The Arctic pelagic environment is expected to strongly alter due to global climate change. As a consequence, modification of the unicellular plankton species composition and biomass, with consequences to biogeochemical cycling and pelagic food web, is expected. In this study we used meta-barcoding of the V4 region of the 18S rRNA gene to profile eukaryotic microbial communities exported to deeper water layers at the Long-Term Ecological Research Site HAUSGARTEN in the northeastern Fram Strait. We collected sinking particles at ca. 80 to 300 m depths using long-term deployed sediment traps and analyzed selected samples of spring and summer periods from 2000-2011. Acknowledging the limitations and biases of currently used 18S rRNA gene meta-barcoding primers in detecting certain taxa especially from environmental samples, we developed new primer sets and compared them with those already in use. Using the information generated by three different primer sets, the results of our study suggest decreasing trends in the abundances of large-cell phytoplankton (i.e., diatoms) and increasing pico-phytoplankton (Micromonas sp. and haptophytes) during the warm anomaly of 2005-2007. Phylogenetic analyses further revealed the displacement of cold-adapted with warm-adapted phylotypes of Micromonas and haptophytes, which could be related to the warming event. Ecotype-level changes observed in this study do not only suggest changing structures in community composition and ecosystem functioning but also in the biogeography and distribution of some species. These data provided new insights and information on the potential diversity changes and species displacement brought about by the environmental changes occurring in the Arctic Ocean.

Common Variable Immunodeficiency Disorders (CVIDs) are rare Primary Immunodeficiency diseases (PIDs) associated with late onset antibody failure leading to immune system failure. Most patients suffer recurrent and severe infections, while some have predominantly autoimmune and inflammatory disorders. In recent years a large number of genetic defects have become associated with these disorders. Next Generation Sequencing (NGS) allows the analysis of multiple genes simultaneously. The mutations identified from NGS are evaluated with the American College of Medical Genetics (ACMG) variant interpretation criteria to determine their pathogenicity (causality). We have advocated all patients with a CVID phenotype should undergo genetic testing but acknowledge the complexity of the genetics associated with these disorders. Variants of Unknown Significance (VUS) remain a significant barrier to realising the full potential of NGS in CVID and CVID-like disorders. We review the nuances of the application of the ACMG variant interpretation criteria to patients with a CVID phenotype.

Background and Purpose: Colorectal cancer (CRC) is one of the most diagnosed cancer worldwide, and effective chemotherapeutic drugs for CRC still remain a challenge. Ziyuglycoside II (Ziyu II) is one of the major active compounds of Sanguisorba officinalis L. Previous study has identified Ziyu II as a potent anti-tumor agent, but limited data on the efficacy and potential mechanism of Ziyu II in the treatment of CRC. Experimental Approach: CRC cells were used to examine the tumor suppression effect of Ziyu II alone or in combination with autophagy inhibitors in vitro and in vivo. A variety of biochemical assays were conducted to elucidate the underlying mechanisms of Ziyu II in CRC cells. Key Results: Ziyu II exhibits antitumor activity against CRC cells both in vitro and in vivo. It demonstrated that treatment with Ziyu II induced apoptosis via accumulation of reactive oxygen species (ROS). Intriguingly, Ziyu II treatment triggered complete autophagic flux in CRC cells. Inhibition of autophagy partially reversed Ziyu II-induced growth inhibition in CRC cells, suggesting a cytotoxic role of Ziyu II-induced autophagy. Mechanistic studies showed that Ziyu II induced autophagy by inhibiting Akt/mTOR pathway, and Akt reactivation partially reduced Ziyu II-induced autophagy. Notably, Ziyu II improves the sensitivity of CRC cells to the first-line chemotherapeutic drugs 5-fluorouracil. Conclusion and Implications:This study provides new insights into the molecular mechanisms of Ziyu II-mediated CRC suppression involving induction of both apoptosis and autophagy, and establishes potential applications of Ziyu II for clinical CRC treatment.

