Enhancing urban blue-green landscape quality assessment through hybrid genetic algorithm-back propagation (GA-BP) neural network approach: a case study in Fucheng, China.

This study employs an artificial neural network optimization algorithm, enhanced with a Genetic Algorithm-Back Propagation (GA-BP) network, to assess the service quality of urban water bodies and green spaces, aiming to promote healthy urban environments. From an initial set of 95 variables, 29 key variables were selected, including 17 input variables, such as water and green space area, population size, and urbanization rate, six hidden layer neurons, such as patch number, patch density, and average patch size, and one output variable for the comprehensive value of blue-green landscape quality. The results indicate that the GA-BP network achieves an average relative error of 0.94772%, which is superior to the 1.5988% of the traditional BP network. Moreover, it boasts a prediction accuracy of 90% for the comprehensive value of landscape quality from 2015 to 2022, significantly outperforming the BP network's approximate 70% accuracy. This method enhances the accuracy of landscape quality assessment but also aids in identifying crucial factors influencing quality. It provides scientific and objective guidance for future urban landscape structure and layout, contributing to high-quality urban development and the creation of exemplary living areas.

Huangqi-Guizhi-Wuwu decoction regulates differentiation of CD4+ T cell and prevents against experimental autoimmune encephalomyelitis progression in mice.

BACKGROUND: Multiple sclerosis (MS) is a demyelination disorder caused by an overactive immune response. Its pathological characteristics include CNS inflammation, white matter demyelination, glial cell proliferation, and so on. Huangqi-Guizhi-Wuwu Decoction (HGWD), which is recorded in the Synopsis of the Golden Chamber, is used clinically for the therapy of MS, but its mechanism is still elusive. PURPOSE: This study was aimed to investigate the impact of HGWD on the classical animal model for MS, experimental autoimmune encephalomyelitis (EAE), and explore the underlying action mechanism. RESULTS: HGWD ameliorated the pathogenesis of EAE mice, and improved their neurobehavior and pathological tissue damage. Network pharmacology predictions revealed the action mechanism of HGWD in EAE mice might be related to its effect on the immune system of mice. HGWD effectively suppressed the inflammatory infiltration in CNS, while also preventing the elevation of CD4+T cells of mice with EAE. HGWD could increase the ratio of Treg cells, up-regulate the secretion of IL-10 and Foxp3 mRNA expression, inhibit the ratio of Th1 and Th17 cells, down-regulate the IFN-γ and IL-17 protein expression, as well as the RORγT and T-bet gene expression in EAE mice. In addition, HGWD-containing serum modulated Th1/Th17/Treg cell differentiation in vitro. Moreover, HGWD inhibited the p-JAK1, p-JAK2, p-STAT1, p-STAT3 and p-STAT4 proteins and elevated the p-STAT5 protein in lymphoid tissues of EAE mice. CONCLUSION: HGWD improved the progress of EAE by regulating the proportion of CD4+T cell subtype differentiation, which might be exerted through JAK/STAT signaling pathway, providing a pharmacological basis for the clinical treatment of MS.

Early Growth Response Gene-1 Deficiency Interrupts TGFß1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice.

Early growth response protein 1 (Egr-1) triggers the transcription of many genes involved in cell growth, differentiation, synaptic plasticity, and neurogenesis. However, its mechanism in neuronal survival and degeneration is still poorly understood. This study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) mice. Egr-1 knockout exacerbated EAE progression in mice, as shown by increased disease severity and incidence; it also aggravated neuronal apoptosis, which was associated with weakened activation of the BDNF/TGFß 1/MAPK/Akt signaling pathways in the CNS of EAE mice. Consistently, Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFß 1/MAPK/Akt signaling in SH-SY5Y cells. Our results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFß 1-mediated signaling activation, implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

Young SINEs in pig genomes impact gene regulation, genetic diversity, and complex traits.

