Defect-rich N, S Co-doped porous carbon with hierarchical channel network for ultrafast capacitive deionization.

Developing an eco-friendly and effective approach for preparing N, S co-doped hierarchical porous carbons (NSHPC) for capacitive deionization (CDI) is a huge task for desalination. Herein, NSHPCSKK with interconnected hierarchical pore structures, manufactured via self-activation/co-activation of sodium lignosulfonate (SLS) encapsulation using KNO3-KHCO3 activators, inducing N, S co-doping. Different from NSHPCS and NSHPCSK, NSHPCSKK exhibits the highest specific surface area (SBET, 2264.67 m2/g) and a unique hierarchical pore structure (mesoporous volume/pore volume (Vmeso/ Vpore), 0.65). Small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM) both reveal the complex interconnected pore structure of NSHPCSKK. Regional Raman imaging conjugated with XPS reveals the presence of extensively distributed N, S co-doped defect structures, providing NSHPCSKK with excellent wettability and electrochemical performance. DFT calculations indicate that the N, S co-doping at the defect sites depicts excellent adsorption capability. Eventually, NSHPCSKK acquired an impressive salt adsorption capacity (SAC) of 20.5 mg/g and the highest average salt adsorption rate (ASAR) of 12.1 mg/g/min, indicating its superior desalting performance. In-situ Raman spectroscopy confirms NSHPCSKK's rapid ion regeneration mechanism. The research introduces a span-new NSHPC synthesis strategy for fabricating advanced NSHPC with rapid desalination response for upgrading CDI desalination.

Cerebral cortex changes in FD, IBS, and GERD: A Mendelian randomization study.

BACKGROUND: Prospective and cross-sectional studies have reported an association between functional gastrointestinal disorders and anxiety and depression. However, the causal relationship remains uncertain. To clarify this, we utilized Mendelian randomization (MR) to assess the causal effects of common gastrointestinal disorders on cortical structures. METHODS: Genome-wide association study (GWAS) data was gathered for functional dyspepsia (FD), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD) from European populations numbering 329,262, 16,792, and 602,604, respectively. GWAS cerebral cortical architecture data for cortical thickness (TH) and surface area (SA) were obtained from 51,665 MRI scans. MR was used to analyze the casual relationship between FD, IBS, GERD, and cortical structures. Inverse-variance weighted, weighted median, and MR-Egger tests were performed as assessment indicators. We also evaluated heterogeneity and pleiotropy. RESULTS: FD significantly decreases the TH in the rostral anterior cingulate cortex (ßTH = -0.022 mm; 95%CI: -0.035 mm to -0.009 mm2; PTH = 6.89 × 10-4), and IBS significantly decreases the SA of the pars triangularis (ßSA = -21.91 mm2; 95%CI: -32.99 mm to -10.83 mm2; PSA = 1.06 × 10-4), precuneus (ßSA = -47.53 mm2; 95%CI: -73.57 mm to-21.48 mm2; PSA = 3.48 × 10-4) and superior frontal regions (ßSA = -78.70 mm2; 95%CI: -122.61 mm to -34.78 mm2; PSA = 4.4 × 10-4). At the local functional level, GERD significantly increases the SA of the inferior temporal region (ßSA = -113.58 mm2, 95%CI: -113.58 mm to -39.01 mm2, PSA = 6.05 × 10-5). CONCLUSIONS: FD, IBS and GERD can affect the cerebral cortex architecture through the brain-gut axis, potentially increasing the risks of mental illness and cognitive impairment.

Synergistic in vitro activity and mechanism of KBN lotion and miconazole nitrate against drug-resistant Candida albicans biofilms.

