Compendium of 5810 genomes of sheep and goat gut microbiomes provides new insights into the glycan and mucin utilization.

BACKGROUND: Ruminant gut microbiota are critical in ecological adaptation, evolution, and nutrition utilization because it regulates energy metabolism, promotes nutrient absorption, and improves immune function. To study the functional roles of key gut microbiota in sheep and goats, it is essential to construct reference microbial gene catalogs and high-quality microbial genomes database. RESULTS: A total of 320 fecal samples were collected from 21 different sheep and goat breeds, originating from 32 distinct farms. Metagenomic deep sequencing and binning assembly were utilized to construct a comprehensive microbial genome information database for the gut microbiota. We successfully generated the largest reference gene catalogs for gut microbiota in sheep and goats, containing over 162 million and 82 million nonredundant predicted genes, respectively, with 49 million shared nonredundant predicted genes and 1138 shared species. We found that the rearing environment has a greater impact on microbial composition and function than the host's species effect. Through subsequent assembly, we obtained 5810 medium- and high-quality metagenome-assembled genomes (MAGs), out of which 2661 were yet unidentified species. Among these MAGs, we identified 91 bacterial taxa that specifically colonize the sheep gut, which encode polysaccharide utilization loci for glycan and mucin degradation. CONCLUSIONS: By shedding light on the co-symbiotic microbial communities in the gut of small ruminants, our study significantly enhances the understanding of their nutrient degradation and disease susceptibility. Our findings emphasize the vast potential of untapped resources in functional bacterial species within ruminants, further expanding our knowledge of how the ruminant gut microbiota recognizes and processes glycan and mucins. Video Abstract.

Acid-resistant chitosan/graphene oxide adsorbent for Cu2+ removal: The role of mixed cross-linking and amino-functionalized.

Copper ions in wastewater pose a significant threat to human and ecological safety. Therefore, preparing macroscopic adsorbents with reusable and high adsorption performance is paramount. This paper used graphene oxide as the adsorbent and chitosan as the thickener. Additionally, a silane coupling agent was employed to enhance the acid resistance of chitosan, and amino-modification of graphene oxide was performed. Macroscopic adsorbents with high adsorption capacity were fabricated using 3D printing technology. The results show that all five proportions of inks exhibit good printability. Dissolution experiments revealed that all materials maintained structural integrity after 180 days across pH values. Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) confirmed the successful preparation of the materials. Adsorption experiments showed that the best performing material ratio was 8 wt% graphene oxide and 7 wt% chitosan. Adsorption kinetics and isothermal adsorption experiments demonstrated that the adsorption process occurred via monolayer chemisorption. The adsorption process was attributed to strong electrostatic forces, van der Waals forces, and nitrogen/oxygen-containing functional group coordination. Cycling experiments showed that the material retained good adsorption performance after 6 cycles, suggesting its potential for practical heavy metal treatment applications.

Sophisticated Structural Ceramics Shaped from 3D Printed Hydrogel Preceramic Skeleton.

Shaping ceramic materials into sophisticated architecture with three dimensional (3D) hierarchical structure is desirable in multiapplication yet remains challenge due to their brittle and stiff nature. Herein, we propose a new method to achieve ceramic architectures with unsupported and large-spanning structure by shaping vat photopolymerization 3D printed hydrogel preceramic skeleton with unique flexible and deformable character. Specifically, the present photopolymerizable hydrogel preceramic achieves one stone, two birds: the photosensitive polymer matrix coupled with ceramic nanoparticles for the first shaping by vat photopolymerization 3D printing and the secondary plasticity of the 3D printed ceramic body through flexible shape deformation of hydrogel networks. Inorganic binder aluminum dihydrogen phosphate serves as hydrogel dispersion medium to achieve ultra-low shrinkage photopolymerization ceramic. Compared with conventional polymer-derived photo-curing ceramics, the linear shrinkage of lamina structure is solely 2%, and which of cubic ceramic structure is just 13.3%. More importantly, one 3D printed preceramic is conducted to reshape repeatedly myriad constructions, realizing reusability of intrinsic brittle ceramic, improving manufacturing fault tolerance rate. Finally, a variety of paradigms for ceramic structure applications are proposed toward stereo circuit, biomedicine, and catalytic applications, breaking the limitation of intrinsic brittleness of ceramic in high-precision manufacturing of complex ceramic devices. This article is protected by copyright. All rights reserved.

