Impact of dietary manganese on intestinal barrier and inflammatory response in broilers challenged with Salmonella Typhimurium

Growing concern for public health and food safety has prompted a special interest in developing nutritional strategies for removing waterborne and foodborne pathogens, including Salmonella. Strong links between manganese (Mn) and intestinal barrier or immune function hint that dietary Mn supplementation is likely to be a promising approach to limit the loads of pathogens in broilers. Here, we provide evidence that Salmonella Typhimurium (S. Typhimurium, 4 × 108 CFUs) challenge-induced intestinal injury along with systemic Mn redistribution in broilers. Further examining of the effect of dietary Mn treatments (a basal diet plus additional 0, 40, or 100 mg Mn/kg for corresponding to Mn-deficient, control, or Mn-surfeit diet, respectively) on intestinal barrier and inflammation status of broilers infected with S. Typhimurium revealed that birds fed the control and Mn-surfeit diets exhibited improved intestinal tight junctions and microbiota composition. Even without Salmonella infection, dietary Mn deficiency alone increased intestinal permeability by impairing intestinal tight junctions. In addition, when fed the control and Mn-surfeit diets, birds showed decreased Salmonella burdens in cecal content and spleen, with a concomitant increase in inflammatory cytokine levels in spleen. Furthermore, the dietary Mn-supplementation-mediated induction of cytokine production was probably associated with the nuclear factor kappa-B (NF-κB)/hydrogen peroxide (H2O2) pathway, as judged by the enhanced manganese superoxide dismutase activity and the increased H2O2 level in mitochondria, together with the increased mRNA level of NF-κB in spleen. Ingenuity-pathway analysis indicated that acute-phase response pathways, T helper type 1 pathway, and dendritic cell maturation were significantly activated by the dietary Mn supplementation. Our data suggest that dietary Mn supplementation could enhance intestinal barrier and splenic inflammatory response to fight against Salmonella infection in broilers

The Roles of Iron and Ferroptosis in Human Chronic Diseases

Ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. A growing number of studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in different diseases. As a double-edged sword, activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. Therefore, the development of more efficacious ferroptosis agonists or inhibitors remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics or cardiovascular and cerebrovascular diseases and neurodegenerative diseases therapeutics

Causal associations of gut microbiota and metabolites on sepsis: a two-sample Mendelian randomization study

BackgroundSepsis stands as a dire medical condition, arising when the body’s immune response to infection spirals into overdrive, paving the way for potential organ damage and potential mortality. With intestinal flora’s known impact on sepsis but a dearth of comprehensive data, our study embarked on a two-sample Mendelian randomization analysis to probe the causal link between gut microbiota and their metabolites with severe sepsis patients who succumbed within a 28-day span.MethodsLeveraging data from Genome-wide association study (GWAS) and combining it with data from 2,076 European descendants in the Framingham Heart Study, single-nucleotide polymorphisms (SNPs) were employed as Instrumental Variables (IVs) to discern gene loci affiliated with metabolites. GWAS summary statistics for sepsis were extracted from the UK Biobank consortium.ResultsIn this extensive exploration, 93 distinct genome-wide significant SNPs correlated with gut microbial metabolites and specific bacterial traits were identified for IVs construction. Notably, a substantial link between Coprococcus2 and both the incidence (OR of 0.80, 95% CI: 0.68-0.94, P=0.007) and the 28-day mortality rate (OR 0.48, 95% CI: 0.27-0.85, P=0.013) of sepsis was observed. The metabolite α-hydroxybutyrate displayed a marked association with sepsis onset (OR=1.08, 95% CI: 1.02-1.15, P=0.006) and its 28-day mortality rate (OR=1.17, 95% CI: 1.01-1.36, P=0.029).ConclusionThis research unveils the intricate interplay between the gut microbial consortium, especially the genus Coprococcus, and the metabolite α-hydroxybutyrate in the milieu of sepsis. The findings illuminate the pivotal role of intestinal microbiota and their metabolites in sepsis’ pathogenesis, offering fresh insights for future research and hinting at novel strategies for sepsis’ diagnosis, therapeutic interventions, and prognostic assessments

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Amorphous Phase Mediated Crystallization: Fundamentals of Biomineralization

Many biomineralization systems start from transient amorphous precursor phases, but the exact crystallization pathways and mechanisms remain largely unknown. The study of a well-defined biomimetic crystallization system is key for elucidating the possible mechanisms of biomineralization and monitoring the detailed crystallization pathways. In this review, we focus on amorphous phase mediated crystallization (APMC) pathways and their crystallization mechanisms in bio- and biomimetic-mineralization systems. The fundamental questions of biomineralization as well as the advantages and limitations of biomimetic model systems are discussed. This review could provide a full landscape of APMC systems for biomineralization and inspire new experiments aimed at some unresolved issues for understanding biomineralization

A new grounding model for complex soil environments

The purpose of arranging the grounding electrode is to discharge large currents, such as fault current and ensure the transmission line operate safely. In the grounding system of Chinese transmission network, the common grounding electrodes are horizontal installation and vertical installation. But two installation methods usually have the disadvantages, which are long distance installation and large depth burying, and they are restricted susceptible to uncertain factors such as pipelines, roads and geology, which leads the grounding resistance increasing and affect the normal operation of transmission lines. In order to solve the problem, this paper presents a new grounding model for complex soil environments and analysis from grounding resistance, surface potential and current distribution. The results show that the helix grounding electrode has good resistance reduction performance in complex soil environment, which effectively improves the surface potential distribution and the distribution of the spill current

Plant Interactions with Changes in Coverage of Biological Soil Crusts and Water Regime in Mu Us Sandland, China

Plant interactions greatly affect plant community structure. Dryland ecosystems are characterized by low amounts of unpredictable precipitation as well as by often having biological soil crusts (BSCs) on the soil surface. In dryland plant communities, plants interact mostly as they compete for water resources, and the direction and intensity of plant interaction varies as a function of the temporal fluctuation in water availability. Since BSCs influence water redistribution to some extent, a greenhouse experiment was conducted to test the hypothesis that the intensity and direction of plant interactions in a dryland plant community can be modified by BSCs. In the experiment, 14 combinations of four plant species (Artemisia ordosica, Artemisia sphaerocephala, Chloris virgata and Setaria viridis) were subjected to three levels of coverage of BSCs and three levels of water supply. The results show that: 1) BSCs affected plant interaction intensity for the four plant species: a 100% coverage of BSCs significantly reduced the intensity of competition between neighboring plants, while it was highest with a 50% coverage of BSCs in combination with the target species of A. sphaerocephala and C. virgata; 2) effects of the coverage of BSCs on plant interactions were modified by water regime when the target species were C. virgata and S. viridis; 3) plant interactions were species-specific. In conclusion, the percent coverage of BSCs affected plant interactions, and the effects were species-specific and could be modified by water regimes. Further studies should focus on effects of the coverage of BSCs on plant-soil hydrological processes