Increased intestinal permeability and lipopolysaccharide contribute to swainsonine-induced systemic inflammation.

Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading to liver inflammation and even death in livestock. However, the mechanism by swainsonine induced systemic inflammatory responses remained unclear, especially the effects of swainsonine on intestinal permeability, lipopolysaccharide (LPS) level and oxidative stress response were unknown. In this study, swainsonine increased intestinal permeability as evidenced by the significant down-regulation of colonic goblet cells, Akkermansia muciniphila and intestinal tight junction protein Occludin, Claudin 1 and ZO-1, and the significant up-regulation of mRNA expression level of the intestinal permeability indicator protein tyrosine phosphatase receptor type H (Ptprh) in the ileum of mice. Simultaneously, the elevated LPS biosynthetic genes in intestinal microbiota and increased intestinal permeability facilitated more bacterial endotoxin LPS to enter the blood. High concentration of free-form LPS induced high levels of proinflammatory cytokines and oxidative stress response, thereby causing the systemic inflammation. These findings provided a new perspective on swainsonine-induced systemic inflammation, suggesting that intestinal permeability and free-form LPS level may be the potential trigger factors.

Electrical Sensor Calibration by Fuzzy Clustering with Mandatory Constraint.

Electrical tomography sensors have been widely used for pipeline parameter detection and estimation. Before they can be used in formal applications, the sensors must be calibrated using enough labeled data. However, due to the high complexity of actual measuring environments, the calibrated sensors are inaccurate since the labeling data may be uncertain, inconsistent, incomplete, or even invalid. Alternatively, it is always possible to obtain partial data with accurate labels, which can form mandatory constraints to correct errors in other labeling data. In this paper, a semi-supervised fuzzy clustering algorithm is proposed, and the fuzzy membership degree in the algorithm leads to a set of mandatory constraints to correct these inaccurate labels. Experiments in a dredger validate the proposed algorithm in terms of its accuracy and stability. This new fuzzy clustering algorithm can generally decrease the error of labeling data in any sensor calibration process.

Reconstructing the biological invasion of noxious invasive weed Parthenium hysterophorus and invasion risk assessment in China.

Invasive alien plants (IAPs) present a severe threat to native ecosystems and biodiversity. Comprehending the potential distribution patterns of these plant invaders and their responses to climate change is essential. Parthenium hysterophorus, native to the Americas, has become an aggressively invasive species since its introduction to China in the 1930s. This study aims to collect and reconstruct the historical occurrence and invasion of P. hysterophorus. Using the optimal MaxEnt model, the potential geographical distributions of P. hysterophorus were predicted based on screened species occurrences and environmental variables under the current and three future scenarios in the 2030s, 2050s, and 2070s (i.e., SSP1-2.6, SSP2-4.5, and SSP5-8.5), and the invasion risk of P. hysterophorus in Chinese cities, croplands, forests, and grasslands was assessed. The results show that: (1) The species initially invaded highly suitable areas and further spread to regions with non-analogous climate conditions. (2) Under the current climatic conditions, the overall potential distribution of P. hysterophorus is characterized by more in the southeast and less in the northwest. Climate variables, including mean annual temperature (bio1), precipitation in the wettest month (bio13), isothermality (bio3), and temperature seasonality (bio4), are the primary factors influencing its distribution. (3) The potential distribution of P. hysterophorus will expand further under future climate scenarios, particularly toward higher latitudes. (4) Forests and crop lands are the areas with the most serious potential invasion risk of P. hysterophorus. Therefore, we suggest that the government should strengthen the monitoring and management of P. hysterophorus to prevent its spread and protect agro-ecosystems and human habitats. Depending on the potential risk areas, measures such as quarantine, removal, and publicity should be taken to mitigate the threat of P. hysterophorus invasion and to raise awareness of P. hysterophorus invasion prevention.

Electrical Properties of Human Lung Nodules In Vitro From 100 Hz to 100 MHz.