Co-Doped Porous Carbon/Carbon Nanotube Heterostructures Derived from ZIF-L@ZIF-67 for Efficient Microwave Absorption.

Carbon-based magnetic metal composites derived from metal-organic frameworks (MOFs) are promising materials for the preparation of broadband microwave absorbers. In this work, the leaf-like co-doped porous carbon/carbon nanotube heterostructure was obtained using ZIF-L@ZIF-67 as precursor. The number of carbon nanotubes can be controlled by varying the amount of ZIF-67, thus regulating the dielectric constant of the sample. An optimum reflection loss of -42.2 dB is attained when ZIF-67 is added at 2 mmol. An effective absorption bandwidth (EAB) of 4.8 GHz is achieved with a thickness of 2.2 mm and a filler weight of 12%. The excellent microwave absorption (MA) ability is generated from the mesopore structure, uniform heterogeneous interfaces, and high conduction loss. The work offers useful guidelines to devise and prepare such nanostructured materials for MA materials.

nCas9 Engineering for Improved Target Interaction Presents an Effective Strategy to Enhance Base Editing.

Base editors (BEs) are a recent generation of genome editing tools that couple a cytidine or adenosine deaminase activity to a catalytically impaired Cas9 moiety (nCas9) to enable specific base conversions at the targeted genomic loci. Given their strong application potential, BEs are under active developments toward greater levels of efficiency and safety. Here, a previously overlooked nCas9-centric strategy is explored for enhancement of BE. Based on a cytosine BE (CBE), 20 point mutations associated with nCas9-target interaction are tested. Subsequently, from the initial positive X-to-arginine hits, combinatorial modifications are applied to establish further enhanced CBE variants (1.1-1.3). Parallel nCas9 modifications in other versions of CBEs including A3A-Y130F-BE4max, YEE-BE4max, CGBE, and split-AncBE4max, as well as in the context of two adenine BEs (ABE), likewise enhance their respective activities. The same strategy also substantially improves the efficiencies of high-fidelity nCas9/BEs. Further evidence confirms that the stabilization of nCas9-substrate interactions underlies the enhanced BE activities. In support of their translational potential, the engineered CBE and ABE variants respectively enable 82% and 25% higher rates of editing than the controls in primary human T-cells. This study thus demonstrates a highly adaptable strategy for enhancing BE, and for optimizing other forms of Cas9-derived tools.

Micro- and Mesoporous Structural Effects of Beta Zeolites for Volatile Organic Compound Sorption.

To fully exploit pore engineering in the design of more efficient zeolite adsorbents for volatile organic compound (VOC) treatment, the roles of meso- and micropores need to be clarified to provide the theoretical basis and feasible measures. In this work, the three VOC sorption properties of conventional and hierarchical porous beta zeolites were comparatively investigated to study the roles of meso- and micropores. There is a division of functions between micro- and mesopores, with micropores being the main VOC adsorption sites and mesopores greatly enhancing VOC diffusion and adsorbent reusability. On the one hand, micropores should be preserved as much as possible because obtaining mesopores by sacrificing micropores (i.e., alkali treatment) results in 28-60% decreases in adsorption capacities. On the other hand, mesopore introduction is highly desirable, which results in an enhancement of VOC intraparticle diffusion rates by 1.3-2.3 times (at the VOC concentration of 600 ppm) and chlorobenzene adsorption capacity on the 20th cycle increasing from 78% of the initial value to 89 and 93%. The findings may provide valuable information about zeolite-based adsorbents for adsorption removal or recovery of VOCs.

Study on the Mechanical Properties of a Carbon-Fiber/Glass-Fiber Hybrid Foam Sandwich Structure.

Considering the different structural strength requirements of different parts of fiberglass yachts, carbon fiber/glass fiber hybrid reinforcement can be applied to the skins of sandwich panels in special areas. This paper designs and prepares 12 foam sandwich panel samples composed of pure carbon fiber, a carbon fiber/glass fiber hybrid, pure glass fiber skin, and PVC and SAN foam sandwich, with reference to the layup structure of the outer panel of a fiberglass yacht. Through a comparative analysis of low-speed impact experiments, edge compression experiments, and short beam three-point bending experiments, we seek the optimal carbon fiber/glass fiber hybrid layup design scheme for local structures to guide production. The results show that a reasonable hybrid carbon fiber layup in fiberglass skin can effectively reduce the low-speed impact damage of the sandwich structure, reduce edge compression damage, and improve the bending and compression resistance of sandwich structure. The impact resistance, compression resistance, and shear resistance of the SAN sandwich structure are stronger than the PVC sandwich structure. The carbon fiber/glass fiber hybrid SAN foam sandwich structure can be used for the local structural reinforcement of special parts such as the bow, side, and main deck of fiberglass yachts.

