Carbohydrate Metabolism Research Articles

Abstract 1257: Response to primary therapy predicts tumor evolution dynamics at relapse in ovarian cancer

Abstract Chemotherapy resistance is a major contributor of cancer-related deaths. Resistance can either be acquired during treatments or pre-exist at the time of the diagnosis. Previous studies on high-grade serous carcinoma (HGSC) have shown contradictory findings on the role of genetic causes explaining emergence of chemotherapy resistance at relapses, for example selection of resistant clones during chemotherapy. HGSC is often diagnosed at an advanced stage, showing multiple genetically heterogeneous clones present before therapeutic intervention. While most patients respond well to primary therapy, cancer relapses within few years, leading to treatment resistance. To understand genetic impact on emergence of resistance, we used matched pretreatment and treated samples from 214 unselected HGSC patients collected at DECIDER trial (NCT04846933). We constructed phylogenetic trees based on whole-genome sequencing of 804 tumor samples and whole-exome sequencing of 63 circulating tumor DNA (ctDNA) samples from plasma. Cancer evolution analysis identified patients with and without selection during treatments: patients with remained heterogeneity with stalled evolution, and others dominated by subclones originating from single resistant clone. Patients with better primary therapy outcome were linked to re-expansion of a single major clone at relapse, while multiple ancestral clones founded relapse populations in poorer outcome patients. The single-clone expansion pattern also emerged in later relapses, after multiple lines of therapy. Majority of the relapsed cancers evolved further from the ancestral clones already present at pretreatment. The relapse emerging subclonal mutations affected pathways such as carbohydrate metabolism and cAMP signaling. In contrast, sensitive clones eliminated by treatment carried mutations affecting extracellular matrix and NTRK3 signaling. Interestingly, some cancers did not acquire new mutations at relapse, despite becoming chemoresistant, suggesting that non-genetic mechanisms, such as phenotypic plasticity or microenvironmental factors, might underlie their resistance. In summary, we discovered heterogeneous cancer evolution trajectories during treatment which were linked to mutations in key pathways and prior therapy responses. While chemotherapy often selects persistent cancer subclones that seed later relapses, some patients acquire resistance through non-genetic mechanisms, highlighting the complexity of cancer evolution and resistance dynamics. Understanding these dynamics is crucial to define better therapeutic interventions in these poor prognosis patients with advanced HGSC. Citation Format: Jaana Oikkonen, Giulia Micoli, Susanna Holmström, Kari Lavikka, Mai T. Nguyen, Yilin Li, Giovanni Marchi, Anna Rajavuori, Heidi Koskela, Johanna Hynninen, Sampsa Hautaniemi. Response to primary therapy predicts tumor evolution dynamics at relapse in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1257.

Abstract 4065: Unveiling drivers of esophageal adenocarcinoma with CRISPR pooled screen and single-cell RNA-sequencing

