Search

Bile acid (BA) and its receptor FXR play crucial roles in metabolism, and dysregulated BA synthesis regulated by hepatic and bacterial enzymes causes metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC). Moreover, because ~ 75% of hepatic blood is from the gut, liver metabolism is influenced by intestinal bacteria and their metabolites. Thus, we used gut microbiota and metabolites from the urine and serum to uncover biomarkers for metabolic distress caused by Western diet (WD) intake, aging, and FXR inactivity. Hepatic transcriptomes were profiled to define liver phenotypes. There were 654 transcriptomes commonly altered by differential diet intake, ages, and FXR functional status, representing the signatures of liver dysfunction, and 76 of them were differentially expressed in healthy human livers and HCC. Machine learning approaches classified urine and serum metabolites for differential dietary intake and age difference. Additionally, the gut microbiota could predict FXR functional status. Furthermore, FXR was essential for differentiating dietary effects in colonizing age-related gut microbes. The integrated analysis established the relationships between the metabolites and gut microbiota correlated with hepatic transcripts commonly altered by diet, age, and FXR functionality. Remarkably, the changes in metabolites involved in the urea cycle, mitochondrial metabolism, and amino acid metabolism are associated with hepatic dysfunction (i.e. FXF deactivation). Taken together, noninvasive specimens and biomarkers are promising resources for identifying metabolic distress.

Western diet (WD) intake, aging, and inactivation of farnesoid X receptor (FXR) are risk factors for metabolic and chronic inflammation-related health issues ranging from metabolic dysfunction-associated steatotic liver disease (MASLD) to dementia. The progression of MASLD can be escalated when those risks are combined. Inactivation of FXR, the receptor for bile acid (BA), is cancer prone in both humans and mice. The current study used multi-omics including hepatic transcripts, liver, serum, and urine metabolites, hepatic BAs, as well as gut microbiota from mouse models to classify those risks using machine learning. A linear support vector machine with K-fold cross-validation was used for classification and feature selection. We have identified that increased urine sucrose alone achieved 91% accuracy in predicting WD intake. Hepatic lithocholic acid and serum pyruvate had 100% and 95% accuracy, respectively, to classify age. Urine metabolites (decreased creatinine and taurine as well as increased succinate) or increased gut bacteria (Dorea, Dehalobacterium, and Oscillospira) could predict FXR deactivation with greater than 90% accuracy. Human disease relevance is partly revealed using the metabolite-disease interaction network. Transcriptomics data were also compared with the human liver disease datasets. WD-reduced hepatic Cyp39a1 (cytochrome P450 family 39 subfamily a member 1) and increased Gramd1b (GRAM domain containing 1B) were also changed in human liver cancer and metabolic liver disease, respectively. Together, our data contribute to the identification of noninvasive biomarkers within the gut-liver axis to predict metabolic status.

BackgroundAging and diet are risks for metabolic diseases. Bile acid receptor farnesoid X receptor (FXR) knockout (KO) mice develop metabolic liver diseases that progress into cancer as they age, which is accelerated by Western diet (WD) intake. The current study uncovers the molecular signatures for diet and age-linked metabolic liver disease development in an FXR-dependent manner.MethodsWild-type (WT) and FXR KO male mice, either on a healthy control diet (CD) or a WD, were euthanized at the ages of 5, 10, or 15 months. Hepatic transcriptomics, liver, serum, and urine metabolomics as well as microbiota were profiled.ResultsWD intake facilitated hepatic aging in WT mice. In an FXR-dependent manner, increased inflammation and reduced oxidative phosphorylation were the primary pathways affected by WD and aging. FXR has a role in modulating inflammation and B cell-mediated humoral immunity which was enhanced by aging. Moreover, FXR dictated neuron differentiation, muscle contraction, and cytoskeleton organization in addition to metabolism. There were 654 transcripts commonly altered by diets, ages, and FXR KO, and 76 of them were differentially expressed in human hepatocellular carcinoma (HCC) and healthy livers. Urine metabolites differentiated dietary effects in both genotypes, and serum metabolites clearly separated ages irrespective of diets. Aging and FXR KO commonly affected amino acid metabolism and TCA cycle. Moreover, FXR is essential for colonization of age-related gut microbes. Integrated analyses uncovered metabolites and bacteria linked with hepatic transcripts affected by WD intake, aging, and FXR KO as well as related to HCC patient survival.ConclusionFXR is a target to prevent diet or age-associated metabolic disease. The uncovered metabolites and microbes can be diagnostic markers for metabolic disease.