Clinical Presentation and Outcomes of Hospitalized Patients with Chronic Kidney Disease and COVID-19 Variant Omicron.

Purpose: To investigate the clinical characteristics of hospitalized patients with chronic kidney disease (CKD) and novel coronavirus (SARS-CoV-2) infection and identify potential risk factors that contribute to mortality. Patients and Methods: This is a retrospective study, conducted on patients with CKD who were admitted to the First Medical Center of the People's Liberation Army General Hospital between December 1, 2022, and February 28, 2023. All patients were also infected with SARS-CoV-2. We analyzed the clinical characteristics of patients, and the patients were categorized into a survival group and a death group whose characteristics were compared. Cox regression analysis was used to identify risk factors that affected patient prognosis. Results: A total of 406 patients were enrolled in this study, including 298 males (73.4%). The average age was 80.5 (67.0, 88.0) years, and the patients had an average estimated glomerular filtration rate (eGFR) of 50.3 (25.0-79.0) mL/min/1.73m². A total of 158 individuals died during hospitalization, resulting in a mortality rate of 38.9%. Renal function was worse in the death group than in the survival group (P < 0.001). Patients in the death group had more severe COVID-19 disease and higher CKD staging than those in the survival group (all P values < 0.001). Multivariate Cox regression analysis identified several risk factors that affected patient mortality, including being male, a higher resting heart rate (RHR) upon admission, dyspnea, a low lymphocyte count (Lym), a high international standardized ratio (INR), a high Acute Physiology and Chronic Health Evaluation II (APACHE II) score, heart failure, and the need for mechanical ventilation during the disease. Conclusion: Hospitalized patients with CKD who were infected with SARS-CoV-2 (38.9%) had a relatively high mortality rate (38.9%). Furthermore, a marked correlation was observed between a reduced eGFR and an increased risk of mortality.

Assessing eco-geographic influences on COVID-19 transmission: a global analysis.

COVID-19 has been massively transmitted for almost 3 years, and its multiple variants have caused serious health problems and an economic crisis. Our goal was to identify the influencing factors that reduce the threshold of disease transmission and to analyze the epidemiological patterns of COVID-19. This study served as an early assessment of the epidemiological characteristics of COVID-19 using the MaxEnt species distribution algorithm using the maximum entropy model. The transmission of COVID-19 was evaluated based on human factors and environmental variables, including climate, terrain and vegetation, along with COVID-19 daily confirmed case location data. The results of the SDM model indicate that population density was the major factor influencing the spread of COVID-19. Altitude, land cover and climatic factor showed low impact. We identified a set of practical, high-resolution, multi-factor-based maximum entropy ecological niche risk prediction systems to assess the transmission risk of the COVID-19 epidemic globally. This study provided a comprehensive analysis of various factors influencing the transmission of COVID-19, incorporating both human and environmental variables. These findings emphasize the role of different types of influencing variables in disease transmission, which could have implications for global health regulations and preparedness strategies for future outbreaks.

Development of a novel membrane-based quorum-quenching microbial isolator for biofouling control: Process performance and microbial mechanism.

Quorum quenching (QQ) can mitigate biofouling in membrane bioreactors (MBRs) by inhibiting cell-to-cell communication. However, it is difficult to maintain long-term QQ activity. Here, a novel microbial isolator composed of tubular microfiltration membranes was developed to separate QQ bacteria (Rhodococcus sp. BH4) from sludge. The time to reach a transmembrane pressure of 50 kPa was delayed by 69.55 % (p = 0.002, Student's t test) in MBR with QQ microbial isolator (MBR-Q), compared to that in the control MBR (MBR-C) during stable operation. The concentration of proteins in the extracellular polymeric substances of sludge was reduced by 20.61 % in MBR-Q relative to MBR-C. The results of the bacterial community analyses indicated less enrichment of fouling-associated bacteria (e.g., Acinetobacter) but a higher abundance of QQ enzymes in MBR-Q than in MBR-C. This environmentally friendly technique can decrease the cleaning frequency and increase the membrane lifespan, thus improving the sustainability of MBR technology.