Abstract Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a rising incidence and limited treatment options. It develops from Barrett’s esophagus, a pre-cancerous metaplastic condition, yet the molecular mechanisms driving its progression remain poorly understood. Genomic studies have identified ∼76 candidate genes as potential drivers of EAC. In our previous work, we demonstrated that in the context of mutant TP53, the inactivation of one such candidate tumour suppressor, SMAD4, was sufficient to drive tumorigenesis in non-tumorigenic CP-B Barrett’s esophagus xenografts. Building on this, we combined our EAC tumorigenesis model with Perturb-Seq (CRISPR-mediated gene editing coupled with single-cell RNA sequencing (scRNA-Seq)) to enable high-throughput functional characterization of EAC driver genes. The study specifically aimed to: (i) identify the molecular perturbations driving tumorigenesis in EAC, (ii) understand the transcriptional changes underlying the oncogenic effects of these perturbations, and (iii) tackle the genetic heterogeneity of EAC by categorizing driver genes according to shared transcriptional phenotypes. In vivo loss-of-function CRISPR screen was conducted using a boutique pooled CRISPR/Cas9 sgRNA library (6 sgRNAs per gene) targeting 57 known and putative tumour suppressor genes. To analyze the gene knockout-specific effects on the transcriptome at single-cell resolution, capture sequences compatible with 10X Feature Barcoding were incorporated into the sgRNAs. The library was transduced into two independent esophageal pre-malignant cell models, CP-B and CP-D, followed by xenotransplantation in NSG immunodeficient mice. We established that the knockout of 40 out of the 57 candidate tumour suppressors were independently sufficient to induce tumour formation in vivo. By integrating the scRNA-Seq data corresponding to each tumour suppressor knockout, we found that depletion of these tumour suppressor genes inhibited the proteasomal degradation of oncogenes and anti-apoptotic proteins, such as cyclin E, c-Myc, and Mcl-1. Additionally, this depletion led to the upregulation of genes involved in cell cycle progression, DNA repair, and lipid and carbohydrate metabolism. Perturb-seq also showed that driver-dependent transcriptional changes can be categorized into a smaller number of functional pathways allowing us to potentially consider groups of drivers as functional units. Collectively, the findings of this study enhance our understanding of the molecular events driving EAC tumorigenesis and offer a comprehensive view of the transcriptional phenotypes that can be targeted in future research. These insights lay the foundation for the development of novel therapeutic strategies for this highly heterogeneous disease. Citation Format: Ebtihal H. Mustafa, Julia Milne, Ka Meng Wu, Katherine Papastratos, Niko Thio, Wayne Phillips, Nicholas Clemons. Unveiling drivers of esophageal adenocarcinoma with CRISPR pooled screen and single-cell RNA-sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4065.

Abstract 1696: Combination therapy of cell cycle inhibitor and HDAC inhibitor induces metabolic alterations in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC), characterized by several multigene mutations, is one of the lethal solid cancers accounting for several drug treatment challenges. NCI statistics show that the overall 5-year survival rate of PDAC remains at 12.8%. The tumor aggressiveness and invasive-metastatic potential of the cancer, along with drug resistance issues, demand the development of novel and effective multi-drug therapies. Our initial results show that combination therapy of a cell cycle inhibitor Abemaciclib (Abe), and histone deacetylase inhibitor Panobinostat (Pan) effectively decreases pancreatic cancer cell proliferation and growth and causes apoptotic cell death. Cell cycle and epigenetic changes drive tumor progression by rewiring metabolic signaling pathways of pancreatic cancer cells. Therefore, we hypothesized that co-treatment of pancreatic cancer with Abe and Pan modulates cancer cell metabolism, developing energy imbalance leading to cell death. Our Seahorse metabolic experiments depicted a reduced oxygen consumption rate upon combination treatment in pancreatic cancer cells with upregulation of extracellular acidification rate. We also performed metabolomic profiling upon combination treatment in pancreatic cancer cells, revealing alterations in the levels of metabolites involved in carbohydrate, lipid, and amino acid metabolism in the combination treatment group compared to control pancreatic cells. We also observed a moderate increase in mitochondrial membrane potential upon combination treatment, suggesting altered mitochondrial metabolic signatures compared to control and individual drugs along with combination treatments. These results suggest that mitochondrial dysfunction may underlie the Abe and Pan combination treatment, impairing metabolic homeostasis and energy balance. Our future studies include deciphering the in-depth mechanism of alterations in mitochondrial dynamics and metabolic signaling pathways upon combining cell cycle and HDAC inhibitor treatment in pancreatic cancer cells by performing transcriptomic profiling on PDAC cells and in vivo xenograft studies. This study is funded by the College of Pharmacy and Health Sciences at St. John’s University, New York, and is also supported by the National Institute of General Medical Sciences (Award Number R16GM145557). Citation Format: Shraddha P. Bhutkar, Anjali Yadav, Vikas V. Dukhande. Combination therapy of cell cycle inhibitor and HDAC inhibitor induces metabolic alterations in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1696.

Differential Cell Death Pathways Induced by Oxidative Stress in Multi-Organs of Amur Grayling (Thymallus grubii) Under Gradient Ammonia Stress

Ammonia nitrogen is a common contaminant in aquatic environments, and its potential toxicity to organisms has attracted extensive attention. However, few studies have comprehensively evaluated the negative impacts of ammonia stress on cold-water fish. In this study, liver, gill, and intestine specimens of Amur grayling (Thymallus grubii) from three treatment groups (control (0 mg/L), low ammonia (43.683 mg/L), and high ammonia (436.8 mg/L)), were collected for histological observation, biochemical examination, and transcriptomic, metabolomic, and intestinal microbiome analysis. Our results showed that excessive ammonia nitrogen blocked the normal immune function and compromised the integrity of liver and gill tissues through oxidative stress-mediated differential cell death pathways. Meanwhile, the multi-omics analysis revealed that ammonia exposure predominantly altered the carbohydrate, lipid, and amino acid metabolism modes. In addition, it was also demonstrated that ammonia nitrogen stress affected the composition of intestinal microbiota taxa. This study provides insights into the potential risks and hazards of ammonia stress on cold fish in natural waters and provides a reference for the environment control of the water quality in aquaculture.

Antibacterial Effect and Mechanism of Chelerythrine on Xanthomonas oryzae pv. oryzae

Xanthomonas oryzae pv. oryzae (Xoo) is a biotrophic bacterial pathogen, which causes devastating bacterial blight disease worldwide. In this study, we thoroughly investigated the antimicrobial effect of the plant-derived extract chelerythrine against Xanthomonas oryzae pv. oryzae (Xoo) and elucidated its mechanism. Chelerythrine is a quaternary ammonium alkaloid with a 2,3,7,8-tetrasubstituted phenanthridine structure, extracted from plants, such as the whole plant of Chelidonium majus, and the roots, stems, and leaves of Macleaya cordata. We found that chelerythrine significantly inhibited the growth of Xoo at a concentration of 1.25 μg/mL. Further experiments revealed that chelerythrine interfered with the division and reproduction of the bacterium, leading to its filamentous growth. Additionally, it increased the permeability of Xoo cell membranes and effectively decreased the pathogenicity of Xoo, including the inhibition of extracellular polysaccharide production, cellulase secretion, and biofilm formation. Chelerythrine induced the accumulation of reactive oxygen species in the bacterium, triggering oxidative stress. The result showed that chelerythrine inhibited the formation of the Z-ring of Xoo, interfered with the synthesis of pyrimidine and purine nucleotides, inhibited DNA damage repair, and inhibited the formation of peptidoglycan and lipid-like A, thus interfering with cell membrane permeability, inhibiting carbohydrate metabolism and phosphorylation of sugars, reducing pathogenicity, and ultimately inhibiting bacterial growth and leading to the destruction or lysis of bacterial cells. Altogether, our results suggest that the antimicrobial effect of chelerythrine on Xoo exhibits multi-target properties. Additionally, its effective inhibitory concentration is low. These findings provide a crucial theoretical basis and guidance for the development of novel and efficient plant-derived antimicrobial compounds.

Outpatient follow-up of patients with myocardial infarction and early carbohydrate metabolism disorders

