker and therapeutic strategy for atherosclerosis and AIS.

Stroke is one of the major causes of death and long-term disability, of which acute ischemic stroke (AIS) is the most common type. Although circular RNA (circRNA) expression profiles of AIS patients have been reported to be significantly altered in blood and peripheral blood mononuclear cells, the role of exosome-containing circRNAs after AIS is still unknown. Plasma exosomes from 10 AIS patients and 10 controls were isolated, and through microarray and bioinformatics analysis, the profile and putative function of circRNAs in the plasma exosomes were studied. A total of 198 circRNAs were differentially quantified (|log2 fold change| ≥ 1.00, p < 0.05) between AIS patients and controls. The levels of 12 candidate circRNAs were verified by qRT-PCR, and the quantities of 10 of these circRNAs were consistent with the data of microarray. The functions of host genes of differentially quantified circRNAs, including RNA and protein process, focal adhesion, and leukocyte transendothelial migration, were associated with the development of AIS. As a miRNA sponge, differentially quantified circRNAs had the potential to regulate pathways related to AIS, like PI3K-Akt, AMPK, and chemokine pathways. Of 198 differentially quantified circRNAs, 96 circRNAs possessing a strong translational ability could affect cellular structure and activity, like focal adhesion, tight junction, and endocytosis. Most differentially quantified circRNAs were predicted to bind to EIF4A3 and AGO2—two RNA-binding proteins (RBPs)—and to play a role in AIS. Moreover, four of ten circRNAs with verified levels by qRT-PCR (hsa_circ_0112036, hsa_circ_0066867, hsa_circ_0093708, and hsa_circ_0041685) were predicted to participate in processes of AIS, including PI3K-Akt, AMPK, and chemokine pathways as well as endocytosis, and to be potentially useful as diagnostic biomarkers for AIS. In conclusion, plasma exosome-derived circRNAs were significantly differentially quantified between AIS patients and controls and participated in the occurrence and progression of AIS by sponging miRNA/RBPs or translating into proteins, indicating that circRNAs from plasma exosomes could be crucial molecules in the pathogenesis of AIS and promising candidates as diagnostic biomarkers and therapeutic targets for the condition.

Obesity is a risk factor of many diseases, but could be beneficial to the individuals with bacterial infection. The present study was conducted to investigate the relationship between obesity and heart during nonfatal bacterial infection. Male normal (lean) and diet-induced obesity mice (DIO, fed with high-fat diet) were chosen to perform nasal instillation with E. coli to establish a nonfatal acute mouse model. The cardiac histopathology, inflammation and oxidative damage, as well as apoptosis were detected post-infection. The results revealed that the Escherichia coli (E.coli)-infected mice exhibited increased cardiac index, contents of IL-1β, IL-6, IL-8, TNF-α, leptin and resistin, levels of apoptotic proteins (caspase-3 and caspase-9, and bax/bcl-2 ratio), cardiac pathological changes and oxidative stress. Furthermore, these parameters were more serious in the lean mice than those in the DIO mice. In summary, our findings gave a new sight that E.coli infection impaired heart via histopathological lesions, inflammation and oxidative stress and excessive apoptosis of cardiomyocytes. Interestingly, obesity exerted attenuated effects on the heart of mice with non-fatal infection of E.coli through decreased inflammation, oxidative stress and apoptosis of cardiac tissue.

Optimizing the noise model for global navigation satellite system (GNSS) vertical time series is vital to obtain reliable uplift (or subsidence) deformation velocity fields and assess the associated uncertainties. In this study, by thoroughly considering the effects of hydrological loading (HYDL) that dominates the seasonal fluctuations and common mode error (CME), we analyzed the optimal noise characteristics of GNSS vertical time series at 39 stations spanning from January 2011 to August 2019 in the Chuandian region, southeast of the Qinghai–Tibet Plateau. Our results showed that the optimal noise models without HYDL correction were white noise plus flicker noise (WN + FN), white noise plus power law noise (WN + PL), and white noise plus Gauss–Markov noise (WN + GGM), which accounted for 87%, 10%, and 3% of GNSS stations, respectively. By contrast, the optimal noise models at all stations were WN + FN and WN + PL after correction by different HYDLs. The correlation between CME and HYDL provided by the School and Observatory of Earth Sciences (EOST), namely EOST_HYDL, was 0.63~0.8 and the value of RMS reduction was 18.9~40.3% after removing EOST_HYDL time series from the CME, with a mean value of 31.8%, there is a good correlation and consistency between CME and EOST_HYDL. The absolute value of vertical velocity and its uncertainty with and without EOST_HYDL correction varied from 0.11 to 0.55 mm/a and 0 to 0.23 mm/a, respectively, implying that the effect of HYDL should not be neglected when performing optimal noise model analysis for GNSS vertical time series in the Chuandian region.

