Metabolic Processes Research Articles

The regulatory effects of bioactive polysaccharides on intestinal function and bile acids: chemical structures, bioactivities, and mechanisms

Polysaccharides are one of the important components of the human diet, offering a wide range of biological activities, especially in improving inflammation in the digestive system and addressing metabolic diseases. Among all the reported bioactivities of polysaccharides, their regulation effects on intestinal function and bile acids (BAs) are gradually attracting the attention of more researchers. Bile acids, the main components of intestinal lipid digestive fluid, are also key signal factors for metabolic homeostasis and impact overall health. Polysaccharides usually interact directly or indirectly with the gut and gut microbiota to participate in the regulation process of reabsorption, metabolism, and excretion of bile acids in humans, thereby exerting their role in the intervention of human diseases. In this review, we comprehensively reviewed the effects of bioactive polysaccharides on the regulation of intestinal function and bile acids. The chemical structures, bioactivities, and potential mechanisms for their activities were also reviewed. This study aimed to provide a comprehensive reference for future research on the activities and mechanisms of polysaccharides, as well as to offer important strategies and insights for the development of bioactive polysaccharides to prevent inflammatory and metabolic diseases.

ChIP-seq and structural analyses delineating the regulatory mechanism of master regulator EsrB in Edwardsiella piscicida.

As a crucial virulence regulator, EsrB possesses a LuxR-like superfamily domain at the C-terminal, which is conserved within the canonical NarL family regulators. Due to its critically important role in virulence and pathogenicity in fish hosts, the DNA binding ability has been believed to allow EsrB to regulate genes associated with the invasion process of host cells and basal metabolism in response to environmental stimuli. The lack of EsrB's crystal structure has been a major obstacle in understanding the molecular mechanisms of EsrB-DNA interaction which choreographs EsrB-mediated pathogenic behavior. Here, we conducted ChIP-seq and solved the crystal structure of the C-terminal of EsrB (EsrBC) at 2.20-Å resolution, which revealed that EsrB preferred to bind to virulence-associated promoters with a distinct 7'-4-7' pseudopalindromic DNA motif and interacted with metabolic-related promoters with a high AT DNA motif in Dulbecco's Modified Eagle's Medium (DMEM) (mimicking in vivo environments). Our results facilitate a detailed understanding of EsrB's regulatory role in Edwardsiella piscicida pathogenesis and expand our knowledge of virulence regulators in the family Hafniaceae.

Triterpenoids from Ganoderma lucidum inhibit cytochrome P450 enzymes interfering with the metabolic process of specific clinical drugs

BackgroundGanoderma lucidum (G. lucidum), which possesses various biological effects, has been widely used as traditional medicine and functional food in Asian countries, especially China. In consideration of its various biological effects on human healthcare, G. lucidum was usually used in combination with other drugs. However, the potential drug-drug interaction induced by G. lucidum through cytochrome P450 enzymes (CYPs) remain unknown.MethodsUsing the in vivo activity assay of CYPs, the inhibitory effects of G. lucidum and its constituents could be evaluated. The interference of G. lucidum on the metabolic processes of clinical drugs could be investigated. The chemical constituents of G. lucidum could be identified using LC-MS. The interaction between bioactive compounds and CYPs could be proposed through in silico docking analysis and molecular dynamics.ResultsThe dichloromethane extract of G. lucidum could inhibit various CYP450 subtypes in vitro and interfere with the pharmacokinetics of four drugs in rats. Triterpenoids were identified as the main constituents of the dichloromethane extract by Q-TOF-MSn in preliminary analyses. Then, a triterpenoid library containing 66 compounds was established to evaluate their inhibitory effects against CYP 1A2, 2D6, 3A4, 2A6, 2B6, 2C9, and 2C19. CYP 1A2 was inhibited by most lanostane triterpenoids, indicating a strong affinity for these compounds. Among triterpenoids, compound 25 displayed a broad inhibitory effect against CYPs, except for CYP 3A4, 2D6, 2C9, and 2C19. Finally, compounds 6 and 25 exhibited interference with the metabolism of 16 drugs through the inhibition of CYPs in vitro. In silico molecular docking analyses for assaying the interaction between compound 25 and CYPs indicated that the hydrogen bonds formed between the hydroxyl groups and amino acid residues.ConclusionG. lucidum displayed broad inhibitory effects on CYPs, with triterpenoids as the main bioactive constituents, which may induce potential drug-drug interaction. This information should be helpful for the rational use of G. lucidum in promoting human health.

