Northeast Pacific warm blobs sustained via extratropical atmospheric teleconnections.

Large-scale marine heatwaves in the Northeast Pacific (NEP), identified here and previously as 'warm blobs', have devastating impacts on regional ecosystems. An anomalous atmospheric ridge over the NEP is known to be crucial for maintaining these warm blobs, also causing abnormally cold temperatures over North America during the cold season. Previous studies linked this ridge to teleconnections from tropical sea surface temperature anomalies. However, it was unclear whether teleconnections from the extratropics could also contribute to the ridge. Here we show that planetary wave trains, triggered by increased rainfall and latent heat release over the Mediterranean Sea accompanied by decreased rainfall over the North Atlantic, can transport wave energy to the NEP, guided by the westerly jet, and induce a quasi-barotropic ridge there. Our findings provide insights into extratropical teleconnections sustaining the NEP ridge, offering a source of potential predictability for the warm blobs and temperature fluctuations over North America.

Periodontitis and risk of mortality in patients with chronic kidney disease: A systematic review with meta-analysis.

Studies examining the link between periodontitis and survival outcomes have yielded conflicting results in patients with chronic kidney disease (CKD). This systematic review with meta-analysis aims to assess the association between periodontitis and cardiovascular or all-cause mortality in CKD patients. A thorough search was conducted on the PubMed, Web of Science, and Embase databases for studies investigating the association between periodontitis and survival outcomes in CKD patients. Two authors independently scanned the titles or abstracts and then identified the eligible full-text article based on the PECOS criteria: Participants (CKD patients), Exposure (periodontitis), Comparison (mild/no periodontitis), Outcomes (cardiovascular or all-cause mortality), and Study design (retrospective or prospective cohort). Six cohort studies, including 7731 patients, were identified. The included studies had low-to-moderate risk of bias. The mean/median follow-up duration ranged from 18.1 months to 8.67 years. The all-cause mortality rate was 44.8% for patients with periodontitis and 28.0% for controls. Meta-analysis showed that periodontitis, defined through clinical attachment loss (CAL), was significantly associated with an increased risk of all-cause (adjusted hazard ratio [HR] 1.24; 95% confidence intervals [CI] 0.89-1.72; I2 = 80.9%) and cardiovascular mortality (HR 1.57; 95% CI 1.08-2.27; I2 = 34.0%). Additionally, a significant association between periodontitis and the risk of cardiovascular or all-cause mortality was observed in studies with a predominance of females, follow-up duration ≥5 years, all stages of CKD, and low risk of bias subgroups. Periodontitis is significantly associated with an increased risk of all-cause and cardiovascular mortality in CKD patients within low risk of bias subgroup or based on defining periodontitis through CAL. Registration number: PROSPERO CRD42018512391.

Glycosidic linkages of fungus polysaccharides influence the anti-inflammatory activity in mice.

INTRODUCTION: Over decades, the source-function relationships of bioactive polysaccharides have been progressively investigated, however, it is still unclear how a defined structure may conduce to the bioactivities of polysaccharides. OBJECTIVES: To explore the structure-function relationship of fungus polysaccharides, we employed a dextran sulfate sodium (DSS)-induced colitis mouse model to compare the anti-inflammatory activity of two fungus polysaccharides from Dictyophora indusiata (DIP) and Tremella fuciformis (TFP), which exhibit distinct glycosidic linkages. METHODS: The structures of DIP and TFP were characterized through molecular weight detection, molecular morphology analysis, methylation analysis, and NMR analysis. Subsequently, we employed a DSS-induced colitis model to assess the anti-inflammatory efficacy of DIP and TFP. The colitis symptoms, histological morphology, intestinal inflammatory cytokines, and the composition and function of gut microbiota before and after polysaccharides treatment in colitis mice were also investigated. RESULTS: DIP, l,3-ß-D-glucan with 1,4-ß and 1,6-ß-D-Glcp as branched chains, exhibited superior therapeutic effect than that of TFP consisted of a linear 1,3-α-D-mannose backbone with D-xylose and L-fucose in the side chains. Both DIP and TFP relieved DSS-induced colitis in a gut microbiota-dependent manner. Furthermore, metagenomics showed that DIP and TFP could partially reverse the bacterial function in colitis mice. Glycoside Hydrolase 1 (GH1) and GH3 were identified as being involved in hydrolyzing the glucose linkages in DIP, while GH92 and GH29 were predicted to be active in cleaving the α-1,3-linked mannose linkages and the glycosidic bonds of L-fucose residues in TFP. CONCLUSION: Our findings highlight the pivotal role of glycosidic linkages in anti-inflammatory activities of fungus polysaccharides and would promote the design and discovery of polysaccharides with designated activity to be used as functional foods and/or therapeutics.