Background: In the face of increasing antifungal resistance among Candida albicans biofilms, this study explores the efficacy of a combined treatment using Kangbainian lotion (KBN) and miconazole nitrate (MN) to address this challenge. Methods: Using UPLC-Q-TOF/MS Analysis for Identification of Active Compounds in KBN Lotion; FICI for synergy evaluation, XTT and ROS assays for biofilm viability and oxidative stress, fluorescence and confocal laser scanning microscopy (CLSM) for structural and viability analysis, and real-time fluorescence for gene expression. Conclusion: Our study indicates that the combined application of KBN and MN somewhat impacts the structural integrity of Candida albicans biofilms and affects the expression of several key genes involved in biofilm formation, including ALS1, ALS3, HWP1, HSP90, and CSH1. These preliminary findings suggest that there may be a synergistic effect between KBN and MN, potentially influencing not only the structural aspects of fungal biofilms but also involving the modulation of genetic pathways during their formation.

Gut microbiome and serum metabolome alterations associated with lactose intolerance (LI): a case‒control study and paired-sample study based on the American Gut Project (AGP).

Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms that arise following lactose consumption. Recent evidence suggests that the gut microbiome may influence lactose levels in the gut. However, there is limited understanding regarding the alterations in microbiota and metabolism between individuals with LI and non-LI. This study conducted a paired-sample investigation utilizing data from the American Gut Project (AGP) and performed metagenomic and untargeted metabolomic analyses in a Chinese cohort to explore the interaction between the gut microbiome and serum metabolites. In addition, fecal microbiota transplantation (FMT) experiments were conducted to further examine the impact of the LI-associated gut microbiome on inflammatory outcomes. We identified 14 microbial genera that significantly differed between LI and controls from AGP data. Using a machine learning approach, group separation was predicted based on seven species and nine metabolites in the Chinese cohort. Notably, increased levels of Escherichia coli in the LI group were negatively correlated with several metabolites, including PC (22:6/0:0), indole, and Lyso PC, while reduced levels of Faecalibacterium prausnitzii and Eubacterium rectale were positively correlated with indole and furazolidone. FMT-LI rats displayed visceral hypersensitivity and an altered gut microbiota composition compared to FMT-HC rats. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI, which was confirmed by FMT-LI rats showing higher expression of ERK and RAS, along with increased concentrations of proinflammatory cytokines. This study provides valuable insights into the disrupted microbial and metabolic traits associated with LI, emphasizing potential microbiome-based approaches for its prevention and treatment. IMPORTANCE: Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms after lactose consumption due to a deficiency of lactase. There is limited understanding regarding the microbiota and metabolic alterations between individuals with LI and non-LI. This study represents the first exploration to investigate metagenomic and metabolomic signatures among subjects with lactose intolerance as far as our knowledge. We identified 14 microbial genera in the Western cohort and 7 microbial species, along with 9 circulating metabolites in the Chinese cohort, which significantly differed in LI patients. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI patients. This finding was confirmed by FMT-LI rats, exhibiting increased expression of ERK and RAS, along with higher concentrations of pro-inflammatory cytokines. Our study provides insights into the disrupted functional and metabolic traits of the gut microbiome in LI, highlighting potential microbiome-based approaches for preventing and treating LI.

Combined effects of physical activity and life events on depression and PTSD in Chinese students aged 16-24 years.

Background: Life events are important risk factors for depression and post-traumatic stress disorder (PTSD). Physical activity is a beneficial behavior to physiological and psychological health. While it has not been reported at present the combined effect of physical activity and life events on individual depression and PTSD, and whether it can alleviate the psychological risks induced by life events. Objective: To comprehensively investigate the current status of life events experiences in Chinese students aged 16-24 years and analyze the combined effects of physical activity and life events on their depression and PTSD. Methods: An online cross-sectional survey was conducted on physical activity levels, life events experiences, depression and PTSD of 1,552 Chinese students aged 16-24 using short version of International Physical Activity Questionnaire (IPAQ-S), adolescent self-rating life events checklist (ASLEC), PTSD Check List-Civilian Version (PCL-C) and Patient Health Questionnaire Depression Scale. Then, logistic regression equation and stratified analysis were used to explore the combined effects of physical activity and life events on depression and PTSD. Results: Regression analysis showed that, except for female, <8 h of sleep, smoking, single parent/reorganized families and poor family economic status, experiencing medium-intensity and high-intensity life events were both risk factors for depression. Compared with those who experienced low-intensity life events, those who experienced medium- and high-intensity life events had a 27 and 131% increased risk of depression, respectively. In contrast, medium- and high-level physical activity could reduce the risk of depression by 49 and 53%, respectively. Similar results were obtained with PTSD as a dependent variable. Combined correlation analysis showed that, compared with those with high-level physical activity and low-intensity life events, those with low-level physical activity and high-intensity life events had a 209 and 121% increased risk of depression and PTSD, respectively. Stratified analysis showed that the threshold for life events induced depression and PTSD rose with the increase in the level of physical activity. Conclusion: Lack of physical activity and experience of high-intensity life events are independent risk factors for depression and PTSD, and strengthening physical activity can compensate for the harm of depression and PTSD caused by life events to some extent.

