Cinchophen induces RPA1 related DNA damage and apoptosis to impair ENS development of zebrafish.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become contaminants widely distributed in the environment due to improper disposal and discharge. Previous study has found several components might involve in impairing enteric nervous system (ENS) development of zebrafish, including NSAIDs cinchophen. Deficient ENS development in fetal could lead to Hirschsprung disease (HSCR), a congenital neurocristopathy characterized by absence of enteric neurons in hindgut. However, the intrinsic mechanism of neurotoxicity of cinchophen is unclear. We confirmed that cinchophen could impair ENS development of zebrafish and transcriptome sequencing revealed that disfunction of Replication protein A1 (RPA1), which is involved in DNA replication and repairment, might be relevant to the neurotoxicity effects induced by cinchophen. Based on previous data of single cell RNA sequencing (scRNA-seq) of zebrafish gut cells, we observed that rpa1 mainly expressed in proliferating, differentiating ENS cells and neural crest progenitors. Interestingly, cinchophen induced apoptosis and impaired proliferation. Furthermore, cinchophen caused DNA damage and abnormal activation of ataxia telangiectasia mutated/ Rad3 related (ATM/ATR) and checkpoint kinase 2 (CHK2). Finally, molecular docking indicated cinchophen could bind and antagonize RPA1 more effectively. Our study might provide a better understanding and draw more attention to the role of environmental factors in the pathogenesis of HSCR. And the mechanism of cinchophen neurotoxicity would give theoretical guidance for clinical pharmacy.

Virulence and Molecular characterization reveal sign of sexual genetic recombination of Puccinia striiformis f. sp. tritici and Puccinia striiformis f. sp. hordei in Tibet.

Stripe rust of wheat and stripe rust of barley are caused by different formae speciales, Puccinia striiformis f. sp. tritici (Pst) and P. striiformis f. sp. hordei (Psh), respectively. To understand the relationship between the populations of the two formae speciales, a total of 260 P. striiformis isolates, including 140 from barley and 120 from wheat collected from Linzhi, Tibet, China from 2018 to 2020, were tested on 18 barley and 13 wheat genotypes, and genotyped with 26 single-nucleotide polymorphism (SNP)-based Kompetitive Allele Specific PCR (KASP) markers. As a result, 260 isolates were identified as 83 virulence phenotypes (VPs), 115 of which as 9 VPs and can only infect wheat (wheat population), 111 as 54 VPs and can only infect barley (barley population), and 34 belonged to 20 VPs that can attack both wheat and barley (mixed population). Of 149 multi-locus genotypes (MLGs) that were identified, 92 were from wheat, 56 from barley, and 1 from both wheat and barley. Phenotypic and genotypic diversity was high in the populations from wheat and barley. Low linkage disequilibrium was found in most of sampling sites of both crops, indicating strong signs of sexual reproduction (|¬r(_)d| = 0.022-0.393, P = 0.004-0.847). Whereas, it was not observed in the overall population (wheat and barley sources), and the wheat, barley, and mixed populations, which may be due to complex composition of isolates. Population structure analyses based on phenotyping and SNP-KASP genotypes supported the separations of the two formae speciales. However, MLGs and clusters containing isolates from both wheat and barley indicated obvious indication of sexual genetic recombination between the two formae speciales. The results of the study provided an insight into evolution of Pst and Psh, and showed the importance of management strategy for stripe rust of wheat and barley in regions where both crops are grown.

Association of carotid atherosclerotic plaque and intima-media thickness with the monocyte to high-density lipoprotein cholesterol ratio among low-income residents of rural China: a population-based cross-sectional study.

BACKGROUND: The monocytes to high-density lipoprotein cholesterol ratio (MHR) has been identified as a potential biomarker for cardiovascular and cerebrovascular diseases. In this population-based cross-sectional study, we explored the relationships among carotid artery disease (CAD), including the presence of carotid atherosclerotic plaque (CAP) and carotid artery intima-media thickness (CIMT), the MHR, and related parameter changes. METHODS: This cross-sectional study, Conducted from April to June 2019 in a rural area of Tianjin, involved middle-aged and elderly participants. Based on carotid ultrasound examinations, participants were divided into CAP and non-CAP groups. Logistic regression and Receiver Operating Characteristic (ROC) curve analyses were utilized to assess MHR's predictive value for CAP. Gender-specific analyses were also performed to examine predictive variations. The relationship between CIMT and MHR was evaluated using linear regression. RESULTS: Of the 2109 participants meeting the inclusion criteria, 51.6% were identified with CAP. Multivariate analysis revealed a significant association between MHR and CAP prevalence, (OR, 9.670; 95% CI, 2.359-39.631; P = 0.002), particularly in females (OR, 5.921; 95% CI, 1.823-19.231; P = 0.003), after adjusting for covariates. However, no significant correlation was found between CIMT and MHR when adjusted for other factors. The ROC analysis showed the area under the curve for MHR and CAP to be 0.569 (95% CI: 0.544-0.593; P < 0.001). CONCLUSIONS: These findings suggested that it is crucial to enhance early screening and intervention for CAD, specifically focusing on the prevention and progression of CAP, to address the unique health challenges faced by low-income groups in rural settings. Emphasizing these preventive measures could significantly contribute to improving cardiovascular health outcomes in this vulnerable population.