Transposable elements (TEs) are a major source of genetic polymorphisms and play a role in chromatin architecture, gene regulatory networks, and genomic evolution. However, their functional role in pigs and contributions to complex traits are largely unknown. We created a catalog of TEs (n = 3,087,929) in pigs and found that young SINEs were predominantly silenced by histone modifications, DNA methylation, and decreased accessibility. However, some transcripts from active young SINEs showed high tissue-specificity, as confirmed by analyzing 3570 RNA-seq samples. We also detected 211,067 dimorphic SINEs in 374 individuals, including 340 population-specific ones associated with local adaptation. Mapping these dimorphic SINEs to genome-wide associations of 97 complex traits in pigs, we found 54 candidate genes (e.g., ANK2 and VRTN) that might be mediated by TEs. Our findings highlight the important roles of young SINEs and provide a supplement for genotype-to-phenotype associations and modern breeding in pigs.

Total Flavonoids of Astragalus Inhibit Activated CD4[Formula: see text] T Cells and Regulate Differentiation of Th17/Th1/Treg Cells in Experimental Autoimmune Encephalomyelitis Mice by JAK/STAT and NF[Formula: see text]B Signaling Pathways.

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4[Formula: see text] T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4[Formula: see text] T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NF[Formula: see text]B signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases.

Alleviative Effect of Probiotic Ferment on Lawsonia intracellularis Infection in Piglets.

(1) Background: Lawsonia intracellularis (LI) is an obligate intracellular Gram-negative bacterium that causes porcine ileitis. Pigs infected with LI have severe ileal lesions and show symptoms of diarrhea, indigestion, and growth retardation. Previous studies found that probiotic ferment (FAM) improved the growth performance, gut barrier, and function in piglets. Therefore, we aimed to reveal the mechanism that FAM alleviates negative performance in LI-challenged piglets by characterizing the changes in intestinal integrity, function, and gut microbiota following FAM supplementation. (2) Methods: Twenty-four healthy piglets were randomly allotted to four treatments. Three groups were challenged with LI; both FAM addition and vaccination were performed to explore their positive effects on LI-infected piglets. (3) Results: Piglets infected with LI showed lower growth performance and typical pathological symptoms. Moreover, microscopic images showed that observed intestinal morphological damage could be repaired by FAM and vaccine. To explore the digestion of nutrients in piglets, both digestive enzyme activity and ileal transporter expression were performed to reveal the promoting effect of additives. Reduction of LI colonization intervention by FAM could also ameliorate abnormal differentiation and function of intestinal epithelial cells and alleviate severe inflammatory responses in piglets. Regarding the gut microbiota, both the structure and function of the ileal and colonic microbiota were altered following FAM supplementation. (4) Conclusions: In conclusion, probiotic ferment can reduce the colonization of LI in the ileum, improve intestinal damage, barrier function and microbiota structure, and enhance digestive enzyme activity and nutrient transport proteins expression, thereby improving piglet growth performance, which has the effect of preventing ileitis in pigs.

Evaluation of Potential Probiotic Properties of Limosilactobacillus fermentum Derived from Piglet Feces and Influence on the Healthy and E. coli-Challenged Porcine Intestine.

In this work, we evaluated the probiotic properties of Limosilactobacillus fermentum strains (FL1, FL2, FL3, FL4) isolated from feces of healthy piglets. The in vitro auto-aggregation, hydrophobicity, biofilm-forming capacity, survival in the gastrointestinal tract, antimicrobial activity and anti-oxidation capacity were evaluated. Four strains were resistant to simulated gastrointestinal conditions, including low pH, pepsin, trypsin and bile salts. They also maintained strong self-aggregation and cell surface hydrophobicity. Limosilactobacillus fermentum FL4, which had the strongest adhesion ability and antimicrobial effect on Enterotoxigenic Escherichia coli K88 (ETEC K88), was then tested in porcine intestinal organoid models. The in vitro experiments in basal-out and apical-out organoids demonstrated that L. fermentum FL4 adhered to the apical surfaces more efficiently than basolateral surfaces, had the ability to activate the Wnt/ß-catenin pathway to protect the mucosal barrier integrity, stimulated the proliferation and differentiation of the intestinal epithelium, and repaired ETEC K88-induced damage. Moreover, L. fermentum FL4 inhibited inflammatory responses induced by ETEC K88 through the reduced expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IFN-γ) and higher levels of anti-inflammatory cytokines (TGF-ß and IL-10). These results show that L. fermentum FL4 isolated from feces of healthy Tunchang piglets has the potential to be used as an anti-inflammatory probiotic and for mitigation of intestinal damage in piglets.

Taurochenodeoxycholic acid reduces astrocytic neuroinflammation and alleviates experimental autoimmune encephalomyelitis in mice.