Clinical efficacy of HI-NPPV in the treatment of AECOPD combined with severe type II respiratory failure. / HI-NPPV治疗AECOPD合并严重II型呼吸衰竭的临床疗效.

OBJECTIVES: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with severe type II respiratory failure have a high probability of ventilation failure using conventional non-invasive positive pressure ventilation (NPPV). This study aims to investigate the clinical efficacy of high intensity NPPV (HI-NPPV) for the treatment of AECOPD combined with severe type II respiratory failure. METHODS: The data of patients with AECOPD combined with severe type II respiratory failure (blood gas analysis pH≤7.25) treated with NPPV in the Second Affiliated Hospital of Chongqing Medical University from July 2013 to July 2023 were collected to conduct a retrospective case-control study. The patients were divided into 2 groups according to the inspired positive airway pressure (IPAP) used during the NPPV treatment: a NPPV group (IPAP<20 cmH2O, 1 cmH2O=0.098 kPa) and a HI-NPPV group (20 cmH2O≤IPAP< 30 cmH2O). Ninety-nine and 95 patients were included in the NPPV group and the HI-NPPV group, respectively. A total of 86 pairs of data were matched using propensity score matching (PSM) for data matching. The primary outcome indexes (mortality and tracheal intubation rate) and secondary outcome indexes [blood gas analysis pH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), adverse reaction rate, and length of hospitalization] were compared between the 2 groups. RESULTS: The tracheal intubation rates of the NPPV group and the HI-NPPV group were 6.98% and 1.16%, respectively, and the difference between the 2 groups was statistically significant (χ2=4.32, P<0.05); the mortality of the NPPV group and the HI-NPPV group was 23.26% and 9.30%, respectively, and the difference between the 2 groups was statistically significant (χ2=11.64, P<0.01). The PaO2 at 24 h and 48 h after treatment of the HI-NPPV group was higher than that of the NPPV group, and the PaCO2 of the HI-NPPV group was lower than that of the NPPV group, and the differences were statistically significant (all P<0.05). The differences of pH at 24 h and 48 h after treatment between the 2 groups were not statistically significant (both P>0.05). The differences between the 2 groups in adverse reaction rate and hospitalization length were not statistically significant (both P>0.05). CONCLUSIONS: HI-NPPV can reduce mortality and tracheal intubation rates by rapidly improving the ventilation of patients with AECOPD combined with severe type II respiratory failure. This study provides a new idea for the treatment of patients with AECOPD combined with severe type II respiratory failure.

Analysis the molecular similarity of least common amino acid sites in ACE2 receptor to predict the potential susceptible species for SARS-CoV-2.

SARS-CoV-2 infections in animals have been reported globally. However, the understanding of the complete spectrum of animals susceptible to SARS-CoV-2 remains limited. The virus's dynamic nature and its potential to infect a wide range of animals are crucial considerations for a One Health approach that integrates both human and animal health. This study introduces a bioinformatic approach to predict potential susceptibility to SARS-CoV-2 in both domestic and wild animals. By examining genomic sequencing, we establish phylogenetic relationships between the virus and its potential hosts. We focus on the interaction between the SARS-CoV-2 genome sequence and specific regions of the host species' ACE2 receptor. We analyzed and compared ACE2 receptor sequences from 29 species known to be infected, selecting 10 least common amino acid sites (LCAS) from key binding domains based on similarity patterns. Our analysis included 49 species across primates, carnivores, rodents, and artiodactyls, revealing complete consistency in the LCAS and identifying them as potentially susceptible. We employed the LCAS similarity pattern to predict the likelihood of SARS-CoV-2 infection in unexamined species. This method serves as a valuable screening tool for assessing infection risks in domestic and wild animals, aiding in the prevention of disease outbreaks.

Effects of different hydrological conditions on the taxonomic structure and functional traits of mollusk communities in a large floodplain wetland.

Floodplain wetlands are critical to the conservation of aquatic biodiversity and the ecological integrity of river networks. However, increasing drought severity and frequency caused by climate change can reduce floodplain wetlands' resistance and recovery capacities. Mollusks, which are common inhabitants of floodplain wetlands, are among the most vulnerable species to drought. However, the response of mollusk communities to drought has received little attention. Here, we investigated how the structure and functional traits of mollusk communities changed in response to varying hydrological conditions, including a flash drought (FD) in the Poyang Lake floodplain wetland. Our findings showed that FD strongly reduced mollusk abundance and biomass, decreased both α- and ß-diversity, and resulted in the extinction of bivalve taxa. A sudden shift in community trait structure was discovered due to the extinction of many species. These traits, which include deposit feeding, crawling, scraping, aerial respiration, and dormancy, help mollusks survive in FD and tolerate completely dry out of their Changhuchi habitat. Finally, we discovered that dissolved oxygen was an important controlling variable for mollusk communities during drought. Our findings provide a scientific basis for the management and conservation of floodplain wetland biodiversity in the context of increasing drought frequency and intensity.

