Disruption of CAD oligomerization by pathogenic variants.

CAD, the multi-enzymatic protein essential for initiating the de novo biosynthesis of pyrimidine nucleotides, forms large hexamers whose structure and function are not fully understood. Defects in CAD cause a severe neurometabolic disorder that is challenging to diagnose. We developed a cellular functional assay to identify defective CAD variants, and in this study, we characterized five pathogenic missense mutations in CAD's dihydroorotase (DHO) and aspartate transcarbamylase (ATC) domains. All mutations impaired enzymatic activities, with two notably disrupting the formation of DHO dimers and ATC trimers. Combining crystal structures and AlphaFold predictions, we modeled the hexameric CAD complex, highlighting the central role of the DHO and ATC domains in its assembly. Our findings provide insight into CAD's stability, function, and organization, revealing that correct oligomerization of CAD into a supramolecular complex is required for its function in nucleotide synthesis and that mutations affecting this assembly are potentially pathogenic.

Metabolism: an important player in glioma survival and development.

Gliomas are malignant tumors originating from both neuroglial cells and neural stem cells. The involvement of neural stem cells contributes to the tumor's heterogeneity, affecting its metabolic features, development, and response to therapy. This review provides a brief introduction to the importance of metabolism in gliomas before systematically categorizing them into specific groups based on their histological and molecular genetic markers. Metabolism plays a critical role in glioma biology, as tumor cells rely heavily on altered metabolic pathways to support their rapid growth, survival, and progression. Dysregulated metabolic processes, involving carbohydrates, lipids, and amino acids not only fuel tumor development but also contribute to therapy resistance and metastatic potential. By understanding these metabolic changes, key intervention points, such as mutations in genes like RTK, EGFR, RAS, and IDH can be identified, paving the way for novel therapeutic strategies. This review emphasizes the connection between metabolic pathways and clinical challenges, offering actionable insights for future research and therapeutic development in gliomas.

Increases in 4-Acetaminobutyric Acid Generated by Phosphomevalonate Kinase Suppress CD8+ T Cell Activation and Allow Tumor Immune Escape.

Certain metabolites in the tumor microenvironment (TME) can alter innate immunity. Here, it is shown how phosphomevalonate kinase (PMVK) allows hepatocellular carcinoma (HCC) cells to overcome the anti-tumor immunity mediated by CD8+ T cells. In HCCs, depletion of PMVK is required to facilitate CD8+ T cell activation and their subsequent suppression of tumor growth. Mechanistically, PMVK phosphorylates and stabilizes glutamate decarboxylase 1 (GAD1), thus increasing the synthesis of γ-aminobutyric acid (GABA), which normally functions as a neurotransmitter. However, PMVK also recruits acetyl-CoA acetyltransferase 1 (ACAT1) and allows it to convert GABA, to 4-acetaminobutyric acid (4-Ac-GABA), which is released into the TME. There, 4-Ac-GABA activates the GABAA receptor (GABAAR) on CD8+ T cells, which inhibits AKT1 signaling. This in turn suppresses CD8+ T cell activation, intratumoral infiltration, and the anti-tumor response. Inhibiting PMVK or GABAAR in HCC mouse models overcomes resistance to anti-PD-1 immune checkpoint therapy. These findings reveal non-canonical and cooperative functions among the key metabolic enzymes PMVK, GAD1, and ACAT1 that reprogram glutamine metabolism to synthesize a potent CD8+ T cell inhibitor 4-Ac-GABA. Blocking 4-Ac-GABA signaling in CD8+ T cells, particularly when combined with immune checkpoint inhibition, potentially represents a new and potent form of immunotherapy.

Comparative network analysis reveals the regulatory mechanism of 1-methylcyclopropene on sugar and acid metabolisms in yellow peach stored at non-chilling temperatures.

