Lysimachia capillipes Hemsl. saponins ameliorate colorectal cancer in mice via regulating gut microbiota and restoring metabolic profiles.

Lysimachia capillipes Hemsl., a traditional Chinese medicine (TCM), is commonly prescribed for its anti-inflammatory and anti-tumor properties. Pharmacological studies have demonstrated that Lysimachia capillipes Hemsl. saponins (LCS) are the primary bioactive component. However, its mechanism for treating colorectal cancer (CRC) is still unknown. Increasing evidence suggests a close relationship between CRC, intestinal flora, and host metabolism. Thus, this study aims to investigate the mechanism of LCS amelioration of CRC from the perspective of the gut microbiome and metabolome. As a result, seven gut microbiotas and fourteen plasma metabolites were significantly altered between the control and model groups. Among them, one gut microbiota genera (Monoglobus) and six metabolites (Ureidopropionic acid, Cytosine, L-Proline, 3-hydroxyanthranilic acid, Cyclic AMP and Suberic acid) showed the most pronounced callback trend after LCS administration. Subsequently, the correlation analysis revealed significant associations between 68 pairs of associated metabolites and gut microbes, with 13 pairs of strongly associated metabolites regulated by the LCS. Taken together, these findings indicate that the amelioration of CRC by LCS is connected to the regulation of intestinal flora and the recasting of metabolic abnormalities. These insights highlight the potential of LCS as a candidate drug for the treatment of CRC.

In-depth LC-MS and in-vitro studies of a triterpenoid saponin capilliposide-A metabolism modulation in gut microbiota of mice.

Introduction: Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug metabolism. A large number of studies have reported that saponins are biotransformed under the action of intestinal microorganisms to improve drug efficacy and bioavailability. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis in vivo is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A. Methods: This study established a colitis mouse model, collected sterile feces from normal mice and colitis mice, and incubated CPS-A with two different intestinal flora in vitro. Based on LC-MS, the metabolic process of CPS-A mediated by intestinal microbes and the intervention effect of CPS-A on intestinal microbiome derived metabolites were studied. Results: The results of experiments indicate that intestinal microorganisms can mediate the biotransformation of CPS-A and metabolize it into corresponding deglycosylation products, thereby promoting its drug effect. Not only that, CPS-A can also promote metabolites such as Deoxycholic acid, Histamine, 3-Hydroxytridecanoic acid, and Indole-3-acetic acid in the intestinal microbiota of mice with colitis. This may result in anti-colitis effects. CPS-A mainly involved in metabolic pathways such as azathioprine and mercaptopurine, which may also have beneficial or adverse effects. Discussion: This study on the interaction between CPS-A and microbiota provides a new idea for the study of traditional Chinese medicine with poor oral bioavailability. The regulatory effect of CPS-A on the metabolites of intestinal flora in colitis mice was also found. It laid a foundation for exploring the mechanism of action of saponins on colitis mice.

Transcription profiles and phenotype reveal global response of Staphylococcus aureus exposed to ultrasound and ultraviolet stressors.

Ultrasound and ultraviolet light have good inactivation performance against pathogens in sewage. In this study, the inactivation mechanisms of 60 kHz ultrasound and ultraviolet radiation against Staphylococcus aureus (S. aureus) were studied from the perspectives of cell phenotype and transcriptome for the first time. The results showed that both ultrasound and ultraviolet treatments had adverse impacts on the cellular morphology of S. aureus to varying degrees at cellular level. The transcriptomic analysis revealed that there were 225 and 1077 differentially expressed genes (DEGs) in the ultrasound and ultraviolet treatments, respectively. The result revealed that both ultrasound and ultraviolet could interfere with the expression of the genes involved in ABC transporters, amino acid and fatty acid metabolism to influence the membrane permeability. Besides the membrane permeability, ultraviolet also could disturb the ATP synthesis, DNA replication and cell division through restraining the expression of several genes related to carbohydrate metabolism, peptidoglycan synthesis, DNA-binding/repair protein synthesis. Compared with the single inactivation pathway of ultrasound, ultraviolet inactivation of S. aureus is multi-target and multi-pathway. We believe that the bactericidal mechanisms of ultrasound and ultraviolet radiation presented by this study could provide theoretical guidance for the synergistic inactivation of pathogens in sewage by ultrasound and ultraviolet radiation in the future.

Chitosan nonwoven fabric composited calcium alginate and adenosine diphosphate as a hemostatic bandage for acute bleeding wounds.