CircTRIM1 encodes TRIM1-269aa to promote chemoresistance and metastasis of TNBC via enhancing CaM-dependent MARCKS translocation and PI3K/AKT/mTOR activation.

Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.

Huanglian Jiedu decoction inhibits vascular smooth muscle cell-derived foam cell formation by activating autophagy via suppressing P2RY12.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is a Chinese medicine with a long history of therapeutic application. It is widely used in treating atherosclerosis (AS) in Chinese medicine theory and clinical practice. However, the mechanism of HLJDD in treating AS remains unclear. AIM OF THE STUDY: To investigate the efficacy and mechanism of HLJDD in treating AS. MATERIALS AND METHODS: AS was induced on high-fat diet-fed ApoE-/- mice, with the aorta pathological changes evaluated with lipid content and plaque progression. In vitro, foam cells were induced by subjecting primary mouse aortic vascular smooth muscle cells (VSMCs) to oxLDL incubation. After HLJDD intervention, VSMCs were assessed with lipid stack, apoptosis, oxidative stress, and the expression of foam cell markers. The effects of P2RY12 were tested by adopting clopidogrel hydrogen sulfate (CDL) in vivo and transfecting P2RY12 over-expressive plasmid in vitro. Autophagy was inhibited by Chloroquine or transfecting siRNA targeting ATG7 (siATG7). The mechanism of HLJDD treating atherosclerosis was explored using network pharmacology and validated with molecular docking and co-immunoprecipitation. RESULTS: HLJDD exhibited a dose-dependent reduction in lipid deposition, collagen loss, and necrosis within plaques. It also reversed lipid accumulation and down-regulated the expression of foam cell markers. P2RY12 inhibition alleviated AS, while P2RY12 overexpression enhanced foam cell formation and blocked the therapeutic effects of HLJDD. Network pharmacological analysis suggested that HLJDD might mediate PI3K/AKT signaling pathway-induced autophagy. P2RY12 overexpression also impaired autophagy. Similarly, inhibiting autophagy counteracted the effect of CDL, exacerbated AS in vivo, and promoted foam cell formation in vitro. However, HLJDD treatment mitigated these detrimental effects by suppressing the PI3K/AKT signaling pathway. Immunofluorescence and molecular docking revealed a high affinity between P2RY12 and PIK3CB, while co-immunoprecipitation assays illustrated their interaction. CONCLUSIONS: HLJDD inhibited AS in vivo and foam cell formation in vitro by restoring P2RY12/PI3K/AKT signaling pathway-suppressed autophagy. This study is the first to reveal an interaction between P2RY12 and PI3K3CB.

Blood cellular membrane-coated Au/polydopamine nanoparticle-targeted NIR-II antibacterial therapy.

Bacterial infections are the primary causes of infectious diseases in humans. In recent years, the abuse of antibiotics has led to the widespread enhancement of bacterial resistance. Concerns have been raised about the identification of a common treatment platform for bacterial infections. In this study, a composite nanomaterial was used for near-infrared II (NIR-II) photothermal antibacterial treatment. Red blood cell membrane was peeled and coated onto the surface of the Au/polydopamine nanoparticle-containing aptamer. The composite nanomaterials based on Au/polydopamine exhibit highest photothermal conversion capability. Moreover, these assembled nanoparticles can quickly enter the body's circular system with a specific capability to recognise bacteria. In vivo experiments demonstrated that the composites could kill bacteria from infected blood while significantly reducing the level of bacteria in various organs. Such assemblies offer a paradigm for the treatment of bacterial infections caused by the side effects of antibiotics.

Plasma Metabolic Profiling and Multiclass Diagnostic Model Development for Stable Angina Pectoris and Acute Myocardial Infarction.