Ultraflexible Temperature-Strain Dual-Sensor Based on Chalcogenide Glass-Polymer Film for Human-Machine Interaction.

Skin-like thermoelectric (TE) films with temperature- and strain-sensing functions are highly desirable for human-machine interaction systems and wearable devices. However, current TE films still face challenges in achieving high flexibility and excellent sensing performance simultaneously. Herein, for the first time, a facile roll-to-roll strategy is proposed to fabricate an ultraflexible chalcogenide glass-polytetrafluoroethylene composite film with superior temperature- and strain-sensing performance. The unique reticular network of the composite film endows it with efficient Seebeck effect and flexibility, leading to a high Seebeck coefficient (731 µV/K), rapid temperature response (≈0.7 s), and excellent strain sensitivity (gauge factor = 836). Based on this high-performance composite film, an intelligent robotic hand for action feedback and temperature alarm is fabricated, demonstrating its great potential in human-machine interaction. Such TE film fabrication strategy not only brings new inspiration for wearable inorganic TE devices, but also sets the stage for a wide implementation of multifunctional human-machine interaction systems.

Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

The fusion of multi-omics profile and multimodal EEG data contributes to the personalized diagnostic strategy for neurocognitive disorders.

BACKGROUND: The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority. RESULTS: Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups. CONCLUSIONS: Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract.

Agaricus bisporus polysaccharides ameliorate ulcerative colitis in mice by modulating gut microbiota and its metabolism.

The gut microbiota plays a central role in maintaining human health and has been linked to many gastrointestinal diseases such as ulcerative colitis (UC). Agaricus bisporus is a famous edible mushroom, and Agaricus bisporus polysaccharides (ABPs) and the two purified fractions (ABP-1 and ABP-2) were demonstrated to exhibit immunomodulatory activity in our previous study. Herein, we further found that ABPs, ABP-1, and ABP-2 possessed therapeutic effects against dextran sodium sulfate (DSS)-induced colitis in mice. ABPs, ABP-1, and ABP-2 could relieve body weight loss, colon atrophy, and histological injury, increase tight junction proteins, restore gut-barrier function, and inhibit inflammation. ABP-2 with a lower molecular weight (1.76 × 104 Da) showed a superior therapeutic effect than ABP-1 with a higher molecular weight (8.86 × 106 Da). Furthermore, the effects of ABP-1 and ABP-2 were microbiota-dependent, which worked by inducing Norank_f__Muribaculaceae and Akkermansia and inhibiting Escherichia-Shigella and Proteus. In addition, untargeted fecal metabolomic analysis revealed distinct modulation patterns of ABP-1 and ABP-2. ABP-1 mainly enriched steroid hormone biosynthesis, while ABP-2 significantly enriched bile secretion and tryptophan metabolism. In summary, ABPs, especially low-molecular-weight fraction, represent novel prebiotics for treatment of inflammatory gastrointestinal diseases.

Long-term simulated microgravity fosters carotid aging-like changes via Piezo1.

AIMS: Elucidating the impacts of long-term spaceflight on cardiovascular health is urgently needed in face of the rapid development of human space exploration. Recent reports including the NASA Twins Study on vascular deconditioning and aging of astronauts in spaceflight are controversial. The aims of this study were to elucidate whether long-term microgravity promotes vascular aging and the underlying mechanisms. METHODS AND RESULTS: Hindlimb unloading (HU) by tail suspension was used to simulate microgravity in rats and mice. The dynamic changes of carotid stiffness in rats during 8 weeks of HU were determined. Simulated microgravity led to carotid artery aging-like changes as evidenced by increased stiffness, thickness, fibrosis and elevated senescence biomarkers in the HU rats. Specific deletion of the mechanotransducer Piezo1 in vascular smooth muscles significantly blunted these aging-like changes in mice. Mechanistically, mechanical stretch-induced activation of Piezo1 elevated microRNA-582-5p in vascular smooth muscle cells, with resultant enhanced synthetic cell phenotype and increased collagen deposition via PTEN/PI3K/Akt signaling. Importantly, inhibition of miRNA-582-5p alleviated carotid fibrosis and stiffness not only in HU rats but also in aged rats. CONCLUSIONS: Long-term simulated microgravity induces carotid aging-like changes via the mechanotransducer Piezo1-initiated and miRNA-mediated mechanism.