Counting d-Orbital Vacancies of Transition-Metal Catalysts for the Sulfur Reduction Reaction.

The electrocatalytic sulfur reduction reaction (SRR) would allow the production of renewable high-capacity rechargeable lithium-sulfur (Li-S) batteries using sustainable and nontoxic elemental sulfur as a cathode material, but its slow reaction rate causes a serious shuttle effect and dramatically reduces the capacity. We found that a catalyst composed of Pd nanoparticles supported by ordered mesoporous carbon (Pd/OMC) had a high reaction rate in the SRR, and a Li-S battery assembled with this catalyst had a low shuttle constant of 0.031 h-1 and a high-rate performance with a specific capacity of 1527 mAh g-1 at 0.1 C which is close to the theoretical value. The high activity of Pd/OMC with a d-orbital vacancy of 0.87 e was predicted from a volcano relationship between the d charge for the metal and the adsorption activation entropy and reaction rate for the SRR by examining Pd, Au, Pt, Rh, and Ru transition-metal nanocatalysts. The strategy of using a single electronic structure descriptor to design high-efficiency SRR catalysts has suggested a way to produce practical Li-S batteries.

Countrywide inter-epidemic region migration pattern suggests the role of southwestern population in wheat stripe rust epidemics in China.

Understanding countrywide pathogen population structure and inter-epidemic region spread is crucial for deciphering crop potential losses. Wheat stripe rust caused by Puccinia striiformis f. sp. tritici is a destructive disease that affects worldwide wheat production, widespread in China, representing largest epidemic region globally. This study aimed to understand the population structure and migration route of P. striiformis f. sp. tritici across China based on sampling from 15 provinces representing six epidemic zones, viz., over-summering, over-wintering, eastern, Yun-Gui, Xinjiang and Tibet epidemic regions. High genotypic diversity was recorded in over-summering, Tibet and over-wintering epidemic regions. Epidemic regions partly explain population subdivision with variable divergence (FST  = 0.005-0.344). Xinjiang and Tibet epidemic regions were independent epidemic zones with least sharing of genotypes. Among other epidemic zones, i.e. over-summering, over-wintering, eastern and Yun-Gui epidemic zones, re-sampling MLGs, clustering-based structure, DAPC analyses, relative migration and low divergence (FST from 0.006 to 0.073) revealed frequent geneflow. Yun-Gui epidemic regions, with a potential for both over-summering and over-wintering, could play an important role in causing epidemics in main wheat-cultivating areas of China. High diversity, recombination signatures and inter-epidemic region migration patterns need to be considered in host-resistant cultivar development in China and neighbouring countries, considering risk of long-distance migration capacity of pathogen.

Dissipative Phase Transition with Driving-Controlled Spatial Dimension and Diffusive Boundary Conditions.

We investigate theoretically and experimentally a first-order dissipative phase transition, with diffusive boundary conditions and the ability to tune the spatial dimension of the system. The considered physical system is a planar semiconductor microcavity in the strong light-matter coupling regime, where polariton excitations are injected by a quasiresonant optical driving field. The spatial dimension of the system from 1D to 2D is tuned by designing the intensity profile of the driving field. We investigate the emergence of criticality by increasing the spatial size of the driven region. The system is nonlinear due to polariton-polariton interactions and the boundary conditions are diffusive because the polaritons can freely diffuse out of the driven region. We show that no phase transition occurs using a 1D driving geometry, while for a 2D geometry we do observe both in theory and experiments the emergence of a first-order phase transition. The demonstrated technique allows all-optical and in situ control of the system geometry, providing a versatile platform for exploring the many-body physics of photons.