Coronary heart disease remains a major global health challenge, with a clear need for enhanced early risk assessment. This study aimed to elucidate metabolic signatures across various stages of coronary heart disease and develop an effective multiclass diagnostic model. Using metabolomic approaches, gas chromatography-mass and liquid chromatography-tandem mass spectrometry were used to analyze plasma samples from healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction. Pathway enrichment analysis was conducted on metabolites exhibiting significant differences. The key metabolites were identified using Random Forest and Recursive Feature Elimination strategies to construct a multiclass diagnostic model. The performance of the model was validated through 10-fold cross-validation and evaluated using confusion matrices, receiver operating characteristic curves, and calibration curves. Metabolomics was used to identify 1491 metabolites, with 216, 567, and 295 distinctly present among the healthy controls, patients with stable angina pectoris, and those with acute myocardial infarction, respectively. This implicated pathways such as the glucagon signaling pathway, d-amino acid metabolism, pyruvate metabolism, and amoebiasis across various stages of coronary heart disease. After selection, testosterone isobutyrate, N-acetyl-tryptophan, d-fructose, l-glutamic acid, erythritol, and gluconic acid were identified as core metabolites in the multiclass diagnostic model. Evaluating the diagnostic model demonstrated its high discriminative ability and accuracy. This study revealed metabolic pathway perturbations at different stages of coronary heart disease, and a precise multiclass diagnostic model was established based on these findings. This study provides new insights and tools for the early diagnosis and treatment of coronary heart disease.

Enterococcus durans 98D alters gut microbial composition and function to improve DSS-induced colitis in mice.

Enterococcus durans, is a potential functional strain with the capacity to regulate intestinal health and ameliorate colonic inflammation. However, the strain requires further investigation regarding its safety profile and potential mechanisms of colitis improvement. In this study, the safety of E. durans 98D (Ed) as a potential probiotic was studied using in vitro methods. Additionally, a dextran sulfate sodium (DSS)-induced murine colitis model was employed to investigate its impact on the intestinal microbiota and colitis. In vitro antimicrobial assays revealed Ed sensitivity to common antibiotics and its inhibitory effect on the growth of Escherichia coli O157, Streptococcus pneumoniae CCUG 37328, and Staphylococcus aureus ATCC 25923. To elucidate the functional properties of Ed, 24 weight-matched 6-week-old female C57BL/6J mice were randomly divided into three groups (n = 8): NC group, Con group (DSS), and Ed group (DSS + Ed). Ed administration demonstrated a protective effect on colitis mice, as evidenced by improvements in body weight, colonic length, reduced disease activity index, histological scores, diminished splenomegaly, and decreased goblet cell loss. Furthermore, Ed downregulated the expression of the pro-inflammatory cytokine genes (IL-6, IL-1ß, and TNF-α) and upregulated the expression of the anti-inflammatory cytokine gene IL-10. The 16S rRNA gene sequencing revealed significant alterations in microbial α-diversity, with principal coordinate analysis indicating distinct differences in microbial composition among the three groups. At the phylum level, the relative abundance of Actinomycetota significantly increased in the Ed-treated group. At the genus level, Ed treatment markedly elevated the relative abundance of Paraprevotella, Rikenellaceae_RC9, and Odoribacter in DSS-induced colitis mice. In conclusion, Ed exhibits potential as a safe and effective therapeutic agent for DSS-induced colitis by reshaping the colonic microbiota.

Voacangine protects hippocampal neuronal cells against oxygen-glucose deprivation/reoxygenation-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.

Voacangine, a naturally occurring alkaloid, has been testified to display beneficial effects on a variety of human diseases, but its role in ischemic stroke is unclear. The impacts of voacangine on oxygen-glucose deprivation/reoxygenation (OGD/R)-tempted hippocampal neuronal cells are investigated. The bioinformatics analysis found that voacangine is a bioactive ingredient that may have good effects on ischemic stroke. KEGG pathways analysis found that voacangine may regulate ischemic stroke through modulating the PI3K-Akt-FoxO signaling pathway. Voacangine could mitigate OGD/R-tempted cytotoxicity in HT22 cells. Voacangine mitigated OGD/R-tempted oxidative stress in HT22 cells by diminishing reactive oxygen species level and enhancing superoxide dismutase level. Voacangine mitigated OGD/R-tempted ferroptosis in HT22 cells. Voacangine promoted activation of the PI3K-Akt-FoxO signaling in OGD/R-induced HT22 cells. Inactivation of the PI3K-Akt-FoxO signaling pathway reversed the protective effects of voacangine against OGD/R-tempted oxidative stress, cytotoxicity, and ferroptosis in HT22 cells. In conclusion, voacangine protects hippocampal neuronal cells against OGD/R-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling.