The application of antimicrobial peptides as growth and health promoters for swine

With the widespread ban on the use of antibiotics in swine feed, alternative measures need to be sought to maintain swine health and performance, Antimicrobial peptides （AMPs） are part of the nonspecific defense system and are natural antibiotics produced by plants, insects, mammalians, and micro-organisms as well as by chemical synthesis. Due to their broad microbicidal activity against various fungi, bacteria and enveloped viruses AMPs are a potential alternative to conventional antibiotics for use in swine production. This review focuses on the structure and mechanism of action of AMPs, as well as their effects on performance, immune function and intestinal health in pigs. The aim is to provide support for the application of AMPs as feed additives replacing antibiotics in swine nutrition.

Soil Geochemical Background Value and Environmental Quality Assessment in Jinan City

[Objectives]This study was conducted to accurately assess soil and environmental quality in Jinan City. [Methods] Based on the multipurpose regional geochemical survey data of 1∶250 000 in Shandong Province, the differences between the soil geochemical background values of 54 indexes in Jinan City and the soil in the whole province and the comprehensive geochemical class of soil quality were studied. [Results] The contents of C and Cao in Jinan soil was significantly higher than the background values of Shandong Province. The Cd, Cr, Cu, F, Ni, Sn, MgO, Cao and Na_(2)O contents and pH value were higher than the abundance of the A soil layer in China, but the nutrient index contents of Se, I and OrgC were lower than the national background values. The surface soil quality in the study area was generally good, with the sum of superior, good and medium accounting for 99.76% of the total area of the study area. The distribution area of poor soil was the least, accounting for only 0.24%, and it was scattered near industrial and mining enterprises in the urban area of Jinan City, Laiwu District, Gangcheng District and Zhangqiu District, which was closely related to human activities. [Conclusions] This study has practical guiding significance for improving land use efficiency.

Excitatory amino acid transporter supports inflammatory macrophageresponses

Excitatory amino acid transporters(EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues.However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study,we demonstrated that LPS stimulation increases expression of EAAT2(coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type Ⅱ diabetes(T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells,which provides potential therapeutic targets for the treatment of inflammatory diseases.

Cross section measurement for the ^(232)Th(n,f)reaction in the 4.50−5.40 MeV region using a time projection chamber

Accurate cross sections of neutron induced fission reactions are required in the design of advanced nuclear systems and the development of fission theory.Time projection chambers(TPCs),with their track reconstruction and particle identification capabilities,are considered the best detectors for high-precision fission cross section measurements.The TPC developed by the back-streaming white neutron source(Back-n)team of the China Spallation Neutron Source(CSNS)was used as the fission fragment detector in measurements.In this study,the cross sections of the ^(232)Th(n,f)reaction at five neutron energies in the 4.50−5.40 MeV region were measured.The fission fragments and α particles were well identified using our TPC,which led to a higher detection efficiency of the fission fragments and smaller uncertainty of the measured cross sections.Ours is the first measurement of the ^(232)Th(n,f)reaction using a TPC for the detection of fission fragments.With uncertainties less than 5%,our cross sections are consistent with the data in different evaluation libraries,including JENDL-4.0,ROSFOND-2010,CENDL-3.2,ENDF/B-VⅢ.0,and BROND-3.1,whose uncertainties can be reduced after future improvement of the measurement.

Gut microbiota bridges dietary nutrients and host immunity

Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other,and thus affect host health and immune-mediated diseases.Here,we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions,emphasizing how this axis might influence host immunity in health and diseases.Of relevance,we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.

Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization

Echinacea purpurea modulates tumor progression,but the underlying mechanism is poorly defined.We isolated and purified a novel homogeneous polysaccharide from E.purpurea(EPPA),which was shown to be an arabinogalactan with a mean molecular mass(Mr)of 3.8×10^(4)Da and withα-(1→5)-L-Arabinan as the backbone and a-L-Araf-(1→,→6)-b-D-Galp-(1→,and →4)-α-D-GalpA-(1/as the side chains.Interestingly,oral administration of EPPA suppresses tumor progression in vivo and shapes the immune cell profile(e.g.,facilitating M1 macrophages)in tumor micro-environment by single-cell RNA sequencing(scRNA-seq)analysis.

Phenylalanine diminishes M1 macrophage inflammation

Emerging evidence suggests that amino acids dictate the effector functions of immune cells;however, whether and how phenylalanine(Phe) orchestrates the polarization of macrophages is not understood. Here, we determined that Phe attenuated lipopolysaccharide(LPS) and P. multocida serotype A strain CQ2(PmCQ2) infection-induced inflammation in vivo. Furthermore, we demonstrated that Phe inhibited the production of interleukin(IL)-1β and tumor necrosis factor(TNF)-α in proinflammatory(M1) macrophages. Phe reprogrammed the transcriptomic and metabolic profiles and enhanced oxidative phosphorylation in M1 macrophages, which reduced the activation of caspase-1. Notably, the valine-succinyl-CoA axis played a critical role in Phe-mediated inhibition of IL-1β production in M1 macrophages. Taken together, our findings suggest that manipulating the valine-succinyl-CoA axis provides a potential target for preventing and/or treating macrophage-related diseases.