Gene-environment interactions in the influence of maternal education on adolescent neurodevelopment using ABCD study.

Maternal education was strongly correlated with adolescent brain morphology, cognitive performances, and mental health. However, the molecular basis for the effects of maternal education on the structural neurodevelopment remains unknown. Here, we conducted gene-environment-wide interaction study using the Adolescent Brain Cognitive Development cohort. Seven genomic loci with significant gene-environment interactions (G×E) on regional gray matter volumes were identified, with enriched biological functions related to metabolic process, inflammatory process, and synaptic plasticity. Additionally, genetic overlapping results with behavioral and disease-related phenotypes indicated shared biological mechanism between maternal education modified neurodevelopment and related behavioral traits. Finally, by decomposing the multidimensional components of maternal education, we found that socioeconomic status, rather than family environment, played a more important role in modifying the genetic effects on neurodevelopment. In summary, our study provided analytical evidence for G×E effects regarding adolescent neurodevelopment and explored potential biological mechanisms as well as social mechanisms through which maternal education could modify the genetic effects on regional brain development.

Various microbial taxa couple arsenic transformation to nitrogen and carbon cycling in paddy soils.

Arsenic (As) metabolism pathways and their coupling to nitrogen (N) and carbon (C) cycling contribute to elemental biogeochemical cycling. However, how whole-microbial communities respond to As stress and which taxa are the predominant As-transforming bacteria or archaea in situ remains unclear. Hence, by constructing and applying ROCker profiles to precisely detect and quantify As oxidation (aioA, arxA) and reduction (arrA, arsC1, arsC2) genes in short-read metagenomic and metatranscriptomic datasets, we investigated the dominant microbial communities involved in arsenite (As(III)) oxidation and arsenate (As(V)) reduction and revealed their potential pathways for coupling As with N and C in situ in rice paddies. Five ROCker models were constructed to quantify the abundance and transcriptional activity of short-read sequences encoding As oxidation (aioA and arxA) and reduction (arrA, arsC1, arsC2) genes in paddy soils. Our results revealed that the sub-communities carrying the aioA and arsC2 genes were predominantly responsible for As(III) oxidation and As(V) reduction, respectively. Moreover, a newly identified As(III) oxidation gene, arxA, was detected in genomes assigned to various phyla and showed significantly increased transcriptional activity with increasing soil pH, indicating its important role in As(III) oxidation in alkaline soils. The significant correlation of the transcriptional activities of aioA with the narG and nirK denitrification genes, of arxA with the napA and nirS denitrification genes and of arrA/arsC2 with the pmoA and mcrA genes implied the coupling of As(III) oxidation with denitrification and As(V) reduction with methane oxidation. Various microbial taxa including Burkholderiales, Desulfatiglandales, and Hyphomicrobiales (formerly Rhizobiales) are involved in the coupling of As with N and C metabolism processes. Moreover, these correlated As and N/C genes often co-occur in the same genome and exhibit greater transcriptional activity in paddy soils with As contamination than in those without contamination. Our results revealed the comprehensive detection and typing of short-read sequences associated with As oxidation and reduction genes via custom-built ROCker models, and shed light on the various microbial taxa involved in the coupling of As and N and C metabolism in situ in paddy soils. The contribution of the arxA sub-communities to the coupling of As(III) oxidation with nitrate reduction and the arsC sub-communities to the coupling of As(V) reduction with methane oxidation expands our knowledge of the interrelationships among As, N, and C cycling in paddy soils. Video Abstract.