Soluble carbohydrates and organic acids are critical determinants of fruit flavor and consumer preference, both of which are susceptible to postharvest treatments and storage conditions. While the individual effectiveness of 1-methylcyclopropene (1-MCP) and non-chilling temperature storage in delaying fruit ripening and influencing flavor development has been established, their combined effects on peach storage traits remain unexplored. This study investigated the impact of 1-MCP combined with non-chilling temperature storage on the quality and flavor attributes of yellow peach. Our results revealed that 1-MCP treatment reduced ethylene production during storage and delayed ripening and softening by down-regulating ethylene biosynthesis and signaling genes. Transcriptomic analysis indicated that 1-MCP maintained higher levels of soluble carbohydrates by up-regulating sucrose phosphate synthase (PpSPS1/2) and sorbitol dehydrogenase (PpSDH1) while down-regulating hexokinase (PpHXK1). Concurrently, 1-MCP preserved citric and malic acid levels by suppressing aconitate hydratase (PpACO1) and inducing malate dehydrogenase (PpMDH1), thereby delaying flavor degradation. Co-expression network analysis implicated ethylene response factors (PpERFs) as major regulators of sugar and acid metabolisms genes, with PpERF19 potentially functioning as a key transcriptional controller. Overall, this study verified the efficacy of combined 1-MCP and non-chilling storage for yellow peach preservation, identified key 1-MCP-modulated genes involved in sugar and acid metabolisms, and provided insights into regulating peach flavor development via postharvest approaches.

Advanced application of slightly acidic electrolyzed water for fresh-cut fruits and vegetables preservation.

Fresh-cut fruits and vegetables (F&V) play a pivotal role in modern diets due to their convenience and nutritional value. However, their perishable nature renders them susceptible to rapid spoilage, causing quality deterioration, safety risks, and economic losses along the supply chain. Traditional preservation methods, while effective to some extent, often fall short in maintaining the quality and safety of fresh-cut F&V. This comprehensive review examines the utilization of slightly acidic electrolyzed water (SAEW) as a novel preservation technique for fresh-cut F&V. The review encompasses the production mechanisms, sterilization principles, classifications and application of SAEW. It explores the effects of SAEW on microbial inactivation, quality parameters, and metabolic pathways in fresh-cut F&V. Additionally, it assesses the synergistic effects of SAEW when combined with other preservation methods. SAEW demonstrates remarkable potential in extending the shelf life of fresh-cut F&V by effectively inhibiting microbial growth, suppressing browning, preserving chemical content, and influencing various metabolic processes. Moreover, its synergy with different treatments enhances its overall efficacy in maintaining fresh-cut F&V quality. The review highlights the promising role of SAEW as an innovative preservation approach for fresh-cut F&V. However, challenges regarding its widespread implementation and potential limitations require further exploration. Overall, SAEW stands as a significant contender in ensuring the safety and quality of fresh-cut F&V paving the way for future research and application in the food industry.

Amyloid-like Aggregation Propensities of Metabolites - Homogentisic acid, N-Acetyl aspartic acid and Isovaleric acid.

The transformation of metabolites into amyloidogenic aggregates represent an intriguing dimension in the pathophysiology of metabolic disorders, including alkaptonuria, canavan disease, and isovaleric acidemia. Central to this phenomenon are the metabolites homogentisic acid (HA), N-acetyl aspartic acid (NAA), and isovaleric acid (IVA), which we found, weave an intricate network of self-assembled structures. Leveraging an array of microscopy techniques, we traced the morphological behavior of these assemblies that exhibit concentration and time-dependent morphological transitions from isolated globules to clustered aggregates. MD simulation studies suggest significant role of hydrogen bonding interactions in the aggregation process. While displaying strong amyloidogenic propensity in solution, these aged aggregates were significantly cytotoxic to mouse neural N2a cell lines.  In vivo effect in Caenorhabditis elegans (C. elegans) nematode further validated cytotoxicity of aggregates. Our findings provide fresh insights to amyloidogenic nature of HA, NAA, and IVA aggregates and their possible role in associated metabolic disorders such as alkaptonuria, canavan disease and isovaleric acidemia.

Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.

Limiting Resources Define the Global Pattern of Soil Microbial Carbon Use Efficiency.

Microbial carbon (C) use efficiency (CUE) delineates the proportion of organic C used by microorganisms for anabolism and ultimately influences the amount of C sequestered in soils. However, the key factors controlling CUE remain enigmatic, leading to considerable uncertainty in understanding soil C retention and predicting its responses to global change factors. Here, we investigate the global patterns of CUE estimate by stoichiometric modeling in surface soils of natural ecosystems, and examine its associations with temperature, precipitation, plant-derived C and soil nutrient availability. We found that CUE is determined by the most limiting resource among these four basic environmental resources within specific climate zones (i.e., tropical, temperate, arid, and cold zones). Higher CUE is common in arid and cold zones and corresponds to limitations in temperature, water, and plant-derived C input, while lower CUE is observed in tropical and temperate zones with widespread limitation of nutrients (e.g., nitrogen or phosphorus) in soil. The contrasting resource limitations among climate zones led to an apparent increase in CUE with increasing latitude. The resource-specific dependence of CUE implies that soils in high latitudes with arid and cold environments may retain less organic C in the future, as warming and increased precipitation can reduce CUE. In contrast, oligotrophic soils in low latitudes may increase organic C retention, as CUE could be increased with concurrent anthropogenic nutrient inputs. The findings underscore the importance of resource limitations for CUE and suggest asymmetric responses of organic C retention in soils across latitudes to global change factors.