Abstract: Background Aging and diet are risks for metabolic diseases. Bile acid receptor farnesoid X receptor (FXR) knockout (KO) mice develop metabolic liver diseases that progress into cancer as they age, which is accelerated by Western diet (WD) intake. The current study uncovers the molecular signatures for diet and age-linked metabolic liver disease development in an FXR-dependent manner.Methods Wild-type (WT) and FXR KO male mice, either on a healthy control diet (CD) or a WD, were euthanized at the ages of 5-, 10-, or 15-months. Hepatic transcriptomics, liver, serum, and urine metabolomics as well as microbiota were profiled.Results WD intake facilitated hepatic aging in WT mice. In an FXR-dependent manner, increased inflammation and reduced oxidative phosphorylation were the primary pathways affected by WD and aging. FXR has a role in modulating inflammation and B cell-mediated humoral immunity which was enhanced by aging. Moreover, FXR dictated neuron differentiation, muscle contraction, and cytoskeleton organization in addition to metabolism. There were 654 transcripts commonly altered by diets, ages, and FXR KO, and 76 of them were differentially expressed in human hepatocellular carcinoma (HCC) and healthy livers. Urine metabolites differentiated dietary effects in both genotypes, and serum metabolites clearly separated ages irrespective of diets. Aging and FXR KO commonly affected amino acid metabolism and TCA cycle. Moreover, FXR is essential for colonization of age-related gut microbes. Integrated analyses uncovered metabolites and bacteria linked with hepatic transcripts affected by WD intake, aging, and FXR KO as well as related to HCC patient survival.Conclusion FXR is target to prevent diet or age-associated metabolic disease. The uncovered metabolites and microbes can be diagnostic markers for metabolic disease.

Bile acids (BAs), produced in the liver and further transformed in the gut, are cholesterol-derived molecules involved in essential physiological processes. Recent studies suggest that BAs regulate T helper 17 cell function, but the underlying mechanism of this action and their therapeutic value in disease models remains unclear. Using an IL-23 minicircle DNA-based murine model of psoriasiform dermatitis, we showed that oral administration of secondary BAs, including lithocholic acid (LCA), deoxycholic acid, and 3-oxoLCA, significantly improved psoriasiform dermatitis without inducing apparent hepatotoxicity. Of the BAs tested, LCA possessed the greatest potency in treating psoriasiform dermatitis. Intravenous administration of LCA at a much lower dosage (compared with oral treatment) showed a comparable antipsoriatic effect and markedly suppressed the IL-17A response. Ex vivo experiments revealed that LCA reduced IL-17A production in IL-23-stimulated murine T cells in the absence of BA receptors TGR5 or FXR. Strikingly, BAs inhibited CCL20 expression in keratinocytes, which led to reduced migration of CCR6-expressing Jurkat cells cultured in the conditioned medium of stimulated keratinocytes. Thus, BAs improve psoriasiform dermatitis with minimal toxicity via direct inhibition of IL-17A production and blockade of CCL20-mediated trafficking, supporting the potential use of BAs in psoriasis.

AIM: To investigate the clinical value of serum vitamin A(Vit A)and basic fibroblast growth factor(bFGF)levels predicting retinopathy of prematurity(ROP).METHODS: Prospective cohort studies. A total of 411 premature or low birth weight infants with gestational age less than 37 wk or birth weight less than 2 500 g who were delivered in Hainan Branch, Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2020 to December 2022 were selected as subjects. The Vit A and bFGF levels in peripheral blood were detected at 7 d and 35 d after birth, respectively.RESULTS: A total of 392 premature infants or low birth weight infants completed clinical study, including 51 cases in stage 1-2 ROP group, 23 cases in stage 3-5 ROP group and 318 cases in the group without ROP. At 7 d postnatal, the serum Vit A(0.44±0.17 μmol/L)and bFGF(0.53±0.16 ng/L)levels in stage 1-2 ROP group were lower than those in the group without ROP(0.50±0.12 μmol/L and 0.63±0.15 ng/L; all P

Malaria parasite infection weakens colonization resistance against Salmonella enterica serovar (S.) Typhimurium. S. Typhimurium is a member of the Enterobacterales, a taxon that increases in abundance when the colonic microbiota is disrupted or when the colonic mucosa is inflamed. However, here, we show that infection of mice with Plasmodium yoelii enhances S. Typhimurium colonization by weakening host control in the upper GI tract. P. yoelii-infected mice had elevated gastric pH. Stimulation of gastric acid secretion during P. yoelii infection restored stomach acidity and colonization resistance, demonstrating that parasite-induced hypochlorhydria increases gastric survival of S. Typhimurium. Furthermore, blockade of P. yoelii-induced TNF-α signaling was sufficient to prevent elevation of gastric pH and enhance S. Typhimurium colonization during concurrent infection. Collectively, these data suggest that abundance in the fecal microbiota of facultative anaerobes, such as S. Typhimurium, can be increased by suppressing antibacterial defenses in the upper GI tract, such as gastric acid.