Modified Gegen Qinlian Decoction modulated the gut microbiome and bile acid metabolism and restored the function of goblet cells in a mouse model of ulcerative colitis.

Objective: Modified Gegen Qinlian Decoction (MGQD) has been shown to effectively relieve ulcerative colitis (UC) without a known pharmacological mechanism. In this study, the anti-colitis efficaciousness of MGQD and its underlying mechanisms in UC were evaluated. Methods: Mice with colitis were administered MGQD for 7 days. Following the evaluation of clinical symptoms, gut microbiota in the feces of UC mice was examined using 16S rRNA sequencing and bile acids (BAs) were examined using LC/MS. Gut microbiota consumption and fecal microbiota transplantation (FMT) were used to explore the involvement of gut microbiota in the anti-UC action of MGQD. Results: MGQD relieved colitis as shown by weight loss protection, a lower disease activity index (DAI), restoration of intestinal length reduction, and lower histopathologic scores. MGQD also restored crypt stem cell proliferation and function of colonic goblet cells, and promoted MUC2 protein secretion. Interestingly, investigations using gut bacterial depletion and FMT showed that MGQD attenuated colonic damage in a gut-dependent way. The modulation of the gut microbiota by MGQD might be attributed to a decrease in Odoribacter and an increase in norank_f_Muribaculaceae. In addition, MGQD modulated the metabolism of BAs while restoring the structure of the gut microbiota. Conclusion: MGQD significantly alleviated colitis in mice, which may be associated with the modulation of gut microbiota and BA metabolism and restoration of function of goblet cells. However, factors other than the gut microbiota may also be involved in the amelioration of UC by MGQD.

Reliability of the evidence to guide decision-making in the treatment of gastroesophageal reflux disease with acupuncture: protocol for an overview of systematic reviews.

BACKGROUND: Growing numbers of randomized clinical trials-based systematic reviews and meta-analyses (SRs/MAs) have been conducted to examine the effectiveness of acupuncture in treating gastroesophageal reflux disease (GERD). An overview of SRs/MAs will be conducted with the aim of systematically compiling, evaluating, and synthesizing the evidence regarding acupuncture for GERD. METHODS: SRs/MAs of acupuncture on GERD will be searched in eight databases. Two independent reviewers will conduct the literature search, data extraction, and review quality assessment. Utilizing the AMSTAR-2 tool, PRISMA checklists, and GRADE system, respectively, the methodological quality, reporting quality, and evidence quality will be evaluated. In relation to the subject and the overview's objects, the results will be given. This study will aid in identifying gaps between evidence and its clinical application and serve as a roadmap for further high-quality research. DISCUSSION: The results of the overview will aid in closing the gap between clinical evidence and its use in clinical practice. This study will identify significant faults in the use of evidence, point out areas where methodology needs to be improved, and provide guidance for future high-quality research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022371850. ETHICS AND DISSEMINATION: Ethics approval is not necessary because no personal information about individuals is collected. A peer-reviewed journal or pertinent conferences will publish the results, whichever comes first.

Validation of an AI-Powered Automated X-ray Bone Age Analyzer in Chinese Children and Adolescents: A Comparison with the Tanner-Whitehouse 3 Method.

INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.

Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established Tanner­Whitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.

Exploring the immune landscape of disulfidptosis in ulcerative colitis and the role of modified gegen qinlian decoction in mediating disulfidptosis to alleviate colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC), a recurrent inflammatory bowel disease, continues to challenge effective pharmacologic management. Disulfidptosis, a recently identified form of cell death, appears implicated in the progression of various diseases. Scientific studies have demonstrated that Modified Gegen Qinlian decoction (MGQD) alleviates UC symptoms. However, the underlying mechanisms remain inadequately elucidated. AIM OF THE STUDY: This study investigated the role of disulfidptosis in UC and explored the potential of MGQD to ameliorate UC by mediating disulfidptosis. METHODS: Microarray data were utilized to identify disulfidptosis-related genes stably expressed in UC, and integrated genomic analyses were conducted to elucidate the landscape of disulfidptosis in UC. Subsequently, C57BL/6J mice were administered 3% dextran sodium sulfate (DSS) to induce experimental colitis and treated with MGQD. Quantitative real-time polymerase chain reaction and immunohistochemical analysis of colonic tissues from colitis mice were performed to validate the microarray data findings. Finally, molecular docking was employed to explore the binding interactions between MGQD components and disulfidptosis biomarkers. RESULTS: Myosin heavy chain 10 (MYH10) and filamin A (FLNA) were identified as stably expressed in UC, demonstrating high diagnostic value for the disease. Correlation analysis indicated that disulfidptosis-related genes are associated with elevated levels of immune cells in UC. Single gene set enrichment analysis further clarified that these genes might be involved in the pathological processes of UC via immune-related pathways. Subsequent animal experiments revealed that MYH10 and FLNA were significantly upregulated in mice with colitis, a condition reversed by MGQD treatment. Molecular docking results showed that MYH10 and FLNA serve as stable binding targets for the primary components of MGQD. CONCLUSIONS: The study identified a connection between the disulfidptosis-related landscape and immune infiltration in UC, suggesting that MGQD may modulate disulfidptosis by inhibiting MYH10 and FLNA, thereby alleviating UC.

The association between frailty and in-hospital mortality in critically ill patients with congestive heart failure: results from MIMIC-IV database.

Background: Frailty correlates with adverse outcomes in many cardiovascular diseases and is prevalent in individuals with heart failure (HF). The Hospital Frailty Risk Score (HFRS) offers an integrated, validated solution for frailty assessment in acute care settings, but its application in critically ill patients with congestive HF lacks exploration. This study aimed to identify the association between frailty assessed by the HFRS and in-hospital mortality in critically ill patients with congestive HF. Methods: This observational study retrospectively enrolled 12,179 critically ill patients with congestive HF. Data from the Medical Information Mart for Intensive Care IV database was used. The HFRS was calculated to assess frailty. Patients were categorized into three groups: non-frailty (HFRS < 5, n = 7,961), pre-frailty (5 ≤ HFRS < 15, n = 3,684), and frailty (HFRS ≥ 15, n = 534). Outcomes included in-hospital mortality, length of intensive care unit stay, and length of hospital stay. Multiple logistic regression and Locally Weighted Scatterplot Smoothing (LOWESS) smoother were used to investigate the association between frailty and outcomes. Subgroup analysis was employed to elucidate the correlation between frailty levels and in-hospital mortality across diverse subgroups. Results: 12,179 patients were enrolled, 6,679 (54.8%) were male, and the average age was 71.05 ± 13.94 years. The overall in-hospital mortality was 11.7%. In-hospital mortality increased with the escalation of frailty levels (non-frailty vs. pre-frailty vs. frailty: 9.7% vs. 14.8% vs. 20.2%, P < 0.001). The LOWESS curve demonstrated that the HFRS was monotonically positively correlated with in-hospital mortality. Upon controlling for potential confounders, both pre-frailty and frailty statuses were found to be independently linked to a heightened risk of mortality during hospitalization (odds ratio [95% confidence interval]: pre-frailty vs. non-frailty: 1.27 [1.10-1.47], P = 0.001; frailty vs. non-frailty: 1.40 [1.07-1.83], P = 0.015; P for trend < 0.001). Significant interactions between frailty levels and in-hospital mortality were observed in the following subgroups: race, heart rate, creatinine, antiplatelet drug, diabetes, cerebrovascular disease, chronic renal disease, and sepsis. Conclusion: In critically ill patients with congestive HF, frailty as assessed by the HFRS emerged as an independent predictor for the risk of in-hospital mortality. Prospective, randomized studies are required to determine whether improvement of frailty levels could improve clinical prognosis.

Investigating the proliferative inhibition of HepG2 cells by exosome-like nanovesicles derived from Centella asiatica extract through metabolomics.

Nano-particles demonstrating excellent anticancer properties have gradually found application in cancer therapy. However, their widespread use is impeded by their potential toxicity, high cost, and the complexity of the preparation process. In this study, we achieved exosome-like Centella asiatica-derived nanovesicles (ADNVs) through a straightforward juicing and high-speed centrifugation process. We employed transmission electron microscopy and nanoparticle flow cytometry to characterize the morphology, diameter, and stability of the ADNVs. We evaluated the in vitro anticancer effects of ADNVs using Cell Counting Kit-8 and apoptosis assays. Through sequencing and bicinchoninic acid protein analysis, we discovered the abundant presence of proteins and microRNAs in ADNVs. These microRNAs can target various diseases such as cancer and infection. Furthermore, we demonstrated the effective internalization of ADNVs by HepG2 cells, resulting in an increase in reactive oxygen species levels, mitochondrial damage, cell cycle arrest at the G1 phase, and apoptosis. Finally, we analyzed changes in cellular metabolites post-treatment using cell metabolomics techniques. Our findings indicated that ADNVs primarily influence metabolic pathways such as amino acid metabolism and lipid biosynthesis, which are closely associated with HepG2 treatment. Our results demonstrate the potential utility of ADNVs as anticancer agents.

The relationship between oxidative balance scores and chronic diarrhea and constipation: a population-based study.

BACKGROUND: Oxidative stress is closely related to gut health. Exposures to oxidative stress in one's diet and lifestyle can be evaluated by the oxidative balance score (OBS). However, the relationship between OBS and intestinal habits is unknown. This study aimed to investigate the relationships between OBS and intestinal habits (chronic diarrhea and chronic constipation) and the underlying mechanisms involved. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2010, we included a total of 8065 participants. Twenty dietary and lifestyle factors were selected for the OBS calculates. Chronic constipation and chronic diarrhea were defined using the Bristol stool form scale (BSFS) types 1 and 2 and the BSFS 6 and 7, respectively. Multivariate logistic regression, subgroup analysis, and restricted cubic splines (RCS) analysis were used to evaluate the relationship between OBS and defecation habits. Finally, we used mediation analysis to explore the indirect effects of oxidative stress and inflammatory markers on these associations. RESULTS: After adjusting for all the covariates, multivariate logistic regression analysis revealed that OBS was negatively correlated with diarrhea (OR = 0.57; 95%CI = 0.39-0.83; P = 0.008)and positively correlated with constipation (OR = 1.75; 95%CI = 1.19-2.25; P = 0.008). The RCS showed a nonlinear relationship between OBS and diarrhea (P for nonlinearity = 0.02) and a linear relationship between OBS and constipation (P for nonlinearity = 0.19). Mediation analysis showed that the C-reactive protein (CRP) concentration and white blood cell (WBC) count mediated the correlation between OBS and diarrhea by 6.28% and 6.53%, respectively (P < 0.05). CONCLUSIONS: OBS is closely related to changes in patients' defecation habits. Oxidative stress and inflammation may play a role in the relationship between the two. This result emphasizes the importance of the public adjusting their lifestyle and dietary habits according to their own situation. However, further prospective studies are needed to analyze the relationship between oxidative stress and changes in defecation habits.

Comprehensive bibliometric and visualized analysis of research on gut-liver axis published from 1998 to 2022.