Background and purpose: The Chinese medicine monomer solasonine has been shown to be an effective inhibitor of Lung adenocarcinoma in vitro and in vivo. The research on the application of solasonine in lung cancer mostly involves the cell level, the lack of information on the spatial distribution of drugs and related metabolic pathways are common problems faced by many Chinese medicine monomers. Experimental Approach: LC-MS/MS metabolomics analysis was performed to reveal the underlying regulatory mechanism, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and 3D computational reconstruction were applied to illustrated the spatial-temporal distribution of solasonine. Solamargine was chosen as the internal standard to correct the calibration curve due to the similarity in structure. Key Results: Metabolomics analysis illustrated that solasonine promotes A549 cells ferroptosis via GPX4-induced destruction of the glutathione redox system. Detailed distribution features of solasonine in different organs were revealed by MALDI-MSI after intravenous administration in the mice. The heterogeneity of solasonine distribution and penetration in tumor demonstrated that significant drug deposits around the necrotic area. Conclusion and Implication: The anti-tumor mechanism of solasonine associated with ferroptosis is identified for the first time. It provides an additional basis for the previous conclusion that solasonine promotes tumor necrosis. Quantitative spatial-temporal information obtained here can improve our understanding of pharmacokinetics (PK), pharmacodynamics (PD), potential transient toxicities of solasonine in organs, and possibly direct further optimization of drug properties to reduce drug-induced organ toxicity and broaden the scope of application.

A tunable mid-infrared (MIR) laser (quantum cascade laser, QCL) was used for the detection of TNT and RDX in soil samples at a concentration range from 0 to ~20% w/w. This type of sensing is complicated due to the complexity of the matrix, i.e., the diversity of compounds contained in soil. Thus, the high explosives (HE) detection in soil by QCL was assisted with an Artificial Intelligence (AI) system. AI managed to predict these HE in seven kinds of soils using minimum information Machine Learning (ML). The models were generated only from neat HE and soil spectra, without necessity using experimental spectra of the mixes. AI used these neat spectra to simulate the spectra of HEs/soil mixes. The simulated data was used to train the ML models and then were tested with real spectra of HEs/soils mixes. The method was designated as “Self-Simulated Learning Artificial Intelligence” (SSLAI). This methodology has advantages for applications in field scenarios where the matrices are unknown because SSLAI models do not need to be trained with real samples a priori. Models would only have to be fed with spectra for the neat components to train itself. The methodology was tested with mixes of seven soils and two explosives. Test samples were classified into three concentrations ranges: high concentration test (Test_H > 10% w/w), medium concentration test (10% w/w > Test_M > 3% w/w), and low concentration test (Test_L < 3% w/w). The results show that it is possible to correctly predict these two HE/soil mixes from the simulated data. Specifically, for TNT and RDX, SSLAI achieved a high precision in the prediction for the high and medium concentration tests (Test_H and Test_M). However, for both samples with concentrations below 3% w/w (Test_L), the number of false positives increased, and the precision was reduced.

High salinity is one of the major limiting factors that reduces crop productivity and quality. Herein, we report that small SALT TOLERANCE ENHANCER1 (STE1) protein without any known conserved domains is required for tomato salt tolerance. Overexpression (OE) of SlSTE1 enhanced the tolerance to multiple chloride salts (NaCl, KCl and LiCl) and oxidative stress, along with elevated antioxidant enzyme activities, increased ABA and chlorophyll contents, and reduced MDA and ROS accumulations compared to that of WT plants. Moreover, decreased K+ efflux and increased H+ efflux were detected in the OE plants, which induced a higher K+/Na+ ratio. In contrast, SlSTE1-RNAi plants displayed decreased tolerance to salt stress. RNA-seq data revealed 1330 DEGs in the OE vs WT plants under salt stress, and the transcription of numerous and diverse genes encoding TFs, stress-related proteins, secondary metabolisms, kinases and proteins related to hormone synthesis/signalling (notably ABA and ACC), etc. was greatly elevated. Furthermore, SlSTE1-OE plants showed increased sensitivity to ABA, and the results suggest that SlSTE1 promotes ABA-dependent salt stress-responsive pathways by interacting with SlPYLs and SlSnRK2s. Collectively, our findings reveal that the small SlSTE1 protein confers salt tolerance via ABA signalling and ROS scavenging and improves ion homeostasis in tomato.