Disseminated disease from non-typhoidal Salmonella enterica strains results in >20% mortality globally. Barriers to effective treatment include emerging multidrug resistance, antibiotic treatment failure, and risk factors such as malnutrition and related micronutrient deficiencies. Individuals in sub-Saharan Africa are disproportionately affected by non-typhoidal S. enterica bloodstream infections. To inform a clinical trial in people, we investigated vitamin A as a treatment in the context of antibiotic treatment failure in a mouse model of vitamin A deficiency. Vitamin A-deficient (VAD) mice exhibited higher systemic bacterial levels with a multidrug-resistant clinical isolate in comparison to mice on a control diet. Sex-specific differences in vitamin A deficiency and disseminated infection with S. enterica serotype Typhimurium (S. Typhimurium) were observed. VAD male mice had decreased weight gain compared to control male mice. Further, infected VAD male mice had significant weight loss and decreased survival during the course of infection. These differences were not apparent in female mice. In a model of disseminated S. Typhimurium infection and antibiotic treatment failure, we assessed the potential of two consecutive doses of vitamin A in alleviating infection in male and female mice on a VAD or control diet. We found that subtherapeutic antibiotic treatment synergized with vitamin A treatment in infected VAD male mice, significantly decreasing systemic bacterial levels, mitigating weight loss and improving survival. These results suggest that assessing vitamin A as a therapy during bacteremia in malnourished patients may lead to improved health outcomes in a subset of patients, especially in the context of antibiotic treatment failure.

Jiaosu is a healthy food that has received increasing attention in recent years, while it mainly uses fruits as raw materials. In order to explore the feasibility of using Chinese medicinal plants to make Jiaosu, the study took Houttuynia cordata and Gynostemma pentaphyllum as examples to make Jiaosu products, and measured the main components and antioxidant capacity. The results showed that the color of the Jiaosu was dark yellow and the pH was acidic. Jiaosu products were rich in total protein, total sugar, vitamin E, and total0 phenols, of which total protein content was the highest. At the same time, Jiaosu products had strong antioxidant capacity. Enriching the form of healthy food is of great significance for maintaining human health in the post-epidemic era and the ageing era.

Abstract Walnut is an important economic tree species while confronting with global environmental stress, resulting in decline in quality and yield. Therefore, it is urgent to elucidate the molecular mechanism for the regulation of walnut response to adversity. The protein phosphatase 2C (PP2C) gene family participates in cellular processes in eukaryotes through reversible phosphorylation of proteins and signal transduction regulation. However, the stress response function of PP2C genes was far to be clarified. Therefore, to understand the stress response mechanism of walnut tree, in this study, a total of 41 PP2C genes with complete ORFs were identified from Juglans regia, whose basic bio-information and expression patterns in response to multiple stresses and ABA were confirmed. The results showed that the ORFs of JrPP2Cs were 495 ~ 3231 bp in length, the predicted JrPP2C proteins contained 164 to 1076 amino acids and the molecular weights were 18,581.96 ~ 118,853.34 Da, the pI was 4.55 ~ 9.58. These JrPP2C genes were unevenly distributed on 14 chromosomes, among which Chr11 and Chr13 contained the most genes. Phylogenetic analysis found that these JrPP2C proteins were classed into 9 subfamilies, among which group F covered most JrPP2Cs. The JrPP2Cs in the same subfamily exhibited similarities in the composition of conserved domains, amino acid sequences of motifs and exon/intron organization in DNA sequences. Each JrPP2C includes 4 ~ 10 motifs and each motif contained 15 ~ 37 amino acids. Among the motifs, motif1, motif2, motif3 and motif8 were most abundant. Most of the JrPP2C genes diversely response to osmotic, cadmium, and Colletotrichum gloeosporioide stress as well as ABA treatments, among which JrPP2C28, JrPP2C17, JrPP2C09, JrPP2C36 were more obvious and deserves further attention. All these results indicated that JrPP2C genes play potential vital roles in plant response to multiple stimulus, and are possibly involved in ABA-dependent signaling pathway.