The Th17/Treg cell balance: crosstalk among the immune system, bone and microbes in periodontitis.

Periodontopathic bacteria constantly stimulate the host, which causes an immune response, leading to host-induced periodontal tissue damage. The complex interaction and imbalance between Th17 and Treg cells may be critical in the pathogenesis of periodontitis. Furthermore, the RANKL/RANK/OPG system plays a significant role in periodontitis bone metabolism, and its relationship with the Th17/Treg cell imbalance may be a bridge between periodontal bone metabolism and the immune system. This article reviews the literature related to the Th17/Treg cell imbalance mediated by pathogenic periodontal microbes, and its mechanism involving RANKL/RANK/OPG in periodontitis bone metabolism, in an effort to provide new ideas for the study of the immunopathological mechanism of periodontitis.

Microsatellite analysis of genetic diversity in wild and cultivated Portunus trituberculatus in Bohai Bay.

BACKGROUND: Previous studies have revealed a reduction in the genetic diversity of P. trituberculatus in Bohai Sea. However, because swimming crabs have been released into this area for some time, it is unclear whether the release of cultured populations from the national breeding farms of swimming crabs in Bohai Bay have affected the population genetics of wild populations of P. trituberculatus. METHODS AND RESULTS: In this study, the genetic diversity and population structure of 120 P. trituberculatus specimens in Bohai Bay were investigated using six microsatellite loci, including one wild population and one cultivated population. A total of 132 alleles were identified for all loci. The mean expected (He) and observed heterozygosity (Ho) were 0.8185 and 0.7759, respectively, thus indicating high levels of genetic diversity for these two populations. Molecular variance analysis (AMOVA) (FST = 0.0180), genetic distance (D = 0.1168) and similarity (S = 0.8898) indicated that these two populations could not be distinguished genetically. Structural analysis, phylogenetic tree construction, and principal component analysis, showed no significant distinction between the wild and cultivated populations. Finally, we investigated genetic exchange between the two populations by analyzing migration rate (M) and gene flow (Nm), thus demonstrating significant flow of genetic information. CONCLUSIONS: These findings contribute information for further breeding schemes for P. trituberculatus, evaluation of its genetic potential and programs for the protection of wild resources.

Inheritance and Linkage of Virulence Genes of Puccinia striiformis f. sp. hordei.

Puccinia striiformis f. sp. hordei (Psh) causing barley stripe rust has only recently been known to be heteroecious, for which reason the inheritance of its virulence has not been analyzed. Herein, we selfed a Psh isolate, XZ-19-972, on Berberis aggregata and obtained 53 progenies. The virulence phenotypes (VPs) for these progenies were identified on 11 barley differentials, and their genotypes were assessed with 22 Kompetitive allele specific PCR-single nucleotide polymorphism (KASP-SNP) markers. In total, 18 VPs were detected among progenies, 17 (VP2-VP18) of which, corresponding to 43 isolates, were different from the parental isolate showing VP1. Of the 53 progenies, 8 exhibited increased virulence and 34 decreased virulence. One progeny, belonging to VP18, showed a different virulence formula but without a virulence increase or decrease. The parental isolate and all progenies were avirulent to yrc6 but virulent to yrc7. The parental isolate was heterozygous in terms of avirulence/virulence to nine barley resistance gene loci. KASP-SNP marker analysis identified 36 multilocus genotypes, based on which a linkage map was constructed, with total genetic distance intervals of 516.07 cM, spanning 16 avirulence or virulence loci. Taken together, our results provide important insights into the inheritance and virulence diversity of Psh.

Rab35 regulates insulin secretion via phogrin in pancreatic ß cells.

Dysfunction of pancreatic ß cell insulin secretion is related to the pathogenesis of type 2 diabetes (T2D). Rab proteins have been shown to be key players in insulin secretion by pancreatic ß cells, and phogrin is a marker for the processes of exocytosis and insulin secretion. The purposes of this study were to clarify the regulatory role of Rab35 in insulin secretion and analyse the Rab35/phogrin interaction mechanism in ß-TC-6 cells. We studied the effects of Rab35 gene overexpression and interference on insulin secretion and phogrin expression and levels in ß-TC-6 cells. The Rab35/phogrin interaction was verified by GST pulldown, co-IP and co-localisation experiments. Here, we report that Rab35 is mainly distributed in the ß-TC-6-cell plasma membrane and cytoplasm. Rab35 overexpression promotes insulin secretion and decreases phogrin expression in ß-TC-6 cells, whereas its silencing significantly inhibits insulin secretion, promotes phogrin expression (p < 0.05) and causes phogrin redistribution. Furthermore, Rab35 silencing suppresses exocytosis of insulin. Rab35 interacts with phogrin, and both proteins co-localise in the plasma membranes and cytoplasm of ß-TC-6 cells. Our study presents novel evidence that Rab35 regulates insulin secretion by inhibiting phogrin expression and causing intracellular phogrin redistribution in pancreatic ß cells.

