Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Mulberry branch fiber improved lipid metabolism and egg yolk fatty acid composition of laying hens via the enterohepatic axis.

BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.

Multi-omics reveals that alkaline mineral water improves the respiratory health and growth performance of transported calves.

BACKGROUND: Long-distance transportation, a frequent practice in the cattle industry, stresses calves and results in morbidity, mortality, and growth suppression, leading to welfare concerns and economic losses. Alkaline mineral water (AMW) is an electrolyte additive containing multiple mineral elements and shows stress-mitigating effects on humans and bovines. RESULTS: Here, we monitored the respiratory health status and growth performance of 60 Simmental calves subjected to 30 hours of road transportation using a clinical scoring system. Within the three days of commingling before the transportation and 30 days after the transportation, calves in the AMW group (n = 30) were supplied with AMW, while calves in the Control group (n = 29) were not. On three specific days, namely the day before transportation (day -3), the 30th day (day 30), and the 60th day (day 60) after transportation, sets of venous blood, serum, and nasopharyngeal swab samples were collected from 20 calves (10 from each group) for routine blood testing, whole blood transcriptomic sequencing, serology detection, serum untargeted metabolic sequencing, and 16S rRNA gene sequencing. The field data showed that calves in the AMW group displayed lower rectal temperatures (38.967 ℃ vs. 39.022 ℃; p = 0.004), respiratory scores (0.079 vs. 0.144; p < 0.001), appetite scores (0.024 vs. 0.055; p < 0.001), ocular and ear scores (0.185 vs. 0.338; p < 0.001), nasal discharge scores (0.143 vs. 0.241; p < 0.001), and higher body weight gains (30.870 kg vs. 7.552 kg; p < 0.001). The outcomes of laboratory and high throughput sequencing data revealed that the calves in the AMW group demonstrated higher cellular and humoral immunities, antioxidant capacities, lower inflammatory levels, and intestinal absorption and lipogenesis on days -3 and 60. The nasopharynx 16S rRNA gene microbiome analysis revealed the different composition and structure of the nasopharyngeal microflora in the two groups of calves on day 30. Joint analysis of multi-omics revealed that on days -3 and 30, bile secretion was a shared pathway enriched by differentially expressed genes and metabolites, and there were strong correlations between the differentially expressed metabolites and the main genera in the nasopharynx. CONCLUSIONS: These results suggest that AMW supplementation enhances peripheral immunity, nutrition absorption, and metabolic processes, subsequently affecting the nasopharyngeal microbiota and improving the respiratory health and growth performance of transported calves. This investigation provided a practical approach to mitigate transportation stress and explored its underlying mechanisms, which are beneficial for the development of the livestock industry. Video Abstract.

Qijiao Shengbai Capsule alleviated leukopenia by interfering leukotriene pathway: Integrated network study of multi-omics.

BACKGROUND: Leukopenia could be induced by chemotherapy, which leads to bone marrow suppression and even affects the therapeutic progression of cancer. Qijiao Shengbai Capsule (QSC) has been used for the treatment of leukopenia in clinic, but its bioactive components and mechanisms have not yet been elucidated clearly. PURPOSE: This study aimed to elucidate the molecular mechanisms of QSC in treating leukopenia. STUDY DESIGN: Serum pharmacochemistry, multi-omics, network pharmacology, and validation experiment were combined to study the effect of QSC in murine leukopenia model. METHODS: First, UPLC-QTOF-MS was used to clarify the absorbed components of QSC. Then, cyclophosphamide (CTX) was used to induce mice model with leukopenia, and the therapeutic efficacy of QSC was assessed by an integrative approach of multi-omics and network pharmacology strategy. Finally, molecular mechanisms and potential therapeutic targets were identified by validated experiments. RESULTS: 121 compounds absorbed in vivo were identified. QSC significantly increase the count of white blood cells (WBCs) in peripheral blood of leukopenia mice with 15 days treatment. Multi-omics and network pharmacology revealed that leukotriene pathway and MAPK signaling pathway played crucial roles during the treatment of leukopenia with QSC. Six targets (ALOX5, LTB4R, CYSLTR1, FOS, JUN, IL-1ß) and 13 prototype compounds were supposed to be the key targets and potential active components, respectively. The validation experiment further confirmed that QSC could effectively inhibit the inflammatory response induced by leukopenia. The inhibitors of ALOX5 activity can significantly increase the number of WBCs in leukopenia mice. Molecular docking of ALOX5 suggested that calycosin, daidzein, and medicarpin were the potentially active compounds of QSC. CONCLUSION: Leukotriene pathway was found for the first time to be a key role in the development of leukopenia, and ALOX5 was conformed as the potential target. QSC may inhibit the inflammatory response and interfere the leukotriene pathway, it is able to improve hematopoiesis and achieve therapeutic effects in the mice with leukopenia.