Greenhouse gas emission potential of tropical coastal sediments in densely urbanized area inferred from metabarcoding microbial community data.

Although benthic microbial community offers crucial insights into ecosystem services, they are underestimated for coastal sediment monitoring. Sepetiba Bay (SB) in Rio de Janeiro, Brazil, holds long-term metal pollution. Currently, SB pollution is majorly driven by domestic effluents discharge. Here, functional prediction analysis inferred from 16S rRNA gene metabarcoding data reveals the energy metabolism profiles of benthic microbial assemblages along the metal pollution gradient. Methanogenesis, denitrification, and N2 fixation emerge as dominant pathways in the eutrophic/polluted internal sector (Spearman; p < 0.05). These metabolisms act in the natural attenuation of sedimentary pollutants. The methane (CH4) emission (mcr genes) potential was found more abundant in the internal sector, while the external sector exhibited higher CH4 consumption (pmo + mmo genes) potential. Methanofastidiosales and Exiguobacterium, possibly involved in CH4 emission and associated with CH4 consumers respectively, are the main taxa detected in SB. Furthermore, SB exhibits higher nitrous oxide (N2O) emission potential since the norB/C gene proportions surpass nosZ up to 4 times. Blastopirellula was identified as the main responsible for N2O emissions. This study reveals fundamental contributions of the prokaryotic community to functions involved in greenhouse gas emissions, unveiling their possible use as sentinels for ecosystem monitoring.

Multiomics reveals the ameliorating effect and underlying mechanism of aqueous extracts of polygonatum sibiricum rhizome on obesity and liver fat accumulation in high-fat diet-fed mice.

BACKGROUND: Polygonatum sibiricum polysaccharides protect against obesity and NAFLD. However, the potential effects of PS rhizome aqueous extracts (PSRwe) on adiposity and hepatic lipid accumulation remains unexplored. PURPOSE: Elucidating the impact and underlying mechanism of PSRwe on HFD-induced obesity and liver fat depostition. STUDY DESIGN: 56 male mice, aged eight weeks, were divided into seven groups: Positive, four doses of PSRwe, Model, and Control. HFD was fed for eight weeks, followed by alternate-day gavage of orlistat and PSRwe for an additional eight-week period. Integrative analysis encompassing multiomics, physiological and histopathological, and biochemical indexes was employed. METHODS: Body weight (BW); liver, fat and Lee's indexes; TC, TG, LDL-C, HDL-C, AST, ALT, FFA, leptin, and adiponectin in the liver and blood; TNFα, IL-6, and LPS in the colon, plasma, and liver; H&E, PAS and oil red O staining on adipose and liver samples were examined. OGTT and ITT were conducted The gut microbiome, microbial metabolome, colonic and liver transcriptome, plasma and liver metabolites were investigated. RESULTS: PSRwe at the dosage of 7.5 mg/kg demonstrated significant and consistent reduction in BW and hepatic fat deposition than orlistat. PSRwe significantly decreased TC, TG, LDL-C, LEP, FFA levels in blood and liver. PSRwe significantly enhanced the relative abundance of probiotics including Akkermansia muciniphila, Bifidobacterium pseudolongum, Lactobacillus reuteri, and metabolic pathways including glycolysis and fatty acids ß-oxidation. The 70 up-regulated microbial metabolites in PSRwe-treated mice mainly involved in nucleotides and amino acids metabolism, while 40 decreased metabolites primarily associated with lipid metabolism. The up-regulated colonic differentially expressed genes (DEGs) participate in JAK-STAT/PI3K-Akt/FoxO signaling pathway, serotonergic/cholinergic/glutamatergic synapses, while the down-regulated DEGs predominantly focused on fat absorption and transport. The up-regulated liver DEGs mainly concentrated on fatty acid oxidation and metabolism. Liver metabolisms revealed 131 differential metabolites, among which carnitine and oxidized lipids significantly increased in PSRwe-treated mice. In plasma, the 58 up-regulated metabolites mainly participate in co-factors/vitamins metabolism while 154 down-regulated ones in fatty acids biosynthesis. Comprehensive multiomics association analysis revealed significant associations between gut microbiota and colonic/liver gene expression, and suggested exogenous and endogenous betaine may be active compound in alleviating HFD-induced symptoms. CONCLUSION: PSRwe effectively mitigate HFD-induced obesity and hepatic steatosis by increasing beneficial bacteria, reducing colonic fat digestion/absorption, increasing hepatic lipid metabolism, and elevating betaine levels.