Quantitative Detection of Extra Virgin Olive Oil Adulteration, as Opposed to Peanut and Soybean Oil, Employing LED-Induced Fluorescence Spectroscopy.

As it is high in value, extra virgin olive oil (EVOO) is frequently blended with inferior vegetable oils. This study presents an optical method for determining the adulteration level of EVOO with soybean oil as well as peanut oil using LED-induced fluorescence spectroscopy. Eight LEDs with central wavelengths from ultra-violet (UV) to blue are tested to induce the fluorescence spectra of EVOO, peanut oil, and soybean oil, and the UV LED of 372 nm is selected for further detection. Samples are prepared by mixing olive oil with different volume fractions of peanut or soybean oil, and their fluorescence spectra are collected. Different pre-processing and regression methods are utilized to build the prediction model, and good linearity is obtained between the predicted and actual adulteration concentration. This result, accompanied by the non-destruction and no pre-treatment characteristics, proves that it is feasible to use LED-induced fluorescence spectroscopy as a way to investigate the EVOO adulteration level, and paves the way for building a hand-hold device that can be applied to real market conditions in the future.

Classification of Tea Leaves Based on Fluorescence Imaging and Convolutional Neural Networks.

The development of the smartphone and computer vision technique provides customers with a convenient approach to identify tea species, as well as qualities. However, the prediction model may not behave robustly due to changes in illumination conditions. Fluorescence imaging can induce the fluorescence signal from typical components, and thus may improve the prediction accuracy. In this paper, a tea classification method based on fluorescence imaging and convolutional neural networks (CNN) is proposed. Ultra-violet (UV) LEDs with a central wavelength of 370 nm were utilized to induce the fluorescence of tea samples so that the fluorescence images could be captured. Five kinds of tea were included and pre-processed. Two CNN-based classification models, e.g., the VGG16 and ResNet-34, were utilized for model training. Images captured under the conventional fluorescent lamp were also tested for comparison. The results show that the accuracy of the classification model based on fluorescence images is better than those based on the white-light illumination images, and the performance of the VGG16 model is better than the ResNet-34 model in our case. The classification accuracy of fluorescence images reached 97.5%, which proves that the LED-induced fluorescence imaging technique is promising to use in our daily life.

Coordinated Adsorption and Catalytic Conversion of Polysulfides Enabled by Perovskite Bimetallic Hydroxide Nanocages for Lithium-Sulfur Batteries.

Catalysis is an effective remedy for the fast capacity decay of lithium-sulfur batteries induced by the shuttling of lithium polysulfides (LiPSs), but too strong adsorption ability of many catalysts toward LiPSs increases the risk of catalyst passivation and restricts the diffusion of LiPSs for conversion. Herein, perovskite bimetallic hydroxide (CoSn(OH)6 ) nanocages are prepared, which are further wrapped by reduced graphene oxide (rGO) as the catalytic host for sulfur. Because of the coordinated valence state of Co and Sn and the intrinsic defect of the perovskite structure, such bimetallic hydroxide delivers moderate adsorption ability and enhanced catalytic activity toward LiPS conversion. Coupled with the hollow structure and the wrapped rGO as double physical barriers, the redox reaction kinetics, and sulfur utilization are effectively improved with such a host. The assembled battery delivers a good rate performance with a high capacity of 644 mAh g-1 at 2 C and long stability with a capacity decay of 0.068% per cycle over 600 cycles at 1 C. Even with a higher sulfur loading of 3.2 mg cm-2 and a low electrolyte/sulfur ratio of 5 µL mg-1 , the battery still shows high sulfur utilization and good cycling stability.

Non-Hermitian bath model for arrays of coupled nanoresonators.

Nanophotonics systems have recently been studied under the perspective of non-Hermitian physics. Given their potential for wavefront control, nonlinear optics and quantum optics, it is crucial to develop predictive tools to assist their design. We present here a simple model relying on the coupling to an effective bath consisting of a continuum of modes to describe systems of coupled resonators, and test it on dielectric nanocylinder chains accessible to experiments. The effective coupling constants, which depend non-trivially on the distance between resonators, are extracted from numerical simulations in the case of just two coupled elements. The model predicts successfully the dispersive and reactive nature of modes for configurations with multiple resonators, as validated by numerical solutions. It can be applied to larger systems, which are hardly solvable with finite-element approaches.