OBJECTIVE: The incidence of pulmonary nodules has been increasing over the past 30 years. Different types of nodules are associated with varying degrees of malignancy, and they engender inconsistent treatment approaches. Therefore, correct distinction is essential for the optimal treatment and recovery of the patients. The commonly-used medical imaging methods have limitations in distinguishing lung nodules to date. A new approach to this problem may be provided by electrical properties of lung nodules. Nevertheless, difference identification is the basis of correct distinction. So, this paper aims to investigate the differences in electrical properties between various lung nodules. METHODS: At variance with existing studies, benign samples were included for analysis. A total of 252 specimens were collected, including 126 normal tissues, 15 benign nodules, 76 adenocarcinomas, and 35 squamous cell carcinomas. The dispersion properties of each tissue were measured over a frequency range of 100 Hz to 100 MHz. And the relaxation mechanism was analyzed by fitting the Cole-Cole plot. The corresponding equivalent circuit was estimated accordingly. RESULTS: Results validated the significant differences between malignant and normal tissue. Significant differences between benign and malignant lesions were observed in conductivity and relative permittivity. Adenocarcinomas and squamous cell carcinomas are significantly different in conductivity, first-order, second-order differences of conductivity, α-band Cole-Cole plot parameters and capacitance of equivalent circuit. The combination of the different features increased the tissue groups' differences measured by Euclidean distance up to 94.7%. CONCLUSION AND SIGNIFICANCE: In conclusion, the four tissue groups reveal dissimilarity in electrical properties. This characteristic potentially lends itself to future diagnosis of non-invasive lung cancer.

Combining microbiome and pseudotargeted metabolomics revealed the alleviative mechanism of Cupriavidus sp. WS2 on the cadmium toxicity in Vicia unijuga A.Br.

Cadmium (Cd) pollution is one of the most severe toxic metals pollution in grassland. Vicia unijuga (V. unijuga) A.Br. planted nearby the grassland farming are facing the risk of high Cd contamination. Here, we investigated the beneficial effects of a highly Cd tolerant rhizosphere bacterium, Cupriavidus sp. WS2, on Cd contaminated V. unijuga. Through plot experiments, we set up four groups of treatments: the control group (without WS2 or Cd), the Cd group (with only Cd addition), the WS2 group (with only WS2 addition), and the WS2/Cd group (with WS2 and Cd addition), and analyzed the changes in physiological indicators, rhizosphere microorganisms, and stem and leaf metabolites of V. unijuga. Results of physiological indicators indicated that Cupriavidus sp. WS2 had strong absorption and accumulation capacity of Cd, exogenous addition of strain WS2 remarkably decreased the Cd concentrations, and increased the plant heights, the biomass, the total protein concentrations, the chlorophyll contents and the photosynthetic rate in stems and leaves of V. unijuga under Cd stress. Cd treatment increased the abundance of Cd tolerant bacterial genera in rhizosphere microbiome, but these genera were down-regulated in the WS2/Cd group. Pseudotargeted metabolomic results showed that six common differential metabolites associated with antioxidant stress were increased after co-culture with WS2. In addition, WS2 activated the antioxidant system including glutathione (GSH) and catalase (CAT), reduced the contents of oxidative stress markers including malondialdehyde (MDA) and hydrogen peroxide (H2O2) in V. unijuga under Cd stress. Taken together, this study revealed that Cupriavidus sp.WS2 alleviated the toxicity of V. unijuga under Cd exposure by activating the antioxidant system, increasing the antioxidant metabolites, and reducing the oxidative stress markers.

Impaired Indole Acetic Acid and Reduced Indole-Producing Bacteria Contribute to Swainsonine-Induced Liver Inflammation.

Liver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus Akkermansia alleviating inflammation and genus Lactobacillus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.

Multiomics Reveals Mechanisms of Alternaria oxytropis Inhibiting Pathogenic Fungi in Oxytropis ochrocephala.