Hepatitis virus infection is a leading cause of chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). However, the molecular mechanism by which hepatitis causes liver cancer remains unclear. Additionally, new biomarkers for diagnosis, prognosis and therapeutics are needed. Regulatory pathways play important roles in many pathogenic processes, and identifying the pathways by which hepatitis C virus (HCV) induces HCC may lead to better diagnosis and treatment. We employed a systematic approach to identify important regulatory pathways in this disease process, and found several important regulators. First, three networks were constructed based on the gene expression in patients with hepatitis alone, HCC alone, and hepatitis with HCC. A priority algorithm was used to extract the regulatory pathways from the networks, which were then scored based on the disease-related genetic information to identify key pathways. After integrating the regulatory pathways involved in the three networks, we found key regulatory genes, including EZH2 and hsa-miR-155-5p. Based on network analysis, it appeared that in HCC patients the abnormal expression of genes and miRNAs were mostly caused by abnormal expression of these key regulatory factors. This method may help researchers discover the potential pathogenic factors of HCC and could also yield new biomarkers for disease diagnosis.

The shifting defence hypothesis attributes the invasion success of many plant species to the species’ post- introduction evolution of traits that confer high fitness including reduced allocation to physiologically and ecologically costly chemical defence compounds against herbivores. However, to date, most of the studies that compared invasive and conspecific native plants for differences in defence compounds focused only on one or a few compounds. Thus, it remains unclear whether invasive plants may evolve a lower diversity of defence compounds in response to a simplified herbivore community assemblages in the introduced range. Therefore, the present study used B. nigra plants from 11 invasive- and 14 native range populations to test whether invasive B. nigra plants: i) express a lower diversity of glucosinolate compounds and higher concentration of a single dominant glucosinolate compound owing to a reduced diversity of herbivores in the introduced range; ii) are less preferred by generalist herbivores and attract more specialist herbivore species than B. nigra from the native range when grown in a common garden in the native range; iii) are less preferred by generalist herbivores than native-range B. nigra in no- choice feeding bioassays. In support of the shifting defence hypothesis, invasive B. nigra plants expressed a lower diversity of glucosinolates and a higher concentration of sinigrin (a major glucosinolate compound in B. nigra) than native-range B. nigra plants. Moreover, the invasive B. nigra plants were more deterrent to two generalist herbivore species in no-choice feeding bioassays than native B. nigra plants. Brassica nigra plants that expressed higher concentrations and diversities of glucosinolate compounds were visited by a more diverse specialist herbivore community than B. nigra plants with low concentrations and diversities of glucosinolates. The biogeographical differences in glucosinolate profiles observed here may be the result of differential herbivore selection pressures in the respective invaded and native ranges.

Detailed information on the H/D isotope effects for adsorption on the surface and absorption in the bulk is important for understanding the nuclear quantum effect. To achieve this purpose, we developed a new theoretical approach, namely, the combined plane wave and localized basis set (CPLB) method. By using the multi-component quantum chemical method, which takes into account the quantum effect of proton or deuteron, with localized part in CPLB method, direct analysis of H/D isotope effect about adsorption and absorption is achieved. In this study, we performed a theoretical investigation of the H/D isotope effects for adsorption on a Pd(111) surface and absorption in bulk Pd. We clearly showed H/D isotope effect on geometry during adsorption and absorption. Our developed CPLB approach is a powerful tool for analyzing the quantum nature of H/D in surface, bulk, and inhomogeneous systems.

Betancourt, J., Caballero-Gill, R.P., Groff, D., Hillman, A., Johnson, K. R., Kohler, T. A., McLauchlan, K., Williams, J.. (2018) Paleoclimatology: Understanding Earth's Climate Future. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1NaAw9h0oxjkT6lfaDH3wz-23qP61f4LF/view?usp=sharing

Blaauw, M., Fosdick, J., Gehrels, G., McKay, N., Meyers, S., Morgan, L., Renne, P., Robinson, E., Schmitz, M., Singer, B., Smith, M., Walker, D., and Zaffos, A. (2018) Geochronology: Toward a 4D Digital Earth. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/13gnap5D9LLS_H0e-DIfLOm_RjGMoCWK_/view?usp=sharing

Bowen, G., Clapham, M., Currano, E., Hopkins, M., Park Boush, L.E., Sessa, J., Stigall, A., Uhen, M.D. (2018) Paleobiology: Toward a New Modern Synthesis. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1Ikwwi6rt5chlqAL34J7lnctIjBh3-RpN/view?usp=sharing

GridMol is a “one-stop” platform for molecular modeling, scientific computing and molecular visualization aided by High Performance Computing Environment. GridMol version 2.0 emphatically introduces two unique features, the first is fragment-based linear scaling quantum chemistry methods, such as molecular fractionation with conjugate caps and fragment molecular orbital methods; the second is visualization of computational processes, such as structural optimization and intrinsic reaction coordinate calculation. Compared with version 1.0, fragment-based linear scaling quantum chemistry methods implemented in GridMol version 2.0 can be used as a useful tool for performing quantum calculations for large molecular systems to explore the mechanisms involved in protein–ligand or targeted-drug interactions.

