Colonic mucosal biopsy location can not affect the results of mucosal metabolomics and mucosal microbiota analysis in IBS

ObjectiveTo compare and analyze the mucosal metabolites and mucosal microbiota of different parts of colon in patients with IBS.MethodsA total of 10 patients with IBS-D and six healthy controls (HC) were enrolled. All enrolled participants underwent two biopsies of the ileocecal and sigmoid colon during colonoscopy. Metabolomic profiling of one piece of tissue was conducted using desorption electrospray ionization-mass spectrometry (DESI-MS), and the gut flora of the other piece was examined using 16S rRNA sequencing. The metabolic profiles and flora of the ileocecal and sigmoid colonic mucosa in each group were further analyzed in this study.Results(1) Principal components analysis (PCA) indicated that mucosal metabolites did not differ in different parts of the colon in either the IBS-D or HC groups. (2) In the mucosal microbiome analyses, no differences between the microbiota of the two parts of the colon were found by using Principal Co-ordinates Analysis (PCoA). In IBS group, comparing with sigmoid mucosa, the chao1 richness indice was higher and the Shannon index was lower in the ileocecal mucosa (p = 0.40, p = 0.22). However, in the HC group, microbiome analysis of the ileocecal mucosa showed lower values for Chao 1 and Shannon indices than those of the sigmoid colon mucosa (p = 0.06, p = 0.86). (3) Compared with the HC group, 1,113 metabolic signal peaks were upregulated, whereas 594 metabolites were downregulated in the IBS-D samples. Moreover, the PCA of the metabolites showed significant separation between the IBS-D and HC groups. (4) Chao1 expression was significantly higher in the mucosal microbiota with IBS-D than in the HC (p = 0.03). The Shannon index was lower in IBS-D, but the difference was not statistically significant (p = 0.53). PCoA revealed a significant difference in the microflora structure between the IBS-D and HC groups.ConclusionThe mucosal metabolic profile and mucosal flora structure of the colon were similar, despite different locations in IBS and healthy subjects. IBS had abnormal colonic mucosal metabolism and flora disturbances

Electrocatalytic synthesis of C–N coupling compounds from CO2 and nitrogenous species

The authors gratefully acknowledge financial support from the National Natural Science Foundation of China (Nos. 42277485, 21976141, 22272197, 22102184, 22102136, andU22A20392), the Natural Science Foundation of Hubei Province (2022CFB1001 and 2021CFA034), the Department of Education of Hubei Province (Q20221701 and Q20221704), and the Joint Fund of Yulin University and Dalian National Laboratory for Clean Energy (YLU-DNL Fund 2022008).The electrocatalytic synthesis of C–N coupling compounds from CO2 and nitrogenous species not only offers an effective avenue to achieve carbon neutrality and reduce environmental pollution, but also establishes a route to synthesize valuable chemicals, such as urea, amide, and amine. This innovative approach expands the application range and product categories beyond simple carbonaceous species in electrocatalytic CO2 reduction, which is becoming a rapidly advancing field. This review summarizes the research progress in electrocatalytic urea synthesis, using N2, NO2−, and NO3− as nitrogenous species, and explores emerging trends in the electrosynthesis of amide and amine from CO2 and nitrogen species. Additionally, the future opportunities in this field are highlighted, including electrosynthesis of amino acids and other compounds containing C–N bonds, anodic C–N coupling reactions beyond water oxidation, and the catalytic mechanism of corresponding reactions. This critical review also captures the insights aimed at accelerating the development of electrochemical C–N coupling reactions, confirming the superiority of this electrochemical method over the traditional techniques.publishersversionpublishe

A bibliometric and visualization analysis on the association between chronic exposure to fine particulate matter and cancer risk