Unveiling characteristic metabolic accumulation over enzymatic-catalyzed process of Tieguanyin oolong tea manufacturing by DESI-MSI and multiple-omics.

To achieve an integrative understanding of the spatial distribution and chronological flavoring compounds accumulation, desorption-electrospray-ionization coupled mass-spectrometry-imaging (DESI-MSI) and multi-omics techniques were performed on the leaf samples collected from the enzymatic-catalyzed-process (ECP) stage of Tieguanyin oolong tea manufacturing. The result of DESI-MSI visualization indicated transform or re-distribution of catechins, flavonols and amino acids were on-going attributing to the multi-stress over ECP stage. Out of identified 2621 non-volatiles and 45,771 transcripts, 43 non-volatiles and 12 co-expressed pathways were screened out as biomarkers and key cascades in response to adverse conditions. The targeted metabolic analysis on the characteristic flavoring compounds showed that the accumulations of free amino acids were enhanced, while catechins, flavonol glycosides, and alkaloids exhibited dynamic changes. This result suggests withering and turning-over process are compatible and collectively regulate the metabolic accumulation and development of flavoring metabolites, facilitating to the development of characteristic quality of Tieguanyin tea.

Holomics - a user-friendly R shiny application for multi-omics data integration and analysis.

An organism's observable traits, or phenotype, result from intricate interactions among genes, proteins, metabolites and the environment. External factors, such as associated microorganisms, along with biotic and abiotic stressors, can significantly impact this complex biological system, influencing processes like growth, development and productivity. A comprehensive analysis of the entire biological system and its interactions is thus crucial to identify key components that support adaptation to stressors and to discover biomarkers applicable in breeding programs or disease diagnostics. Since the genomics era, several other 'omics' disciplines have emerged, and recent advances in high-throughput technologies have facilitated the generation of additional omics datasets. While traditionally analyzed individually, the last decade has seen an increase in multi-omics data integration and analysis strategies aimed at achieving a holistic understanding of interactions across different biological layers. Despite these advances, the analysis of multi-omics data is still challenging due to their scale, complexity, high dimensionality and multimodality. To address these challenges, a number of analytical tools and strategies have been developed, including clustering and differential equations, which require advanced knowledge in bioinformatics and statistics. Therefore, this study recognizes the need for user-friendly tools by introducing Holomics, an accessible and easy-to-use R shiny application with multi-omics functions tailored for scientists with limited bioinformatics knowledge. Holomics provides a well-defined workflow, starting with the upload and pre-filtering of single-omics data, which are then further refined by single-omics analysis focusing on key features. Subsequently, these reduced datasets are subjected to multi-omics analyses to unveil correlations between 2-n datasets. This paper concludes with a real-world case study where microbiomics, transcriptomics and metabolomics data from previous studies that elucidate factors associated with improved sugar beet storability are integrated using Holomics. The results are discussed in the context of the biological background, underscoring the importance of multi-omics insights. This example not only highlights the versatility of Holomics in handling different types of omics data, but also validates its consistency by reproducing findings from preceding single-omics studies.

Veterinary systems biology for bridging the phenotype-genotype gap via computational modeling for disease epidemiology and animal welfare.

Veterinary systems biology is an innovative approach that integrates biological data at the molecular and cellular levels, allowing for a more extensive understanding of the interactions and functions of complex biological systems in livestock and veterinary science. It has tremendous potential to integrate multi-omics data with the support of vetinformatics resources for bridging the phenotype-genotype gap via computational modeling. To understand the dynamic behaviors of complex systems, computational models are frequently used. It facilitates a comprehensive understanding of how a host system defends itself against a pathogen attack or operates when the pathogen compromises the host's immune system. In this context, various approaches, such as systems immunology, network pharmacology, vaccinology and immunoinformatics, can be employed to effectively investigate vaccines and drugs. By utilizing this approach, we can ensure the health of livestock. This is beneficial not only for animal welfare but also for human health and environmental well-being. Therefore, the current review offers a detailed summary of systems biology advancements utilized in veterinary sciences, demonstrating the potential of the holistic approach in disease epidemiology, animal welfare and productivity.