Background: The concept of the gut-liver axis was proposed by Marshall in 1998, and since then, this hypothesis has been gradually accepted by the academic community. Many publications have been published on the gut-liver axis, making it important to assess the scientific implications of these studies and the trends in this field. Methods: Publications were retrieved from the Web of Science Core Collection. Microsoft Excel, CiteSpace, VOSviewer, and Scimago Graphica software were used for bibliometric analysis. Results: A total of 776 publications from the Web of Science core database were included in this study. In the past 25 years, the number of publications on the gut-liver axis has shown an upward trend, particularly in the past 3 years (2020-2022). China had the highest number of publications (267 articles, 34.4%). However, the United States was at the top regarding influence and international cooperation in this field. The University of California San Diego had contributed the most publications. Suk, Ki Tae and Schnabl, Bernd were tied for the first rank in most publications. Thematic hotspots and frontiers were focused on gut microbiota, microbial metabolite, intestinal permeability, bacterial translocation, bile acid, non-alcoholic steatohepatitis, and alcoholic liver disease. Conclusion: Our study is the first bibliometric analysis of literature using visualization software to present the current research status of the gut-liver axis over the past 25 years. The damage and repair of intestinal barrier function, as well as the disruption of gut microbiota and host metabolism, should be a focus of attention. This study can provide a reference for later researchers to understand the global research trends, hotspots, and frontiers in this field.

GTS-21 attenuates ACE/ACE2 ratio and glycocalyx shedding in lipopolysaccharide-induced acute lung injury by targeting macrophage polarization derived ADAM-17.

Acute lung injury (ALI) has received considerable attention in intensive care owing to its high mortality rate. It has been demonstrated that the selective alpha7 nicotinic acetylcholine receptor agonist Gainesville Tokushima scientists (GTS)-21 is promising for treating ALI caused by lipopolysaccharides (LPS). However, the precise underlying mechanism remains unknown. This study aimed to investigate the potential efficacy of GTS-21 in the treatment of ALI. We developed mouse models of ALI and alveolar epithelial type II cells (AT2s) injury following treatment with LPS and different polarized macrophage supernatants, respectively. Pathological changes, pulmonary edema, and lung compliance were assessed. Inflammatory cells count, protein content, and pro-inflammatory cytokine levels were analysed in the bronchoalveolar lavage fluid. The expression of angiotensin-converting enzyme (ACE), ACE2, syndecan-1 (SDC-1), heparan sulphate (HS), heparanase (HPA), exostosin (EXT)-1, and NF-κB were tested in lung tissues and cells. GTS-21-induced changes in macrophage polarization were verified in vivo and in vitro. Polarized macrophage supernatants with or without recombination a disintegrin and metalloproteinase-17 (ADAM-17) and small interfering (si)RNA ADAM-17 were used to verify the role of ADAM-17 in AT2 injury. By reducing pathological alterations, lung permeability, inflammatory response, ACE/ACE2 ratio, and glycocalyx shedding, as well as by downregulating the HPA and NF-κB pathways and upregulating EXT1 expression in vivo, GTS-21 significantly diminished LPS-induced ALI compared to that of the LPS group. GTS-21 significantly attenuated macrophage M1 polarization and augmented M2 polarization in vitro and in vivo. The destructive effects of M1 polarization supernatant can be inhibited by GTS-21 and siRNA ADAM-17. GTS-21 exerted a protective effect against LPS-induced ALI, which was reversed by recombinant ADAM-17. Collectively, GTS-21 alleviates LPS-induced ALI by attenuating AT2s ACE/ACE2 ratio and glycocalyx shedding through the inhibition of macrophage M1 polarization derived ADAM-17.

Puerarin inhibits inflammation and oxidative stress in female BALB/c mouse models of Graves' disease.