Aim. To assess the quality of treatment of patients with myocardial infarction (MI) and early carbohydrate metabolism disorders as part of outpatient follow-up.Material and methods. The study was conducted within the outpatient registry of patients after myocardial infarction PROFILE-MI, which included all patients who visited a cardiologist at Moscow City Polyclinic № 9 after myocardial infarction from March 1, 2014 to June 30, 2015. A total of 160 people were included as follows: 106 (66,2%) men and 54 (33,8%) women; mean age, 70,4±10,8 (from 39 to 87) years. Visits were carried out every 2 months. Fasting plasma glucose levels were assessed. The follow-up lasted 1 year. Patients with carbohydrate metabolism disorders 68 (42,5%) were divided into 3 following groups: 1: patients with a history of type 2 diabetes (T2D) or diagnosed at the inpatient stage — 45 (28%); 2: patients with a history of impaired glucose tolerance (IGT) or diagnosed at the inpatient stage — 6 (4%); 3: patients without T2D or IGT (n=109), in whom impaired fasting glycemia was recorded for the first time at the outpatient stage — 17 (16%). The prescription rate of metformin was assessed in all groups.Results. There were 23 (14,4%) patients with early carbohydrate metabolism disorders included in the registry. In group 3, there were significantly more men than in groups 1 and 2 — 76,5 vs 42 and 33% (p<0,001), and the mean age of 59,8±11,9 years was lower — 64,04±11,4 and 72,5±6,8 years (p=0,033), respectively. In this group, there were no smoking patients (p=0,007), fewer obese patients (18 vs 44 and 33%), but more overweight individuals compared to group 1 (47 vs 40%). In addition, burdened heredity (47 vs 64 and 67%), hypertension (65 vs 84 and 100%) were less frequently registered, respectively. The proportion of patients with a history of coronary artery disease was lower in group 3 compared to group 1 and amounted to 29 vs 47% (p=0,012). During the follow-up period, the prevalence of blood glucose testing did not exceed 44%. Metformin was prescribed only to patients of group 1 upon discharge from the hospital — 3 (6,7%), while metformin therapy was not prescribed to patients of groups 2 and 3. Conclusion. According to the PROFILE-MI registry, the total prevalence of early carbohydrate metabolism disorders among patients with a history of MI was quite high and amounted to 14,4%. This category of patients had a less complicated cardiovascular history. In real-world practice, metformin was not prescribed to patients with early carbohydrate metabolism disorders.

Metabolic Influence of S. boulardii and S. cerevisiae in Cross-Kingdom Models of S. mutans and C. albicans

Recent studies highlight the potential of Saccharomyces species as probiotics due to their ability to modulate microbial interactions and reduce cariogenic activity, yet the underlying metabolic mechanisms remain unclear. This study investigates the cross-kingdom metabolic effects of Saccharomyces boulardii and Saccharomyces cerevisiae on the metabolic processes of Streptococcus mutans and Candida albicans using a metabolomics-based approach. Untargeted LC-MS/MS analysis was conducted to assess metabolites in a planktonic model, followed by metabolomic profiling and pathway analysis to identify key metabolic alterations. The results revealed that S. boulardii and S. cerevisiae demonstrated metabolic regulatory effects on S. mutans and C. albicans. Specifically, S. boulardii down-regulated 262 metabolites and up-regulated 168, while S. cerevisiae down-regulated 265 metabolites and up-regulated 168. Both yeast species down-regulated carbohydrate and amino acid metabolism in S. mutans and C. albicans, resulting in reduced biomolecule synthesis and a less acidic environment. S. boulardii and S. cerevisiae also up-regulated certain metabolic processes, including purine metabolism, suggesting a compensatory mechanism for nucleotide synthesis. Notably, dual regulatory effects were observed, where specific metabolites were simultaneously up-regulated and down-regulated, indicating complex metabolic crosstalk. These findings suggest that both S. boulardii and S. cerevisiae modulate microbial metabolism through a shared mechanism, offering potentials for dental caries prevention.

Linalool inactivates TORC1, disrupting ribosome biogenesis and inhibitingFusarium oxysporumgrowth.

Fusarium oxysporum, a pathogenic fungus threatening medicinal plants likePanax notoginseng, causes severe root rot.Linalool, the primary component ofAlpinia officinarumHance essential oil (EO), is a biologically active compound with demonstrated anti-inflammatory, antibacterial, and antioxidant properties. Notably, it has garnered considerable attention for its remarkable antifungal efficacy.In vitro studies revealed that linalool significantly inhibitedF. oxysporumhyphal growth. At 12.08 mmol/L, spore germination decreased by 43%, while spore yield dropped by 99%. Transcriptomic analysis identified 562 upregulated and 4,095 downregulated genes in the linalool-treated group. The upregulated genes were predominantly enriched in pathways related to metabolism, oxidative phosphorylation, and carbohydrate metabolism, indicating adaptive stress responses. Downregulated genes were primarily associated with the ribosome biogenesis, transcription, and spliceosome pathways, with ribosome biogenesis showing the most pronounced inhibition. Linalool treatment inactivated TORC1 (target of rapamycin complex 1), a crucial regulator of ribosomal biogenesis and protein synthesis. This disruption led to reduced expression of ribosome-related genes, severely impairing protein synthesis and fungal growth. The study highlights linalool's strong antifungal activity, primarily by targeting ribosome biogenesis. Future research should investigate its effects and safety in field applications, offering potential strategies for managing diseases in medicinal plants such asP. notoginseg.