An advanced strategy for quality evaluation of Xinyi Biyan Pill by UPLC-DAD fingerprinting combined with multi-components UPLC-MS/MS analysis.

Xinyi Biyan Pill (XBP) is a classical Chinese patent medicine and widely used to treat acute and chronic or allergic rhinitis in clinical practice. This study aimed to establish and validate a comprehensive strategy combining ultra-performance liquid chromatography with diode array detector (UPLC-DAD) fingerprinting and multi-component quantification for quality evaluation of XBP. In the fingerprint analysis, 32 peaks were selected as common peaks and used to evaluate the similarity of 12 batches of XBP. In addition, 141 compounds of XBP were identified or preliminarily characterized in both positive and negative ion modes by coupling with an advanced hybrid linear ion trap (LTQ)-Orbitrap mass spectrometer. Moreover, a rapid quantitative method based on UPLC tandem mass spectrometry (UPLC-MS/MS) has been optimized and validated for simultaneous determination of 10 chemical markers within 15 min, and applied to analyzing 12 batches of XBP. The proposed comprehensive strategy combining UPLC-DAD fingerprinting and multi-component UPLC-MS/MS quantification exhibited satisfactory results with high efficiency, accuracy and reliability, which can be used as a reference for overall quality consistency evaluation of Chinese herbal formulations.

A comprehensive quality evaluation for Huangqi Guizhi Wuwu decoction by integrating UPLC-DAD/MS chemical profile and pharmacodynamics combined with chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human "blood impediment" (a type of "Bi" syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA). AIM OF THE STUDY: The characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers. MATERIALS AND METHODS: First, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD. RESULTS: In total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples. CONCLUSION: Combining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

Insights into the effects of fixation methods on the sensory quality of straight-shaped green tea and dynamic changes of key taste metabolites by widely targeted metabolomic analysis.

Fresh leaves of Echa 1 were fixed by roller, steam/hot air and light-wave, and the effects of the three fixation methods on the chemical characteristics of straight-shaped green teas (GTs) were studied by widely targeted metabolomic analysis. 1001 non-volatile substances was identified, from which 97 differential metabolites were selected by the criteria of variable importance in projection (VIP) > 1, p < 0.05, and |log2(fold change)| > 1. Correlation analysis indicated that 14 taste-active metabolites were the major contributors to the taste differences between differently processed GTs. High-temperature fixation induces protein oxidation or degradation, γ-glutamyl peptide transpeptidation, degradation of flavonoid glycosides and epimerization of cis-catechins, resulting in the accumulation of amino acids, peptides, flavonoids and trans-catechins, which have flavor characteristics such as umami, sweetness, kokumi, bitterness and astringency, thereby affecting the overall taste of GTs. These findings provided a scientific basis for the directional processing technology of high-quality green tea.

Microbial Diversity and Characteristic Quality Formation of Qingzhuan Tea as Revealed by Metagenomic and Metabolomic Analysis during Pile Fermentation.

In order to analyze the changes in the microbial community structure during the pile fermentation of Qingzhuan tea and their correlation with the formation of quality compounds in Qingzhuan tea, this study carried out metagenomic and metabolomic analyses of tea samples during the fermentation process of Qingzhuan tea. The changes in the expression and abundance of microorganisms during the pile fermentation were investigated through metagenomic assays. During the processing of Qingzhuan tea, there is a transition from a bacterial dominated ecosystem to an ecosystem enriched with fungi. The correlation analyses of metagenomics and metabolomics showed that amino acids and polyphenol metabolites with relatively simple structures exhibited a significant negative correlation with target microorganisms, while the structurally complicated B-ring dihydroxy puerin, B-ring trihydroxy galloyl puerlin, and other compounds showed a significant positive correlation with target microorganisms. Aspergillus niger, Aspergillus glaucus, Penicillium in the Aspergillaceae family, and Talaromyces and Rasamsonia emersonii in Trichocomaceae were the key microorganisms involved in the formation of the characteristic qualities of Qingzhuan tea.

Digital Prediction of the Purchase Price of Fresh Tea Leaves of Enshi Yulu Based on Near-Infrared Spectroscopy Combined with Multivariate Analysis.