Introduction:As one of the major pollutants in ambient air pollution, fine particulate matter (PM2.5) has attracted public attention. A large body of laboratory and epidemiological research has shown that PM2.5 exposure is harmful to human health.MethodsTo investigate its association with the commonly observed PM-related cancer, a bibliometric study was performed on related publications from 2012 to 2021 from a macroscopic perspective with the help of the Web of Science database and scientometric software VOSviewer, CiteSpace V, HistCite, and Biblioshiny.ResultsThe results indicated that of the 1,948 enrolled documents, scientific productions increased steadily and peaked in 2020 with 348 publications. The most prolific authors, journals, organizations, and countries were Raaschou-Nielsen O, Science of the Total Environment, the Chinese Academy of Sciences, and China, respectively. The top five keywords in frequency order were “air pollution,” “particulate matter,” “lung cancer,” “exposure,” and “mortality.”DiscussionThe toxic mechanism of carcinogenicity was explained and is worthy of further investigation. China and the US collaborated most closely, and it is hoped the two countries can strengthen their collaboration to combat air pollution. There is also a need to identify the components of PM2.5 and refine the models to assess the global burden of disease attributed to PM2.5 exposure

A scientometric analysis of research trends on targeting mTOR in breast cancer from 2012 to 2022

Over the past decade, thousands of articles have been published on the mechanistic target of rapamycin (mTOR) and its role in breast cancer. However, the variability and heterogeneity of academic data may impact the acquisition of published research information. Due to the large number, heterogeneity, and varying quality of publications related to mTOR and breast cancer, sorting out the present state of the research in this area is critical for both researchers and clinicians. Therefore, scientometric techniques and visualization tools were employed to analyze the large number of bibliographic metadata related to the research area of mTOR and breast cancer. The features of relevant publications were searched from 2012 to 2022 to evaluate the present status of research and the evolution of research hotspots in this particular field. Web of Science was utilized to extract all relevant publications from 2012 to 2022. Subsequently, Biblioshiny and VOSviewer were utilized to obtain data on the most productive countries, authors, and institutions, annual publications and citations, the most influential journals and articles, and the most frequently occurring keywords. In total, 1,471 publications were retrieved, comprising 1,167 original articles and 304 reviews. There was a significant rise in publications between 2015 and 2018, followed by a sharp decline in 2019 and a rebound since then. The publication with the highest number of citations was a 2012 review authored by Baselga et al. The United States had the highest number of publications, citations and connections among all countries. Oncotarget had the highest number of published articles among all the journals, and José Baselga had the strongest links with other authors. Excluding the search topics, the most frequently used words were “expression” (n = 297), “growth” (n = 228), “activation” (n = 223), “pathway” (n = 205), and “apoptosis” (n = 195). mTOR is crucially involved in breast cancer pathogenesis, but its exact mechanism of action remains controversial and warrants further investigation. The scientometric analysis provides a distinct overview of the existing state of research and highlights the topical issues that deserve further exploration

ALDH1 Expression and Vasculogenic Mimicry Are Positively Associated with Poor Prognosis in Patients with Breast Cancer

Background/Aims: This study aimed to explore the prognostic value of aldehyde dehydrogenase 1 (ALDH1) expression and vasculogenic mimicry (VM) in patients with breast cancer. Methods: ALDH1 expression and the presence of VM were examined by immunohistochemistry and CD31/PAS double staining, respectively, using formalin-fixed paraffin-embedded tissues from 202 breast cancer patients. The mean follow-up period ranged from 15 to 115 months. The Kaplan-Meier method was used to plot survival curves. Prognostic values were assessed by multivariate analysis using the Cox regression model. Results: ALDH1 expression was strongly associated with VM (P = 0.005). ALDH1 expression was positively correlated with histological grade (P = 0.011). Both ALDH1 expression and VM were negatively related to the status of the estrogen receptor and progesterone receptor and were statistically increased in triple-negative breast cancer. Patients with ALDH1 expression or VM displayed poorer disease-free survival (DFS) and overall survival (OS) than ALDH1-negative or VM-negative patients, with the worst OS and DFS observed in ALDH1/VM-double-positive patients. ALDH1-positive and VM-positive were independent survival risk factors for DFS and OS. Conclusion: ALDH1 expression and VM are correlated with the survival rate of patients with breast cancer. ALDH1 and VM, either alone or together, are prognostic factors in patients with breast cancer

