NOX4-mediated astrocyte ferroptosis in Alzheimer's disease.

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aß and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

Study on the relationship between body mass index and blood pressure indices in children aged 7-17 during COVID-19.

Background: To explore the relationship between body mass index (BMI), age, sex, and blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP) in children during COVID-19, providing reference for the prevention and screening of hypertension in children. Methods: This study adopted a large-scale cross-sectional design to investigate the association between BMI and blood pressure in 7-17-year-old students in City N, China, during COVID-19. Thirty-six primary and secondary schools in City N were sampled using a stratified cluster sampling method. A total of 11,433 students aged 7-17 years in City N, China, were selected for blood pressure (Diastolic blood pressure, DBP, Systolic blood pressure, SBP), height, and weight, Resting heart rate (RHR), chest circumference, measurements, and the study was written using the STROBE checklist. Data analysis was conducted using SPSS 26.0, calculating the mean and standard deviation of BMI and blood pressure for male and female students in different age groups. Regression analysis was employed to explore the impact of BMI, age, and sex on SBP and DBP, and predictive models were established. The model fit was evaluated using the model R2. Results: The study included 11,287 primary and secondary school students, comprising 5,649 boys and 5,638 girls. It was found that with increasing age, BMI and blood pressure of boys and girls generally increased. There were significant differences in blood pressure levels between boys and girls in different age groups. In regression models, LC, Age, BMI, and chest circumference show significant positive linear relationships with SBP and DBP in adolescents, while RHR exhibits a negative linear relationship with SBP. These factors were individually incorporated into a stratified regression model, significantly enhancing the model's explanatory power. After including factors such as Age, Gender, and BMI, the adjusted R2 value showed a significant improvement, with Age and BMI identified as key predictive factors for SBP and DBP. The robustness and predictive accuracy of the model were further examined through K-fold cross-validation and independent sample validation methods. The validation results indicate that the model has a high accuracy and explanatory power in predicting blood pressure in children of different weight levels, especially among obese children, where the prediction accuracy is highest. Conclusion: During COVID-19, age, sex, and BMI significantly influence blood pressure in children aged 7-17 years, and predictive models for SBP and DBP were established. This model helps predict blood pressure in children and reduce the risk of cardiovascular diseases. Confirmation of factors such as sex, age, and BMI provide a basis for personalized health plans for children, especially during large-scale infectious diseases, providing guidance for addressing health challenges and promoting the health and well-being of children.

Advances in nanoporous materials for next-generation battery applications.

In recent years, nanoporous materials, mainly represented by metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have shown unparalleled potential in critical applications such as energy storage, gas separation and catalysis. The integration of MOFs/COFs into battery technology has garnered substantial research attention since it was found that such materials also play important roles in batteries. The highly controllable nanoporous features of MOFs/COFs enable the regulation of the solvation environment of lithium ions, thereby significantly improving the performance of lithium metal batteries. Moreover, the selective adsorption features of MOFs/COFs make them particularly useful for stabilising high nickel cathodes and sulfur cathodes. This review provides an overview of the application of MOFs/COFs in batteries, and explores potential future directions and challenges in this rapidly evolving interdisciplinary field.

A new endophytic Penicillium oxalicum with aphicidal activity and its infection mechanism.

BACKGROUND: Aphid infestation adversely affects the yield and quality of crops. Rapid reproduction and insecticidal resistance have made controlling aphids in the field challenging. Therefore, the present study investigated the insecticidal property of Penicillium oxalicum (QLhf-1) and its mechanism of action against aphids, Hyalopterus arundimis Fabricius. RESULTS: Bioassay revealed that the control efficacy of the spores against aphids (86.30% and 89.05% on the third day and fifth day after infection, respectively) were higher than other components, such as the mycelium. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that QLhf-1 invaded the aphid cuticle through spores and used the aphid tissues as a nutrient source for growth and reproduction, causing stiffness and atrophy and a final death. Three extracellular enzymes, lipase, protease, and chitinase had a synergistic effect with spores, and they acted together to complete the infection process by degrading the aphid body wall and accelerating the infection process. CONCLUSION: The newly discovered endophytic penicillin strain P. oxalicum 'QLhf-1' can effectively kill aphids. The results provided strong evidence for the biological control of aphids, and lay a foundation for the development and utilization of QLhf-1. © 2024 Society of Chemical Industry.

Association between admission pan-immune-inflammation value and short-term mortality in septic patients: a retrospective cohort study.

Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.

Effect of macrophage-to-myofibroblast transition on silicosis.

BACKGROUND: The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition (MMT) in silicosis. METHODS: Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system. Murine macrophage MH-S cells were randomly divided into a control group and an SiO2 group. The pathological changes in lung tissue were observed using hematoxylin and eosin (HE) and Van Gieson (VG) staining. The distribution and location of macrophage marker (F4/80), M1 macrophage marker (iNOS), M2 macrophage marker (CD206), and myofibroblast marker (α-smooth muscle actin [α-SMA]) were detected using immunohistochemical and immunofluorescent staining. The expression changes in iNOS, Arg, α-SMA, vimentin, and type I collagen (Col I) were measured using Western blot. RESULTS: The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group. Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica. Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks. More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks. Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the control group. The results of immunofluorescence staining showed the co-expression of F4/80, α-SMA, and Col I, and CD206 and α-SMA were co-expressed in the lung tissue of the silicosis group. The extracted rat alveolar lavage fluid revealed F4/80+α-SMA+, CD206+α-SMA+, and F4/80+α-SMA+Col I+ cells using immunofluorescence staining. Similar results were also found in MH-S cells induced by SiO2. CONCLUSIONS: The development of silicosis is accompanied by macrophage polarization and MMT.

Pulmonary embolism in patients with chronic coronary syndrome masquerading as acute coronary syndrome: a case report and literature review.

BACKGROUND: Pulmonary embolisms (PEs) exhibit clinical features similar to those of acute coronary syndrome (ACS), including electrocardiographic abnormalities and elevated troponin levels, which frequently lead to misdiagnoses in emergency situations. CASE PRESENTATION: Here, we report a case of PE coinciding with chronic coronary syndrome in which the patient's condition was obscured by symptoms mimicking ACS. A 68-year-old female with syncope presented to the hospital. Upon admission, she was found to have elevated troponin levels and an electrocardiogram showing ST-segment changes across multiple leads, which initially led to a diagnosis of ACS. Emergency coronary arteriography revealed occlusion of the posterior branches of the left ventricle of the right coronary artery, but based on the complexity of the intervention, the occlusion was considered chronic rather than acute. On the 3rd day after admission, the patient experienced recurrent chest tightness and shortness of breath, which was confirmed as acute PE by emergency computed tomography pulmonary angiography. Following standardized anticoagulation treatment, the patient improved and was subsequently discharged. CONCLUSIONS: This case report highlights the importance of recognizing the nonspecific features of PE. Clinicians should be vigilant when identifying other clinical features that are difficult to explain accompanying the expected disease, and it is necessary to carefully identify the causes to prevent missed diagnoses or misdiagnoses.

The evaluation and enhancement strategies of core competencies for older adult caregivers in integrated medical and older adult care institutions.

The study aimed to understand the main skills of older adult caregivers and find ways to improve these skills. We selected participants using a method called random cluster sampling, where caregivers from 17 different medical and nursing care facilities across seven districts in Hangzhou were chosen. We collected 492 valid questionnaires and conducted interviews with 150 people. To analyze the data, we used T-tests and Analysis of Variance (ANOVA) to identify what factors affect caregivers' skills. We also performed multiple regression analysis to explore these factors in more depth. The analysis showed that age (p = 0.041), annual income (p < 0.001), and having a training certificate (p < 0.001) significantly influence the skills of older adult caregivers. Specifically, caregivers' age and whether they had a training certificate were linked to how competent they were, with income being a very strong factor. The study highlighted a gap between the caregivers' current skills and the skills needed for high-quality care. This gap shows the need for training programs that are specifically tailored to the caregivers' diverse needs and cultural backgrounds. Medical and eldercare facilities should adjust their work and educational programs accordingly. It's also important to look at how caregivers are paid to make sure their salary reflects their skills and the quality of care they provide. Finally, it's crucial to integrate a comprehensive training program that leads to certification within eldercare organizations.

2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside promotes liver regeneration after partial hepatectomy in mice: The potential involvement of PPARα-mediated fatty acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

Identification of lignans as selective cyclooxygenase-2 inhibitors from the extract of Acanthopanacis cortex.

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6∼8 and 13∼16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision.

BACKGROUND: Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM: To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS: A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS: Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION: The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

Current Applications of Colorectal Cancer Organoids: A Review.

Colorectal cancer is a prevalent malignancy, with advanced and metastatic forms exhibiting poor treatment outcomes and high relapse rates. To enhance patient outcomes, a comprehensive understanding of the pathophysiological processes and the development of targeted therapies are imperative. The high heterogeneity of colorectal cancer demands precise and personalized treatment strategies. Colorectal cancer organoids, a three-dimensional in vitro model, have emerged as a valuable tool for replicating tumor biology and exhibit promise in scientific research, disease modeling, drug screening, and personalized medicine. In this review, we present an overview of colorectal cancer organoids and explore their applications in research and personalized medicine, while also discussing potential future developments in this field.

The redistribution process of As(â ¢) and Fe(â ¡) caused by As/Fe ratio, organic matter, and co-existing ions: Co-precipitation and co-oxidation.

The contamination of arsenic (As) in aqueous environments has drawn widespread attention, and iron compounds may largely alter the migration ability of As. However, the stability of As(III) in Fe-As system with the intervention of organic matter (OM) remains unclear. Herein, we had explored the co-precipitation and co-oxidation processes of As-Fe system by using batch experiments combined with Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) in this research. The precipitation quantity of As(III) increased (28.85-92.41 %) when the As/Fe ratio decreased, and increased (24.20-64.20 %) with pH increased. The main active substance for oxidizing As(III) was H2O2, which was produced in the As-Fe system. FTIR and XPS revealed that As(III) was first oxidized in neutral, and then absorbed and enteredthe interior of Fe(OH)3 colloids. But under alkaline conditions, As(III) was adsorbed by Fe (Oxyhydr) oxides firstly, and then oxidized. The intervention of OM would inhibit the redistribution process of As(III) in aqueous environments. Functional groups and unsaturation of the carbon chain were the dominant factors that affected the precipitation and oxidation processes of As(III), respectively. Co-existing ions (especially PO43-) also signally affected the precipitation quantity of As(Ⅲ) in the system and, when coexisting with OM, could exacerbate this process. The influence of co-existing ions on the redistributive process of As(III) in the As-Fe system with/without OM were as follows: PO43- > SO42- > mixed ions > SiO32-. Moreover, high concentration of OM and PO43- might lead to morphological alterations of As, acting as a threat to aqueous environments. In summary, the present findings were to further understand and appreciate the changes of As toxicity in the aqueous environments. Particularly, the coexistence of OM and As can potentially increase the risk to drinking water safety.

Association of Delirium with Long-Term Mortality in Critically Ill Patients with COPD Who Survived to Discharge: A Retrospective Cohort Study.

BACKGROUND: Critically ill patients with chronic obstructive pulmonary disease (COPD) face significant mortality after hospital discharge. Delirium is common in patients with COPD, but its impact on long-term mortality in critically ill COPD patients who survive to discharge remains uncertain. METHODS: Critically ill patients with COPD who survived to discharge were selected from the Medical Information Mart for Intensive Care IV database. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. The primary outcome was 365- and 180-day mortality after discharge. The secondary outcomes included 90- and 30-day mortality following discharge, length of intensive care unit (ICU) and hospital stays, and nursing care needs after hospital discharge. RESULTS: Of the 2621 survivors of critically ill COPD patients, 982 had suffered delirium during their ICU stay and 709 died within 365 days after hospital discharge. Delirium was significantly associated with 365-day mortality after hospital discharge (adjusted hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.02-1.47). The results were consistent for 180-, 90-, and 30-day post-discharge mortality (adjusted HR [95% CI]: 1.35 [1.09-1.66], 1.48 [1.16-1.89], and 1.68 [1.21-2.32], respectively). Additionally, patients with delirium had longer ICU and hospital stay (adjusted ß 2.75; 95% CI 2.35-3.16 and 4.25; 95% CI 3.51-4.98, respectively) and increased nursing care needs after hospital discharge (adjusted odds ratio, 1.56; 95% CI 1.13-2.14). CONCLUSION: ICU delirium was an independent risk factor for both long-term and short-term mortality in critically ill patients with COPD who survived to discharge.

cAMP-independent DNA binding of the CRP family protein DdrI from Deinococcus radiodurans.

The cAMP receptor proteins (CRPs) play a critical role in bacterial environmental adaptation by regulating global gene expression levels via cAMP binding. Here, we report the structure of DdrI, a CRP family protein from Deinococcus radiodurans. Combined with biochemical, kinetic, and molecular dynamics simulations analyses, our results indicate that DdrI adopts a DNA-binding conformation in the absence of cAMP and can form stable complexes with the target DNA sequence of classical CRPs. Further analysis revealed that the high-affinity cAMP binding pocket of DdrI is partially filled with Tyr113-Arg55-Glu65 sidechains, mimicking the anti-cAMP-mediated allosteric transition. Moreover, the second syn-cAMP binding site of DdrI at the protein-DNA interface is more negatively charged compared to that of classical CRPs, and manganese ions can enhance its DNA binding affinity. DdrI can also bind to a target sequence that mimics another transcription factor, DdrO, suggesting potential cross-talk between these two transcription factors. These findings reveal a class of CRPs that are independent of cAMP activation and provide valuable insights into the environmental adaptation mechanisms of D. radiodurans.IMPORTANCEBacteria need to respond to environmental changes at the gene transcriptional level, which is critical for their evolution, virulence, and industrial applications. The cAMP receptor protein (CRP) of Escherichia coli (ecCRP) senses changes in intracellular cAMP levels and is a classic example of allosteric effects in textbooks. However, the structures and biochemical activities of CRPs are not generally conserved and there exist different mechanisms. In this study, we found that the proposed CRP from Deinococcus radiodurans, DdrI, exhibited DNA binding ability independent of cAMP binding and adopted an apo structure resembling the activated CRP. Manganese can enhance the DNA binding of DdrI while allowing some degree of freedom for its target sequence. These results suggest that CRPs can evolve to become a class of cAMP-independent global regulators, enabling bacteria to adapt to different environments according to their characteristics. The first-discovered CRP family member, ecCRP (or CAP) may well not be typical of the family and be very different to the ancestral CRP-family transcription factor.

An extracellular vesicle microRNA-initiated 3D DNAzyme motor for colorectal cancer diagnosis.

MicroRNA is regarded as a significant biomarker for cancer diagnosis, disease process evaluation and therapeutic guidance, and dual-parameter measurement may contribute to a more accurate and realistic assessment. To meet the urgent need for simultaneous detection of multiple biomarkers, we combined three-dimensional DNAzyme motors with single molecule imaging technique to construct a convenient, intuitive, and sensitive approach for the simultaneous detection of dual miRNAs in the free state or in extracellular vesicles. Quantification of target miRNAs can be realized through the detection of amplified fluorescence signals generated by the target miRNA-initiated cleavage of fluorescent substrate strands by the DNAzyme motors. The practicability was systematically validated with microRNA-21-5p and microRNA-10b-5p as targets, acquiring a satisfactory sensitivity sufficient to detect low abundance targets at 0.5 or 1 pM to 100 pM. Besides, the extracellular vesicular miRNAs can be conveniently detected without extraction. The clinical applicability was verified with a series of extracellular vesicles from clinical samples, which exhibited good distinguishability between colorectal cancer patients and healthy donors. In addition to the advantages of good specificity and high sensitivity, the system has potential to be easily adapted by minor alteration of the DNA sequences and fluorophore sets for detection of multiple miRNAs and even other types of biomarkers such as proteins. Therefore, it shows promise to be widely applied in various fields such as early diagnosis of cancer and its prognostic assessment.