Effect of co-inoculation of Pseudomonas fragi and Pseudomonas putida on the spoilage of chilled pork after the screening of a variety of different combinations of two Pseudomonas species.

Effect of co-inoculation of Pseudomonas fragi and Pseudomonas putida on the spoilage of chilled pork after the screening of a variety of different combinations of two Pseudomonas species.

Subcellular plant carbohydrate metabolism under elevated temperature.

In many plant species, exposure to a changing environmental temperature regime induces an acclimation response that ultimately increases thermotolerance. Under elevated temperature, membrane systems undergo remodeling to counteract destabilizing thermodynamic effects. Elevated temperature also affects photosynthesis and carbohydrate metabolism due to altered protein functions, enzyme activities, and transport across membrane systems. Here, a combination of electrolyte leakage assays and chlorophyll fluorescence measurements was applied to quantify heat tolerance before and after heat acclimation in Arabidopsis thaliana under different temperature regimes. Subcellular carbohydrate concentrations were determined through non-aqueous fractionation and 3D reconstruction of mesophyll cells and subcellular compartments using serial block-face scanning electron microscopy. Across temperature regimes between 32 °C and 38 °C, seven days of heat acclimation at 34 °C most efficiently increased tissue heat tolerance. Under such conditions, cytosolic sucrose concentrations were stabilized by a shift in sucrose cleavage rates into the vacuolar compartment, while invertase-driven cytosolic sucrose cleavage was efficiently quenched by fructose and glucose acting as competitive and non-competitive inhibitors, respectively. Finally, this study provides strong evidence for a sucrose concentration gradient from the cytosol into the vacuole, which might directly affect the physiological role and direction of sugar transport across cellular membrane systems.

Genome-scale metabolic modeling reveals specific vaginal Lactobacillus strains and their metabolites as key inhibitors of Candida albicans.

As the predominant constituents of the vaginal microbiome in healthy women, Lactobacillus species are considered essential in maintaining a homeostatic vaginal microbiome. Specific Lactobacillus species can produce beneficial metabolites to support their persistence within the host environment and inhibit Candida albicans colonization. Due to the extensive diversity of Lactobacillus species and their metabolites, comprehensively investigating all possible interactions remains challenging. This study employed an integrative approach combining genome-scale metabolic modeling, metagenomic sequencing, and in vitro validation to explore Lactobacillus and C. albicans interactions. Pairwise simulations of 159 Lactobacillus strains with C. albicans revealed that most strains exhibit inhibitory effects, altering fungal amino acid and carbohydrate metabolism. Key inhibitory metabolites identified included formate, L-lactate, and L-malate. Metagenomic analysis of vaginal swabs from 20 vulvovaginal candidiasis (VVC) patients and 20 healthy women showed a correlation between Lactobacillus species abundance and reduced C. albicans colonization. In vitro experiments confirmed the inhibitory effects of these metabolites and the selected Lactobacillus strains on C. albicans growth, thereby validating our computational predictions. These findings provide insights into the metabolic interactions within the vaginal microbiome and pave the way for targeted microbial or metabolite-based therapeutic strategies to manage VVC.IMPORTANCEVulvovaginal candidiasis is a prevalent fungal infection with significant implications for women's health, caused primarily by Candida albicans. Although the protective role of a Lactobacillus-dominated vaginal microbiome is well established, the metabolic mechanisms underlying the interactions between Lactobacillus species and C. albicans remain inadequately understood. Specifically, the Lactobacillus species that effectively inhibit C. albicans and the metabolic pathways involved warrant further investigation. This study offers novel insights into the metabolic mechanisms underlying Lactobacillus antagonism against C. albicans. By identifying critical metabolic pathways and inhibitory metabolites, this study enhances our understanding of vaginal microbiome dynamics and host-microbe interactions. The findings suggest that key Lactobacillus strains and their metabolites could significantly reduce harmful levels of C. albicans, paving the way for future therapeutic strategies that leverage these microbial characteristics to promote vaginal health.