In this study, near-infrared spectroscopy (NIRS) combined with a variety of chemometrics methods was used to establish a fast and non-destructive prediction model for the purchase price of fresh tea leaves. Firstly, a paired t-test was conducted on the quality index (QI) of seven quality grade fresh tea samples, all of which showed statistical significance (p < 0.05). Further, there was a good linear relationship between the QI, quality grades, and purchase price of fresh tea samples, with the determination coefficient being greater than 0.99. Then, the original near-infrared spectra of fresh tea samples were obtained and preprocessed, with the combination (standard normal variable (SNV) + second derivative (SD)) as the optimal preprocessing method. Four spectral intervals closely related to fresh tea prices were screened using the synergy interval partial least squares (si-PLS), namely 4377.62 cm-1-4751.74 cm-1, 4755.63 cm-1-5129.75 cm-1, 6262.70 cm-1-6633.93 cm-1, and 7386 cm-1-7756.32 cm-1, respectively. The genetic algorithm (GA) was applied to accurately extract 70 and 33 feature spectral data points from the whole denoised spectral data (DSD) and the four characteristic spectral intervals data (FSD), respectively. Principal component analysis (PCA) was applied, respectively, on the data points selected, and the cumulative contribution rates of the first three PCs were 99.856% and 99.852%. Finally, the back propagation artificial neural (BP-ANN) model with a 3-5-1 structure was calibrated with the first three PCs. When the transfer function was logistic, the best results were obtained (Rp2 = 0.985, RMSEP = 6.732 RMB/kg) by 33 feature spectral data points. The detection effect of the best BP-ANN model by 14 external samples were R2 = 0.987 and RMSEP = 6.670 RMB/kg. The results of this study have achieved real-time, non-destructive, and accurate evaluation and digital display of purchase prices of fresh tea samples by using NIRS technology.

An enzyme-based system for extraction of small extracellular vesicles from plants.

Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.

Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases.

As a ligand-dependent transcription factor, retinoid-associated orphan receptor γt (RORγt) that controls T helper (Th) 17 cell differentiation and interleukin (IL)-17 expression plays a critical role in the progression of several inflammatory and autoimmune conditions. An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORγt to decrease Th17 cell development and IL-17 production. Several RORγt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORγt by binding to orthosteric- or allosteric-binding sites in the ligand-binding domain. Some of small-molecule inhibitors have entered clinical evaluations. Therefore, in current review, the role of RORγt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted. Notably, the recently developed RORγt inhibitors were summarized, with an emphasis on their optimization from lead compounds, efficacy, toxicity, mechanisms of action, and clinical trials. The limitations of current development in this area were also discussed to facilitate future research.

Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis.

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.

Preparation of Alcohol Dehydrogenase-Zinc Phosphate Hybrid Nanoflowers through Biomimetic Mineralization and Its Application in the Inhibitor Screening.

A biomimetic mineralization method was used in the facile and rapid preparation of nanoflowers for immobilizing alcohol dehydrogenase (ADH). The method mainly uses ADH as an organic component and zinc phosphate as an inorganic component to prepare flower-like ADH/Zn3(PO4)2 organic-inorganic hybrid nanoflowers (HNFs) with the high specific surface area through a self-assembly process. The synthesis conditions of the ADH HNFs were optimized and its morphology was characterized. Under the optimum enzymatic reaction conditions, the Michaelis-Menten constant (Km) of ADH HNFs (ß-NAD+ as substrate) was measured to be 3.54 mM, and the half-maximal inhibitory concentration (IC50) of the positive control ranitidine (0.2-0.8 mM) was determined to be 0.49 mM. Subsequently, the inhibitory activity of natural medicine Penthorum chinense Pursh and nine small-molecule compounds on ADH was evaluated using ADH HNFs. The inhibition percentage of the aqueous extract of P. chinense is 57.9%. The vanillic acid, protocatechuic acid, gallic acid, and naringenin have obvious inhibitory effects on ADH, and their percentages of inhibition are 55.1%, 68.3%, 61.9%, and 75.5%, respectively. Moreover, molecular docking analysis was applied to explore the binding modes and sites of the four most active small-molecule compounds to ADH. The results of this study can broaden the application of immobilized enzymes through biomimetic mineralization, and provide a reference for the discovery of ADH inhibitors from natural products.

Oral Delivery of Transformable Bilirubin Self-Assembled System for Targeted Therapy of Colitis.