Rhizosphere as a hotspot for microbial necromass deposition into the soil carbon pool

Abstract Microbial leftovers, known as necromass, are key players in storing carbon in the soil around plant roots (i.e. rhizosphere), a zone characterized by high‐efficiency microbial anabolism. Yet, the extent and mechanisms through which the rhizosphere contributes to soil organic carbon (SOC) via microbial necromass, especially under changing environments remain unclear. We aimed to evaluate the contributions of microbial necromass to SOC and influencing factors from the rhizosphere perspective. We collected the rhizosphere and bulk soil from 39 alpine coniferous forest sites on the eastern Tibetan Plateau to assess the extent of microbial necromass contribution to SOC in the rhizosphere from a dynamic perspective by calculating the ratio of increased amino sugars (AS) to increased SOC in the rhizosphere relative to that in bulk soil (RAS/SOC). We also collected climate data and determined nutrient concentrations and microbial physiological traits in rhizosphere soil to elucidate the factors affecting RAS/SOC. The results showed that across all sampling sites, the average concentrations of SOC‐normalized AS in the rhizosphere were significantly higher than those in the bulk soil. Furthermore, the average RAS/SOC was greater than 1, indicating a faster microbial necromass accumulation than SOC accumulation in the rhizosphere. These results implied that the rhizosphere sustains a greater capacity for microbial necromass contribution to the SOC pool than the bulk soil does. Soil nutrient availability was the primary factor affecting RAS/SOC, and precipitation indirectly affected microbial anabolism and RAS/SOC by changing soil nutrient status. Additionally, with increasing rhizosphere soil nutrient availability, microbial carbon‐use efficiency and growth rate increased but the biomass‐specific enzyme activity declined, indicating that microorganisms tended to exhibit high‐yield strategies with increasing soil nutrient availability. Synthesis. Our findings underpin the vital effect of microbial necromass in SOC accumulation from the rhizosphere perspective and offer valuable insights into mechanisms underlying microbial C metabolic processes in rhizosphere SOC accumulation under changing environments.

Zooming in the plastisphere: the ecological interface for phytoplankton-plastic interactions in aquatic ecosystems.

Phytoplankton is an essential resource in aquatic ecosystems, situated at the base of aquatic food webs. Plastic pollution can impact these organisms, potentially affecting the functioning of aquatic ecosystems. The interaction between plastics and phytoplankton is multifaceted: while microplastics can exert toxic effects on phytoplankton, plastics can also act as a substrate for colonisation. By reviewing the existing literature, this study aims to address pivotal questions concerning the intricate interplay among plastics and phytoplankton/phytobenthos and analyse impacts on fundamental ecosystem processes (e.g. primary production, nutrient cycling). This investigation spans both marine and freshwater ecosystems, examining diverse organisational levels from subcellular processes to entire ecosystems. The diverse chemical composition of plastics, along with their variable properties and role in forming the "plastisphere", underscores the complexity of their influences on aquatic environments. Morphological changes, alterations in metabolic processes, defence and stress responses, including homoaggregation and extracellular polysaccharide biosynthesis, represent adaptive strategies employed by phytoplankton to cope with plastic-induced stress. Plastics also serve as potential habitats for harmful algae and invasive species, thereby influencing biodiversity and environmental conditions. Processes affected by phytoplankton-plastic interaction can have cascading effects throughout the aquatic food web via altered bottom-up and top-down processes. This review emphasises that our understanding of how these multiple interactions compare in impact on natural processes is far from complete, and uncertainty persists regarding whether they drive significant alterations in ecological variables. A lack of comprehensive investigation poses a risk of overlooking fundamental aspects in addressing the environmental challenges associated with widespread plastic pollution.

Assessment of myco-fabricated Al2O3 NPs toxicity on cancer cells and pathogenic microbes by suppression of bacterial metabolic key enzymes.