Multi-omics reveal the effects and regulatory mechanism of dietary neutral detergent fiber supplementation on carcass characteristics, amino acid profiles, and meat quality of finishing pigs.

This study aimed to reveal the effects and regulatory mechanism of dietary NDF on the performance of pigs by multi-omics analysis. Results showed that 16 % dietary NDF significantly improved meat quality, increased flavor amino acid content, and reduced backfat thickness and the feed-to-gain ratio. 16S rDNA sequencing showed that 16 % NDF significantly increased the abundance of Akkermansia, Lachnoclostridium, and Ruminococcus. Transcript analysis showed that genes related to muscle development and lipid metabolism were significantly modified. Metabonomic analysis showed that 16 % NDF significantly increased amino and fatty acid related metabolites. Correlation analysis suggested that 16 % NDF treatment may alter the gut microbiota and metabolites, regulate the expression of genes related to lipid and amino metabolism, and ultimately affect the flavor and performance of pigs. This study provides a novel understanding about the effect and regulatory mechanism of NDF supplements on the finishing pigs and a relevant reference for the improvement of diet formulation.

Multi-omics analysis on the mechanism of the effect of Isatis leaf on the growth performance of fattening sheep.

Introduction: This study evaluated the effects of Isatis Leaf (ISL) on the growth performance, gastrointestinal tissue morphology, rumen and intestinal microbiota, rumen, serum and urine metabolites, and rumen epithelial tissue transcriptome of fattening sheep. Methods: Twelve 3.5-month-old healthy fattening sheep were randomly divided into two groups, each with 6 replicates, and fed with basal diet (CON) and basal diet supplemented with 80 g/kg ISL for 2.5 months. Gastrointestinal tract was collected for histological analysis, rumen fluid and feces were subjected to metagenomic analysis, rumen fluid, serum, and urine for metabolomics analysis, and rumen epithelial tissue for transcriptomics analysis. Results: The results showed that in the ISL group, the average daily gain and average daily feed intake of fattening sheep were significantly lower than those of the CON group (P < 0.05), and the rumen ammonia nitrogen level was significantly higher than that of the CON group (P < 0.01). The thickness of the reticulum and abomasum muscle layer was significantly increased (P < 0.05). At the genus level, the addition of ISL modified the composition of rumen and fecal microorganisms, and the relative abundance of Methanobrevibacter and Centipeda was significantly upregulated in rumen microorganisms, The relative abundance of Butyrivibrio, Saccharofermentans, Mogibacterium, and Pirellula was significantly downregulated (P < 0.05). In fecal microorganisms, the relative abundance of Papillibacter, Pseudoflavonifractor, Butyricicoccus, Anaerovorax, and Methanocorpusculum was significantly upregulated, while the relative abundance of Roseburia, Coprococcus, Clostridium XVIII, Butyrivibrio, Parasutterella, Macellibacteroides, and Porphyromonas was significantly downregulated (P < 0.05). There were 164, 107, and 77 different metabolites in the rumen, serum, and urine between the ISL and CON groups (P < 0.05). The differential metabolic pathways mainly included thiamine metabolism, niacin and nicotinamide metabolism, vitamin B6 metabolism, taurine and taurine metabolism, beta-Alanine metabolism and riboflavin metabolism. These metabolic pathways were mainly involved in the regulation of energy metabolism and immune function in fattening sheep. Transcriptome sequencing showed that differentially expressed genes were mainly enriched in cellular physiological processes, development, and immune regulation. Conclusion: In summary, the addition of ISL to the diet had the effect of increasing rumen ammonia nitrogen levels, regulating gastrointestinal microbiota, promoting body fat metabolism, and enhancing immunity in fattening sheep.

Intergrative metabolomic and transcriptomic analyses reveal the potential regulatory mechanism of unique dihydroxy fatty acid biosynthesis in the seeds of an industrial oilseed crop Orychophragmus violaceus.