Application of Metabolomics and Microbiome Analysis for Revealing the Endogenous Mechanism of Baizhu Xiaozhong San in Postpartum Rats with Spleen-qi Deficiency.

Postpartum women are in a state of physical weakness and suffering from fatigue. Metabolic disturbances in the postpartum period may lead to an increased prevalence of postpartum depression, hemorrhage, and obesity, underscoring the importance of prioritizing maternal health. The combination (Baizhu Xiaozhong San, BZXZS) of charred Atractylodis macrocephalae Koidz. (Baizhu, BZ) and charred Fructus Aurantii Immaturus (Zhishi, ZS) has primary applications for invigorating the spleen and promoting diuresis. This study utilized serum/spleen metabolomics in conjunction with 16S rDNA sequencing analysis to investigate the endogenous metabolic alterations and intestinal homeostasis in postpartum rats exhibiting spleen-deficiency syndrome (SDS). The pathological symptoms of postpartum SDS rats in the administration groups were gradually restored, in particular, the symptoms of the BZXZS-H group rats improved significantly. As a result, 32 differential metabolites and 7 correlated metabolic pathways (impact value > 0.1) demonstrated the improvement effect of BZXZS on postpartum SDS rats mostly focusing on disorders of energy, carbohydrate, and lipid metabolism. 16S rDNA gene sequencing indicated that BZXZS had a significantly better regulatory effect on Lactobacillus faecis. The findings suggest that BZXZS exerts a positive impact on the intestinal health and the immune system of postpartum SDS rats through an intricate cascade of interactions with various targets.

Response patterns and community assembly processes of gut microbiota in grass carp subjected to various protein sources and their implications for growth and metabolism.

Feed nutrients are crucial in shaping the gut microbial community, especially for complex interactions. While much research focused on the impacts of dietary protein levels, exploration of protein sources remains insufficient. Accordingly, this study specifically investigated the effects of four protein sources [Clostridium autoethanolicum protein (CAP), cottonseed protein concentrate (CPC), Chlorella vulgaris meal (CVP), and Tenebrio molitor meal(TM)] replacing dietary soybean meal on microbial co-occurrence networks and key metabolic taxa. A 56-day feeding trial involved 1500 grass carp (20.00 g) fed five experimental diets, each incorporating one of the experimental protein sources. Results revealed that CPC and CVP diets improved the weight gain and specific growth rate, with the CPC group demonstrating the highest biomass gain and the CVP group exhibiting the best feed conversion ratio. Findings further indicated that SM-free diets enhanced intestinal immunity and barrier function while negatively impacting microbial diversity. Additional profiling revealed that each treatment exhibited distinct abundance profiles and unique species, with Firmicutes, Bacteroidota, and Proteobacteria as the dominant phyla and key genera such as Bacteroides, Erysipelatoclostridium, and Cetobacterium. Stochastic mechanisms drove the community assembly process, and prolonged SM-free diets led to simplified networks with increased generalists and specialists. Functional gene analysis highlighted roles in amino acid, carbohydrate, and lipid metabolism, underscoring the impact of protein sources on aquatic microbial communities and host-microbiome interactions. Overall, the study suggests the potential suitability of several protein sources as soybean meal substitutes, emphasizing the importance of further investigation into optimal inclusion levels for diverse proteins.

Exogenous Mogroside V Drove Microbial Carbohydrate Metabolism and Consequently Enhanced Fruity Aroma in Greengage Wine.