High-performance lithium-sulfur batteries enabled by regulating Li2S deposition.

Lithium-sulfur batteries (LSBs) have received intensive attention in recent years due to their high theoretical energy density derived from the lithiation of sulfur. In the discharge process, sulfur transforms into lithium polysulfides (LiPSs) that dissolve in liquid electrolytes and then into insoluble Li2S precipitated on the electrode surface. The electronically and ionically insulating Li2S leads to two critical issues, including the sluggish reaction kinetics from LiPSs to Li2S and the passivation of the electrode. In this regard, controlling the Li2S deposition is significant for improving the performance of LSBs. In this perspective, we have summarized the recent achievements in regulating the Li2S deposition to enhance the performance of LSBs, including the solution-mediated growth of Li2S, sulfur host enhanced nucleation and catalysis induced kinetic improvement. Moreover, the challenges and possibilities for future research studies are discussed, highlighting the significance of regulating the Li2S deposition to realize the high electrochemical performance and promote the practical uses of LSBs.

Variations in Irisin, Bone Mineral Density, Bone Mineral Content, and Body Composition After Laparoscopic Bariatric Procedures in Obese Adults.

INTRODUCTION: This study was aimed to assess irisin levels in obesity (OB) and T2DM individuals and investigate the dynamic changes of irisin, bone mineral density (BMD), bone mineral content, and body composition in 19 OB patients after laparoscopic bariatric procedures, and also to evaluate the correlation of irisin, with BMD and body composition. METHODS: Forty-five OB, 20 T2DM, and 20 healthy adults had been recruited. Levels of irisin were measured in all subjects. Metabolic characteristics were obtained from OB and T2DM patients. Nineteen patients were randomly assigned to be received Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) procedure and to be completed 6-month follow-up. Irisin, BMD, bone mineral content, and body composition were measured at each visit. RESULTS: Significantly higher circulating irisin levels were measured in the OB group compared with T2DM and control groups. FINS, C-P, HOMA-IR, FBCI, HBCI, ALT, AST, and UA levels of OB were significantly higher than those of T2DM patients. While FBG and HbA1c of the OB were significantly lower than T2DM group. There were significant differences among circulating irisin, BMD, and body composition after laparoscopic bariatric surgery. Levels of irisin were decreased after operations including both LRYGB and LSG surgery compared with preoperation. At each time point (1, 3, and 6 months) of postoperation, there was no significant difference in percentage of total weight loss between LSG and LRYGB group. The positive correlation of irisin levels with total BMD, muscle, and fat masses were found during 6-month follow-up after surgery. CONCLUSIONS: The levels of irisin were higher in OB patients. There were positive correlations of irisin levels with total BMD, muscle, and fat masses during 6-month follow-up after surgery. Irisin may be involved in the occurrence and development of obese and it is related to BMD and body composition. Both LRYGB and LSG operations could decrease the circulating levels of irisin.

Robust Classification of Tea Based on Multi-Channel LED-Induced Fluorescence and a Convolutional Neural Network.

A multi-channel light emitting diode (LED)-induced fluorescence system combined with a convolutional neural network (CNN) analytical method was proposed to classify the varieties of tea leaves. The fluorescence system was developed employing seven LEDs with spectra ranging from ultra-violet (UV) to blue as excitation light sources. The LEDs were lit up sequentially to induce a respective fluorescence spectrum, and their ability to excite fluorescence from components in tea leaves were investigated. All the spectral data were merged together to form a two-dimensional matrix and processed by a CNN model, which is famous for its strong ability in pattern recognition. Principal component analysis combined with k-nearest-neighbor classification was also employed as a baseline for comparison. Six grades of green tea, two types of black tea and one kind of white tea were verified. The result proved a significant improvement in accuracy and showed that the proposed system and methodology provides a fast, compact and robust approach for tea classification.

Study on the mechanism of naringin in promoting bone differentiation: In vitro and in vivo study.