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Background/Aims: Emerging evidence suggests a close link between gut microbiota and non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the association between gut microbiota and the DNA methylation of adiponectin (an adipocyte-specific adipocytokine) in rats, following diet-induced NAFLD. Methods: 50 male SD rats were randomly divided into five groups with or without a high fat diet (HFD), antibiotics, and probiotics, in order to establish an imbalanced gut microbiota and probiotic treatment model in NAFLD rats. After 13 weeks of treatment, blood, liver, and cecal tissue samples were collected. Serum lipids, liver function indexes by biochemical analyzers, and changes in liver pathology with hematoxylin-eosin (HE) and masson staining were detected. Furthermore, the serum adiponectin by enzyme-linked immunosorbent assay (ELISA) and liver adiponectin methylation levels in the promoter regions by pyrophosphate sequencing were determined. High throughput Illumina sequencing targeted microbial 16S genes, bioinformatics and statistical analysis identified cecal-associated gut microbiota. Results: HFD with antibiotic exposure showed the most severe steatohepatitis and a severe gut microbiota alteration. Reduced bacterial diversity was also seen and the abundances of Firmicutes, Lactobacillus, Cyanobacteria, Acidobacteria, Chlamydiae, Chlamydiales, Rubrobacteria, Verrucomicrobia, Blautia, Shewanella, Bacteroides, Bacteroides acidifaciens, and Bacteroides uniformis, were shown to be partly reversed by probiotic treatment. Decreased serum adiponectin levels and increased DNA methylation levels of adiponectin promoter regions were also markedly associated with the NAFLD progression during gut microbiota alteration. Conclusion: Our results suggested that both gut microbiota alteration and adiponectin variability may be drivers of NAFLD progression and that targeting the gut microbiota, such as via administration of a probiotic, may delay NAFLD progression via adiponectin

Selective deletion of endothelial cell calpain in mice reduces diabetic cardiomyopathy by improving angiogenesis

Aims/hypothesis: The role of non-cardiomyocytes in diabetic cardiomyopathy has not been fully addressed. This study investigated whether endothelial cell calpain plays a role in myocardial endothelial injury and microvascular rarefaction in diabetes, thereby contributing to diabetic cardiomyopathy. Methods: Endothelial cell-specific Capns1-knockout (KO) mice were generated. Conditions mimicking prediabetes and type 1 and type 2 diabetes were induced in these KO mice and their wild-type littermates. Myocardial function and coronary flow reserve were assessed by echocardiography. Histological analyses were performed to determine capillary density, cardiomyocyte size and fibrosis in the heart. Isolated aortas were assayed for neovascularisation. Cultured cardiac microvascular endothelial cells were stimulated with high palmitate. Angiogenesis and apoptosis were analysed. Results: Endothelial cell-specific deletion of Capns1 disrupted calpain 1 and calpain 2 in endothelial cells, reduced cardiac fibrosis and hypertrophy, and alleviated myocardial dysfunction in mouse models of diabetes without significantly affecting systemic metabolic variables. These protective effects of calpain disruption in endothelial cells were associated with an increase in myocardial capillary density (wild-type vs Capns1-KO 3646.14 ± 423.51 vs 4708.7 ± 417.93 capillary number/high-power field in prediabetes, 2999.36 ± 854.77 vs 4579.22 ± 672.56 capillary number/high-power field in type 2 diabetes and 2364.87 ± 249.57 vs 3014.63 ± 215.46 capillary number/high-power field in type 1 diabetes) and coronary flow reserve. Ex vivo analysis of neovascularisation revealed more endothelial cell sprouts from aortic rings of prediabetic and diabetic Capns1-KO mice compared with their wild-type littermates. In cultured cardiac microvascular endothelial cells, inhibition of calpain improved angiogenesis and prevented apoptosis under metabolic stress. Mechanistically, deletion of Capns1 elevated the protein levels of β-catenin in endothelial cells of Capns1-KO mice and constitutive activity of calpain 2 suppressed β-catenin protein expression in cultured endothelial cells. Upregulation of β-catenin promoted angiogenesis and inhibited apoptosis whereas knockdown of β-catenin offset the protective effects of calpain inhibition in endothelial cells under metabolic stress. Conclusions/interpretation: These results delineate a primary role of calpain in inducing cardiac endothelial cell injury and impairing neovascularisation via suppression of β-catenin, thereby promoting diabetic cardiomyopathy, and indicate that calpain is a promising therapeutic target to prevent diabetic cardiac complications