The microbial community is essential for the formation of aroma development in high-acidity greengage wine fermentation. Recent observations also highlight positive effects of mogroside V (MG V) on microorganisms in fermented foods, but the underlying chemical and biological mechanisms remain inadequate. The results indicated differences in the physicochemical properties among greengage wines, particularly a 50% increase in the ethanol conversion rate. Concurrently, GC-MS and sensory analyses demonstrated that MG V augmented carbohydrate conversion into ethyl esters (twice as much as in the control group), exhibiting tropical fruit and floral aroma profiles. The perceived intensity of these aromatic compounds increased by over 30%, thereby enriching the overall aromatic harmony of the wine. Integrated analysis of KEGG pathways and CAZymes annotations demonstrated that the enhancement of ethyl ester formation by MG V depends on improvement of the transport of carbohydrates and MG V, as well as accelerating the flux of pyruvate to acetyl-CoA in yeast. In conclusion, our study presents a targeted strategy for the high-acidity fruit wine industry of modulating this metabolic node in yeast, thereby achieving a focused enhancement of tropical fruit aroma characteristics in fruit wines.

Update in non-alcoholic fatty liver disease management: role of sodium-glucose cotransporter 2 inhibitors.

Update in non-alcoholic fatty liver disease management: role of sodium-glucose cotransporter 2 inhibitors.

Modulation of the microbial community and the fermentation characteristics of wrapped natural grass silage inoculated with composite bacteria

This study evaluated the effects of composite bacterial inoculants on the fermentation quality, microbial community composition, and nutrient preservation of natural grass silage produced in Hulunbuir, Inner Mongolia. Four treatment groups were set, each using distinct combinations of lactic acid bacteria: a control group (C) with no inoculant and three inoculated groups (Group B: Lentilactobacillus buchneri and Pediococcus pentosaceus; Group P: Lactiplantibacillus plantarum A1 and Lactiplantibacillus plantarum LP-21; and Group M: Lactiplantibacillus plantarum, Enterococcus faecium, and Pediococcus pentosaceus). After 240 days of ensiling, the inoculated groups exhibited significantly higher contents of crude protein and dry matter (DM) and lower ammonia nitrogen, neutral detergent fiber, and acid detergent fiber levels than the control group. The M group demonstrated superior fermentation performance, exhibiting the lowest pH (C 5.15; B 4.77; P 4.64; and M 4.57), the highest lactic acid concentration (C 3.40% DM; B 6.80% DM; P 7.73% DM; and M 8.00% DM), and an optimal microbial composition dominated by Lactiplantibacillus and Lentilactobacillus. These improvements were attributed to Lactiplantibacillus plantarum, a bacterium that can produce a substantial amount of lactic acid through homofermentation, thereby lowering the pH, inhibiting the activity of undesirable microorganisms, and enhancing nutrient preservation. High-throughput sequencing revealed shifts in the dominant bacterial phyla from Proteobacteria in raw grass to Firmicutes in silage, with inoculants significantly influencing microbial diversity and functional profiles. Functional prediction indicated enhanced carbohydrate metabolism and nutrient preservation in the inoculated groups. These findings underscore the potential of tailored bacterial inoculants and advanced wrapping technology to improve the quality of silage and thus support sustainable livestock production.Graphical

Quantitative proteomic analysis based on TMT reveals different responses of Haloxylon ammodendron and Haloxylon persicum to long-term drought

The essence of the plant drought tolerance mechanism lies in determining protein expression patterns, identifying key drought-tolerant proteins, and elucidating their association with specific functions within metabolic pathways. So far, there is limited information on the long-term drought tolerance of Haloxylon ammodendron and Haloxylon persicum grown in natural environments, as analyzed through proteomics. Therefore, this study conducted proteomic research on H. ammodendron and H. persicum grown in natural environments to identify their long-term drought-tolerant protein expression patterns. Totals of 71 and 348 differentially expressed proteins (DEPs) were identified in H. ammodendron and H. persicum, respectively. Bioinformatics analysis of DEPs reveals that H. ammodendron primarily generates a large amount of energy by overexpressing proteins related to carbohydrate metabolism pathways (pyruvate kinase, purple acid phosphatases and chitinase), and simultaneously encodes proteins capable of degrading misfolded/damaged proteins (tam3-transposase, enhancer of mRNA-decapping protein 4, and proteinase inhibitor I3), thus adapting to long-term drought environments. For H. persicum, most DEPs (enolase and UDP-xylose/xylose synthase) involved in metabolic pathways are up-regulated, indicating that it mainly adapts to long-term drought environments through mechanisms related to positive regulation of protein expression. These results offer crucial insights into how desert plants adapt to arid environments over the long term to maintain internal balance. In addition, the identified key drought-tolerant proteins can serve as candidate proteins for molecular breeding in the genus Haloxylon, aiming to develop new germplasm for desert ecosystem restoration.