Raman spectroscopy is a type of scattering spectroscopy with features such as rapid, less susceptible to moisture interference, no sample pre-treatment and in vivo detection. As a powerful characterization tool for analyzing and testing the molecular composition and structure of substances, Raman spectroscopy is also playing an extremely important role in the detection of plant and animal phenotypes, food safety, soil and water quality in the agricultural field with the continuous improvement of Raman spectroscopy technology. In this paper, the detection principles of Raman spectroscopy are introduced, and the new progresses of eight Raman spectroscopy technology are summarized, including confocal microscopy Raman spectroscopy, Fourier transform Raman spectroscopy, surface-enhanced Raman spectroscopy, tip-enhanced Raman spectroscopy, resonance Raman spectroscopy, spatially shifted Raman spectroscopy, frequency-shifted excitation Raman difference spectroscopy and Raman spectroscopy based on nonlinear optics, etc. And their advantages and disadvantages and application scenarios are prerented, respectively. The applications of Raman spectroscopy in plant detection, soil detection, water quality detection, food detection, etc. are summarized. It can be specifically subdivided into plant phenotype, plant stress, soil pesticide residue detection, soil colony detection, soil nutrient detection, food pesticide detection, food quality detection, food adulteration detection, and water quality detection. In future agricultural applications, the elimination of fluorescence background due to complex living organisms in Raman spectroscopy is the next research direction. The study of stable enhanced substrates is an important direction in the application of Surface Enhanced Raman Spectroscopy (SERS). In order to meet the measurement of different scenarios, portable and telemetric Raman spectrometers will also play an important role in the future. Raman spectroscopy needs to be further explored for a wide variety of research objects in agriculture, especially for applications in animal science, for which there is still a paucity of relevant studies up to now. In the existing field of agricultural research, it is necessary to pursue the characterization of more specific substances by Raman spectroscopy, which can prompt the application of Raman spectroscopy for a wider range of uses in agriculture. Further, the pursuit of lower detection limits and higher stability for practical applications is also the direction of development of Raman spectroscopy in the field of agriculture. Finally, the challenges that need to be solved and the future development directions of Raman spectroscopy are proposed in the field of agriculture in order to bring more inspiration to future agricultural production and research.

Juglans regia, an important economic tree species, is planted all over the world, and drought is one of the crucial factors limiting its growth and development. The various polyphenol content in walnut plants constitutes one of the material bases for the differences in stress resistance among various germplasms. However, the molecular mechanism underlying stress response mediated by polyphenol -dependent pathways remains unclear. v-Myb avian myeloblastosis viral oncogene homolog (MYB) protein of transcription factors play important regulatory roles in the process of plant stress responses. Previously, we identified JrMYB44 could be involved in osmotic stress response in walnut. In this study, we confirmed that the drought resistance of four walnut cultivars ('Chandler', 'Xiangling', 'Xilin2' and 'Xifu1') is positively correlated with the accumulation of polyphenols. The content and component changes of polyphenols in JrMYB44 overexpression (OE) and suppression (SE) lines in both walnut and Arabidopsis thaliana demonstrated that JrMYB44 positively regulated polyphenols accumulation. The variation of JrMYB44 expression and polyphenol levels under drought treatment indicated significant correlation between JrMYB44-induced drought tolerance and polyphenol accumulation, which was involved in reactive oxidative species (ROS) balance. The differentially expressed genes (DEGs) between OE and WT implied that JrMYB44 could positively activate downstream genes to participate in the drought stress response. Yeast one-hybrid (Y1H), transient GUS expression assay and dual-luciferase reporter assay (DLR) confirmed that JrMYB44 could recognize downstream JrWRKY7 and JrDREB2A, two transcription factors previously reported to be involved in drought response. Meanwhile, it was confirmed by Y2H, GST-pull down and luciferase complementation imaging assay (LCI) that JrMYB44 could interact with JrMYC2 and JrDof1, another two previously reported potential drought response regulators. Collectively, these results indicated that JrMYB44 could activate JrWRKY7, JrDREB2A and interact with JrMYC2 and JrDof1 to promote walnut polyphenol accumulation and improve drought resistance in a ROS dependent manner. [ABSTRACT FROM AUTHOR]