OBJECTIVE: Multiple sclerosis (MS) is an immune regulatory disease that affects the central nervous system (CNS). The main pathological features include demyelination and neurodegeneration, and the pathogenesis is associated with astrocytic neuroinflammation. Taurochenodeoxycholic acid (TCDCA) is one of the conjugated bile acids in animal bile, and it is not clear whether TCDCA could improve MS by inhibiting the activation of astrocytes. This study was aimed to evaluate the effects of TCDCA on experimental autoimmune encephalomyelitis (EAE)-a classical animal model of MS, and to probe its mechanism from the aspect of suppressing astrocytic neuroinflammation. It is expected to prompt the potential application of TCDCA for the treatment of MS. RESULTS: TCDCA effectively alleviated the progression of EAE and improved the impaired neurobehavior in mice. It mitigated the hyperactivation of astrocytes and down-regulated the mRNA expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 in the brain cortex. In the C6 astrocytic cell line induced by lipopolysaccharide (LPS), TCDCA treatment dose-dependently decreased the production of NO and the protein expression of iNOS and glial fibrillary acidic protein (GFAP). TCDCA consistently inhibited the mRNA expressions of COX2, iNOS and other inflammatory mediators. Furthermore, TCDCA decreased the protein expression of phosphorylated serine/threonine kinase (AKT), inhibitor of NFκB α (IκBα) and nuclear factor κB (NFκB). And TCDCA also inhibited the nuclear translocation of NFκB. Conversely, as an inhibitor of the G-protein coupled bile acid receptor Gpbar1 (TGR5), triamterene eliminated the effects of TCDCA in LPS-stimulated C6 cells. CONCLUSION: TCDCA improves the progress of EAE by inhibiting the astrocytic neuroinflammation, which might be exerted by the regulation of TGR5 mediated AKT/NFκB signaling pathway. These findings may prompt the potential application of TCDCA for MS therapy by suppressing astrocyte inflammation.

Evidence of Flavonoids on Disease Prevention.

A growing body of evidence highlights the properties of flavonoids in natural foods for disease prevention. Due to their antioxidative, anti-inflammatory, and anti-carcinogenic activities, flavonoids have been revealed to benefit skeletal muscle, liver, pancreas, adipocytes, and neural cells. In this review, we introduced the basic classification, natural sources, and biochemical properties of flavonoids, then summarize the experimental results and underlying molecular mechanisms concerning the effects of flavonoid consumption on obesity, cancers, and neurogenerative diseases that greatly threaten public health. Especially, the dosage and duration of flavonoids intervening in these diseases are discussed, which might guide healthy dietary habits for people of different physical status.

Effects of Dietary Supplementation with Lactobacillus acidophilus and Bacillus subtilis on Mucosal Immunity and Intestinal Barrier Are Associated with Its Modulation of Gut Metabolites and Microbiota in Late-Phase Laying Hens.

We investigated the effects of dietary supplementation with Lactobacillus acidophilus and Bacillus subtilis on the intestinal immune response, intestinal barrier function, cecal microbiota profile, and metabolite profile in late-phase laying hens. Hens were divided into three groups and fed with the basal diet (NC group), basal diet supplementation with 250 mg/kg B. subtilis and L. acidophilus mixture powder (LD group), and basal diet supplementation with 500 mg/kg B. subtilis and L. acidophilus mixture powder (HD group), respectively. The results indicated that the dietary supplementation with L. acidophilus and B. subtilis increased the integrity of the intestinal barrier as evidenced by the significant increase in the number of ileal goblet cells and improve the expression of occludin, claudin-1, and ZO-1 genes in the HD group. Moreover, the levels of IL-6, TNF-α, and IFN-γ were significantly decreased in the LD and HD groups. The levels of immunoglobulin G (IgG) increased in the LD and HD group, and the levels of secretory immunoglobulin A (sIgA) increased with the HD treatment. Furthermore, 16 s rRNA sequencing revealed L. acidophilus in combination with B. subtilis increased the diversity of gut microbiota. The metabolomic analysis revealed beneficial changes in the amino acid metabolism and lipid metabolism (decrease in LysoPC and LysoPE levels). In conclusion, dietary supplementation with L. acidophilus and B. subtilis could improve intestinal barrier function and maintain immune homeostasis. These beneficial effects may be associated with the modulation of the intestinal microbiome and metabolites.