Amyloid Mimicking Assemblies Formed by Glutamine, Glutamic Acid, and Aspartic Acid.

The aggregation of amino acids into amyloid-like structures is a critical phenomenon for understanding the pathophysiology of various diseases, including inborn errors of metabolism (IEMs) associated with amino acid imbalances. Previous studies have primarily focused on self-assembly of aromatic amino acids, leading to a limited understanding of nonaromatic, polar amino acids in this context. To bridge this gap, our study investigates the self-assembly and aggregation behavior of specific nonaromatic charged and uncharged polar amino acids l-glutamine (Gln), l-aspartic acid (Asp), and l-glutamic acid (Glu), which have not been reported widely in the context of amyloid aggregation. Upon aging these amino acids under controlled conditions, we observed the formation of uniform, distinct aggregates, with Gln forming fibrillar gel-like structures and Glu exhibiting fibrous globular morphologies. Computational simulations validated these findings, identifying Gln as the most potent in forming stable aggregates, followed by Glu and Asp. These simulations elucidated the driving forces behind the distinct morphologies and stabilities of the aggregates. Thioflavin T assays were employed to confirm the amyloid-like nature of these aggregates, suggesting their potential cytotoxic impact. To assess toxicity, we performed in vitro studies on neural cell lines and in vivo experiments in Caenorhabditis elegans (C. elegans), which demonstrated measurable cytotoxic effects, corroborated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and heat shock survival assays. Importantly, this study fills a critical gap in our understanding on the role of nonaromatic amino acids in amyloidogenesis and its implications for IEMs. Our findings provide a foundation for future investigations into the mechanisms of diseases associated with amino acid accumulation and offer potential avenues for the development of targeted therapeutic strategies.

Unexpected omega-3 activities in intracellular lipolysis and macrophage foaming revealed by fluorescence lifetime imaging.

Omega-3 polyunsaturated fatty acids (PUFA) found primarily in fish oil have been a popular supplement for cardiovascular health because they can substantially reduce circulating triglyceride levels in the bloodstream to prevent atherosclerosis. Beyond this established extracellular activity, here, we report a mode of action of PUFA, regulating intracellular triglyceride metabolism and lipid droplet (LD) dynamics. Real-time imaging of the subtle and highly dynamic changes of intracellular lipid metabolism was enabled by a fluorescence lifetime probe that addressed the limitations of intensity-based fluorescence quantifications. Surprisingly, we found that among omega-3 PUFA, only docosahexaenoic acid (DHA) promoted the lipolysis in LDs and reduced the overall fat content by approximately 50%, and consequently helped suppress macrophage differentiation into foam cells, one of the early steps responsible for atherosclerosis. Eicosapentaenoic acid, another omega-3 FA in fish oil, however, counteracted the beneficial effects of DHA on lipolysis promotion and cell foaming prevention. These in vitro findings warrant future validation in vivo.

Polystyrene nanoplastics cause reproductive toxicity in zebrafish: PPAR mediated lipid metabolism disorder.