The initiation of mitochondrial DNA replication.

Mitochondrial DNA replication is initiated by the transcription of mitochondrial RNA polymerase (mtRNAP), as mitochondria lack a dedicated primase. However, the mechanism determining the switch between continuous transcription and premature termination to generate RNA primers for mitochondrial DNA (mtDNA) replication remains unclear. The pentatricopeptide repeat domain of mtRNAP exhibits exoribonuclease activity, which is required for the initiation of mtDNA replication in Drosophila. In this review, we explain how this exonuclease activity contributes to primer synthesis in strand-coupled mtDNA replication, and discuss how its regulation might co-ordinate mtDNA replication and transcription in both Drosophila and mammals.

Correction: Deng et al. Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke. Cells 2022, 11, 820.

The authors wish to make the following changes to their paper [...].

Immunomodulation in Endometriosis: Investigating the interrelationship between VISTA expression and Escherichia.Shigella-Associated metabolites.

AIMS: Endometriosis is characterized by an abnormal immune microenvironment. Despite the extensive use of immune therapies, the application of immune checkpoint inhibitors in endometriosis lacks confidence due to the instability of preclinical research data. This study aims to elucidate the regulation of the immune inhibitory checkpoint VISTA and its effects on T cells from the perspective of microbiota and metabolism. MAIN METHODS: We divided endometriosis patients into high and low groups based on the expression levels of VISTA in lesion tissues. We collected peritoneal fluid samples from these two groups and performed 16 s RNA sequencing and metabolomics analysis to investigate microbial diversity and differential metabolites. Through combined analysis, we identified microbial-associated metabolites and validated their correlation with VISTA and CD8 + T cells using ELISA and immunofluorescence. In vitro experiments were conducted to confirm the regulatory relationship among these factors. KEY FINDINGS: Our findings revealed a distinct correlation between VISTA expression and the microbial colony Escherichia.Shigella. Moreover, we identified the metabolites LTD4-d5 and 2-n-Propylthiazolidine-4-carboxylic acid as being associated with both Escherichia.Shigella and VISTA expression. In vitro experiments confirmed the inhibitory effects of these metabolites on VISTA expression, while they demonstrated a positive regulation of CD8 + T cell infiltration into endometriotic lesions. SIGNIFICANCE: This study reveals the connection between microbial diversity, metabolites, and VISTA expression in the immune microenvironment of endometriosis, providing potential targets for therapeutic interventions.

Albiflorin alleviates neuroinflammation of rats after MCAO via PGK1/Nrf2/HO-1 signaling pathway.

Ischemic stroke is acknowledged as one of the most frequent causes of death and disability, in which neuroinflammation plays a critical role. Emerging evidence supports that the PGK1/Nrf2/HO-1 signaling can modulate inflammation and oxidative injury. Albiflorin (ALB), a main component of Radix paeoniae Alba, possesses anti-inflammatory and antioxidative properties. However, how it exerts a protective role still needs further exploration. In our study, the middle cerebral artery occlusion (MCAO) model was established, and the Longa score was applied to investigate the degree of neurological impairment. Dihydroethidium (DHE) staining and Malondialdehyde (MDA) assay were used to detect the level of lipid peroxidation. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to measure the infarct area. Evans blue staining was employed to observe the integrality of the blood-brain barrier (BBB). The injury of brain tissue in each group was observed via HE staining. Immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and western blot assay were used for the measurement of inflammatory factors and protein levels. We finally observed that ALB relieved cerebral infarction symptoms, attenuated oxidative damage in brain tissues, and reduced neuroinflammation and cell injury in MCAO rats. The overexpression of PGK1 abrogated the protective effect of ALB after experimental cerebral infarction. ALB promoted PGK1 degradation and induced Nrf2 signaling cascade activation for subsequent anti-inflammatory and antioxidant damage. Generally speaking, ALB exerted a protective role in treating cerebral ischemia, and it might target at PGK1/Nrf2/HO-1 signaling. Thus, ALB might be a potential therapeutic agent to alleviate neuroinflammation and protect brain cells after cerebral infarction.