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ObjectivePatients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).DesignCharacterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.ResultsA group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.ConclusionAberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.Trial registration numberThis study was registered at ClinicalTrials.gov (NCT03010696).

The plant hormone ABA (abscisic acid) plays an extremely important role in plant growth and adaptive stress, including but are not limited to seed germination, stomatal closure, pathogen infection, drought and cold stresses. Reactive oxygen species (ROS) are response molecules widely produced by plant cells under biotic and abiotic stress conditions. The production of apoplast ROS is induced and regulated by ABA, and participates in the ABA signaling pathway and its regulated plant immune system. In this review, we summarize ABA and ROS in apoplast ROS production, plant response to biotic and abiotic stresses, plant growth regulation, ABA signal transduction, and the regulatory relationship between ABA and other plant hormones. In addition, we also discuss the effects of protein post-translational modifications on ABA and ROS related factors.

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases. The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

During plant growth and development, ethylene and abscisic acid (ABA) play important roles and exert synergistic or antagonistic effects on various biological processes, but the detailed mechanism underlying the interaction of the two phytohormones, especially in the regulation of the accumulation of reactive oxygen species (ROS), is largely unclear. Here, we report that ethylene inhibits but ABA promotes the accumulation of ROS in Arabidopsis (Arabidopsis thaliana) seedlings. Furthermore, changes in the biosynthesis of ascorbic acid (AsA) act as a key factor in integrating the interaction of ethylene and ABA in the regulation of ROS levels. We found that ethylene and ABA antagonistically regulate AsA biosynthesis via ETHYLENE-INSENSITIVE3 (EIN3) and ABA INSENSITIVE4 (ABI4), which are key factors in the ethylene and ABA signaling pathways, respectively. In addition, ABI4 is transcriptionally repressed by EIN3 in ethylene-regulated AsA biosynthesis. Via transcriptome analysis and molecular and genetic experiments, we identified VITAMIN C DEFECTIVE2as the direct target of ABI4 in the regulation of AsA biosynthesis and ROS accumulation. Thus, the EIN3-ABI4- VITAMIN C DEFECTIVE2 transcriptional cascade involves a mechanism by which ethylene and ABA antagonistically regulate AsA biosynthesis and ROS accumulation in response to complex environmental stimuli.

Soil salt crust can change the structure of aeolian soil and improve its resistance to wind erosion. Four ions (Na + , Ca 2+ , Cl − , and SO 4 2− ) with high contents in aeolian soil were selected for a salt crust experiment. The experiment set a variety of gradients of soil salt contents and salt mixing ratios of Na 2 SO 4 and CaCl 2 . The physical properties of the salt crust were tested, and the wind erosion resistance of the salt crust was discussed. The results showed that the soil salt contents and salt mixing ratio influenced the resistance of the salt crust, especially in terms of its compressive strength and toughness. The former affected the compressive strength of the salt crust by changing the amount of cemented soil salt. The latter affected the kinds of crystals by changing the ion ratio, thus changing the structure of the salt crust and affecting its wind erosion resistance. The wind erosion resistance of the salt crust is complicated by the interaction between the soil salt conten t and salt mixing ratio. A multilayer crust can be formed in mixed salt, which has a strong wind erosion resistance. This result provides new findings on flowing sand soil and a new method for the treatment of flowing sand soil.

Background Abscisic acid (ABA) plays an important role in plant abiotic stress responses, and ABA INSENSITIVE 4 (ABI4) is a pivotal transcription factor in the ABA signaling pathway. In Arabidopsis , ABI4 negatively regulates salt tolerance; however, the mechanism through which ABI4 regulates plant salt tolerance is poorly understood. Our previous study showed that ABI4 directly binds to the promoter of the VITAMIN C DEFECTIVE 2 ( VTC2 ) gene, inhibiting the transcription of VTC2 and ascorbic acid (AsA) biosynthesis. Results In the present study, we found that treatment with exogenous AsA could alleviate salt stress sensitivity of ABI4- overexpressing transgenic plants. The decreased AsA content and increased reactive oxygen species (ROS) levels in ABI4- overexpressing seedlings under salt treatment indicated that AsA-promoted ROS scavenging was related to ABI4-mediated salt tolerance. Gene expression analysis showed that ABI4 was induced at the early stage of salt stress, giving rise to reduced VTC2 expression. Accordingly, the abundance of the VTC2 protein decreased under the same salt stress conditions, and was absent in the ABI4 loss-of-function mutants, suggesting that the transcriptional inhibition of ABI4 on VTC2 resulted in the attenuation of VTC2 function. In addition, other encoding genes in the AsA biosynthesis and recycling pathways showed different responses to salt stress, demonstrating that AsA homeostasis is complicated under salinity stress. Conclusions This study elucidates the negative modulation of ABI4 in salt stress tolerance through the regulation of AsA biosynthesis and ROS accumulation in plants.