BACKGROUND: Orychophragmus violaceus is a potentially important industrial oilseed crop due to the two 24-carbon dihydroxy fatty acids (diOH-FA) that was newly identified from its seed oil via a 'discontinuous elongation' process. Although many research efforts have focused on the diOH-FA biosynthesis mechanism and identified the potential co-expressed diacylglycerol acyltranferase (DGAT) gene associated with triacylglycerol (TAG)-polyestolides biosynthesis, the dynamics of metabolic changes during seed development of O. violaceus as well as its associated regulatory network changes are poorly understood. RESULTS: In this study, by combining metabolome and transcriptome analysis, we identified that 1,003 metabolites and 22,479 genes were active across four stages of seed development, which were further divided into three main clusters based on the patterns of metabolite accumulation and/or gene expression. Among which, cluster2 was mostly related to diOH-FA biosynthesis pathway. We thus further constructed transcription factor (TF)-structural genes regulatory map for the genes associated with the flavonoids, fatty acids and diOH-FA biosynthesis pathway in this cluster. In particular, several TF families such as bHLH, B3, HD-ZIP, MYB were found to potentially regulate the metabolism associated with the diOH-FA pathway. Among which, multiple candidate TFs with promising potential for increasing the diOH-FA content were identified, and we further traced the evolutionary history of these key genes among species of Brassicaceae. CONCLUSION: Taken together, our study provides new insight into the gene resources and potential relevant regulatory mechanisms of diOH-FA biosynthesis uniquely in seeds of O. violaceus, which will help to promote the downstream breeding efforts of this potential oilseed crop and advance the bio-lubricant industry.

Mechanistic study of C5F10O-induced lung toxicity in rats: An eco-friendly insulating gas alternative to SF6.

The global warming and other environmental problems caused by SF6 emissions can be reduced due to the widespread use of eco-friendly insulating gas, perfluoropentanone (C5F10O). However, there is an exposure risk to populations in areas near C5F10O equipment, so it is important to clarify its biosafety and pathogenesis before large-scale application. In this paper, histopathology, transcriptomics, 4D-DIA proteomics, and LC-MS metabolomics of rats exposed to 2000 ppm and 6000 ppm C5F10O are analyzed to reveal the mechanisms of toxicity and health risks. Histopathological shows that inflammatory cell infiltration, epithelial cell hyperplasia, and alveolar atrophy accompanied by alveolar wall thickening are present in both low-dose and high-dose groups. Analysis of transcriptomic and 4D-DIA proteomic show that Cell cycle and DNA replication can be activated by both 2000 ppm and 6000 ppm C5F10O to induce cell proliferation. In addition, it also leads to the activation of pathways such as Antigen processing and presentation, Cell adhesion molecules and Complement and coagulation cascades, T cell receptor signal path, Th1 and T cell receptor signal path, Th1 and Th2 cell differentiation, complement and coagulation cascades. Finally, LC-MS metabolomics analysis confirms that the metabolic pathways associated with glycerophospholipids, arachidonic acid, and linoleic acid are disrupted and become more severe with increasing doses. The mechanism of lung toxicity caused by C5F10O is systematically expounded based on the multi-omics analysis and provided biosafety references for further promotion and application of C5F10O.

Gut microbiota and metabolic modulation by supplementation of polysaccharide-producing Bacillus licheniformis from Tibetan Yaks: A comprehensive multi-omics analysis.

Gut microbiota and their metabolic processes depend on the intricate interplay of gut microbiota and their metabolic processes. Bacillus licheniformis, a beneficial food supplement, has shown promising effects on stabilizing gut microbiota and metabolites. However, the precise mechanisms underlying these effects remain elusive. In this study, we investigated the impact of polysaccharide-producing B. licheniformis as a dietary supplement on the gut microbiome and metabolites through a combination of scanning electron microscopy (SEM), histological analysis, high-throughput sequencing (HTS), and metabolomics. Our findings revealed that the B. licheniformis-treated group exhibited significantly increased jejunal goblet cells. Moreover, gut microbial diversity was lower in the treatment group as compared to the control, accompanied by noteworthy shifts in the abundance of specific bacterial taxa. Enrichment of Firmicutes, Lachnospiraceae, and Clostridiales_bacterium contrasted with reduced levels of Campylobacterota, Proteobacteria, Parasutterella, and Helicobacter. Notably, the treatment group showed significant weight gain after 33 days, emphasizing the polysaccharide's impact on host metabolism. Delving into gut metabolomics, we discovered significant alterations in metabolites. Nine metabolites, including olprinone, pyruvic acid, and 2-methyl-3-oxopropanoate, were upregulated, while eleven, including defoslimod and voclosporin were down-regulated, shedding light on phenylpropanoid biosynthesis, tricarboxylic acid cycle (TCA cycle), and the glucagon signaling pathway. This comprehensive multi-omics analysis offers compelling insights into the potential of B. licheniformis as a dietary polysaccharide supplement for gut health and host metabolism, promising significant implications for gut-related issues.