In this note, a linear mean stress model is presented on basis of the multiaxial model of fatigue life of metal materials proposed by Liu and Yan. By using the experimental data of fatigue life of metal materials reported in the literature, the model is systematically validated.

Czaplewski, J., Fils, D., Goring, S., Lehnert, K., Sluyter, A., Tikoff, B., Uhen, M.D., Zaslavsky, I.. (2018) Cyberinfrastructure: Earth Data System Sustainability. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/11QSnDFKD8C_vMbIVwlyWzaTaVy5lM7Xd/view?usp=sharing

Benison, K., Brown, E., Carroll, A., Goring, S., Maxbauer, D., McLauchlan, K., Noren, A., Olsen, P., Russell, J., and Shapley, M. (2018) Continental Drilling for Records of Earth System Evolution. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1CJDJHi1KxC8jOd87lAVj-gkp-0-p5W5I/view?usp=sharing

Yacobucci, P. Lundgren, L., Myrbo, A., Loeffler, S., and Kirakosian, K. (2018) Diversity and Inclusion: Creating an Equitable Future. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1fyokuqN4-PBLhZEfL8gJth1BgrAL4oav/view?usp=sharing

Harper, H., Benison, K., Lascu, I., Carroll, A., Foreman, B., and Peters, S. (2018) EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1gy5Rrh0EvW6N9b38TSwV7blEwxrGamH6/view?usp=sharing

Lyons, T., Hren, M., Fox, D., Hyland, E., and Kehrwald, N.. (2018) Earth-Life Transitions: Towards a New Understanding of Earth Systems. EarthRates, Minneapolis, MN. https://drive.google.com/file/d/1Yo6SclBfS_YPWg8JJWKQ3rKbgRnOqKOm/view?usp=sharing