There has been a recent change in global attention towards addressing antimicrobial resistance (AMR) as a result of the concerning increase in mortality rates. Nanomaterials have become highly favorable options for a wide range of industrial and biological uses. The objective of this study was to produce aluminum oxide nanoparticles (Al2O3 NPs) using a crude extract from the fungus Aspergillus sp. WAH23, and then analyze the nanoparticles using UV-analysis, electron microscopy (TEM and SEM), and (FT-IR) and X-ray diffraction (XRD). Results revealed that formed nanoparticles are spherical with an average size of 8.5 nm. XRD analysis confirmed the crystalline nature of the synthesized Al2O3 NPs. The Al2O3 nanoparticles exhibited antibacterial properties against a wide range of pathogenic microbes. The antibacterial efficacy of these nanoparticles on the examined bacterial strains was exhibited through their ability to hinder several metabolic processes, including phosphofructokinase (PFK), enolase, and glutamine synthetase. Additionally, the nanoparticles increased the activity of NADH-oxidase, the content of MDA, and the formation of H2O2. The study also examined the anticancer properties of Al2O3 nanoparticles on various types of cancer cells.

An integrated approach for studying exposure, metabolism, and disposition of traditional Chinese medicine using PATBS and MDRB tools: a case study of semen Armeniacae Amarum.

Deciphering the in vivo processes of traditional Chinese medicine (TCM) is crucial for identifying new pharmacodynamic substances and new drugs. Due to the complexity and diversity of components, investigating the exposure, metabolism, and disposition remains a major challenge in TCM research. In recent years, a number of non-targeted smart mass-spectrometry (MS) techniques, such as precise-and-thorough background-subtraction (PATBS) and metabolomics, have realized the intelligent identification of in vivo components of TCM. However, the metabolites characterization still largely relies on manual identification in combination with online databases. We developed a scoring approach based on the structural similarity and minimal mass defect variations between metabolites and prototypes. The current method integrates three dimensions of mass spectral data including m/z, mass defect of MS1 and MS2, and the similarity of MS2 fragments, which was sequentially analyzed by a R-based mass dataset relevance bridging (MDRB) data post-processing technique. The MDRB technology constructed a component relationship network for TCM, significantly improving metabolite identification efficiency and facilitating the mapping of translational metabolic pathways. By combining MDRB with PATBS through this non-targeted identification technology, we developed a comprehensive strategy for identification, characterization and bridging analysis of TCM metabolite in vivo. As a proof of concept, we adopted the proposed strategy to investigate the process of exposure, metabolism, and disposition of Semen Armeniacae Amarum (CKXR) in mice. The currently proposed analytical approach is universally applicable and demonstrates its effectiveness in analyzing complex components of TCMs in vitro and in vivo. Furthermore, it enables the correlation of in vitro and in vivo data, providing insights into the metabolic transformationsamong components sharing the same parent nucleus structure. Finally, the developed MDRB platform is publicly available for ( https://github.com/933ZhangDD/MDRB ) for accelerating TCM research for the scientific community.

Skin fragility in autoimmune blistering diseases of the skin

In many disorders, skin and/or mucosal changes are dominated by blisters, wounds, or erosions. While these changes can be observed during infective, traumatic, metabolic, or inflammatory processes, these are normally clinical hallmarks of the disruption of the cytoarchitectural stability of the skin. Several proteins, such as those located in the dermal-epidermal junction zone and forming the hemidesmosomes, or those forming epidermal desmosomes are crucial for the maintenance of skin integrity. Defective function may be genetically determined due to impaired or absent production of specific proteins (i.e., epidermolysis bullosa) or due to autoimmune disorders that lead to the production of autoreactive antibodies targeting desmosomal or hemidesmosomal skin antigens. The latter group of diseases are classically named autoimmune blistering diseases of the skin. These can be divided in the pemphigoid group, where antigens are components of the hemidesmosomes, and pemphigus group, where desmosomal proteins are targeted. In this review, we provide ashort vademecum of autoimmune skin disorders that are associated with skin fragility.

Multigenerational impact of global change: Increased mercury toxicity in a marine copepod.