Glutamine metabolism in Th17/Treg cell fate:applications in Th17 cell-associated diseases

Alteration in the Th17/Treg cell balance is implicated in various autoimmune diseases and these disease-associated pathologies.Increasing investigations have shown that glutamine metabolism regulates the differentiation of Th17 and Treg cells.Here we summarize the mechanisms by which glutamine metabolism regulates Th17/Treg cell fate.Some examples of a glutamine metabolism-dependent modulation of the development and progression of several Th17/Treg cell-associated diseases are provided afterward.This review will provide a comprehensive understanding of the importance of glutamine metabolism in the fate of Th17/Treg cell differentiation.

Exploring polyamines:Functions in embryo/fetal development

Polyamines such as putrescine, spermidine, spermine and agmatine are aliphatic polycationic compounds present in all living cells, and are derived from amino acids, intestinal bacteria, exfoliated enterocytes and supported from diet. Polyamines as the key compounds play essential role in cell proliferation, growth and differentiation. They also exert significant effects on embryonic development,implantation, embryonic diapause, placentation, angiogensis and fetal development. This review paper summarizes the functions of polyamines and embryo/fetus development and its regulatory mechanism which should help to provide some evidences for clinic.

A novel long-term intravenous combined with local treatment with human amnion-derived mesenchymal stem cells for a multidisciplinary rescued uremic calciphylaxis patient and the underlying mechanism

Calciphylaxis is a rare disease characterized histologically by microvessel calcification and microthrombosis,with high mortality and no proven therapy.Here,we reported a severe uremic calciphylaxis patient with progressive skin ischemia,large areas of painful malodorous ulcers,and mummified legs.Because of the worsening symptoms and signs refractory to conventional therapies,treatment with human amnion-derived mesenchymal stem cells(hAMSCs)was approved.Preclinical release inspections of hAMSCs,efficacy,and safety assessment,including cytokine secretory ability,immunocompetence,tumorigenicity,and genetics analysis in vitro,were introduced.We further performed acute and long-term hAMSC toxicity evaluations in C57BL/6 mice and rats,abnormal immune response tests in C57BL/6 mice,and tumorigenicity tests in neonatal Balbc-nu nude mice.After the preclinical research,the patient was treated with hAMSCs by intravenous and local intramuscular injection and external supernatant application to the ulcers.When followed up to 15 months,the blood-based markers of bone and mineral metabolism improved,with skin soft tissue regeneration and a more favorable profile of peripheral blood mononuclear cells.Skin biopsy after 1-month treatment showed vascular regeneration with mature noncalcified vessels within the dermis,and 20 months later,the re-epithelialization restored the integrity of the damaged site.No infusion or local treatment-related adverse events occurred.Thus,this novel long-term intravenous combined with local treatment with hAMSCs warrants further investigation as a potential regenerative treatment for uremic calciphylaxis due to effects of inhibiting vascular calcification,stimulating angiogenesis and myogenesis,anti-inflammatory and immune modulation,multidifferentiation,re-epithelialization,and restoration of integrity.

Characterizing the influence of gut microbiota on host tryptophan metabolism with germ-free pigs

Intestinal microbes are closely associated with host health,depending on metabolic crosstalk between the microbiota and host.Tryptophan metabolism is one of the best examples of metabolic crosstalk between intestinal microbiota and host;however,our understanding about the influence of intestinal microbiota on host tryptophan metabolism is limited.Thus,we established germ-free(GF)pig models to systemically explore the influence of intestinal microbiota on tryptophan metabolism.Five GF pigs were kept in GF conditions throughout the experiment(GF group).Six GF pigs were transplanted with fecal microbiota from donor sows to act as control pigs.Compared with control pigs,the GF pigs had remarkable alterations in tryptophan metabolism.The differential metabolites(P<0.05)were mainly found in the liver,circulation system and large intestine.Notably,the alteration of metabolites in tryptophan metabolism varied among organs,especially for the serotonin pathway.In GF pigs,tryptophan and kynurenine in the large intestine and 5-hydroxytryptophan in most organs were increased(P<0.05),while metabolites in the indole pathway in most organs were decreased(P<0.05).Collectively,our study reveals changes in tryptophan metabolism in GF pigs,highlighting the critical role of gut microbes in shaping host tryptophan metabolism.

Insights into host-microbe interaction:What can we do for the swine industry?

Recent discoveries have underscored the cross-talk between intestinal microbes and their hosts.Notably,intestinal microbiota impacts the development,physiological function and social behavior of hosts.This influence usually revolves around the microbiota-gut-brain axis(MGBA).In tbis review,we firstly outline the impacts of the host on colonization of intestinal microorganisms,and then highlight the influence of intestinal microbiota on hosts focusing on short-chain fatty acid(SCFA)and tryptophan metabolite-mediated MGBA.We also discuss the intervention of intestinal microbial metabolism by dietary sup-plements,which may provide new strategies for improving the welfare and production of pigs.Overall,we summarize a state-of-the-art theory that gut microbiome affects brain functions via metabolites from dietary macronutrients.

Evaluation of the Mechanisms Underlying Amino Acid and Microbiota Interactions in Intestinal Infections Using Germ-Free Animals

Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases.As an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections.In turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic bacteria.As a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies.This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms.The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.

Melatonin inhibits Gram-negative pathogens by targeting citrate synthase

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide.Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria,very few compounds are currently under development or approved in the clinical setting.Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics.Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection.Mechanistically,melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300,D363,and H265 sites,particularly for the notorious Pasteurella multocida.These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.