Is termination of early pregnancy indicated in women with COVID-19?Yan-Ting Wu, M.D.1,2, Cheng Li, M.D.1, Chen-Jie Zhang, M.D.1, Yan-fen Chen, M.D.3, He-Feng Huang, M.D.1,2, FRCOG1 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai2 Chinese Maternal and Child Health Association3 The Central Hospital of WuHan, Tongji Medical College, Hua Zhong University of Science and TechnologyCorresponding to He-Feng Huang, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910, Hengshan Rd., Shanghai 200030, China. E-mail: huanghefg@sjtu.edu.cn.By Mar 2nd, 2020, more than 80174 confirmed cases and 715 suspected cases infected with 2019 novel coronavirus disease (COVID-19) have been reported in China.1 Besides the human-to-human transmission via respiratory droplet, vertical transmission has been concerned and not determined since one case of a mother and neonate was laboratory-confirmed with COVID-19. Several days ago, a news program of Hubei TV suggested that early pregnant women infected with COVID-19 should terminate their pregnancies. This viewpoint seems oversimplified but has triggered controversy widely. In February, there were 3 pregnant women with mild COVID-19 infection in the Wuhan Central Hospital (Houhu District) who terminated their pregnancy in the first trimester.Early pregnancy is a challenging and vulnerable period, and viral infection at this stage could potentially affect embryogenesis and fetal organ development, but there is still no evidence for the vertical transmission of COVID-19 so far. In February 13rd, 2020, Chen et al . reviewed nine cases of COVID-19 infected pregnant women, and reported none of their neonates had been infected through vertical transmission.2 Prior to COVID-19, there were a total of six coronavirus species that induced human infection including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) which led to the outbreak of pneumonia, but no vertical transmission of the coronavirus had been confirmed.3,4 With reference to the experience to SARS or MERS, they can cause preterm, miscarriage, stillbirth, and fetal growth restriction in pregnant women, associated with placental insufficiency, but not vertical transmission. There is no evidence that SARS-CoV or MERS-CoV itself can cause fetal malformations, because neither of them passes across the placental barrier.3,4 Children born to pregnant women infected with SARS showed similar physical and mental development when followed up to 10 months in both full-term and preterm babies. Current research on long-term health of pregnant women of SARS or MERS is not available, but we anticipate that maternal SARS-CoV-2 infection would not result in significant, long-term health risks to the offspring.Pregnant women with SARS-CoV infection have a three times higher mortality rate than non-pregnant populations. However, SARS-CoV-2 infection outcome seems to have a better prognosis than SARS-CoV infection.5 Only 7.45% of all confirmed cases are defined as “severe” according to an announcement by National Health Commission of China on Feb 15th, 2020. Based on the limited number of cases reported, there is no evidence indicating a worse outcome of maternal patients than that of general population. On the other hand, pregnancy terminations in early pregnancy may result in post-abortion infection, which might aggravate the maternal COVID-19 illness. Therefore, consideration of termination of pregnancy has to be individualized during this COVID-19 outbreak. For pregnant patients with mild symptoms, treatment should be modified to avoid using teratogenic drugs near the fetus. Patients are commonly at higher oxygen demand during early pregnancy, so hypoxemia should be monitored, and interventions should be provided without delay. For severe patients during early pregnancy, the first priority is to ensure maternal safety. Decisions of early pregnancy termination should be considered upon risk factors including viral load, transmission generations, range of lung lesions by CT (more than two lobes), maternal age, and coexisting disorders (diabetes, cardiovascular diseases etc.).Although we have made a judgment from a rational level, that is, early pregnant women infected with COVID-19 need to make a careful decision to terminate the pregnancy. However, the reality is that many mild COVID-19 pregnant women still choose to terminate the pregnancy without medical indications (request initiatively or recommended). why? As a sudden public disaster, doctors often overlook the social effects of the epidemic. Even more terrifying than viruses is terror itself. When pregnant women or doctors’ fear of the virus is beyond the bounds of reason, people inadvertently exaggerate the adverse consequences of the virus infection. For example, worrying that the current mild illness will worsen, fearing that the teratogenicity of the virus will appear to herself in the form of an individual case, and eventually some COVID-19 pregnant women decide to terminate the pregnancy full of uncertainty (request initiatively or recommended).Is termination of early pregnancy indicated in women with COVID-19? It’s not just a medical issue.AcknowledgementsThanks to everyone involved in the fight against the epidemic.Disclosure of interestsNo conflict of interest.Contribution to authorshipYan-fen Cai shared case information from the front line of the outbreak. He-feng Huang put forward the initial ideas and opinions, which were drafted by Yan-ting Wu, Cheng Li, and Chen-jie Zhang.Ethics approvalNot applicable.FundingNot applicable.

INTRODUCTION Diagnostic difficulty is frequent in primary care, yet little is known about which clinical scenarios present uncertainty to primary care practitioners (PCPs) and how they respond. We describe types of clinical scenarios causing uncertainty that PCPs brought to regularly scheduled, confidential practice meetings. Information about these patients’ characteristics and how clinicians responded could better define diagnostic uncertainty in primary care, explain and acknowledge the value of PCPs’ uncertainty work, and promote deliberate attention to its management. METHODS We analyzed case log data from 459 case scenarios where PCPs presented patients involving uncertainty to peers in “Practice Inquiry (PI) Colleague Group” meetings held in 17 San Francisco-Bay Area primary care practices between 2002–2015. Case log data included: 1) uncertainty statement/question; 2) patient and clinician information provided by PCP during first 2-3 minutes of presentation (e,g,, presenting symptoms), 3) colleagues’ responses to presentation; and 4) patient follow-up offered by presenter at subsequent meetings. Using published criteria and ones designed to identify less-objectively presented diagnostic quandaries, diagnostic uncertainty cases were selected from the larger cohort and coded to describe patients’ current status, already- known diagnoses/conditions; and diagnoses/conditions identified by presenter as possible uncertainty explanations. RESULTS Of 459 patients that PCPs presented in PI meetings, 258 (56%) involved diagnostic uncertainty. Patients’ already-known diagnoses were discussed in 72%; 44% had at least two diseases/conditions. In 52%, clinicians discussed possible diagnoses that could explain uncertainty. For these, mental health/ behavioral/ neurodevelopmental conditions were discussed as potential uncertainty contributors for approximately 25% of patients. Both diagnostic and management dilemmas were presented in 30%; diagnostic adverse events were discussed in 14% including 6 deaths. DISCUSSION PI Colleague Groups are a useful forum where clinicians can admit to being ‘stuck’ and ask for help. Certain clinical scenarios, such as patients with mental health, behavioral/neurodevelopmental conditions, presenting with new complaints, pose special diagnostic challenges. This small-group process also facilitates discussions of diagnostic error and patient harm. Further qualitative analysis of the dataset should focus on case presenters’ specific diagnostic questions, colleagues’ responses to cases presented, and how patient follow-up reported at subsequent meetings contributes to uncertainty resolution.