Acute bleeding following accidental injury is a leading cause of mortality. However, conventional hemostatic bandages impede wound healing by inducing excessive blood loss, dehydration, and adherence to granulation tissue. Strategies such as incorporating active hemostatic agents and implementing chemical modifications can augment the properties of these bandages. Nevertheless, the presence of remote thrombosis and initiators may pose risks to human health. Here, a hemostatic bandage was developed by physically combined chitosan nonwoven fabric, calcium alginate sponge, and adenosine diphosphate. The presented hemostatic bandage not only exhibits active and passive mechanisms for promoting clotting but also demonstrates excellent mechanical properties, breathability, ease of removal without causing damage to the wound bed or surrounding tissues, as well as maintaining an optimal moist environment conducive to wound healing. In vitro evaluation results indicated that the hemostatic bandage possesses favorable cytocompatibility with low levels of hemolysis. Furthermore, it effectively aggregates various blood cells while activating platelets synergistically to promote both extrinsic and intrinsic coagulation pathways. In an in vivo rat model study involving liver laceration and femoral artery injury scenarios, our developed hemostatic bandage demonstrated rapid clot formation capabilities along with reduced blood loss compared to commercially available fabrics.

Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.

BACKGROUND: Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. RESULTS: In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. CONCLUSIONS: Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.

Whole-genome and genome-wide association studies improve key agricultural traits of safflower for industrial and medicinal use.

Safflower (Carthamus tinctorius) is widely cultivated around the world for its seeds and flowers. The presence of linoleic acid (LA) in its seeds and hydroxysafflor yellow A (HSYA) in its flowers are the crucial traits that enable safflower to be used for industrial and medicinal purposes. Understanding the genetic control of these traits is essential for optimizing the quality of safflower and its breeding. To further this research, we present a chromosome-scale assembly of the genome of the safflower variety 'Chuanhonghua 1', which was achieved using an integrated strategy combining Illumina, Oxford Nanopore, and Hi-C sequencing. We obtained a 1.17-Gb assembly with a contig N50 of 1.08 Mb, and all assembled sequences were assigned to 12 pseudochromosomes. Safflower's evolution involved the core eudicot γ-triplication event and a whole-genome duplication event, which led to large-scale genomic rearrangements. Extensive genomic shuffling has occurred since the divergence of the ancestor of dicotyledons. We conducted metabolite and transcriptome profiles with time- and part-dependent changes and screened candidate genes that significantly contribute to seed lipid biosynthesis. We also analyzed key gene families that participate in LA and HSYA biosynthesis. Additionally, we re-sequenced 220 safflower lines and carried out a genome-wide association study using high-quality SNP data for eight agronomic traits. We identified SNPs related to important traits in safflower. Besides, the candidate gene HH_034464 (CtCGT1) was shown to be involved in the biosynthesis of HSYA. Overall, we provide a high-quality reference genome and elucidate the genetic basis of LA and HSYA biosynthesis in safflower. This vast amount of data will benefit further research for functional gene mining and breeding in safflower.

Femtosecond-laser-assisted high-aspect-ratio nanolithography in lithium niobate.

We report the successful fabrication of high-aspect-ratio lithium niobate (LN) nanostructures by using femtosecond-laser-assisted chemical etching. In this technique, a 1 kHz femtosecond laser is first used to induce local modifications inside the LN crystal. Then, selective chemical wet etching is conducted using a buffered oxide etch (BOE) solution. The etching rate in the laser-modified area reaches 2 µm h-1, which is enhanced by a factor of ∼660 in comparison to previous reports without laser irradiation. Such high selectivity in chemical etching helps realize high-performance maskless nanolithography in lithium niobate. In the experiment, we have fabricated high-quality LN nanohole arrays. The nanohole size reaches ∼100 nm and its aspect ratio is above 40 : 1. The minimal period of the LN hole array is 300 nm. Our work paves a way to fabricate LN nano-integrated devices for advanced optic and electronic applications.

Chronic pulmonary bacterial infection facilitates breast cancer lung metastasis by recruiting tumor-promoting MHCIIhi neutrophils.