The ubiquitous presence of micro-and nanoplastics (MNPs) in the environment and everyday products has attracted attention due to their hazardous risks. However, the effects of MNPs on reproduction and the underlying mechanisms remain unclear. The present study investigated the impact of polystyrene (PS) nanoplastics of 80, 200 and 500 nm diameters on zebrafish reproduction at an environmentally relevant concentration of 0.5 mg/L. Exposure to PS delayed spermatogenesis and caused aberrant follicular growth, resulting in dysgenesis in F0 adults and impacting F1 embryo development. Notably, the reproductive toxicity exhibited size-dependency, with the 500 nm PS being the most detrimental. Combined analyses of transcriptomics and metabolomics in ovary tissue revealed that treatment with 500 nm PS affected the peroxisome proliferator-activated receptor (PPAR) signaling pathway, dysregulated lipid transport, binding and activity processes, and led to dysgenesis in zebrafish. Specifically, the ovulatory dysfunction induced by PS exposure resembled clinical manifestations of polycystic ovary syndrome (PCOS) and can be attributed to lipid metabolism disorder involving glycerophospholipid, sphingolipid, arachidonic acid, and alpha-linolenic acid. Collectively, our results provide new evidence revealing the molecular mechanisms of PS-induced reproductive toxicity, highlighting that MNPs may pose a risk to female reproductive health.

Low Nitrogen Input Mitigates Quantitative but Not Qualitative Reconfiguration of Leaf Primary Metabolism in Brassica napus L. Subjected to Drought and Rehydration.

In the context of climate change and the reduction of mineral nitrogen (N) inputs applied to the field, winter oilseed rape (WOSR) will have to cope with low-N conditions combined with water limitation periods. Since these stresses can significantly reduce seed yield and seed quality, maintaining WOSR productivity under a wide range of growth conditions represents a major goal for crop improvement. N metabolism plays a pivotal role during the metabolic acclimation to drought in Brassica species by supporting the accumulation of osmoprotective compounds and the source-to-sink remobilization of nutrients. Thus, N deficiency could have detrimental effects on the acclimation of WOSR to drought. Here, we took advantage of a previously established experiment to evaluate the metabolic acclimation of WOSR during 14 days of drought, followed by 8 days of rehydration under high- or low-N fertilization regimes. For this purpose, we selected three leaf ranks exhibiting contrasted sink/source status to perform absolute quantification of plant central metabolites. Besides the well-described accumulation of proline, we observed contrasted accumulations of some "respiratory" amino acids (branched-chain amino acids, lysineand tyrosine) in response to drought under high- and low-N conditions. Drought also induced an increase in sucrose content in sink leaves combined with a decrease in source leaves. N deficiency strongly decreased the levels of major amino acids and subsequently the metabolic response to drought. The drought-rehydration sequence identified proline, phenylalanine, and tryptophan as valuable metabolic indicators of WOSR water status for sink leaves. The results were discussed with respect to the metabolic origin of sucrose and some amino acids in sink leaves and the impact of drought on source-to-sink remobilization processes depending on N nutrition status. Overall, this study identified major metabolic signatures reflecting a similar response of oilseed rape to drought under low- and high-N conditions.

Degradation of pyrene by Xanthobacteraceae bacterium strain S3 isolated from the rhizosphere sediment of Vallisneria natans: active conditions, metabolite identification, and proposed pathways.

Polycyclic aromatic hydrocarbons (PAHs) were typical environmental contaminants that accumulated continuously in sediment. Microbial degradation is the main way of PAH degradation in the natural environment. Therefore, expanding the available pool of microbial resources and investigating the molecular degrading mechanisms of PAHs are critical to the efficient control of PAH-polluted sites. Here, a strain (identified as Xanthobacteraceae bacterium) with the ability to degrade pyrene was screened from the rhizosphere sediment of Vallisneria natans. Response surface analysis showed that the strain could degrade pyrene at pH 5-7, NaCl addition 0-1.5%, and temperature 25-40 °C, and the maximum pyrene degradation (~ 95.4%) was obtained under the optimum conditions (pH 7.0, temperature 28.5 °C, and NaCl-free addition) after 72 h. Also, it was observed that the effect of temperature on the degradation ratio was the most significant. Furthermore, eighteen metabolites were identified by mass spectrometry, among which (2Z)-2-hydroxy-3-(4-oxo-4H-phenalen-3-yl) prop-2-enoic acid, 7-(carboxymethyl)-8-formyl-1-naphthyl acetic acid, phthalic acid, naphthalene-1,2-diol, and phenol were the main metabolites. And the degradation pathway of pyrene was proposed, suggesting that pyrene undergoes initial ortho-cleavage under the catalysis of metapyrocatechase to form (2Z)-2-hydroxy-3-(4-oxo-4H-phenalen-3-yl) prop-2-enoic acid. Subsequently, this intermediate was progressively oxidized and degraded to phthalic acid or phenol, which could enter the tricarboxylic acid cycle. Furthermore, the pyrene biodegradation by the strain followed the first-order kinetic model and the degradation rate changed from fast to slow, with the rate remaining mostly slow in the later stages. The slow biodegradation rate was probably caused by a significant amount of phenol accumulation in the initial stage of degradation, which resulted in a decrease in bacterial activity or death.