Mechanisms of multi-omics and network pharmacology to explain traditional chinese medicine for vascular cognitive impairment: A narrative review.

BACKGROUND: The term "vascular cognitive impairment" (VCI) describes various cognitive conditions that include vascular elements. It increases the risk of morbidity and mortality in the elderly population and is the most common cognitive impairment associated with cerebrovascular disease. Understanding the etiology of VCI may aid in identifying approaches to target its possible therapy for the condition. Treatment of VCI has focused on vascular risk factors. There are no authorized conventional therapies available right now. The medications used to treat VCI are solely approved for symptomatic relief and are not intended to prevent or slow the development of VCI. PURPOSE: The function of Chinese medicine in treating VCI has not yet been thoroughly examined. This review evaluates the preclinical and limited clinical evidence to comprehend the "multi-component, multi-target, multi-pathway" mechanism of Traditional Chinese medicine (TCM). It investigates the various multi-omics approaches in the search for the pathological mechanisms of VCI, as well as the new research strategies, in the hopes of supplying supportive evidence for the clinical treatment of VCI. METHODS: This review used the Preferred Reporting Items for Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. Using integrated bioinformatics and network pharmacology approaches, a thorough evaluation and analysis of 25 preclinical studies published up to July 1, 2023, were conducted to shed light on the mechanisms of TCM for vascular cognitive impairment. The studies for the systematic review were located using the following databases: PubMed, Web of Science, Scopus, Cochrane, and ScienceDirect. RESULTS: We discovered that the multi-omics analysis approach would hasten the discovery of the role of TCM in the treatment of VCI. It will explore components, compounds, targets, and pathways, slowing the progression of VCI from the perspective of inhibiting oxidative stress, stifling neuroinflammation, increasing cerebral blood flow, and inhibiting iron deposition by a variety of molecular mechanisms, which have significant implications for the treatment of VCI. CONCLUSION: TCM is a valuable tool for developing dementia therapies, and further research is needed to determine how TCM components may affect the operation of the neurovascular unit. There are still some limitations, although several research have offered invaluable resources for searching for possible anti-dementia medicines and treatments. To gain new insights into the molecular mechanisms that precisely modulate the key molecules at different levels during pharmacological interventions-a prerequisite for comprehending the mechanism of action and determining the potential therapeutic value of the drugs-further research should employ more standardized experimental methods as well as more sophisticated science and technology. Given the results of this review, we advocate integrating chemical and biological component analysis approaches in future research on VCI to provide a more full and objective assessment of the standard of TCM. With the help of bioinformatics, a multi-omics analysis approach will hasten the discovery of the role of TCM in the treatment of VCI, which has significant implications for the treatment of VCI.

Multi-omics analysis reveals the roles of purple acid phosphatases in organic phosphorus utilization by the tropical legume Stylosanthes guianensis.

Stylo (Stylosanthes guianensis) is a tropical legume known for its exceptional tolerance to low phosphate (Pi), a trait believed to be linked to its high acid phosphatase (APase) activity. Previous studies have observed genotypic variations in APase activity in stylo; however, the gene encoding the crucial APase responsible for this variation remains unidentified. In this study, transcriptomic and proteomic analyses were employed to identify eight Pi starvation-inducible (PSI) APases belonging to the purple APase (PAP) family in the roots of stylo and seven in the leaves. Among these PSI-PAPs, SgPAP7 exhibited a significantly positive correlation in its expression levels with the activities of both internal APase and root-associated APase across 20 stylo genotypes under low-Pi conditions. Furthermore, the recombinant SgPAP7 displayed high catalytic activity toward adenosine 5'-diphosphate (ADP) and phosphoenolpyruvate (PEP) in vitro. Overexpression (OE) of SgPAP7 in Arabidopsis facilitated exogenous organic phosphorus utilization. Moreover, SgPAP7 OE lines showed lower shoot ADP and PEP levels than the wild type, implying that SgPAP7 is involved in the catabolism and recycling of endogenous ADP and PEP, which could be beneficial for plant growth in low-Pi soils. In conclusion, SgPAP7 is a key gene with a major role in stylo adaptation to low-Pi conditions by facilitating the utilization of both exogenous and endogenous organic phosphorus sources. It may also function as a PEP phosphatase involved in a glycolytic bypass pathway that minimizes the need for adenylates and Pi. Thus, SgPAP7 could be a promising target for improving tolerance of crops to low-Pi availability.

Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats.

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

Mechanism of Sophorae Flavescentis Radix (Kushen) in treating NSCLC: Insights from miRNA-mRNA network analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae Flavescentis Radix (Kushen) is the primary herb component of Compound Kushen Injection (CKI), an approved clinical treatment for tumors. Despite CKI's widespread use, the underlying mechanisms of Kushen regarding microRNA-target and pathway remain unclear in non-small cell lung cancer (NSCLC). AIM OF THE STUDY: This study aimed to elucidate the crucial miRNAs-targets and pathways responsible for the Kushen's impact on NSCLC. MATERIALS AND METHODS: CCK8, colony formation, and apoptosis assays were performed to assess the effects of Kushen on NSCLC cells. Subsequently, we treated the A549 cell line with varying concentrations of Kushen to obtain mRNA and miRNA expression profiles. A DE (differentially expressed) miRNAs-DEGs network was then constructed to identify the critical miRNA-mRNA interaction influenced by Kushen. Furthermore, we performed clinical significance and prognosis analyses of hub genes to narrow down key genes and their corresponding miRNAs. Finally, the effects of Kushen on critical miRNA-mRNA interaction and related pathway were verified by in vitro and in vivo experiments. RESULTS: In this study, we initially demonstrated that Kushen significantly inhibited cell proliferation, suppressed colony formation, and induced apoptosis in the A549 cells, PC9 cells, and the A549 zebrafish xenograft model. Through expression profile analysis, a DE miRs-DEGs network was constructed with 16 DE miRs and 68 DEGs. Through the network analysis and expression validation, we found Kushen could significantly down-regulate miR-183-5p expression and up-regulate EGR1 expression. Additionally, Kushen affected the PTEN/Akt pathway, increasing PTEN expression and decreasing pAkt expression. Finally, matrine, the essential active compound of Kushen, also inhibited cell growth, induced apoptosis, and regulated miR-183-5p/EGR1 and PTEN/AKT pathway. CONCLUSIONS: Altogether, these findings supported the critical role of miR-183-5p/EGR1 and the PTEN/AKT pathway in the beneficial effects of Kushen on NSCLC, highlighting the therapeutic potential of Kushen in NSCLC treatment.

Effects and mechanisms of polystyrene micro- and nano-plastics on the spread of antibiotic resistance genes from soil to lettuce.

Effects of microplastics (MPs) and nanoplastics (NPs) on the spread of antibiotic resistance genes (ARGs) in soil-plant systems are still unclear. To investigate the spread and mechanisms of ARGs from soil to lettuce, lettuce was exposed to soil spiked with two environmentally relevant concentrations of polystyrene MPs (100 µm) and NPs (100 nm). Results showed that microorganisms that carried ARGs in soil were increased after exposure to MPs/NPs, which led to an increase in ARGs in roots. NPs were absorbed by roots and can be transported to leaves. Analysis of transcriptomics, proteomics and metabolomics indicated that high concentration of NPs regulated the expression of related genes and proteins and improved the accumulation of flavonoids in the lettuce, therefore decreased the abundance of microorganisms that contained ARGs. Our work emphasizes the size and dose influences of MPs and NPs on the spread of ARGs from soil to plant.

An integrated study of glutamine alleviates enteritis induced by glycinin in hybrid groupers using transcriptomics, proteomics and microRNA analyses.