Background Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic brain injury (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout the brain tissue of TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, the biological function and underlying mechanisms of NETs in TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor of NETs to investigate the role of NETs in neural damage after TBI. Methods Controlled cortical impact model was performed to establish TBI. Cl-amidine, 2′3′-cGAMP (an activator of stimulating Interferon genes (STING)), C-176 (a selective STING inhibitor), and Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] were administrated to explore the mechanism by which NETs promote neuroinflammation and neuronal apoptosis after TBI. Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil extracellular trap formation, is overexpressed with adenoviruses in the cortex of mice 1 day before TBI. The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative-PCR were performed in this study. Results Neutrophils form NETs presenting in the circulation and brain at 3 days after TBI. NETs inhibitor Cl-amidine treatment improved short-term neurological functions, reduced cerebral lesion volume, reduced brain edema, and restored cerebral blood flow (CBF) after TBI. In addition, Cl-amidine exerted neuroprotective effects by attenuating BBB disruption, inhibiting immune cell infiltration, and alleviating neuronal death after TBI. Moreover, Cl-amidine treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization at 3 days after TBI. Mechanistically, STING ligand 2′3′-cGAMP abolished the neuroprotection of Cl-amidine via IRE1α/ASK1/JNK signaling pathway after TBI. Importantly, overexpression of PAD4 promotes neuroinflammation and neuronal death via the IRE1α/ASK1/JNK signaling pathway after TBI. However, STING inhibitor C-176 or IRE1α inhibitor Kira6 effectively abolished the neurodestructive effects of PAD4 overexpression after TBI. Conclusion Altogether, we are the first to demonstrate that NETs inhibition with Cl-amidine ameliorated neuroinflammation, neuronal apoptosis, and neurological deficits via STING-dependent IRE1α/ASK1/JNK signaling pathway after TBI. Thus, Cl-amidine treatment may provide a promising therapeutic approach for the early management of TBI. Graphical Abstract

Background Akkermansia muciniphila is one of the most dominant bacteria that resides on the mucus layer of intestinal tract and plays key role in human health, however, little is known about its genomic content. Results Herein, we for the first time characterized the genomic architecture of A. muciniphila based on whole-genome sequencing, assembling, and annotating of 39 isolates derived from human and mouse feces. We revealed a flexible open pangenome of A. muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis identified three species-level A. muciniphila phylogroups exhibiting distinct metabolic and functional features. Based on the comprehensive genome catalogue, we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs) from available metagenomic datasets of human, mouse and pig gut microbiomes, revealing a transcontinental distribution of A. muciniphila phylogroups across mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila phylogroups in human subjects further demonstrated its strong correlation with body mass index and anti-diabetic drug usage. Furthermore, we found that, during their mammalian gut evolution history, A. muciniphila acquired extra genes, especially antibiotic resistance genes, from symbiotic microbes via recent lateral gene transfer. Conclusions The genome repertoire of A. muciniphila provided insights into population structure, evolutionary and functional specificity of this significant bacterium.

Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner. Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing. Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, spp., spp., and were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, spp. and , were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension. These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

Modern battlefield perception systems, which rely on multi-modal target detection technologies such as optical and infrared sensing, pose a serious threat to the survivability of large mobile assets. Existing adversarial camouflage research has predominantly focused on single-band (optical or infrared) reconnaissance, lacking a comprehensive solution capable of simultaneously deceiving both optical and infrared detectors while maintaining visual concealment. To address this gap, this study proposes a Multi-modal Adversarial Camouflage (MAC) patch framework. Firstly, the Scene-Adaptive Digital Camouflage Generation (SADCG) algorithm is designed to generate a digital camouflage base for tanks that exhibits high fusion with the background. Secondly, a joint loss optimization function is devised to train a YOLOv5-based patch generation model for producing optical adversarial patches. Simultaneously, a shape parameterization method utilizing multi-anchor representation and Catmull-Rom splines, along with a three-layer constrained boundary restriction system, is developed to optimize infrared shape adversarial patches. These optical and infrared patches are then integrated onto the camouflage base using Indium Tin Oxide (ITO) transparent thin films, forming a unified multi-modal stealth system. Experimental results demonstrate that the MAC framework can effectively reduce the mean Average Precision (mAP) of both optical and infrared detectors (including Faster R-CNN and YOLOv4) by over 75%, while significantly suppressing the response of infrared detectors. Furthermore, subjective evaluations confirm its excellent visual and infrared concealment properties. This research provides a verifiable solution and a technical pathway for achieving multi-spectral stealth for equipment in the physical world.