The pressure responsiveness property of a skirt-cushion system, which is closely related to the overall performance of Air Cushion Vehicles (ACVs), has always been the difficulty and challenging problem involving cushion aerodynamics and flexible skirt dynamics. Based on a widely used bag and finger skirt-cushion system, the pressure responsiveness properties are investigated numerically. The physical process and mechanism are analyzed and a numerical method for evaluating the pressure responsiveness property is proposed. A cushion-skirt information communication platform is also presented for interchanging the force and the skirt configuration between cushion aerodynamics and flexible skirt dynamics. The pressure responsiveness of a typical skirt-cushion system is calculated and the results demonstrate that the pressure responsiveness property helps alleviate the influence of the cushion height changing on the overall performance of ACVs. Finally, the influences of skirt geometrical and cushion aerodynamic parameters on the pressure responsiveness properties are discussed systematically, giving insight into the design of skirt-cushion systems.

The authors here investigate in the 2019 Ridgecrest earthquakes in Searles Valley, California. Based on geodetic and seismological data, the authors separate the event into two earthquakes (Mw 6.5 and 7.1) and produce kinematic slip models of the event.

N6-methyladenosine (m6A) modification is a newly discovered regulatory mechanism in eukaryotes. As one of the most common epigenetic mechanisms, m6A’s role in the development of atherosclerosis (AS) and atherosclerotic diseases (AD) has also received increasing attention. Herein, we elucidate the effect of m6A on major risk factors for AS, including lipid metabolism disorders, hypertension, and hyperglycemia. We also describe how m6A methylation contributes to endothelial cell injury, macrophage response, inflammation, and smooth muscle cell response in AS and AD. Subsequently, we illustrate the m6A-mediated aberrant biological role in the pathogenesis of AS and AD, and analyze the levels of m6A methylation in peripheral blood or local tissues of AS and AD, which helps to further discuss the diagnostic and therapeutic potential of m6A regulation for AS and AD. In summary, studies on m6A methylation provide new insights into the pathophysiologic mechanisms of AS and AD, and m6A methylation could be a novel diagnostic biomarker and therapeutic target for AS and AD.

Cell migration through extracellular matrices is critical to many physiological processes, such as tissue development, immunological response and cancer metastasis. Previous models including persistent random walk (PRW) and Lévy walk only explain the migratory dynamics of some cell types in a homogeneous environment. Recently, it was discovered that the intracellular actin flow can robustly ensure a universal coupling between cell migratory speed and persistence for a variety of cell types migrating in the in vitro assays and live tissues. However, effects of the correlation between speed and persistence on the macroscopic cell migration dynamics and patterns in complex environments are largely unknown. In this study, we developed a Monte Carlo random walk simulation to investigate the motility, the search ability and the search efficiency of a cell moving in both homogeneous and porous environments. The cell is simplified as a dimensionless particle, moving according to PRW, Lévy walk, random walk with linear speed-persistence correlation (linear RWSP) and random walk with nonlinear speed-persistence correlation (nonlinear RWSP). The coarse-grained analysis showed that the nonlinear RWSP achieved the largest motility in both homogeneous and porous environments. When a particle searches for targets, the nonlinear coupling of speed and persistence improves the search ability (i.e. find more targets in a fixed time period), but sacrifices the search efficiency (i.e. find less targets per unit distance). Moreover, both the convex and concave pores restrict particle motion, especially for the nonlinear RWSP and Lévy walk. Overall, our results demonstrate that the nonlinear correlation of speed and persistence has the potential to enhance the motility and searching properties in complex environments, and could serve as a starting point for more detailed studies of active particles in biological, engineering and social science fields.