Endophytic fungi can benefit the host plant and increase the plant resistance. Now, there is no in-depth study of how Alternaria oxytropis (A. oxytropis) is enhancing the ability of inhibiting pathogenic fungi in Oxytropis ochrocephala (O. ochrocephala). In this study, the fungal community and metabolites associated with endophyte-infected (EI) and endophyte-free (EF) O. ochrocephala were compared by multiomics. The fungal community indicated that there was more A. oxytropis, less phylum Ascomycota, and less genera Leptosphaeria, Colletotrichum, and Comoclathris in the EI group. As metabolic biomarkers, the levels of swainsonine and apigenin-7-O-glucoside-4-O-rutinoside were significantly increased in the EI group. Through in vitro validation experiments, swainsonine and apigenin-7-O-glucoside-4-O-rutinoside can dramatically suppress the growth of pathogenic fungi Leptosphaeria sclerotioides and Colletotrichum americae-borealis by increasing the level of oxidative stress. This work suggested that O. ochrocephala containing A. oxytropis could increase the resistance to fungal diseases by markedly enhancing the content of metabolites inhibiting pathogenic fungi.

Phage P2-71 against multi-drug resistant Proteus mirabilis: isolation, characterization, and non-antibiotic antimicrobial potential.

Proteus mirabilis, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in multidrug-resistant (MDR) strains. This upsurge calls for innovative approaches in infection control, beyond traditional antibiotics. Our research introduces bacteriophage (phage) therapy as a novel non-antibiotic strategy to combat these drug-resistant infections. We isolated P2-71, a lytic phage derived from canine feces, demonstrating potent activity against MDR P. mirabilis strains. P2-71 showcases a notably brief 10-minute latent period and a significant burst size of 228 particles per infected bacterium, ensuring rapid bacterial clearance. The phage maintains stability over a broad temperature range of 30-50°C and within a pH spectrum of 4-11, highlighting its resilience in various environmental conditions. Our host range assessment solidifies its potential against diverse MDR P. mirabilis strains. Through killing curve analysis, P2-71's effectiveness was validated at various MOI levels against P. mirabilis 37, highlighting its versatility. We extended our research to examine P2-71's stability and bactericidal kinetics in artificial urine, affirming its potential for clinical application. A detailed genomic analysis reveals P2-71's complex genetic makeup, including genes essential for morphogenesis, lysis, and DNA modification, which are crucial for its therapeutic action. This study not only furthers the understanding of phage therapy as a promising non-antibiotic antimicrobial but also underscores its critical role in combating emerging MDR infections in both veterinary and public health contexts.

The characteristic of the complete chloroplast genome of Lithocarpus konishii (Fagaceae), a rare and endemic species in South China.

Lithocarpus konishii, a rare species endemic to islands in South China, was evaluated as a vulnerable species (VU) by the 'China Species Red List.' Here, we first presented the complete chloroplast genome sequence of L. konishii. The chloroplast genome was 161,059 bp in length with 36.76% GC content, containing a small single-copy region (SSC, 18,967 bp), a large single-copy region (LSC, 90,250 bp), and a pair of inverted repeats (IRs, 25,921 bp each). A total of 139 genes were predicted, including 87 protein-coding genes (CDS), 8 rRNAs, and 44 tRNAs. Based on the concatenated shared unique CDS sequence dataset, maximum-likelihood and Bayesian inference methods were used to build the phylogenetic trees of 18 species from the Fagaceae family. Results indicated that L. konishii is closely related to L. longnux and L. pachyphyllus var. fruticosus, and forms a monophyly of the subfamily Castaneoideae with Castanopsis and Castanea. This study provides a theoretical basis for the conservation genomics of this endangered plant.

Oral immunocontraceptive vaccines: A novel approach for fertility control in wildlife.