A multi-generational experiment (F1-F4) was conducted for a marine copepod Tigriopus japonicus to investigate its physiological and molecular responses to mercury (Hg) pollution and/or its combination with ocean acidification (OA) plus ocean warming (OW). The projected future scenario, i.e., OA plus OW (AW) significantly increased methylmercury accumulation in copepods by 1.14 times, despite insignificant change for total Hg bioaccumulation. Transcriptomic analysis indicated that copepods initiated several detoxification defense processes, including reactive oxygen species metabolic process, glutathione metabolism, and protein refolding, in response to increased Hg toxicity under combined exposure of AW and Hg; meanwhile, inhibited energy metabolism was observed in this case, linking to reduced number of nauplii/clutch but accelerated development in copepods probably due to an energetic trade-off. Increased Hg toxicity due to AW could also be ascribed to the impairment in immune defense (e.g., lysosome and vitamin metabolism) and reproduction-related processes (e.g., growth factor activity). Collectively, this study reveals the multi-generational response mechanism of copepods to Hg pollution under global change, emphasizing an exacerbated adverse effect of Hg, and it provides a scientific basis for an accurate understanding of the potential impact of Hg pollution on marine ecosystems.

The effects of muscle factors irisin on lipid metabolism in breast cancer: A possible mechanism anti-tumor mechanism of physical activity

Breast cancer is the most prevalent cancer in the female population and is a significant cause of global cancer deaths in this group. Obesity increases a woman’s risk of developing breast cancer and has a negative impact on prognosis. Metabolic alterations are an important part of the process of cancer migration; invasion and proliferation, with lipids being a major metabolic substrate for rapid cancer progression, capable of influencing the metabolic crosstalk between tumor cells and other cells in the tumor microenvironment. Physical activity-induced irisin affects the progression of obesity-associated breast cancer and is a new indicator for breast cancer diagnosis. Existing evidence suggests a potential inhibitory effect of physical activity-induced irisin on the progression of breast cancer. A strong association exists between obesity and breast cancer progression and outcomes. This paper discusses how physical activity-induced irisin may achieve cancer suppression by affecting lipid metabolic processes between breast cancer cells and cancer-associated adipocytes, and elucidates the molecular pathways involved in the effects of irisin on cancer lipid reprogramming, thereby helping to prevent the metastatic progression of breast cancer, and ultimately improving the survival rate of this patient group.

Abstract PR015: Decoding RNA metabolism by RNA-linked CRISPR screening in human cells

Abstract RNAs undergo a complex choreography of metabolic processes in human cells that are regulated by thousands of RNA-associated proteins. While the effects of individual RNA-associated proteins on RNA metabolism have been extensively characterized, the full complement of regulators for most RNA metabolic events remain unknown. Here we present a massively parallel RNA-linked CRISPR (ReLiC) screening approach to measure the responses of diverse RNA metabolic events to knockout of 2,092 human genes encoding all known RNA-associated proteins. ReLiC screens highlight modular interactions between gene networks regulating splicing, translation, and decay of mRNAs. When combined with biochemical fractionation of polysomes, ReLiC reveals striking pathway-specific coupling between growth fitness and mRNA translation. Perturbing different components of the translation and proteostasis machineries have distinct effects on ribosome occupancy, while perturbing mRNA transcription leaves ribosome occupancy largely intact. Isoform-selective ReLiC screens capture differential regulation of intron retention and exon skipping by SF3b complex subunits. Chemogenomic screens using ReLiC decipher translational regulators upstream of mRNA decay and uncover a role for the ribosome collision sensor GCN1 during treatment with the anti-leukemic drug homoharringtonine. Our work demonstrates ReLiC as a versatile platform for discovering and dissecting regulatory principles of human RNA metabolism. Citation Format: Patrick J Nugent, Heungwon Park, Arvind Rasi Subramaniam. Decoding RNA metabolism by RNA-linked CRISPR screening in human cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr PR015.