Objective: Osteoporosis is a common clinical bone disease that occurs most frequently in middle-aged and elderly people. Various traditional herbal medicine formulations have shown significant benefits in models of osteoporosis. In this study, we aim to investigate the osteogenic efficacy of naringin (NRG) in the osteoporotic state. Design: We treated Bone marrow stromal cells (BMSCs) with various concentrations of NRG for 3 and 7 days. BMSC proliferation was measured by the MTT assay. The effect of NRG on the osteogenic differentiation of BMSCs was detected by ALP and alizarin red staining. The effect of NRG on the BMP2/Runx2/Osterix signaling pathway was analyzed by using real-time PCR. The effect of NRG on the oestrogen receptor was measured by Enzyme-linked immunosorbent assay. In vivo animal experiments were performed by micro-computed tomography and ALP immunohistochemistry to determine the ectopic osteogenic effect of NRG sustained-release nanoparticles in a mouse model of osteoporosis. Results: NRG promoted the proliferation and osteogenic differentiation of BMSCs. Moreover, it also activated the BMP2/Runx2/Osterix signaling pathway. When NRG sustained-release nanoparticles were added in vivo in animal experiments, we found that NRG sustained-release nanoparticles had better ectopic osteogenic effects in a mouse model of osteoporosis. Conclusions: NRG induced osteoblastic differentiation of BMSCs by activating the BMP2/Runx2/Osterix signaling pathway and promoted the regulation of oestrogen receptor pathway protein expression, and NRG sustained-release nanoparticles exerted a more significant in vivo ectopic osteogenic effect in an osteoporosis mouse model. Therefore, naringin is expected to be developed as a novel treatment for inducing osteogenesis, because of its ubiquitous, cost-efficient, and biologically active characteristics. However, further research is needed on how to improve the pharmacokinetic properties of naringin and its specific mechanism.

Precise healing of oral and maxillofacial wounds: tissue engineering strategies and their associated mechanisms.

Precise healing of wounds in the oral and maxillofacial regions is usually achieved by targeting the entire healing process. The rich blood circulation in the oral and maxillofacial regions promotes the rapid healing of wounds through the action of various growth factors. Correspondingly, their tissue engineering can aid in preventing wound infections, accelerate angiogenesis, and enhance the proliferation and migration of tissue cells during wound healing. Recent years, have witnessed an increase in the number of researchers focusing on tissue engineering, particularly for precise wound healing. In this context, hydrogels, which possess a soft viscoelastic nature and demonstrate exceptional biocompatibility and biodegradability, have emerged as the current research hotspot. Additionally, nanofibers, films, and foam sponges have been explored as some of the most viable materials for wound healing, with noted advantages and drawbacks. Accordingly, future research is highly likely to explore the application of these materials harboring enhanced mechanical properties, reduced susceptibility to external mechanical disturbances, and commendable water absorption and non-expansion attributes, for superior wound healing.

Mesenchymal Stem Cells Attenuates Hirschsprung diseases - Associated Enterocolitis by Reducing M1 Macrophages Infiltration via COX-2 Dependent Mechanism.

OBJECTIVE AND DESIGN: Hirschsprung disease-associated enterocolitis (HAEC) is a common life-threatening complication of Hirschsprung disease (HSCR). We aimed to investigate the effectiveness, long-term safety and the underlying mechanisms of Mesenchymal stem cells (MSCs) based therapy for HAEC. MATERIAL OR SUBJECTS: Specimens from HSCR and HAEC patients were used to assess the inflammatory condition. Ednrb knock-out mice was used as HAEC model. MSCs was intraperitoneally transplanted into HAEC mice. The therapy effects, long-term outcome, safety and toxicity and the mechanism of MSCs on the treatment of HAEC were explored in vivo and in vitro. RESULTS: Intestinal M1 macrophages infiltration and severe inflammation condition were observed in HAEC. After the injection of MSCs, HAEC mice showed significant amelioration of the inflammatory injury and inhibition of M1 macrophages infiltration. The expression levels of pro-inflammatory cytokines (TNF-α and IFN-γ) were decreased and anti-inflammatory cytokines (IL-10 and TGF-ß) were increased. In addition, we found that effective MSCs homing to the inflamed colon tissue occurred without long-term toxicity response. However, COX-2 inhibitor could diminish the therapeutic effects of MSCs. Using MSCs and macrophages co-culture system, we identified that MSCs could alleviate HAEC by inhibiting M1 macrophages activation through COX-2-dependent MAPK/ERK signaling pathway. CONCLUSIONS: MSCs ameliorate HAEC by reducing M1 macrophages polarization via COX-2 mediated MAPK/ERK signaling pathway, thus providing novel insights and potentially promising strategy for the treatment or prevention of HAEC.