Breast cancer can metastasize to various organs, including the lungs. The immune microenvironment of the organs to be metastasized plays a crucial role in the metastasis of breast cancer. Infection with pathogens such as viruses and bacteria can alter the immune status of the lung. However, the effect of chronic inflammation caused by bacteria on the formation of a premetastatic niche within the lung is unclear, and the contribution of specific immune mediators to tumor metastasis also remains largely undetermined. Here, we used a mouse model revealing that chronic pulmonary bacterial infection augmented breast cancer lung metastasis by recruiting a distinct subtype of tumor-infiltrating MHCIIhi neutrophils into the lung, which exhibit cancer-promoting properties. Functionally, MHCIIhi neutrophils enhanced the lung metastasis of breast cancer in a cell-intrinsic manner. Furthermore, we identified CCL2 from lung tissues as an important environmental signal to recruit and maintain MHCIIhi neutrophils. Our findings clearly link bacterial-immune crosstalk to breast cancer lung metastasis and define MHCIIhi neutrophils as the principal mediator between chronic infection and tumor metastasis.

An integrated multi-omics analysis of identifies distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and cause chronic infections, commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we performed assays for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To identify the pivotal factors that are involved in host immune defense, we integrated chromatin accessibility and gene expression to investigate molecular changes in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics. Our multi-omics investigation discovered a significant concordance for innate immunological and inflammatory responses following P. aeruginosa infection between hosts and alveolar macrophages. Furthermore, we discovered that multi-omics changes in pioneer factors Stat1 and Stat3 play a crucial role in the immunological regulation of P. aeruginosa infection and that their downstream molecules (e.g., Fas) may be implicated in both immunosuppressive and inflammation-promoting processes. Taken together, these findings indicate that transcription factors and their downstream signaling molecules play a critical role in the mobilization and rebalancing of the host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, providing insights and resources for omics analyses.

[Metabolomics study of Berberidis Radix in intervening ulcerative colitis based on UPLC-Q-TOF-MS].

The effect of Tujia medicine Berberidis Radix on endogenous metabolites in the serum and feces of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) was analyzed by metabolomics technology to explore the metabolic pathway and underlying mechanism of Berberidis Radix in the intervention of UC. The UC model was induced in mice by DSS. Body weight, disease activity index(DAI), and colon length were recorded. The levels of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10) in colon tissues were determined by ELISA. The levels of endogenous metabolites in the serum and feces were detected by ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites. The potential metabolic pathways were analyzed by MetaboAnalyst 5.0. The results showed that Berberidis Radix could significantly improve the symptoms of UC mice and increase the level of the anti-inflammatory factor IL-10. A total of 56 and 43 differential metabolites were identified in the serum and feces, respectively, belonging to lipids, amino acids, fatty acids, etc. After the intervention by Berberidis Radix, the metabolic disorder gradually recovered. The involved metabolic pathways included biosynthesis of phenylalanine, tyrosine, and tryptophan, linoleic acid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism. Berberidis Radix can alleviate the symptoms of mice with DSS-induced UC, and the mechanism may be closely related to the re-gulation of lipid metabolism, amino acid metabolism, and energy metabolism.

Enhanced inactivation of Escherichia coli by ultrasound combined with peracetic acid during water disinfection.

Peracetic acid (PAA) is a desirable disinfectant for municipal wastewater because of its potent disinfection performance and limited toxic by-products. This study explored the efficiency and mechanism of Escherichia coli inactivation by PAA combined with ultrasound simultaneously (ultrasound + PAA) or (ultrasound → PAA) sequentially. The result showed that 60 kHz ultrasound combined with PAA sequentially (60 kHz → PAA) had excellent inactivation performance on E. coli, up to 4.69-log10. The result also showed that the increase of pH and humic acid concentration in solution significantly reduced the inactivation efficiency of 60 kHz → PAA treatment. We also observed that the increase of temperature was beneficial to the disinfection, while anions (Cl-; HCO3-) had little effect. With 60 kHz → PAA, the PAA and the synergism between PAA and ultrasound played major contribution to the inactivation, which we assumed might be due to both the diffusion of PAA into the cells and the damage to the cytomembrane by ultrasound, as evidenced through the laser confocal microscopy (LSCM), scanning electron microscope (SEM) and transmission electron microscope (TEM). The inactivation mechanism involved the destruction of cell membrane and loss of intracellular material. Empirically, 60 kHz → PAA was found to be effective for the inactivation of E. coli in actual wastewater, and the regrowth potential of E. coli treated by 60 kHz → PAA was significantly lower than that treated only by PAA.