Abstract PR013: Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers

Abstract Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide, and early detection is critical for successful treatment and improved survival rates. However, precancerous and early-stage CRC present significant diagnostic challenges due to the small size of lesions and the very low expression of tumor-specific biomarkers in the bloodstream. Current genomics-based diagnostic methods struggle to detect these lesions, making it imperative to develop more sensitive and specific approaches. Circulating extracellular vesicles (EVs) are emerging as a promising solution for early-stage CRC detection, since EVs are produced by tumor cells as well as the tumor microenviroment and host immune cells. Thus, EVs may offer the means to detect and monitor small early-stage tumors through both direct detection of tumor- associated biomarkers as well through tumor specific host response and tumor microenvironment biomarkers. Methods: To identify novel early-stage CRC specific biomarkers, we performed proteomics analysis on EVs purified from patient plasma using size exclusion chromatography and a proprietary buffer system that enhances EV and corona protein recovery. TrueDiscovery™ Data-independent acquisition (DIA) mass spectrometry (MS) analysis was conducted on 24 pre- cancer/stage 0 and 25 stage 1 CRC patients and 75 normal patient plasma samples. An in-house developed machine learning pipeline was used to identify differentially expressed proteins and model candidate multiplexes to identify those with extremely high diagnostic accuracy (> 0.99). Results: An average of ∼2,500 proteins were identified per sample and included in bioinformatics analysis. Comparative analysis between control patient EVs and either pre- cancerous/Stage 0, or Stage 1 colon cancer EVs using an in-house Machine Learning pipeline identified 336 and 493 differentially expressed proteins for each group (FDR adjusted p-value < 0.001). Of these, the best 17 pre/stage 0 proteins and 53 stage 1 proteins were trained and tested using Support Vector Machine to assess all potential 3-plexes in order to identify those with mean diagnostic accuracy > 99%. This yielded 5 3-plexes in precancer/stage 0 and 34 3-plexes in stage 1 with near perfect diagnostic accuracy. These plexes are currently being assessed in single analyte and multiplex immunoassays with the goal of translating candidate 3-plexes to the clinical. Conclusions: Key biomarkers from CRC patient EVs indicate the potential to detect and diagnose early-stage and low tumor burden cancers using our methods. Interestingly, the most accurate 3-plexes consist of proteins from immune, inflammatory and metabolic processes, suggesting that for the detection of early stage cancer it may be critical to include both tumor and host specific biomarkers. Citation Format: Poorva Mudgal, Cheryl Bandoski, Zachary Opheim, Martin Mehnert, Valesca Anschau, Issa Isaac, Alan Ezrin, Todd Hembrough. Highly accurate detection of early-stage colorectal cancer using tumor and immune extracellular vesicles biomarkers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR013.

Effect of micronutrients on growth and bulb production of LA hybrid lilium (Lilium longiflorum) cv. pavia

The experiment was conducted during the 2021–22 at ICAR-Indian Agricultural Research Institute, New Delhi to determine the effect of micronutrients on the growth and bulb production of LA hybrid lilium cv. pavia. The experiment's findings showed that applying micronutrients topically in combination was more beneficial than doing so topically alone. In contrast, a combination of ZnSO4 + MnSO4 @6 g/litre each sprayed at 40 and 60 days after planting performed better in terms of growth attributes, such as net assimilation rate (4.07 g/m2 leaf area/day), relative growth rate (9.46 mg/g/day), and specific leaf area (46.68 m2/kg). Bulb attributes included number of bulblets/plant (4.60), bulb circumference (14.97 cm), bulblets circumference (3.77 cm), weight of bulb (30.44 g), and bulblets (2.64 g) in LA hybrid lilium cv. pavia, whereas the control group showed the lowest interaction effect levels. This demonstrates that the growth of bulbous ornamental crops such as lilium benefits more from the combined administration of micronutrients. It results from the application of the ideal concentration of micronutrients at regular intervals, which increases photosynthetic rate. These micronutrients help plants accumulate biosynthates through a variety of activities and control metabolic processes that occur in plants. Additionally, they activate enzymes that enhance development and better distribute carbohydrates to various regions of the plant, such as carbonic dehydrogenase, peroxidase, tryptophan synthase, and catalase. Micronutrients are essential for all cellular and metabolic processes, and their optimal utilization enhances the quality of the crop.