Hydraulic properties control plant responses to climate and are likely to be under strong selective pressure, but their macro-evolutionary history remains poorly characterized. We compiled a global dataset of hydraulic traits describing xylem efficiency, xylem safety, sapwood allocation relative to leaf area and drought exposure and matched it with a newly derived genus-level phylogeny to shed light on woody-plant hydraulic eco-evolutionary patterns. All hydraulic traits present medium to high levels of phylogenetic signal, being evolutionarily segregated into two phylogenetically conserved adaptive modules: the safety-exposure coordination, whereby lineages exposed to drought adapted to withstand low water potentials by evolving a xylem with higher embolism resistance; and the efficiency-allocation coordination, whereby higher water availability and deeper, water-retentive soils led to the evolution of hydraulically efficient species with higher leaf area relative to sapwood area. Moreover, the lack of evolutionary correlation between xylem safety and efficiency suggest that both adaptive modules are independent.

Both in natural and in human-made agroecosystems, biodiversity can be understood as a direct function of landscape complexity and an inverse function of energy dissipation. The main difference between them is the external energy driven by farmers’ information that transforms natural ecosystems into agroecosystems. If this is true, can an energy-information-structure model predict biodiversity in cultural landscapes? To that aim, we have developed an Energy-Landscape Integrated Analysis (ELIA) that measures the energy stored through internal loops (E) and the information incorporated into the energy network of agroecosystems (I), to correlate them with the resulting patterns and processes of cultural landscapes (L). This approach integrates the energy flow accounting of agricultural landscapes from an Ecological Economics point of view, and the Landscape Ecology metrics that assess the functional structure of their land covers. ELIA uses the E-I-L indicators to predict the biodiversity location in human-transformed landscapes. We have tested this model on biodiversity data through two different taxonomic groups, butterflies and birds, in the metropolitan region of Barcelona (Spain). The results show positive relationships between butterflies and birds species richness with ELIA, and especially with the variable I: information. This emphasizes how different strategies of agricultural management combined with nature conservation can be approached at some optimal points in the relationship between the energy-information-structure of cultural landscapes and the biodiversity located on them. The ELIA modelling opens a new research agenda that will be very useful for designing more sustainable agroecosystems, metropolitan green infrastructures and land use policies.

Background and Purpose The colonic epithelium is highly sensitive to ionizing radiation, leading to impaired barrier function. Lysophosphatidic acid (LPA) is protective against radiation-induced intestinal mucosal injury and genotoxic stress. We evaluated the effect of LPA and its analog, Radioprotein-1 in radiation-induced colonic epithelial barrier dysfunction. Experimental approach Caco-2 and m-ICC12 cell monolayers were exposed up to g-radiation, and the barrier function was evaluated by measuring and unidirectional flux of FITC-inulin. Mice were subjected to either total body irradiation (TBI) or partial body irradiation (PBI-BM5). Intestinal barrier function was analyzed by evaluating mucosal permeability to inulin and measuring plasma lipopolysaccharide (LPS) levels. Tight junction and adherens junction integrity was examined by confocal microscopy. Oxidative stress was assessed by measuring protein thiol oxidation and antioxidant mRNA. Key Results In Caco-2 and m-ICC12 cell monolayers, LPA attenuates radiation-induced redistribution of tight junction proteins from the junctions, which was blocked by Rho-kinase inhibitor. In mice, TBI and PBI-BM5 disrupt colonic epithelial tight junction and adherens junction, increases mucosal inulin permeability and elevates plasma LPS. RP1 administered 30 min pre-irradiation or 24 hours post-irradiation alleviates TBI and PBI-BM5-induced tight junction disruption, barrier dysfunction, and endotoxemia. The RP1 effects on radiation-induced colonic injury was associated with protein thiol oxidation, suppression of antioxidant gene expression, cofilin activation and remodeling of actin cytoskeleton. Conclusion and Implications These data demonstrate that LPA2 receptor agonists prevent and mitigate g-irradiation-induced colonic mucosal barrier dysfunction and endotoxemia, indicating their potential therapeutic benefit in the treatment of the gastrointestinal acute radiation syndrome.