Co-Cultures of Lactobacillus acidophilus and Bacillus subtilis Enhance Mucosal Barrier by Modulating Gut Microbiota-Derived Short-Chain Fatty Acids.

Weaning stress induces intestinal barrier dysfunction and immune dysregulation in mammals. Various interventions based on the modulation of intestinal microbiota have been proposed. Our study aims to explore the effects of co-cultures from Lactobacillus acidophilus and Bacillus subtilis (FAM®) on intestinal mucosal barrier from the perspective of metabolic function of gut microbiota. A total of 180 piglets were allocated to three groups, i.e., a control group (C, basal diet), a FAM group (F, basal diet supplemented with 0.1% FAM), and an antibiotic group (A, basal diet supplemented with antibiotic mixtures). Here, we showed FAM supplementation significantly increased body weight and reduced diarrhea incidence, accompanied by attenuated mucosal damage, increased levels of tight junction proteins, serum diamine oxidase (DAO) and antimicrobial peptides. In addition, 16S rRNA sequencing and metabolomic analysis revealed an increase in relative abundance of Clostridiales, Ruminococcaceae, Firmicutes and Muribaculaceae and a significant increase in the total short-chain fatty acids (SCFAs) and butyric acid in FAM-treated piglets. FAM also increased CD4+ T cells and SIgA+ cells in intestinal mucosa and SIgA production in colon contents. Furthermore, FAM upregulated the expression of IL-22, short-chain fatty acid receptors GPR43 and GPR41, aryl hydrocarbon receptor (AhR), and hypoxia-inducible factor 1α (HIF-1α). FAM shows great application prospect in gut health and provides a reference for infant weaning.

Total astragalosides promote oligodendrocyte precursor cell differentiation and enhance remyelination in cuprizone-induced mice through suppression of Wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Astragali is a traditional Chinese medicine with various pharmacological effects. Total astragalosides (TA), the main effective ingredients in Radix Astragali, exert properties including anti-oxidative stress, anti-neuroinflammation, and neuroprotection. We previously found that TA alleviated experimental autoimmune encephalomyelitis (EAE) progression, a widely used animal model of multiple sclerosis (MS). As a chronic demyelination disease, MS generally manifests myelin loss and fails to myelin regeneration. Regulation of oligodendrocyte progenitor cells (OPCs) differentiation and remyelination is the fundamental strategy for MS treatment. However, whether TA could directly promote OPCs differentiation and remyelination is still unknown. AIMS OF THE STUDY: This study was aimed to investigate pro-differentiation and myelin regeneration effects of TA on OPCs and Cuprizone (CPZ)-induced demyelination mice, an animal model of MS, and to explore mechanism underlying from regulation of OPCs differentiation and maturation. MATERIALS AND METHODS: Mice were orally given CPZ (400 mg/kg) daily for 4 weeks to induce myelin loss, and then treated with TA (25 and 50 mg/kg) daily for 1 week. Cell proliferation assay, Western blot, RT-PCR, immunocytochemistry and immunohistochemistry were performed to explore the mechanisms. The role of TA in oligodendrocyte differentiation and maturation was evaluated using MO3.13, a human oligodendrocytic hybrid cell line. RESULTS: TA was shown to mitigate behavioral impairment in CPZ-induced mice. It markedly ameliorated myelin loss and enhanced remyelination in the corpus callosum of mice, evidenced by increased expression of myelin basic protein (MBP) and the number of CC1+ newly generated oligodendrocytes (OLs). TA also enhanced the expression of MBP at both mRNA and protein levels in MO3.13 cells. In CPZ-induced mice and MO3.13 cells, TA remarkably promoted the activation of GSK3ß, repressed the phosphorylation of ß-catenin, reduced the expression of transcription factor 4 and inhibitor of DNA binding 2. The agonist of ß-catenin, SKL2001, partially abolished the pro-differentiation effect of TA in MO3.13 cells. CONCLUSIONS: Taken together, we clarified that TA could effectively enhance the differentiation and maturation of OPCs and accelerate remyelination in CPZ-induced mice through inhibition of Wnt/ß-catenin signaling pathway. This study provides new insight into the beneficial effect of TA in the treatment of MS.