Using Bayesian networks with Tabu-search algorithm to explore risk factors for hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is a condition closely associated with cardiovascular and cerebrovascular diseases. Detecting its risk factors and taking some relevant interventions still represent the top priority to lower its prevalence. Yet, in discussing risk factors, Logistic regression model is usually adopted but accompanied by some defects. In this study, a Tabu Search-based BNs was first constructed for HHcy and its risk factors, and the conditional probability between nodes was calculated using Maximum Likelihood Estimation. Besides, we tried to compare its performance with Hill Climbing-based BNs and Logistic regression model in risk factor detection and discuss its prospect in clinical practice. Our study found that Age, sex, α1-microgloblobumin to creatinine ratio, fasting plasma glucose, diet and systolic blood pressure represent direct risk factors for HHcy, and smoking, glycosylated hemoglobin and BMI constitute indirect risk factors for HHcy. Besides, the performance of Tabu Search-based BNs is better than Hill Climbing-based BNs. Accordingly, BNs with Tabu Search algorithm could be a supplement for Logistic regression, allowing for exploring the complex network relationship and the overall linkage between HHcy and its risk factors. Besides, Bayesian reasoning allows for risk prediction of HHcy, which is more reasonable in clinical practice and thus should be promoted.

Insight into core -shell microporous zinc silicate adsorbent to eliminate antibiotics in aquatic environment under the COVID-19 pandemic.

Under the new crown pneumonia (COVID-19) epidemic, the intensive use of therapeutic drugs has caused certain hidden danger to the safety of the water environment. Therefore, the core-shell microporous zinc silicate (SiO2@ZSO) was successfully prepared and used for the adsorption of chloroquine phosphate (CQ), tetracycline (TC) and ciprofloxacin (CIP) for eliminating the threat of COVID-19. The adsorption efficiencies of 20 mg L-1 of CQ, TC and CIP by SiO2@ZSO were all up to 60% after 5 min. The adsorption capacity of SiO2@ZSO for CQ, TC and CIP can reach 49.01 mg g-1, 56.06 mg g-1 and 104.77 mg g-1, respectively. The adsorption process is primarily physical adsorption, which is heterogeneous, spontaneous and preferential. Moreover, the effects of temperature, pH, salinity, and reusability on the adsorption of CQ, TC, and CIP on SiO2@ZSO were investigated. The adsorption mechanism mainly involves electrostatic attraction, partitioning and hydrogen bonding, which is insightful through the changes of the elements and functional groups before and after adsorption. This work provides a solution to the problems faced by the treatment of pharmaceuticals wastewater under the COVID-19 epidemic.

Gut microbiota landscape and potential biomarker identification in female patients with systemic lupus erythematosus using machine learning.

Objectives: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that disproportionately affects women. Early diagnosis and prevention are crucial for women's health, and the gut microbiota has been found to be strongly associated with SLE. This study aimed to identify potential biomarkers for SLE by characterizing the gut microbiota landscape using feature selection and exploring the use of machine learning (ML) algorithms with significantly dysregulated microbiotas (SDMs) for early identification of SLE patients. Additionally, we used the SHapley Additive exPlanations (SHAP) interpretability framework to visualize the impact of SDMs on the risk of developing SLE in females. Methods: Stool samples were collected from 54 SLE patients and 55 Negative Controls (NC) for microbiota analysis using 16S rRNA sequencing. Feature selection was performed using Elastic Net and Boruta on species-level taxonomy. Subsequently, four ML algorithms, namely logistic regression (LR), Adaptive Boosting (AdaBoost), Random Forest (RF), and eXtreme gradient boosting (XGBoost), were used to achieve early identification of SLE with SDMs. Finally, the best-performing algorithm was combined with SHAP to explore how SDMs affect the risk of developing SLE in females. Results: Both alpha and beta diversity were found to be different in SLE group. Following feature selection, 68 and 21 microbiota were retained in Elastic Net and Boruta, respectively, with 16 microbiota overlapping between the two, i.e., SDMs for SLE. The four ML algorithms with SDMs could effectively identify SLE patients, with XGBoost performing the best, achieving Accuracy, Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and AUC values of 0.844, 0.750, 0.938, 0.923, 0.790, and 0.930, respectively. The SHAP interpretability framework showed a complex non-linear relationship between the relative abundance of SDMs and the risk of SLE, with Escherichia_fergusonii having the largest SHAP value. Conclusions: This study revealed dysbiosis in the gut microbiota of female SLE patients. ML classifiers combined with SDMs can facilitate early identification of female patients with SLE, particularly XGBoost. The SHAP interpretability framework provides insight into the impact of SDMs on the risk of SLE and may inform future scientific treatment for SLE.

