PubMed

Plant Physiol Biochem. 2024 Dec 24;219:109445. doi: 10.1016/j.plaphy.2024.109445. Online ahead of print.ABSTRACTExtreme conditions, such as cold and high humidity in northeast China's high-latitude maize region, can hinder crop yield and stability during the vegetative stage. However, there is a paucity of research examining the effects of simultaneous cold and high humidity stress on plant responses. In this study, we characterized the acclimation of JD558 (cold- and high humidity-sensitive hybrid) and JD441 (cold- and high humidity-tolerant hybrid) to stress at sowing caused by cold (4 °C), high humidity (25%), and their combined stress for five days, using physiological measurements and metabolomics during the stress treatments and recovery stages. Cold, high humidity, and their combined stress prolonged seed development and restricted material transport, with high humidity harming seed survival more than cold. Combined stress exhibited a more significant inhibitory effect on growth than individual stress. Individual and combined stress reduced α-amylase activity, disrupted antioxidants levels, increased malondialdehyde content, disturbed the oxidative balance within seeds, and impeded seed growth and development. Most carboxylic acids and their derivatives were downregulated caused by combined stress. In JD558, sucrose, D-glucose, glucose-1-phosphate, and fructose-1,6-bisphosphate were downregulated, while these metabolites were upregulated in JD441, leading to a blockage of glycolysis in JD558. After eliminating stress, JD441 showed greater α-amylase activity and a smaller decrease in MDA levels, resulting in a smaller reduction in root growth and transport rate than JD558. In summary, the different responses of the cold and high humidity sensitive hybrid and the tolerant hybrid to combined stress are related to the recovery ability after stress elimination.PMID:39731983 | DOI:10.1016/j.plaphy.2024.109445

Plant Physiol Biochem. 2024 Dec 24;219:109447. doi: 10.1016/j.plaphy.2024.109447. Online ahead of print.ABSTRACTNAC (NAM, ATAF1/2 and CUC2) is a transcription factor which contributes to the response for both biotic and abiotic stresses. In this study, the regulatory effects and potential mechanisms of SNAC4/9 on resistance to Botrytis cinerea (B. cinerea) were investigated by the differences in physiological and biochemical indices as well as transcriptional and metabolic profiles between SNAC4/9 overexpressed (OE-SNAC4/9) and wild-type (WT) tomato fruit inoculated with B. cinerea. The results showed that OE-SNAC4/9 accelerated the infection to tomato fruit by B. cinerea. Specifically, OE-SNAC4/9 mediated the differential expression of genes related to defense signaling such as ROS, phytohormones (SA and JA) and MAPK cascade, and inhibited the activities of PAL, CHI and GLU. Additionally, SNAC4/9 altered the metabolic flux redirection in each branch pathway of phenylpropane metabolism by regulating the expression of 4CL, CHS1/2, FLS and F3H, with overexpression of SNAC4/9 leading to a decrease in the accumulation of rutin, quercetin, naringenin chalcone and naringenin in tomato fruit. In conclusion, SNAC4/9 may inhibit tomato fruit resistance to B. cinerea by modulating signaling, inhibiting PRs (pathogenesis related proteins) synthesis, and altering metabolic flux flow.PMID:39731978 | DOI:10.1016/j.plaphy.2024.109447

J Pharm Biomed Anal. 2024 Dec 17;255:116641. doi: 10.1016/j.jpba.2024.116641. Online ahead of print.ABSTRACTPharmacologic intervention in chronic heart failure (HF) with renal insufficiency is one of the clinical challenges due to the fact that the mechanisms of cardio-renal interactions in chronic heart failure (CHF) progressing have not been fully revealed. In this paper, C57BL/6 mice were applied thoracic aortic narrowing surgery to establish pressure overload CHF model. Cardiac function, serum markers, renal pathologic changes and kidney metabolism were analyzed at 4th, 8th, 12th, and 16th week after surgery respectively to evaluate the heart-Kidney pathologic overlap. Kidney proteomic analysis was performed at 16th week after operation. As a result, renal hypofiltration and exacerbation of pathological damage was observed accompanying cardiac function deterioration after 12th week. 66 differentially expressed proteins and 13 differential metabolites were found to be involved in the cardio-renal pathological overlap. Joint proteomic and metabolomic analysis revealed that signal pathways like Phosphatidylinositol signaling system, Glucagon signaling pathway, the Glyoxylate and dicarboxylate metabolism; DEPs of Pten, Mtmr4, PLC and CPT1, differential metabolites like aspartic acid and isocitrate deserve further investigation.PMID:39731929 | DOI:10.1016/j.jpba.2024.116641