Pharmacokinetic/Pharmacodynamic Target Attainment of Different Antifungal Agents in De-escalation Treatment in Critically Ill Patients: a Step toward Dose Optimization Using Monte Carlo Simulation.

Differences in pharmacokinetics/pharmacodynamics (PK/PD) target attainment are rarely considered when antifungals are switched in critically ill patients. This study intends to explore whether the antifungal de-escalation treatment strategy and the new intermittent dosing strategy of echinocandins in critically ill patients are able to achieve the corresponding PK/PD targets. The published population PK models of antifungals in critically ill patients and a public data set from the MIMIC-III database (n = 662) were employed to evaluate PK/PD target attainment of different dosing regimens of antifungals. Cumulative fraction of response (CFR) was calculated for each dosing regimen. Most guideline-recommended dosing regimens of fluconazole and voriconazole could achieve target exposure as de-escalation treatment in critically ill patients. For initial echinocandin treatment, achievement of the target exposure decreased as body weight increased, and the intermittent dosing strategy had a slightly higher CFR value in most simulations compared to conventional dosing strategy. For Candida albicans and Candida glabrata infection, caspofungin at the lowest dose achieved a CFR of >90%, while micafungin or anidulafungin required almost the highest doses simulated in this study to achieve the same effect. None of the echinocandins other than 150 mg every 24 h (q24h) or 200 mg q48h of caspofungin achieved the target CFR for Candida parapsilosis infection. These findings support the guideline-recommended dose of triazoles for antifungal de-escalation treatment and confirm the insufficient dosage of echinocandins in critically ill patients, indicating that a dosing regimen based on body weight or intermittent dosing of echinocandins may be required.

Coated tannin supplementation improves growth performance, nutrients digestibility, and intestinal function in weaned piglets.

To explore the effect of coated tannin (CT) on the growth performance, nutrients digestibility, and intestinal function in weaned piglets, a total of 180 piglets Duroc × Landrace × Yorkshire (28 d old) weighing about 8.6 kg were randomly allotted to three treatments: 1) Con: basal diet (contains ZnSO4); 2) Tan: basal diet + 0.15% CT; and 3) ZnO: basal diet + ZnO (Zn content is 1,600 mg/kg). The results showed that 0.15% CT could highly increase the average daily gain and average daily feed intake of weaned piglets compared with the control group, especially decreasing diarrhea incidence significantly (P < 0.05). Compared with the control group, crude protein apparent digestibility and digestive enzyme activity of the piglets fed with 0.15% CT were enhanced obviously (P < 0.05). Meanwhile, the intestinal villi and microvilli arranged more densely, while the content of serum diamine oxidase was decreased, and the protein expressions of zonula occludens-1 (ZO-1) and claudin-1 were significantly upregulated (P < 0.05). In addition, CT altered the structure of intestinal microbiota and augmented some butyrate-producing bacteria such as Ruminococcaceae and Megasphaera. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis also showed that the abundances of pathways related to butyrate metabolism and tryptophan metabolism were increased; however, the function of lipopolysaccharide biosynthesis proteins was significantly decreased. The results demonstrated that 0.15% CT could improve growth performance, digestibility, and intestinal function of weaned piglets, and it had the potential to replace ZnO applied to farming.

Studies in recent years have shown that tannic acid has various biological functions such as astringency, anti-inflammatory effect, and anti-oxidation property, which has good potential to improve diarrhea and intestinal health of animals. However, it can also lead to oxidative moisture absorption, poor palatability, and feed intake reduction when added to feed. Fortunately, coating treatment can effectively solve these problems. Under the above background, we hypothesized that tannic acid can repair the above shortcomings and improve growth and gut health parameters in weaned piglets with the help of coatings. Therefore, this study explored the effects of coated tannin (CT) on the growth performance, nutrients digestibility, and intestinal function in weaned piglets, which aimed to provide a scientific basis for CT replacing ZnO as a green and safe additive in farming and simultaneously also provide a reference for the application of other polyphenols in animals' health.