Single-cell transcriptomics reveals distinct cell response between acute and chronic pulmonary infection of Pseudomonas aeruginosa.

Knowledge of the changes in the immune microenvironment during pulmonary bacterial acute and chronic infections is limited. The dissection of immune system may provide a basis for effective therapeutic strategies against bacterial infection. Here, we describe a single immune cell atlas of mouse lungs after acute and chronic Pseudomonas aeruginosa infection using single-cell transcriptomics, multiplex immunohistochemistry, and flow cytometry. Our single-cell transcriptomic analysis revealed large-scale comprehensive changes in immune cell composition and high variation in cell-cell interactions after acute and chronic P. aeruginosa infection. Bacterial infection reprograms the genetic architecture of immune cell populations. We identified specific immune cell types, including Cxcl2+ B cells and interstitial macrophages, in response to acute and chronic infection, such as their proportions, distribution, and functional status. Importantly, the patterns of immune cell response are drastically different between acute and chronic infection models. The distinct molecular signatures highlight the importance of the highly dynamic cell-cell interaction process in different pathological conditions, which has not been completely revealed previously. These findings provide a comprehensive and unbiased immune cellular landscape for respiratory pathogenesis in mice, enabling further understanding of immunologic mechanisms in infection and inflammatory diseases.

Evaluating the role of algae in algal-bacterial granular sludge: Nutrient removal, microbial community and granular characteristics.

Algal-bacterial granular sludge (ABGS) and bacterial granular sludge (BGS, control group) were operated over 240 days to investigate the role of algae in treating synthetic municipal wastewater. The results showed that algae significantly improved the removal efficiency of total nitrogen (TN). The nitrogen removal load of ABGS was 2.6 mg-N/g-VSS/day (22.8 %, light) and 1.1 mg-N/g-VSS/day (9.6 %, dark) higher than that of BGS, respectively, which was attributed to algae enhanced NH3-N removal capacity in the anaerobic stage and increased the utilization efficiency of organics in denitrification. Algae increased the relative abundance of denitrifying bacteria, and ABGS (28.83 %) was higher than BGS (14.28 %). Moreover, the dominant phylum of algae was Chlorophyta (98.39 %), the chlorophyll-a was sustained at 1.28 ± 0.26 mg/g-VSS. Algae significantly increased the content of extracellular polymeric substances (EPS), and the increased polysaccharide came from the tightly bound EPS. This study expands the understanding of the role of algae in ABGS.

Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link.

Background: IgA nephropathy (IgAN) is an autoimmune disease that affects people of any age and is an important cause of end-stage renal disease. However, the pathogenesis and pathophysiology of IgAN is not clear. This article aimed to explore the immune-mediated inflammation and genetic mechanisms in IgAN. Methods: The transcriptome sequencing data of IgAN glomeruli in the Gene Expression Omnibus database were downloaded. Single-sample gene set enrichment analysis was used to estimate the immune microenvironment of the merged microarray data and GSE141295. IgAN samples were divided into two clusters by cluster analysis. "limma" and "DEseq2" package in R were used to identify differentially expressed genes (DEGs). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression modules related to inflammation in IgAN. R software package "clusterProfiler" was used for enrichment analysis, whereas Short Time-Series Expression Miner (STEM) analysis was used to identify the trend of gene expression. Machine-learn (ML) was performed using the shiny app. Finally, Drug Signatures Database (DSigDB) was used to identify potential molecules for treating IgAN. Results: The infiltration of macrophages in IgAN glomeruli was increased, whereas CD4+ T cells, especially inducedregulatory T cells (iTregs) were decreased. A total of 1,104 common DEGs were identified from the merged data and GSE141295. Brown module was identified to have the highest inflammatory correlation with IgAN using WGCNA, and 15 hub genes were screened from this module. Among these 15 hub genes, 14 increased with the severity of IgAN inflammation based on STEM analysis. Neural network (nnet) is considered as the best model to predict the severity of IgAN. Fucose identified from DSigDB has a potential biological activity to treat IgAN. Conclusion: The increase of macrophages and the decrease of iTregs in glomeruli represent the immune-mediated inflammation of IgAN, and fucose may be a potential therapeutic molecule against IgAN because it affects genes involved in the severe inflammation of IgAN.