Transcriptomic analysis reveals long non-coding RNA involved in the key metabolic pathway in response to Botrytis cinerea in kiwifruit

BackgroundUnderstanding the molecular mechanisms that confer kiwifruit resistance to Botrytis cinerea is essential for developing resistant cultivars. Long non-coding RNAs (lncRNAs), known to participate in various physiological processes including plant defense against diseases, have an undefined role in kiwifruit’s resistance.ResultsOur study aimed to identify lncRNAs induced by B. cinerea infection in ‘Hongyang’ kiwifruit at 0 to 3 days post-inoculation (dpi) through high-throughput sequencing. The differential expression analysis identified 126 differentially expressed lncRNAs (DELs). Subsequent GO and KEGG analyses indicated that these lncRNAs’ target genes were predominantly associated with plant-pathogen interactions, carbohydrate metabolism including starch and sucrose, mitogen-activated protein kinase (MAPK) signaling pathways, and plant hormone signal transduction. Co-expression analysis revealed that lncRNAs modulate the expression of genes involved in phytohormone signaling pathways, such as those for auxin, ethylene (ETH), abscisic acid (ABA), jasmonic acid (JA), and salicylic acid (SA), as well as the MAPK signaling pathway. This regulation affects the biosynthesis of defense-related secondary metabolites like ADP-glucose, sucrose, 1,3-β-glucan, and cellulose, thereby enhancing the fruit’s disease resistance.ConclusionOur findings offer valuable insights into the mechanisms by which lncRNAs respond to biotic stress in kiwifruit, potentially aiding in the development of strategies for breeding kiwifruit with improved resistance to B. cinerea.

Rainbow Trout (Oncorhynchus mykiss) Pre-Smolts Treated with 11-Deoxycorticosterone Regulate Liver Carbohydrate Metabolism and Gill Osmoregulation

Rainbow Trout (Oncorhynchus mykiss) Pre-Smolts Treated with 11-Deoxycorticosterone Regulate Liver Carbohydrate Metabolism and Gill Osmoregulation

Metabolic response of tellurite resistant Bacillus altitudinis strain 3W19 highlights the potential as a model organism for bioremediation

Contaminated environments can pose new challenges when new contaminants appear and can select organisms with new genetic and metabolic strategies. The increased presence of Te(IV) in the environment is becoming more important. This highlights how underexplored the investigation of how bacteria molecularly respond to less common environmental contaminants, such as tellurite when compared to other metals/ metalloids. Understanding what tools an organism uses from its genetic pool when responding to a new contaminant requires a multiple-technique approach, such as metabolic tests and differential omics analysis. These analyses provide a full metabolic and phenotypical map of stress response that can include new resistance mechanisms, whether specific or not. This study aimed to determine if Bacillus altitudinis strain 3W19, isolated from a Te(IV) contaminated site, presents specific changes at the proteomic level when exposed to the metalloid. In strain 3W19, growth in the presence of Te(IV) upregulated pathways of amino acid metabolism and membrane transport and downregulated pathways of carbohydrate metabolism. Growth in the presence of Te(IV) also induced the formation of reactive oxygen species and lowered the metabolic activity of the strain. This metal led to the overexpression of the proteins of the ter gene cluster. When compared with other strains, the ter system identified in this strain differed in genomic organization from related Bacillus sp. strains. Together, these strain-specificities can contribute to understanding its Te(IV) resistance phenotype.