J Pharm Biomed Anal. 2024 Dec 24;255:116653. doi: 10.1016/j.jpba.2024.116653. Online ahead of print.ABSTRACTFlavonoids serve as bioactive components and contribute to medicinal and nutritional profile of Lycii fructus. However, there is limited information regarding the influence of ecological environments on the flavonoid biosynthesis pathway. In this study, we integrated transcriptome sequencing and metabonomic techniques across three distinct cultivation regions to elucidate the processes of flavonoids biosynthesis and the associated gene expression levels in L. fructus. LC-MS/MS based metabolomics revealed significant variations in metabolite profiles including 43 differential flavonoid metabolites, predominantly consisting of flavanol compounds across diverse regions. Additionally, 154 significantly differentially expressed genes (DEGs) were categorized in the flavonoid biosynthesis identified by de novo transcriptome assembly. Transcription factors C2C2 MYB, NAC, WRKY, AP2/ERF and B3 superfamily were the mainly hub genes regulating the flavonoids biosynthesis. The flavonoid pathway was built through integrated analysis of DEGs and DAMs to illustrate the molecular mechanism of flavonoid biosynthesis. Precipitation and temperature may serve as the primary environmental factors that affected the flavonoids variations. This study proposed a schematic of flavonoid biosynthesis in L. fructus, and further provided evidence for environmental response of L. fructus.PMID:39731927 | DOI:10.1016/j.jpba.2024.116653

J Hazard Mater. 2024 Dec 24;486:136968. doi: 10.1016/j.jhazmat.2024.136968. Online ahead of print.ABSTRACTBiodegradable plastics, regarded as an ideal substitute for traditional plastics, are increasingly utilized across various industries. However, due to their unique degradation properties, they can generate microplastics (MPs) at a faster rate, potentially posing a threat to plant development. This study employed transcriptomics and metabolomics to investigate the effects of polylactic acid microplastics (PLA-MPs) on the physiological and biochemical characteristics of Brassica chinensis L. over different periods. The findings indicated that exposure to varying concentrations of PLA-MPs had distinct influences on the growth and development of Brassica chinensis L. Transcriptomic analysis showed different concentrations of PLA-MPs directly influenced the expression of genes associated with plant hormones, such as SnRK2 and BnaA01g27170D. In addition, it was observed that these PLA-MPs also impacted plant growth and development by modulating the expression of other genes, eg. related to sulfur metabolism and glycerophosphate metabolism. Metabolomic analysis demonstrated alterations levels of metabolites such as L-glutamine, and arginine in response to PLA-MPs, which influenced pathways related to vitamin B6 metabolism, the one-carbon folate pool, glycerophospholipid metabolism, and cysteine. This study offers new insights into the potential impacts of biodegradable microplastics (BMPs) on plants and underscores the need for further investigation into the potentially more significant effects of BMPs on terrestrial ecosystems.PMID:39731891 | DOI:10.1016/j.jhazmat.2024.136968

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Dec 23;54:101408. doi: 10.1016/j.cbd.2024.101408. Online ahead of print.ABSTRACTThe intestinal microbiota plays a crucial role in the health and development of fish, engaging in intricate interactions with the host organism. As a significant species in aquaculture, Lateolabrax japonicus serves as an exemplary model for investigating these interactions and their subsequent effects on growth and health. This study utilized a multi-omics approach, incorporating metagenomic sequencing and non-targeted metabolomics, to delineate the gut microbiota and metabolome of L. japonicus throughout various developmental phases. Collected from a meticulously controlled aquaculture setting, the intestinal microbiota of L. japonicus underwent high-throughput sequencing to scrutinize microbial DNA and enumerate metabolites. The metagenomic analysis uncovered a heterogeneous gut microbiota in L. japonicus, predominantly composed of Proteobacteria and Firmicutes, with marked heterogeneity in microbial composition across developmental stages. A particularly noteworthy discovery was the prevalence of the genus Acinetobacter, which may significantly influence health and disease resistance. The metabolomic profiling discerned 4479 metabolites, each exhibiting pronounced stage-specific metabolic signatures, particularly within lipid, amino acid, and energy metabolism pathways. The correlation analysis between microbiota and metabolites highlighted the substantial impact of specific genera, such as Acinetobacter and Gaeumannomyces, on the metabolic milieu. This study provides a comprehensive overview of the dynamic shifts in the gut microbiota and metabolome of L. japonicus, highlighting stage-specific transitions that could be pivotal for refining aquaculture practices. The findings underscore the complex interdependence between microbiota composition and metabolic function, providing valuable insights into the modulation of fish health and growth.PMID:39731826 | DOI:10.1016/j.cbd.2024.101408