Seasonal variations in the vertical Global Positioning System (GPS) time series are mainly caused by environmental loading, e.g., hydrological loading (HYDL), atmospheric loading (ATML), and nontidal oceanic loading (NTOL), which can be synthesized based on models developed by various institutions. A comprehensive comparison among these models is essential to extract reliable vertical deformation data, especially on a regional scale. In this study, we selected 4 HYDL, 5 ATML, 2 NTOL, and their 40 combined products to investigate their effects on seasonal variations in vertical GPS time series at 27 GPS stations in Yunnan, southwest China. These products were provided by the German Research Center for Geosciences (GFZ), School and Observatory of Earth Sciences (EOST), and International Mass Loading Service (IMLS). Furthermore, we used the Cross Wavelet Transform (XWT) method to analyze the relative phase relationship between the GPS and the environmental loading time series. Our result showed that the largest average Root-Mean-Square (RMS) reduction value was 1.32 mm after removing the deformation associated with 4 HYDL from the vertical GPS time series, whereas the RMS reductions after 5 ATML and 2 NTOL model corrections were negative at most stations in Yunnan. The average RMS reduction value of the optimal combination of environmental loading products was 1.24 mm, which was worse than the HYDL (IMLS_GEOSFPIT)-only correction, indicating that HYDL was the main factor responding for seasonal variations at most stations in Yunnan. The XWT result showed that HYDL also explained the annual variations reasonably. Our finding implies that HYDL (IMLS_GEOSFPIT) contributes the most to the environmental loading in Yunnan, and that the ATML and NTOL models used in this paper cannot be effective to correct seasonal variations.

Hepatic oxidative stress, as one important mechanism of cadmium (Cd)-induced hepatic toxicity, could, as known, be ameliorated by vitamin E (VE). However, the underlying mechanism remains to be elucidated. To investigate whether the antioxidant vitamin E can protect against Cd-induced sub-chronic liver injury associated with oxidative stress and nuclear factor erythrocyte 2-related factor 2 (Nrf2) pathway, male Sprague-Dawley rats (nine-week-old) were randomly divided into four groups (eight rats/group), namely, control, VE (100 mg/kg VE), Cd (5 mg/kg CdCl2) and VE+Cd (100 mg/kg VE+5 mg/kg CdCl2), and received intragastric administration of Cd and/or VE for four weeks. Cd-exposure alone resulted in reduced liver weight, liver histological alteration and oxidative stress, accumulation of Cd in the liver, elevated ALT and AST concentrations in serum together with decreased mRNA and protein expressions of Nrf2 pathway related molecules (Nrf2, HO-1, NQO-1, GCLC, GCLM and GST). However, the co-treatment of Cd and VE significantly ameliorated the changes mentioned above, and promoted the expression of genes and proteins of Nrf2 pathway related molecules in comparison to the Cd-exposure alone. Our results indicate that the protective effect of VE against Cd-induced sub-chronic hepatic damage in rats is associated with the inhibition of oxidative stress and activation of Nrf2 pathway.

Abstract We determine rupture kinematics of the 2020 Mw 6.7 Elazig, Turkey earthquake from joint inversion of interferometric synthetic aperture radar (InSAR) measurements, regional 1 Hz Global Navigation Satellite System (GNSS), strong motion, and teleseismic waveforms, and we also use dynamic modeling to assess the faulting properties to explain the observed kinematics. Our work shows that this event predominantly ruptured unilaterally toward the SW along the East Anatolian Fault Zone at a speed as slow as 2.0 km/s for ~20 s, and three main asperities are formed with a depth ranging from 20 km to the surface, but the surface rupture seems negligible. Besides, the dynamic model reveals an initial heterogeneous stress distribution with variations up to 30 MPa, which has been probably built up during the interseismic period. While this event does not seem to promote the failure of Pazarcık seismic gap, it remains elusive to evaluate the disturbed seismic potential between Elazig and Bingol regions.

The current tsunami early warning systems always issue alarms once large undersea earthquakes are detected, inevitably resulting in false warnings since there are no deterministic scaling relations between earthquake size and tsunami potential. In this paper, we assess tsunami potential by analyzing co-seismic ionospheric disturbances (CIDs). We examined CIDs of three megathrusts (the 2014 Mw 8.2 Iquique, the 2015 Mw 8.3 Illapel, and the recent 2021 Mw 8.2 Alaska events) as detected by Global Navigation Satellite System (GNSS) observations. We found that CIDs near the epicenter generated by the 2021 Mw 8.2 Alaska event were significantly weaker than those of the two Chilean events, despite having similar earthquake magnitudes. The propagation direction of CIDs from the Mw 8.2 Alaska earthquake further revealed ruptures toward the deeper seismogenic zone, implying less seafloor uplift and hazardous flooding. Our work sheds light on incorporating GNSS-based CIDs for more trustworthy tsunami warning systems.

The weighted mean temperature (Tm) is a crucial parameter for determining the tropospheric delay in transforming precipitable water vapor. We used the reanalysis data provided by European Centre for Medium-Range Weather Forecasts (ECMWF) to analyze the distribution characteristics of Tm in the vertical direction in China. To address the problem that the precision of the traditional linear function model is limited in fitting the Tm profile, a scheme using the linear and Fourier functions to fit the Tm profile was constructed. Based on the least squares principle (LSQ) to fit the change in its coefficients over time, a Tm model for China with nonlinear elevation correction (CTm-h) was constructed. The experimental results show that, using ECMWF and radiosonde data to evaluate the precision of the CTm-h model, the RMS is 3.43 K and 4.64 K, respectively. Compared to GPT2w, the precision of the CTm-h model in China is increased by about 26.8%. The CTm-h model provides a significant improvement in the correction effect of Tm in the vertical direction, and the Tm profile calculated by the model is closer to the reference value.