Artemisia annua water extract attenuates DNCB-induced atopic dermatitis by restraining Th2 cell mediated inflammatory responses in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. (A. annua) is a traditional Chinese medicine that has been used since ancient times to treat malaria, eczema, dermatomycosis, jaundice, and boils. Modern pharmacological studies show that it has immunosuppressive and anti-inflammatory effects. However, the mechanism of A. annua in the treatment of atopic dermatitis (AD) remains unclear. AIM OF THE STUDY: This study was aimed to investigate the effect of A. annua water extract (AWE) on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model and tried to explore its possible underlying mechanisms. MATERIALS AND METHODS: AD was induced in BALB/c mice by the topical repeated application of DNCB. Oral drug intervention of AWE and dexamethasone (DEX, positive control) began from the 7th day and continued for 13 consecutive days. The clinical skin score, ear thickness and the weight of ear and spleen were assessed. The ear tissue were stained with toluidine blue and hematoxylin and eosin (H&E) to detect inflammatory cell infiltration. IgE, terleukin (IL)-4 and IL-13 levels in the serum and IgE level in splenocytes were quantified by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-6, IL-13, IL-17, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin (TSLP) were measured by quantitative real time polymerase chain reaction. The phosphorylation levels of mitogen-activated protein kinases (MAPKs)-p38 and nuclear factor (NF)-κB in ear tissue were detected by Western blot. RESULTS: Results demonstrated that AWE treatment significantly attenuated the AD-like symptoms in DNCB-induced BALB/c mice, including the skin dermatitis severity and ear edema. Further study disclosed that AWE treatment suppressed the expressions of IgE, IL-4, IL-6, IL-13, IL-17, TNF-α and TSLP at mRNA and protein levels. Moreover, AWE showed inhibitory effect on the phosphorylation of p38 MAPK and NFκB in ear tissues of AD mice. CONCLUSIONS: Collectively, our results suggested that AWE suppressed DNCB-induced AD in mice probably by restraining Th2 type inflammatory response. These findings might pave the road for the potential clinical application of AWE for AD treatment.

Faecal microbiota transplantation alleviates early-life antibiotic-induced gut microbiota dysbiosis and mucosa injuries in a neonatal piglet model.

Faecal microbiota transplantation (FMT) is a promising approach to modulate the gut microbiota. Gut microbiota dysbiosis caused by antibiotic administration is a universal problem. This study aimed to evaluate the effect of FMT on the dysbiosis of gut microbiota and metabolic profiles and injury of the intestinal barrier induced by antibiotics and used a neonatal piglet model. Neonatal piglets were administered ampicillin for 3 days, and antibiotic-induced dysbiosis was evaluated by the occurrence of diarrhoea and alteration of gut microbiota. Then, FMT was conducted for 3 days to rebuild the gut microbiota. High-throughput sequencing and a mass spectrometry platform were used for integrated microbiome-metabolome analysis. The results showed that antibiotics led to a decline in the diversity of gut microbiota. Furthermore, there was an increase in the relative abundance of potential pathogenic bacteria, such as Oscillibacter, Pseudomonas and Eubacterium, and an increase in the relative abundance of tetracycline resistance genes (tet genes). FMT restored the diversity and promoted the relative abundance of beneficial bacteria, such as Parabacteroides, Dorea and Parasutterella, while decreasing the relative abundance of tet genes. Untargeted metabolomics analysis found that alpha linolenic acid and linoleic acid metabolism were the key metabolic pathways utilized in the FMT group, and targeted metabolomics analysis further verified the variation in the associated metabolites arachidonic acid and conjugated linoleic acid. FMT also significantly enhanced the relative expression of tight junction (ZO-1, claudin-1 and occludin) and adherens junction (ß-catenin, E-cadherin) proteins and anti-inflammatory cytokines (IL-10, TGF-ß1) and reduced the production of proinflammatory cytokines (IL-6, IL-1ß, TNF-α and IFN-γ) in the colon. FMT not only modulated the gut microbiota composition and microbial metabolism but also reduced the relative abundance of tet genes, improving the intestinal barrier function and inflammatory responses in antibiotic-treated piglets.

Effects of Zinc Sources and Levels on Growth Performance, Zinc Status, Expressions of Zinc Transporters, and Zinc Bioavailability in Weaned Piglets.