The overabundant populations of wildlife have caused many negative impacts, such as human-wildlife conflicts and ecological degradation. The existing approaches like injectable immunocontraceptive vaccines and lethal methods have limitations in many aspects, which has prompted the advancement of oral immunocontraceptive vaccine. There is growing interest in oral immunocontraceptive vaccines for reasons including high immunization coverage, easier administration, frequent boosting, the ability to induce systemic and mucosal immune responses, and cost-effectiveness. Delivery systems have been developed to protect oral antigens and enhance the immunogenicity, including live vectors, microparticles and nanoparticles, bacterial ghosts, and mucosal adjuvants. However, currently, no effective oral immunocontraceptive vaccine is available for field trials because of the enormous development challenges, including biological and physicochemical barriers of the gastrointestinal tract, mucosal tolerance, pre-existing immunity, antigen residence time in the small intestine, species specificity and other safety issues. To overcome these challenges, this article summarizes achievements in delivery systems and contraceptive antigens in oral immunocontraceptive vaccines and explores the potential barriers for future vaccine design and application.

Kynurenic acid mediates bacteria-algae consortium in resisting environmental cadmium toxicity.

Cadmium (Cd2+) is a toxic heavy metal in the environment, posing severe damage to animal health and drinking water safety. The bacteria-algae consortium remediates environmental Cd2+ pollution by secreting chelating reagents, but the molecular mechanisms remain elusive. Here, we showed that Cellulosimicrobium sp. SH8 isolated from a Cd2+-polluted lake could interact with Synechocystis sp. PCC6803, a model species of cyanobacteria, in strengthening Cd2+ toxicity resistance, while SH8 or PCC6803 alone barely immobilized Cd2+. In addition, the SH8-PCC6803 consortium, but not SH8 alone, could grow in a carbon-free medium, suggesting that autotrophic PCC6803 enabled the growth of heterotrophic SH8. Totally, 12 metabolites were significantly changed when SH8 was added to PCC6803 culture in the presence of Cd2+ (PCC6803/Cd2+). Among them, kynurenic acid was the only metabolite that precipitated Cd2+. Remarkably, adding kynurenic acid increased the growth of PCC6803/Cd2+ by 14.1 times. Consistently, the expressions of kynA, kynB, and kynT genes, known to be essential for kynurenic acid synthesis, were considerably increased when SH8 was added to PCC6803/Cd2+. Collectively, kynurenic acid secreted by SH8 mitigates Cd2+ toxicity for algae, and algae provide organic carbon for the growth of SH8, unveiling a critical link that mediates beneficial bacteria-algae interaction to resist Cd2+.

Swainsonine Induces Liver Inflammation in Mice via Disturbance of Gut Microbiota and Bile Acid Metabolism.

Swainsonine induced liver inflammation in livestock; however, the underlying mechanisms, especially the role of bile acids (BAs), in the pathogenesis remained elusive. Here, our results showed that swainsonine induced hepatic inflammation via changing BA metabolism and gut microbiota in mice. Swainsonine significantly upregulated the levels of deoxycholic acid (DCA) and taurine-ß-muricholic acid (T-ß-MCA) in the serum and liver of mice due to the markedly increased genus Clostridium and the decreased genus Lactobacillus in the gut. As antagonists of the farnesoid X receptor (FXR), elevated DCA and T-ß-MCA inhibited hepatic Fxr gene expression and thus suppressed FXR-SHP signaling and activated hepatic Cyp7a1 gene expression, which induced a significant upregulation of the total BA level in serum, contributing to liver inflammation. These findings offer new insights into the underlying mechanisms in which swainsonine induced liver inflammation in mice via the gut-liver axis and suggest that gut microbiota and its metabolite BAs may be underlying triggering factors.

Distribution and association of antimicrobial resistance and virulence characteristics in Enterococcus spp. isolates from captive Asian elephants in China.