Ulcerative colitis (UC) is a high incidence disease worldwide and clinically presents as relapsing and incurable inflammation of the colon. Bilirubin (BR), a natural antioxidant with significant anti-colitic effects, is utilized in preclinical studies as an intestinal disease therapy. Due to their water-insolubility, the design of BR-based agents usually involves complicated chemosynthetic processes, introducing various uncertainties in BR development. After screening numerous materials, it is identified that chondroitin sulfate can efficiently mediate the construction of BR self-assembled nanomedicine (BSNM) via intermolecular hydrogen bonds between dense sulfate and carboxyl of chondroitin sulfate and imino groups of BR. BSNM exhibits pH sensitivity and reactive oxygen species responsiveness, enabling targeted delivery to the colon. After oral administration, BSNM significantly inhibits colonic fibrosis and apoptosis of colon and goblet cells; it also reduces the expression of inflammatory cytokines. Moreover, BSNM maintains the normal level of zonula occludens-1 and occludin to sustain the integrity of intestinal barrier, regulates the macrophage polarization from M1 to M2 type, and promotes the ecological recovery of intestinal flora. Collectively, the work provides a colon-targeted and transformable BSNM that is simple to prepare and is useful as an efficient targeted UC therapy.

Dietary Bile Acid Supplementation Could Regulate the Glucose, Lipid Metabolism, and Microbiota of Common Carp (Cyprinus carpio L.) Fed with a High-Lipid Diet.

This study sought to examine the role of bile acids in the regulation of glucose and lipid metabolism, intestinal flora, and growth in high-fat diet-fed common carp (Cyprinus carpio L.). Fish (6.34 ± 0.07 g) were fed for 56 days with three different diets, the control diet (CO, 5.4% lipid), high-fat diet (HF, 11% lipid), and high-fat diet with 60 mg/kg bile acids (BAs, 11% lipid). The results showed that high-fat diets resulted in poor growth performance and increased triglyceride (TG) in serum and the liver. The addition of bile acids significantly alleviated the adverse effects of a high-fat diet. The mRNA expression results indicated that bile acids may improve lipid metabolism through the enhancement of the peroxisome proliferator-activated receptor (PPARa). The expression of gluconeogenesis-related phosphoenolpyruvate carboxykinase (PEPCK) mRNA was inhibited, while fibroblast growth factor 19 (FGF19) was significantly higher. Bile acids reshaped the intestinal microflora community, with the level of Bacteroidetes increasing. The correlation analysis indicated that Patescibacteria, Dependentiae, Myxococcota, and Planctomycetota in the gut are associated with genes involved in glucose and lipid metabolism. These results indicated that bile acids could ameliorate the negative effects of high-fat diets on common carp.

FTZ polysaccharides ameliorate kidney injury in diabetic mice by regulating gut-kidney axis.

BACKGROUND: The Fufang-zhenzhu-tiaozhi formula (FTZ), a traditional Chinese medicine (TCM) commonly used to treat metabolic diseases, potentially impacts the microbial ecosystem. Increasing evidence suggests that polysaccharides, bioactive components of TCMs, have great potential on kinds of diseases such as DKD by regulating intestinal flora. PURPOSE: This study aimed to investigate whether the polysaccharide components in FTZ (FTZPs) have beneficial effects in DKD mice via the gut-kidney axis. STUDY DESIGN AND METHODS: The DKD model in mice was established by streptozotocin combined with a high-fat diet (STZ/HFD). Losartan was used as a positive control, and FTZPs were administered at doses of 100 and 300 mg/kg daily. Renal histological changes were measured by H&E and Masson staining. Western blotting, quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry were performed to analyze the effects of FTZPs on renal inflammation and fibrosis, which were further confirmed using RNA sequencing. Immunofluorescence was used to analyze the effects of FTZPs on colonic barrier function in DKD mice. Faecal microbiota transplantation (FMT) was used to evaluate the contribution of intestinal flora. 16S rRNA sequencing was utilized to analyze the composition of intestinal bacteria, and UPLC-QTOF-MS-based untargeted metabolomics was used to identify the metabolite profiles. RESULTS: Treatment with FTZPs attenuated kidney injury, as indicated by the decreased urinary albumin/creatinine ratio and improved renal architecture. FTZPs downregulated the expression of renal genes associated with inflammation, fibrosis, and systematically blunted related pathways. FTZPs also restored the colonic mucosal barrier and increased the expression of tight junction proteins (E-cadherin). The FMT experiment confirmed the substantial contribution of the FTZPs-reshaped microbiota to relieving DKD symptoms. Moreover, FTZPs elevated the content of short-chain fatty acids (propionic acid and butanoic acid) and increased the level of the SCFAs transporter Slc22a19. Intestinal flora disorders caused by diabetes, including the growth of the genera Weissella, Enterococcus and Akkermansia, were inhibited by FTZPs treatment. Spearman's analysis revealed that these bacteria were positively correlated with indicators of renal damage. CONCLUSION: These results show that oral administration of FTZPs, by altering SCFAs levels and the gut microbiome, is a therapeutic strategy for the treatment of DKD.