Glutamine has been used to improve intestinal development and immunity in fish. We previously found that dietary glutamine enhances growth and alleviates enteritis in juvenile hybrid groupers (Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂). This study aimed to further reveal the protective role of glutamine on glycinin-induced enteritis by integrating transcriptome, proteome, and microRNA analyses. Three isonitrogenous and isolipidic trial diets were formulated: a diet containing 10% glycinin (11S group), 10% glycinin diet supplemented with 2% alanine-glutamine (Gln group), and a diet containing neither glycinin nor alanine-glutamine (fishmeal, FM group). Each experimental diet was fed to triplicate hybrid grouper groups for 8 weeks. The analysis of intestinal transcriptomic and proteomics revealed a total of 570 differentially expressed genes (DEGs) and 169 differentially expressed proteins (DEPs) in the 11S and FM comparison group. Similarly, a total of 626 DEGs and 165 DEPs were identified in the Gln and 11S comparison group. Integration of transcriptome and proteome showed that 117 DEGs showed consistent expression patterns at both the transcriptional and translational levels in the Gln and 11S comparison group. These DEGs showed significant enrichment in pathways associated with intestinal epithelial barrier function, such as extracellular matrix (ECM)-receptor interaction, tight junction, and cell adhesion molecules (P < 0.05). Further, the expression levels of genes (myosin-11, cortactin, tenascin, major histocompatibility complex class I and II) related to these pathways above were significantly upregulated at both the transcriptional and translational levels (P < 0.05). The microRNA results showed that the expression levels of miR-212 (target genes colla1 and colla2) and miR-18a-5p (target gene colla1) in fish fed Gln group were significantly lower compared to the 11S group fish (P < 0.05). In conclusion, ECM-receptor interaction, tight junction, and cell adhesion molecules pathways play a key role in glutamine alleviation of hybrid grouper enteritis induced by high-dose glycinin, in which miRNAs and target mRNAs/proteins participated cooperatively. Our findings provide valuable insights into the RNAs and protein profiles, contributing to a deeper understanding of the underlying mechanism for fish enteritis.

Radiotranscriptomics of non-small cell lung carcinoma for assessing high-level clinical outcomes using a machine learning-derived multi-modal signature.

BACKGROUND: Multi-omics research has the potential to holistically capture intra-tumor variability, thereby improving therapeutic decisions by incorporating the key principles of precision medicine. The purpose of this study is to identify a robust method of integrating features from different sources, such as imaging, transcriptomics, and clinical data, to predict the survival and therapy response of non-small cell lung cancer patients. METHODS: 2996 radiomics, 5268 transcriptomics, and 8 clinical features were extracted from the NSCLC Radiogenomics dataset. Radiomics and deep features were calculated based on the volume of interest in pre-treatment, routine CT examinations, and then combined with RNA-seq and clinical data. Several machine learning classifiers were used to perform survival analysis and assess the patient's response to adjuvant chemotherapy. The proposed analysis was evaluated on an unseen testing set in a k-fold cross-validation scheme. Score- and concatenation-based multi-omics were used as feature integration techniques. RESULTS: Six radiomics (elongation, cluster shade, entropy, variance, gray-level non-uniformity, and maximal correlation coefficient), six deep features (NasNet-based activations), and three transcriptomics (OTUD3, SUCGL2, and RQCD1) were found to be significant for therapy response. The examined score-based multi-omic improved the AUC up to 0.10 on the unseen testing set (0.74 ± 0.06) and the balance between sensitivity and specificity for predicting therapy response for 106 patients, resulting in less biased models and improving upon the either highly sensitive or highly specific single-source models. Six radiomics (kurtosis, GLRLM- and GLSZM-based non-uniformity from images with no filtering, biorthogonal, and daubechies wavelets), seven deep features (ResNet-based activations), and seven transcriptomics (ELP3, ZZZ3, PGRMC2, TRAK1, ATIC, USP7, and PNPLA2) were found to be significant for the survival analysis. Accordingly, the survival analysis for 115 patients was also enhanced up to 0.20 by the proposed score-based multi-omics in terms of the C-index (0.79 ± 0.03). CONCLUSIONS: Compared to single-source models, multi-omics integration has the potential to improve prediction performance, increase model stability, and reduce bias for both treatment response and survival analysis.

Prognostic modelling in IBD.

In the ideal world prognostication or predicting disease course in any chronic condition would allow the clinician to anticipate disease behaviour, providing crucial information for the patient and data regarding best use of resources. Prognostication also allows an understanding of likely response to treatment and the risk of adverse effects of a treatment leading to withdrawal in any individual patient. Therefore, the ability to predict outcomes from the onset of disease is the key step to developing precision personalised medicine, which is the design of medical care to optimise efficiency or therapeutic benefit based on careful profiling of patients. An important corollary is to prevent unnecessary healthcare costs. This paper outlines currently available predictors of disease outcome in IBD and looks to the future which will involve the use of artificial intelligence to interrogate big data derived from various important 'omes' to tease out a more holistic approach to IBD.