The present study was conducted to explore the bioavailability of chitosan-zinc chelate (CS-Zn) in weaned piglets, and its characteristics of prepared and oral safety were also involved. A total of 210 crossbred weaned piglets (Duroc × Landrace × Large White) with a mean body weight of 6.30 kg were randomly assigned into seven dietary treatments involving a 2 × 3 factorial arrangement with two Zn sources (CS-Zn and ZnSO4) and three levels of added Zn (50, 100, 150 mg Zn/kg) plus a Zn-unsupplemented control diet. The feeding trial lasted 42 days. The AFM image of CS-Zn showed a rougher appearance and smaller size particles. The changes in spectrum peaks evidenced the successful chelating of Zn2+ with chitosan. The XRD patterns revealed the formation of a new crystalline phase. Moreover, the oral acute toxicity test of CS-Zn showed no lethal effects on mice. Weaned piglets fed dietary CS-Zn showed improved weight gain and decreased diarrhea incidence. Additionally, the bioavailability of CS-Zn was higher than that of ZnSO4 in piglets. Taken together, these results indicate that the prepared CS-Zn chelate, with rough surface and crystalline phase, is non-toxic and show enhanced bioavailability.

LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis.

BACKGROUND: Long noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development. METHODS: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation. RESULTS: UCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells. CONCLUSIONS: UCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

Chlortetracycline alters microbiota of gut or faeces in pigs and leads to accumulation and migration of antibiotic resistance genes.

In this study, we investigated the effect of long-term use of chlortetracycline (CTC) on the gut microbiota composition and metabolism profiles in pigs, and the variation of antibiotic resistance genes (ARGs) and microbial communities in faeces and manure during aerobic composting (AC) and anaerobic digestion (AD). The pigs were fed the same basal diet supplemented with or without 75 mg/kg CTC, and fresh faeces of 30-, 60-, 90-, and 120-day-old pigs were collected from the CTC group. The results showed that CTC reduced the diversity of the gut microbiota significantly and changed its structure. Metabolomics analysis of intestinal contents revealed 23 differentially abundant metabolites, mainly organic acids, carbohydrates, and amino acids. Metabolic pathways, such as the TCA cycle, propionate metabolism, and pyruvate metabolism, were changed. From 30 to 120 days of age, the amount of CTC residues in faeces and the abundance of 3 tetracycline resistance genes increased significantly, and it was positively correlated with tetC, tetG, tetW, sul1 and intI2. CTC residue levels and ARGs abundance gradually decreased with fermentation time, and AC was better than AD at reducing ARGs abundance. The results suggest that in-feed CTC can reduce the diversity of the gut microbiota, change the structure, function and metabolism of the bacterial community, and increase the abundance of ARGs in faeces.

Early-Life Intervention Using Exogenous Fecal Microbiota Alleviates Gut Injury and Reduce Inflammation Caused by Weaning Stress in Piglets.

Fecal microbiota transplantation (FMT) could shape the structure of intestinal microbiota in animals. This study was conducted to explore the changes that happen in the structure and function of microbiota caused by weaning stress, and whether early-life FMT could alleviate weaning stress through modifying intestinal microbiota in weaned piglets. Diarrheal (D) and healthy (H) weaned piglets were observed, and in the same farm, a total of nine litters newborn piglets were randomly allocated to three groups: sucking normally (S), weaned at 21 d (W), and early-life FMT + weaned at 21 d (FW). The results demonstrated that differences of fecal microbiota existed in group D and H. Early-life FMT significantly decreased diarrhea incidence of weaned piglets. Intestinal morphology and integrity were improved in the FW group. Both ZO-1 and occludin (tight junction proteins) of jejunum were greatly enhanced, while the zonulin expression was significantly down-regulated through early-life FMT. The expression of IL-6 and TNF-α (intestinal mucosal inflammatory cytokines) were down-regulated, while IL-10 (anti-inflammatory cytokines) was up-regulated by early-life FMT. In addition, early-life FMT increased the variety of the intestinal microbial population and the relative amounts of some beneficial bacteria such as Spirochaetes, Akkermansia, and Alistipes. Functional alteration of the intestinal microbiota revealed that lipid biosynthesis and aminoacyl-tRNA biosynthesis were enriched in the FW group. These findings suggested that alteration of the microbiota network caused by weaning stress induced diarrhea, and early-life FMT alleviated weaning stress in piglets, which was characterized by decreased diarrhea incidence, improved intestinal morphology, reduced intestinal inflammation, and modified intestinal bacterial composition and function.