Mechanisms of benzene and benzo[a]pyrene biodegradation in the individually and mixed contaminated soils.

There is a lack of knowledge on the biodegradation mechanisms of benzene and benzo [a]pyrene (BaP), representative compounds of polycyclic aromatic hydrocarbons (PAHs), and benzene, toluene, ethylbenzene, and xylene (BTEX), under individually and mixed contaminated soils. Therefore, a set of microcosm experiments were conducted to explore the influence of benzene and BaP on biodegradation under individual and mixed contaminated condition, and their subsequent influence on native microbial consortium. The results revealed that the total mass loss of benzene was 56.0% under benzene and BaP mixed contamination, which was less than that of individual benzene contamination (78.3%). On the other hand, the mass loss of BaP was slightly boosted to 17.6% under the condition of benzene mixed contamination with BaP from that of individual BaP contamination (14.4%). The significant differences between the microbial and biocide treatments for both benzene and BaP removal demonstrated that microbial degradation played a crucial role in the mass loss for both contaminants. In addition, the microbial analyses revealed that the contamination of benzene played a major role in the fluctuations of microbial compositions under co-contaminated conditions. Rhodococcus, Nocardioides, Gailla, and norank_c_Gitt-GS-136 performed a major role in benzene biodegradation under individual and mixed contaminated conditions while Rhodococcus, Noviherbaspirillum, and Phenylobacterium were highly involved in BaP biodegradation. Moreover, binary benzene and BaP contamination highly reduced the Rhodococcus abundance, indicating the toxic influence of co-contamination on the functional key genus. Enzymatic activities revealed that catalase, lipase, and dehydrogenase activities proliferated while polyphenol oxidase was reduced with contamination compared to the control treatment. These results provided the fundamental information to facilitate the development of more efficient bioremediation strategies, which can be tailored to specific remediation of different contamination scenarios.

Involvement of functional metabolism promotes the enrichment of antibiotic resistome in drinking water: Based on the PICRUSt2 functional prediction.

Biofilters are the important source and sink of antibiotic resistance genes (ARGs) and antibiotic resistance bacteria (ARB) in the drinking water. Current studies generally ascribed the prevalence of BAR in biofilter from the perspective of gene behavior, i.e. horizontal gene transfer (HGT), little attentions have been paid on the ARGs carrier- ARB. In this study, we proposed the hypothesis that ARB participating in pollutant metabolism processes and becoming dominant is an important way for the enrichment of ARGs. To verify this, the antibiotic resistome and bacterial functional metabolic pathways of a sand filter was profiled using heterotrophic bacterial plate counting method (HPC), high-throughput qPCR, Illumina Hiseq sequencing and PICRUSt2 functional prediction. The results illustrated a significant leakage of ARB in the effluent of the sand filter with an average absolute abundance of approximately 102-103 CFU/mL. Further contribution analysis revealed that the dominant genera, such as Acinetobacter spp., Aeromonas spp., Elizabethkingia spp., and Bacillus spp., were primary ARGs hosts, conferring resistance to multiple antibiotics including sulfamethoxazole, tetracycline and ß-lactams. Notably, these ARGs hosts were involved in nitrogen metabolism, including extracellular nitrate/nitrite transport and nitrite reduction, which are crucial in nitrification and denitrification in biofilters. For example, Acinetobacter spp., the dominant bacteria in the filter (relative abundance 69.97 %), contributed the majority of ARGs and 53.79 % of nitrite reduction function. That is, ARB can predominate by participating in the nitrogen metabolism pathways, facilitating the enrichment of ARGs. These findings provide insights into the stable presence of ARGs in biofilters from a functional metabolism perspective, offering a significant supplementary to the mechanisms of the emergence, maintenance, and transmission of BARin drinking water.

Amyloidogenic Propensity of Metabolites in the Uric Acid Pathway and Urea Cycle Critically Impacts the Etiology of Metabolic Disorders.