Comprehensive analysis of molecular mechanisms underlying kidney stones: gene expression profiles and potential diagnostic markers

BackgroundThe study aimed to investigate the molecular mechanisms underlying kidney stones by analyzing gene expression profiles. They focused on identifying differentially expressed genes (DEGs), performing gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and screening optimal feature genes using various machine learning algorithms.MethodsData from the GSE73680 dataset, comprising normal renal papillary tissues and Randall’s Plaque (RP) tissues, were downloaded from the GEO database. DEGs were identified using the limma R package, followed by GSEA and WGCNA to explore functional modules. Functional enrichment analysis was conducted using KEGG and Disease Ontology. Various machine learning algorithms were used for screening the most suitable feature genes, which were then assessed for their expression and diagnostic significance through Wilcoxon rank-sum tests and ROC curves. GSEA and correlation analysis were performed on optimal feature genes, and immune cell infiltration was assessed using the CIBERSORT algorithm.Results412 DEGs were identified, with 194 downregulated and 218 upregulated genes in kidney stone samples. GSEA revealed enriched pathways related to metabolic processes, immune response, and disease states. WGCNA identified modules correlated with kidney stones, particularly the yellow module. Functional enrichment analysis highlighted pathways involved in metabolism, immune response, and disease pathology. Through machine learning algorithms, KLK1 and MMP10 were identified as optimal feature genes, significantly upregulated in kidney stone samples, with high diagnostic value. GSEA further elucidated their biological functions and pathway associations.ConclusionThe study comprehensively analyzed gene expression profiles to uncover molecular mechanisms underlying kidney stones. KLK1 and MMP10 were identified as potential diagnostic markers and key players in kidney stone progression. Functional enrichment analysis provided insights into their roles in metabolic processes, immune response, and disease pathology. These results contribute significantly to a better understanding of kidney stone pathogenesis and may inform future diagnostic and therapeutic strategies.

Comparative transcriptomic and metabolomic analysis of FTO knockout and wild-type porcine iliac artery endothelial cells.

The fat mass and obesity associated (FTO) gene, previously identified as a pivotal genetic locus associated with adiposity, has recently been linked to various cancers. In this study, we established an FTO knockout (KO) cell line in porcine iliac artery endothelial cells (PIECs) utilizing CRISPR/Cas9 technology to systematically investigate the gene's function and effect through transcriptomic and metabolomic analysis. Our results revealed significant gene expression and metabolic profiles differences between the FTO KO and wild-type (WT) cells. Furthermore, enrichment analysis highlighted the involvement of differentially expressed genes in metabolic processes, cellular components, and molecular functions, as well as in complement and coagulation cascades, mineral absorption, glutathione metabolism, insulin signaling, fluid shear stress, and atherosclerosis pathways. The metabolomic profiling revealed clear distinctions between the FTO KO and WT cells, indicating profound modifications in cellular metabolism. Correlation analysis of transcriptomic and metabolomic data revealed a significant association between six metabolites and twenty genes, with melatonin showing specific correlations with the expression of several genes, indicating a complex regulatory network between gene expression and metabolic changes. This study provides a foundation for further research on the FTO gene's role in cellular processes and molecular mechanisms underlying physiological and pathological conditions.

Extreme soil salinity reduces N and P metabolism and related microbial network complexity and community immigration rate.