Enterococcus spp., as an opportunistic pathogen, are widely distributed in the environment and the gastrointestinal tracts of both humans and animals. Captive Asian elephants, popular animals at tourist attractions, have frequent contact with humans. However, there is limited information on whether captive Asian elephants can serve as a reservoir of antimicrobial resistance (AMR). The aim of this study was to characterize AMR, antibiotic resistance genes (ARGs), virulence-associated genes (VAGs), gelatinase activity, hemolysis activity, and biofilm formation of Enterococcus spp. isolated from captive Asian elephants, and to analyze the potential correlations among these factors. A total of 62 Enterococcus spp. strains were isolated from fecal samples of captive Asian elephants, comprising 17 Enterococcus hirae (27.4%), 12 Enterococcus faecalis (19.4%), 8 Enterococcus faecium (12.9%), 7 Enterococcus avium (11.3%), 7 Enterococcus mundtii (11.3%), and 11 other Enterococcus spp. (17.7%). Isolates exhibited high resistance to rifampin (51.6%) and streptomycin (37.1%). 50% of Enterococcus spp. isolates exhibited multidrug resistance (MDR), with all E. faecium strains demonstrating MDR. Additionally, nine ARGs were identified, with tet(M) (51.6%), erm(B) (24.2%), and cfr (21.0%) showing relatively higher detection rates. Biofilm formation, gelatinase activity, and α-hemolysin activity were observed in 79.0, 24.2, and 14.5% of the isolates, respectively. A total of 18 VAGs were detected, with gelE being the most prevalent (69.4%). Correlation analysis revealed 229 significant positive correlations and 12 significant negative correlations. The strongest intra-group correlations were observed among VAGs. Notably, we found that vancomycin resistance showed a significant positive correlation with ciprofloxacin resistance, cfr, and gelatinase activity, respectively. In conclusion, captive Asian elephants could serve as significant reservoirs for the dissemination of AMR to humans.

Altitude-dependent metabolite biomarkers reveal the mechanism of plateau pika adaptation to high altitudes.

The harsh environment in the Tibetan plateau, the highest place in the world, poses thermoregulatory challenges and hypoxic stress to animals. The impacts of plateau environment on animal physiology and reproduction include external factors such as strong ultraviolet radiation and low temperature, and internal factors such as animal metabolites and gut microbiota. However, it remains unclear how plateau pika adapt to high altitudes through the combination of serum metabolites and gut microbiota. To this end, we captured 24 wild plateau pikas at the altitudes of 3400, 3600, or 3800 m a.s.l. in a Tibetan alpine grassland. Using the machine learning algorithms (random forest), we identified five biomarkers of serum metabolites indicative of the altitudes, that is, dihydrotestosterone, homo-l-arginine, alpha-ketoglutaric-acid, serotonin, and threonine, which were related to body weight, reproduction, and energy metabolism of pika. Those metabolic biomarkers were positively correlated with Lachnospiraceae_ Agathobacter, Ruminococcaceae, or Prevotellaceae_Prevotella, suggesting the close relationship between metabolites and gut microbiota. By identifying the metabolic biomarkers and gut microbiota analysis, we reveal the mechanisms of adaptation to high altitudes in plateau pika.

Pseudotargeted metabolomics revealed the adaptive mechanism of Draba oreades Schrenk at high altitude.

Strong ultraviolet radiation and low temperature environment on Gangshika Mountain, located in the eastern part of the Qilian Mountains in Qinghai Province, can force plants to produce some special secondary metabolites for resisting severe environmental stress. However, the adaptive mechanism of Draba oreades Schrenk at high altitude are still unclear. In the current study, Draba oreades Schrenk from the Gangshika Mountain at altitudes of 3800 m, 4000 m and 4200 m were collected for comprehensive metabolic evaluation using pseudotargeted metabolomics method. Through KEGG pathway enrichment analysis, we found that phenylpropanoid biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis and phenylalanine metabolism related to the biosynthesis of flavonoids were up-regulated in the high-altitude group, which may enhance the environmental adaptability to strong ultraviolet intensity and low temperature stress in high altitude areas. By TopFc20 distribution diagram, the content of flavonoids gradually increased with the elevation of altitude, mainly including apigenin, luteolin, quercetin, hesperidin, kaempferol and their derivatives. Based on the random forest model, 10 important metabolites were identified as potential biomarkers. L-phenylalanine, L-histidine, naringenin-7-O-Rutinoside-4'-O-glucoside and apigenin related to the flavonoids biosynthesis and plant disease resistance were increased with the elevation of altitude. This study provided important insights for the adaptive mechanism of Draba oreades Schrenk at high altitude by pseudotargeted metabolomics.