Rubus idaeus is one of the primary cultivated species of raspberries, renowned for its appealing color, distinctive flavor and numerous health benefits. WIP proteins, which contain three conserved amino acids (W: Tryptophan, I: Isoleucine, P: Proline) and four zinc finger motifs in a highly conserved C-terminal region, are members of the A1d subgroup of C2H2 zinc finger proteins. Drought is one of the main limiting factors of plant growth and development, which restricts the cultivation and utilization of raspberry in northwest China. In this study, to obtain candidate genes for drought resistance, we identified key related genes, RiWIPs, from R. idaeus and analyzed their bioinformation and tissue stress response expression to drought. We found that there are three RiWIPs in R. idaeus and they are located on chromosomes 3, 4 and 6 of R. idaeus, respectively. The open reading frames (ORFs) of the RiWIPs ranged from 870 to 1056 bp in length, encoding 289 to 372 amino acid residues. The proteins were highly conserved and feature diverse conserved motifs. The promoters of the RiWIPs contained abundant cis-elements related to growth, development and stress response. Tissue-specific expression analysis revealed that the RiWIPs were expressed in the leaves, stems and roots of both drought-susceptible and drought-tolerant cultivars, except for RiWIP2, which was only expressed in the roots of the drought-tolerant one. Under drought stress, the transcriptional activity of the RiWIPs was increased to different degrees with specificity in the leaves, stems and roots. Our study demonstrated the role of WIP genes in raspberry drought response and provided a marker gene, RiWIP2, for drought resistance and candidate genes for subsequent drought-resistant breeding of R. idaeus. [ABSTRACT FROM AUTHOR]

Olea europaea, native to the Mediterranean region, has been widely cultivated for the nutritional content of its fruits and leaves. To adapt to climates beyond the Mediterranean, research on the climatic adaptation of O. europaea is urgently needed. Therefore, in this study, the CBF/DREB1 family genes in olives, which are related to cold tolerance, were genome-wide characterized. In total, four OeCBFs were screened; their open reading frame (ORF) were 552~684 bp in length, the encoded proteins were 20,786.60~25,235.16 Da, with 183~227 amino acids, and the theoretical isoelectric point (pI) were 4.91~9.13. The transcription of four OeCBFs was significantly different in olive tissues, especially OeCBF2 and OeCBF4, which were substantially more highly-expressed in aboveground tissues (terminal buds, young leaves, old leaves, and stems) than in underground tissues (thick and fine roots). Exposed to cold stress, OeCBF2 and OeCBF4 were up-regulated more obviously in olive leaves and stems, while OeCBF3 was induced to higher levels in the roots, implying the adaptation potential of the OeCBFs to low temperature stress. A comparison of the expression of the four OeCBFs in two varieties, Picholine (more tolerant to the other one) and Arbequina, found that the expression of OeCBFs was higher in most tissues of Picholine than that of Arbequina. When exposed to cold stress, the expression of the OeCBFs was also higher in the leaves and roots of Picholine than in Arbequina, further confirming the correlation between OeCBFs and cold tolerance of olive trees. This study not only deepens our understanding of the CBF gene family in olives, but also provides significant genetic information for olive breeding and improvement. [ABSTRACT FROM AUTHOR]

IntroductionHeavy metals negatively affect plant physiology. However, plants can reduce their toxicity through physiological responses. Broussonetia papyrifera is a suitable candidate tree for carrying out the phytoremediation of manganese (Mn)-contaminated soil.MethodsConsidering that Mn stress typically exerts a binary effect on plants, to reveal the dynamic characteristics of the physiological indexes of B. papyrifera to Mn stress, we conducted pot experiments with six different Mn concentrations (0, 0.25, 0.5, 1, 2, and 5 mmol/L) for 60 days. In addition to the chlorophyll content, malondialdehyde (MDA), proline (PRO), soluble sugar, superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), the absorption and transfer characteristics of Mn, and root structure were also measured.ResultsPhytoremedial potential parameters such as the bioconcentration factor (BCF) and translocation factor (TF) displayed an increasing trend with the increase of Mn concentration. At lower Mn concentrations ( stem > root. The root structure analysis revealed that low-level concentrations of Mn (1 mmol/L) promoted root development. Mn concentration and stress duration had significant effects on all measured physiological indexes, and except soluble sugar, Mn concentration and stress time displayed a significant interaction on the physiological indexes.DiscussionOur study demonstrates that the physiological indexes of B. papyrifera display dynamic characteristics under Mn stress. Thus, during the monitoring process of Mn stress, it appears to be necessary to appropriately select sampling parts according to Mn concentration.