Soil microbiomes are well known to suffer from the effects of rising salinity. There are, however, no current understandings regarding its specific effects on microbial metabolic functions associated with nitrogen (N) and phosphorus (P) cycling, particularly in the Yellow River Delta (YRD), one of the largest estuaries in the world. This research examined soil microbiomes at 50 sites in the YRD region to analyze their co-occurrence networks and their relationship with N (nitrification, denitrification, dissimilatory, assimilatory, fixation, and mineralization) and P (solubilization, mineralization, transportation, and regulation) metabolism processes. Our findings indicate a notable reduction in soil multifunctionality as salinity levels increase, with Halofilum-ochraceum playing a significant role in nitrification, whereas Bacteroidetes-SB0662-bin-6 helps solubilize inorganic P in highly saline areas. High soil salinity negatively affected the amoA gene involved in nitrification and increased the nosZ gene involved in denitrification in extreme salinity soil with 8.2g/kg salt content. Extreme salinity significantly reduced the expression of genes involved in inorganic P solubilization, such as ppa and ppx. Additionally, the alkaline P gene phoD exhibited significant decreases in extremely saline soils, thereby impeding the mineralization of organic P. The neutral community models indicated that microbial community immigration rate showed a linear negative relationship with soil EC in the six N and four P processes. Salinization, however, displayed a nonlinear pattern with clearly defined thresholds on the community of microbes involved in N and P cycling. Reduced microbial diversity and interactions are causing a decline in soil multifunctionality, and the soil multifunctionality and network edges jointly limited the microbial community immigration rate involved in N and P cycling. It is crucial to preserve soil microbial functions to support nutrient cycling and predict the ecological effects of soil salinization.

Multi-omics analysis reveals the positive impact of differential chloroplast activity during in vitro regeneration of barley.

Existence of potent in vitro regeneration system is a prerequisite for efficient genetic transformation and functional genomics of crop plants. In this study, two contrasting cultivars differencing in their in vitro regeneration efficiency were identified. Tissue culture friendly cultivar Golden Promise (GP) and tissue culture resistant DWRB91(D91) were selected as contrasting cultivars to investigate the molecular basis of regeneration efficiency through multiomics analysis. Transcriptomics analysis revealed 1487 differentially expressed genes (DEGs), in which 795 DEGs were upregulated and 692 DEGs were downregulated in the GP-D91 transcriptome. Genes encoding proteins localized in chloroplast and involved in ROS generation were upregulated in the embryogenic calli of GP. Moreover, proteome analysis by LC-MS/MS revealed 3062 protein groups and 16,989 peptide groups, out of these 1586 protein groups were differentially expressed proteins (DEPs). Eventually, GC-MS based metabolomics analysis revealed the higher activity of plastids and alterations in key metabolic processes such as sugar metabolism, fatty acid biosynthesis, and secondary metabolism. TEM analysis also revealed differential plastid development. Higher accumulation of sugars, amino acids and metabolites corresponding to lignin biosynthesis were observed in GP as compared to D91. A comprehensive examination of gene expression, protein profiling and metabolite patterns unveiled a significant increase in the genes encompassing various functions, such as ion homeostasis, chlorophyll metabolic process, ROS regulation, and the secondary metabolic pathway.

Advancements and Challenges in Nanoscale Zero-Valent Iron-Activated Persulfate Technology for the Removal of Endocrine-Disrupting Chemicals

Endocrine-disrupting chemicals are a new class of pollutants that can affect hormonal metabolic processes in animals and humans. They can enter the aquatic environment through various pathways and gradually become enriched, thus posing a serious threat to the endocrine and physiological systems of both animals and humans. Nano zero-valent iron has promising applications in endocrine disruptor removal due to its excellent reducing properties and high specific surface area. However, given the dispersed focus and fragmented results of current studies, a comprehensive review is still lacking. In this paper, it was analyzed that the types of endocrine disruptors and their emission pathways reveal the sources of these compounds. Then, the main technologies currently used for endocrine disruptor treatment are introduced, covering physical, chemical, and biological treatment methods, with a special focus on persulfate oxidation among advanced oxidation technologies. Also, the paper summarizes the various activation methods of persulfate oxidation technology and proposes the nZVI-activated persulfate technology as the most promising means of treatment. In addition, this paper reviews the research progress of different modification methods of nZVI in activating persulfate for the removal of EDCs. Finally, the discussion includes recycling studies of nZVI/PS technology and emphasizes the urgency and importance of endocrine disruptor treatment. The review of this paper provides further scientific basis and technical support for nZVI/PS technology in the field of endocrine disruptor management.