Background: Graves' disease (GD) is an autoimmune thyroid disorder. Our previous study has demonstrated a significant decrease in flavone levels among children with GD compared to the control group. Puerarin, a well-known flavonoid with anti-inflammatory and antioxidant properties. We wanted to investigate its potential impact on GD pathogenesis, aiming to determine whether increasing puerarin intake could prevent or delay the onset of GD. Methods: Adenovirus with TSHR-289 subunit was used to establish a GD mice model, and mice were intragastrically administered with puerarin or sterilized water daily. Thyroid function and inflammatory cytokine levels were quantified using ELISA, lymphocyte subsets were analyzed via flow cytometry, oxidative stress (OS) markers were measured with a microplate reader, and the expression of pertinent signaling pathway proteins were assessed by Western blot. Results: The results demonstrated that puerarin treatment significantly decreased thyroxin levels and alleviated thyroid pathological changes in GD mice. Furthermore, the immune imbalance of GD mice was improved, as evidenced by reduced inflammatory indexes, elevated antioxidant levels, and decreased malondialdehyde (MDA) levels compared to untreated GD mice. Puerarin-treated GD mice exhibited significantly lower expressions of heat shock protein (HSP): HSP70, HSP90, phosphorylated extracellular regulated kinases (p-ERK) and phosphorylated protein kinase B (p-AKT) than untreated GD mice. Moreover, low dosage puerarin (400 mg/kg) was associated with a better protective effect than high dosage (1,200 mg/kg). Conclusions: Puerarin may have the potential to mitigate GD by inhibiting inflammatory and OS, through downregulating the expression of HSP70 and HSP90 and suppressing the activation of the PI3K/AKT/ERK signaling pathway. Furthermore, a lower dose exhibited superior protective effects compared to a higher dose.

A ratiometric fluorescence imprinted sensor based on N-CDs and metal-organic frameworks for visual smart detection of malathion.

Sensitive and rapid detection of pesticide residues in food is essential for human safety. A ratiometric imprinted fluorescence sensor N-CDs@Eu-MOF@MIP (BR@MIP) was constructed to sensitively detect malathion (Mal). Europium-based metal organic frameworks (Eu-MOF) were used as supporters to improve the sensitivity of the BR@MIP. N-doped carbon dots (N-CDs) were used as fluorescent source to produce fluorescent signal. A linear relationship between the concentration of Mal and the fluorescence response of the sensor was found in the Mal concentration range of 1-10 µM with a limit of detection (LOD) of 0.05 µM. Furthermore, the sensor was successfully applied for the detection of Mal in lettuce, tap water, and soil samples, with recoveries in the range of 93.0 % - 99.3 %. Additionally, smartphone-based sensors were used to detect Mal in simulated real samples. Thus, the construction of ratiometric imprinted fluorescence sensor has provided a good strategy for the detection of Mal.

Integrated network pharmacology and metabolomics reveal the action mechanisms of vincristine combined with celastrol against colon cancer.

Colon cancer is associated with a high mortality rate. Vincristine (VCR) is a commonly used chemotherapeutic drug. Celastrol (CEL) is an effective component which exerts inhibitory effects on colon cancer. Combination treatment improves resistance to chemotherapeutic drugs and enhances their efficacy. Therefore, we aimed to explore the molecular mechanisms of VCR combined with CEL in colon cancer treatment. We verified the effects of VCR combined with CEL on the proliferation, cell cycle, and apoptosis of HCT-8 cells. Non-targeted metabolomic techniques were used to analyse the changes in cellular metabolites after administration. Finally, network pharmacology technology was used to screen the potential targets and pathways. VCR combined with CEL had synergistic inhibitory effects on HCT-8 colon cancer cells. Cell metabolomics identified 12 metabolites enriched in metabolic pathways, such as the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Network pharmacology revealed that MAPK1, AKT1, PIK3CB, EGFR, and VEGFA were the key targets. Western blotting revealed that VCR combined with CEL activated the P53 pathway by suppressing the PI3K/AKT signalling pathway activation and Bcl-2 expression, promoting the Bax expression. Therefore, VCR combined with CEL potentially treats colon cancer by increasing the apoptosis, improving energy metabolism, and inhibiting PI3K/AKT pathway in colon cancer cells.