Effect of Wu Zhi San supplementation in LPS-induced intestinal inflammation and barrier damage in broilers

Intestinal inflammation and barrier damage can inhibit the absorption and transportation of nutrients in the small intestine, and lead to various chronic diseases. Wu Zhi San (WZS) is a traditional Chinese formula composed of Schisandrae, Anemarrhenae, Lonicerae, and Glycyrrhizae that was made to cure intestinal inflammation and barrier damage in broilers. To evaluate the protective effect of WZS on intestinal inflammation and barrier damage of broilers under lipopolysaccharide (LPS) stress, a total of 200 one-day-old broilers were randomly divided into five groups, namely, the CON group, LPS group, and three WZS groups (WZS-H, WZS-M, and WZS-L). The groups were designed for stress phase I (days 15, 17, 19, and 21) and stress phase II (days 29, 31, 33, and 35). The protective effect of WZS on the intestinal tract was evaluated by measuring the levels of serum myeloperoxidase (MPO), diamine oxidase (DAO), super oxide dismutase (SOD), and serum D-lactate (D-LA) and the expression of inflammatory factors in jejunum. The results showed that the diet supplemented with WZS could significantly reduce serum MPO, DAO, and D-LA levels and jejunal CD in broilers (p < 0.05), increase serum SOD levels and jejunal VH (p < 0.05), significantly downregulate the expression of NF-κB, TLR4, MyD88, and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10), and upregulate Claudin-1, Occludin-1, and ZO-1 in broiler jejunum mucosa (p < 0.05). On the other hand, WZS could significantly reduce the protein expression of NF-κB (p65) in broiler jejunum (p < 0.05). These results indicate that supplementing WZS in the diet can reduce intestinal inflammation and alleviate intestinal barrier damage, and by inhibiting the NF-κB/TLR4/MyD88 signaling pathway, supplementation with WZS intervenes in LPS-induced stress injury in broilers

Short-Term Load Forecasting Using EMD-LSTM Neural Networks with a Xgboost Algorithm for Feature Importance Evaluation

Accurate load forecasting is an important issue for the reliable and efficient operation of a power system. This study presents a hybrid algorithm that combines similar days (SD) selection, empirical mode decomposition (EMD), and long short-term memory (LSTM) neural networks to construct a prediction model (i.e., SD-EMD-LSTM) for short-term load forecasting. The extreme gradient boosting-based weighted k-means algorithm is used to evaluate the similarity between the forecasting and historical days. The EMD method is employed to decompose the SD load to several intrinsic mode functions (IMFs) and residual. Separated LSTM neural networks were also employed to forecast each IMF and residual. Lastly, the forecasting values from each LSTM model were reconstructed. Numerical testing demonstrates that the SD-EMD-LSTM method can accurately forecast the electric load

Identification of PLK1-PBD Inhibitors from the Library of Marine Natural Products: 3D QSAR Pharmacophore, ADMET, Scaffold Hopping, Molecular Docking, and Molecular Dynamics Study

PLK1 is found to be highly expressed in various types of cancers, but the development of inhibitors for it has been slow. Most inhibitors are still in clinical stages, and many lack the necessary selectivity and anti-tumor effects. This study aimed to create new inhibitors for the PLK1-PBD by focusing on the PBD binding domain, which has the potential for greater selectivity. A 3D QSAR model was developed using a dataset of 112 compounds to evaluate 500 molecules. ADMET prediction was then used to select three molecules with strong drug-like characteristics. Scaffold hopping was employed to reconstruct 98 new compounds with improved drug-like properties and increased activity. Molecular docking was used to compare the efficient compound abbapolin, confirming the high-activity status of [(14S)-14-hydroxy-14-(pyridin-2-yl)tetradecyl]ammonium,[(14S)-15-(2-furyl)-14-hydroxypentadecyl]ammonium and [(14S)-14-hydroxy-14-phenyltetradecyl]ammonium. Molecular dynamics simulations and MMPBSA were conducted to evaluate the stability of the compounds in the presence of proteins. An in-depth analysis of [(14S)-15-(2-furyl)-14-hydroxypentadecyl]ammonium and [(14S)-14-hydroxy-14-phenyltetradecyl]ammonium identified them as potential candidates for PLK1 inhibitors