Novel insights into the etiology of metabolic disorders have recently been uncovered through the study of metabolite amyloids. In particular, inborn errors of metabolism (IEMs), including gout, Lesch-Nyhan syndrome (LNS), xanthinuria, citrullinemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, are attributed to the dysfunction of the urea cycle and uric acid pathway. In this study, we endeavored to understand and mechanistically characterize the aggregative property exhibited by the principal metabolites of the urea cycle and uric acid pathway, specifically hypoxanthine, xanthine, citrulline, and ornithine. Employing scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), we studied the aggregation profiles of the metabolites. Insights obtained through molecular dynamics (MD) simulation underscore the vital roles of π-π stacking and hydrogen bonding interactions in the self-assembly process, and thioflavin T (ThT) assays further corroborate the amyloid nature of these metabolites. The in vitro MTT assay revealed the cytotoxic trait of these assemblies, a finding that was substantiated by in vivo assays employing the Caenorhabditis elegans (C. elegans) model, which revealed that the toxic effects were more pronounced and dose-specific in the case of metabolites that had aged via longer preincubation. We hence report a compelling phenomenon wherein these metabolites not only aggregate but transform into a soft, ordered assembly over time, eventually crystallizing upon extended incubation, leading to pathological implications. Our study suggests that the amyloidogenic nature of the involved metabolites could be a common etiological link in IEMs, potentially providing a unified perspective to study their pathophysiology, thus offering exciting insights into the development of targeted interventions for these metabolic disorders.

Soil organic carbon loss decreases biodiversity but stimulates multitrophic interactions that promote belowground metabolism.

Soil organic carbon (SOC) plays an essential role in mediating community structure and metabolic activities of belowground biota. Unraveling the evolution of belowground communities and their feedback mechanisms on SOC dynamics helps embed the ecology of soil microbiome into carbon cycling, which serves to improve biodiversity conservation and carbon management strategy under global change. Here, croplands with a SOC gradient were used to understand how belowground metabolisms and SOC decomposition were linked to the diversity, composition, and co-occurrence networks of belowground communities encompassing archaea, bacteria, fungi, protists, and invertebrates. As SOC decreased, the diversity of prokaryotes and eukaryotes also decreased, but their network complexity showed contrasting patterns: prokaryotes increased due to intensified niche overlap, while that of eukaryotes decreased possibly because of greater dispersal limitation owing to the breakdown of macroaggregates. Despite the decrease in biodiversity and SOC stocks, the belowground metabolic capacity was enhanced as indicated by increased enzyme activity and decreased enzymatic stoichiometric imbalance. This could, in turn, expedite carbon loss through respiration, particularly in the slow-cycling pool. The enhanced belowground metabolic capacity was dominantly driven by greater multitrophic network complexity and particularly negative (competitive and predator-prey) associations, which fostered the stability of the belowground metacommunity. Interestingly, soil abiotic conditions including pH, aeration, and nutrient stocks, exhibited a less significant role. Overall, this study reveals a greater need for soil C resources across multitrophic levels to maintain metabolic functionality as declining SOC results in biodiversity loss. Our researchers highlight the importance of integrating belowground biological processes into models of SOC turnover, to improve agroecosystem functioning and carbon management in face of intensifying anthropogenic land-use and climate change.

Comprehensive analysis of effects of magnetic nanoparticles on aerobic granulation and microbial community composition: From the perspective of acyl-homoserine lactones mediated communication.

As dosing additives benefit for aerobic granular sludge (AGS) cultivation, effects of different concentrations (0, 10, 50 and 100 mg/L) of magnetic nanoparticles (Fe3O4 NPs) on aerobic granulation, contaminant removal and potential microbial community evolution related to acyl-homoserine lactones (AHLs) mediated bacterial communication were investigated with municipal wastewater. Results showed that the required time to achieve granulation ratio > 70 % was reduced by 60, 90 and 30 days in phase II with addition of 10, 50, 100 mg/L Fe3O4 NPs, respectively. 50 mg/L Fe3O4 NPs can improve contaminant removal efficiency. The promotion of relative abundance of AHLs-producing and AHLs-producing/quenching populations and AHLs-related functional genes accompanied with faster granulation. Iron-cycling-related bacteria were closely related with AHLs-related bacteria during AGS formation. Co-occurrence network analyses showed that AHLs-mediated communication may play an important role in coordinating microbial community composition and functional bacteria participating in nitrogen and polyphosphate metabolisms during aerobic granulation process.