Global Positioning System (GPS) has been proved to be a powerful tool for measuring co-seismic ground displacements with an application to seismic source inversion. Whereas most of the tsunamis are triggered by large earthquakes, GPS can contribute to the tsunami early warning system (TEWS) by helping to obtain tsunami source parameters in near real-time. Toward the end of 2012, the second phase of the BeiDou Navigation Satellite System (BDS) constellation was accomplished, and BDS has been providing regional positioning service since then. Numerical results indicate that precision of BDS nowadays is equivalent to that of the GPS. Compared with a single Global Satellite Navigation System (GNSS), combined BDS/GPS real-time processing can improve accuracy and especially reliability of retrieved co-seismic displacements. In the present study, we investigate the potential of BDS to serve for the early warning system of tsunamis in the South China Sea region. To facilitate early warnings of tsunamis and forecasting capabilities in this region, we propose to distribute an array of BDS-stations along the Luzon Island (Philippines). By simulating an earthquake with Mw = 8 at the Manila trench as an example, we demonstrate that such an array will be able to detect earthquake parameters in real time with a high degree of accuracy and, hence, contribute to the fast and reliable tsunami early warning system in this region.

To explore AFB1-induced damage of the small intestine, the changes in structure and expression of TLRs (Toll-like Receptors) in the small intestine of chickens were systematically investigated. Ninety healthy neonatal Cobb chickens were randomized into a control group (0 mg/kg AFB1) and an AFB1 group (0.6 mg/kg AFB1). The crypt depth of the small intestine in the AFB1 group was significantly increased in comparison to the control chickens, while the villus height and area were evidently decreased, as well as the villus:crypt ratio and epithelial thickness. The histopathological observations showed that the villi of the small intestine exposed to AFB1 were obviously shedding. Based on ultrastructural observation, the absorptive cells of small intestine in the AFB1 group exhibited fewer microvilli, mitochondrial vacuolation and the disappearance of mitochondrial cristae, and junctional complexes as well as terminal web. Moreover, the number of goblet cells in the small intestine in the AFB1 group significantly decreased. Also, AFB1 evidently decreased the mRNA expression of TLR2-2, TLR4, and TLR7 in the small intestine. Taken together, our study indicated that dietary 0.6 mg/kg AFB1 could induce histopathological injuries and ultrastructural changes, and depress levels of TLR mRNA in the chicken small intestine.

Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel disease, in part by activating the inflammasome and inducing secretion of interleukin-1ß (IL-1ß). Although much has been learned about inflammasome activation by bacterial pathogens, little is known about how commensals carry out this process. Accordingly, we investigated the mechanism of inflammasome activation by representative commensal bacteria, the Gram-positive Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides fragilis. B. infantis and B. fragilis induced IL-1ß secretion by primary mouse bone marrow-derived macrophages after overnight incubation. IL-1ß secretion also occurred in response to heat-killed bacteria and was only partly reduced when phagocytosis was inhibited with cytochalasin D. Similar results were obtained with a wild-type immortalized mouse macrophage cell line but neither B. infantis nor B. fragilis induced IL-1ß secretion in a mouse macrophage line lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome. IL-1ß secretion in response to B. infantis and B. fragilis was significantly reduced when the wild-type macrophage line was treated with inhibitors of potassium efflux, either increased extracellular potassium concentrations or the channel blocker ruthenium red. Both live and heat-killed B. infantis and B. fragilis also induced IL-1ß secretion by human macrophages (differentiated THP-1 cells or primary monocyte-derived macrophages) after 4 hours of infection, and the secretion was inhibited by raised extracellular potassium and ruthenium red but not by cytochalasin D. Taken together, our findings indicate that the commensal bacteria B. infantis and B. fragilis activate the NLRP3 inflammasome in both mouse and human macrophages by a mechanism that involves potassium efflux and that does not require bacterial viability or phagocytosis.

Background ‒ N6-methyladenosine (m6 A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6 A’s effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods ‒ We analyzed the m6 A enzymes and m6 A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m6 A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results ‒ Methyltransferase-like 3 (METTL3), an m6 A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m6 A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion ‒ The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients. [ABSTRACT FROM AUTHOR]