Using Bayesian networks with Max-Min Hill-Climbing algorithm to detect factors related to multimorbidity.

Objectives: Multimorbidity (MMD) is a medical condition that is linked with high prevalence and closely related to many adverse health outcomes and expensive medical costs. The present study aimed to construct Bayesian networks (BNs) with Max-Min Hill-Climbing algorithm (MMHC) algorithm to explore the network relationship between MMD and its related factors. We also aimed to compare the performance of BNs with traditional multivariate logistic regression model. Methods: The data was downloaded from the Online Open Database of CHARLS 2018, a population-based longitudinal survey. In this study, we included 10 variables from data on demographic background, health status and functioning, and lifestyle. Missing value imputation was first performed using Random Forest. Afterward, the variables were included into logistic regression model construction and BNs model construction. The structural learning of BNs was achieved using MMHC algorithm and the parameter learning was conducted using maximum likelihood estimation. Results: Among 19,752 individuals (9,313 men and 10,439 women) aged 64.73 ± 10.32 years, there are 9,129 ones without MMD (46.2%) and 10,623 ones with MMD (53.8%). Logistic regression model suggests that physical activity, sex, age, sleep duration, nap, smoking, and alcohol consumption are associated with MMD (P < 0.05). BNs, by establishing a complicated network relationship, reveals that age, sleep duration, and physical activity have a direct connection with MMD. It also shows that education levels are indirectly connected to MMD through sleep duration and residence is indirectly linked to MMD through sleep duration. Conclusion: BNs could graphically reveal the complex network relationship between MMD and its related factors, outperforming traditional logistic regression model. Besides, BNs allows for risk reasoning for MMD through Bayesian reasoning, which is more consistent with clinical practice and thus holds some application prospects.

Impact of single-cell RNA sequencing on understanding immune regulation.

Single-cell RNA sequencing (scRNA-seq), one of the most powerful technologies, can describe the transcriptomic heterogeneity of single cells and reveal previously unreported cell types or states in complex tissues. With the rapid development of scRNA-seq, it has renewed our view of cellular heterogeneity and its significance for deeply understanding cell development and function. There are a large number of studies applying scRNA-seq to investigate the heterogeneity of immune cells and disease pathogenesis, focusing on differences among every individual cell, which have provided novel inspiration for disease therapy and biological processes. In this review, we describe the development of scRNA-seq and its application in immune-related physiological states, regulatory mechanisms and diseases. In addition, we further discuss the opportunities and challenges of scRNA-seq in immune regulation.

Differentiation of T Helper 17 Cells May Mediate the Abnormal Humoral Immunity in IgA Nephropathy and Inflammatory Bowel Disease Based on Shared Genetic Effects.

Background: IgA nephropathy (IgAN) is the most frequent glomerulonephritis in inflammatory bowel disease (IBD). However, the inter-relational mechanisms between them are still unclear. This study aimed to explore the shared gene effects and potential immune mechanisms in IgAN and IBD. Methods: The microarray data of IgAN and IBD in the Gene Expression Omnibus (GEO) database were downloaded. The differential expression analysis was used to identify the shared differentially expressed genes (SDEGs). Besides, the shared transcription factors (TFs) and microRNAs (miRNAs) in IgAN and IBD were screened using humanTFDB, HMDD, ENCODE, JASPAR, and ChEA databases. Moreover, weighted gene co-expression network analysis (WGCNA) was used to identify the shared immune-related genes (SIRGs) related to IgAN and IBD, and R software package org.hs.eg.db (Version3.1.0) were used to identify common immune pathways in IgAN and IBD. Results: In this study, 64 SDEGs and 28 SIRGs were identified, and the area under the receiver operating characteristic curve (ROC) of 64 SDEGs was calculated and two genes (MVP, PDXK) with high area under the curve (AUC) in both IgAN and IBD were screened out as potential diagnostic biomarkers. We then screened 3 shared TFs (SRY, MEF2D and SREBF1) and 3 miRNAs (hsa-miR-146, hsa-miR-21 and hsa-miR-320), and further found that the immune pathways of 64SDEGs, 28SIRGs and 3miRNAs were mainly including B cell receptor signaling pathway, FcγR-mediated phagocytosis, IL-17 signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, TRP channels, T cell receptor signaling pathway, Th17 cell differentiation, and cytokine-cytokine receptor interaction. Conclusion: Our work revealed the differentiation of Th17 cells may mediate the abnormal humoral immunity in IgAN and IBD patients and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.