Animal. 2024 Dec 4;19(1):101393. doi: 10.1016/j.animal.2024.101393. Online ahead of print.ABSTRACTMetabolomics can describe the molecular phenome and may contribute to dissecting the biological processes linked to economically relevant traits in livestock species. Comparative analyses of metabolomic profiles in purebred pigs can provide insights into the basic biological mechanisms that may explain differences in production performances. Following this concept, this study was designed to compare, on a large scale, the plasma metabolomic profiles of two Italian heavy pig breeds (Italian Duroc and Italian Large White) to indirectly evaluate the impact of their different genetic backgrounds on the breed metabolomes. We utilised a high-throughput untargeted metabolomics approach in a total of 962 pigs that allowed us to detect and relatively quantify 722 metabolites from various biological classes. The molecular data were analysed using a bioinformatics pipeline specifically designed for identifying differentially abundant metabolites between the two breeds in a robust and statistically significant manner, including the Boruta algorithm, which is a Random Forest wrapper, and sparse Partial Least Squares Discriminant Analysis (sPLS-DA) for feature selection. After thoroughly evaluating the impact of random components on missing value imputation, 100 discriminant metabolites were selected by Boruta and 17 discriminant metabolites (all included within the previous list) were identified with sPLS-DA. About half of the 100 discriminant metabolites had a higher concentration in one or the other breed (48 in Italian Large White pigs, with a prevalence of amino acids and peptides; 52 in Italian Duroc pigs, with a prevalence of lipids). These metabolites were from seven distinct super pathways and had an absolute mean value of percentage difference between the two breeds (|Δ|%) of 39.2 ± 32.4. Six of these metabolites had |Δ|%> 100. A general correlation network analysis based on Boruta-identified metabolites consisted of 31 singletons and 69 metabolites connected by 141 edges, with two large clusters (> 15 nodes), three medium clusters (3-6 nodes) and eight additional pairs, with most metabolites belonging to the same super pathway. The major cluster representing the lipids super-pathway included 24 metabolites, primarily sphingomyelins. Overall, this study identified metabolomic differences between Italian Duroc and Italian Large White pigs explained by the specific genetic background of the two breeds. These biomarkers can explain the biological differences between these two breeds and can have potential practical applications in pig breeding and husbandry.PMID:39731811 | DOI:10.1016/j.animal.2024.101393

J Food Sci. 2024 Dec 28. doi: 10.1111/1750-3841.17630. Online ahead of print.ABSTRACTThe effect of solvents with different polarities on the recovery of phytochemicals (carotenoids, capsaicinoids, and phenolic compounds) from habanero pepper (Capsicum chinense) and their association with antioxidant activity (ABTS•+ and DPPH) was evaluated through Ultra-Performance-Liquid Chromatography coupled with a Photodiode Array Detector and a Electrospray Ionization Mass Spectrometry (UPLC-PDA-ESI-MS)-based chemometric analysis, including linear correlation, multiple linear regression, and principal component analysis (PCA). The solvent polarity scale was established according to solvent dielectric constants (ɛ). Color variation (ΔE) was used to determine the presence of carotenoids, with the highest ΔE obtained using low-polarity solvents (hexane and ethyl acetate). A high content of capsaicin and dihydrocapsaicin was recovered with acetone (4.29 and 3.76 mg g⁻¹ dry weight, respectively). Phenolic compounds such as N-caffeoyl putrescine and derivatives of luteolin and apigenin were identified through mass spectrometry. A high recovery (26.54-31.74 mg GAE g⁻¹ dry weight) of these compounds was obtained using intermediate-polarity solvents. The PCA revealed clustering of solvents based on their affinity for extracting specific compounds and their association with antioxidant activity. A significant correlation was observed between ΔE and DPPH, indicating that carotenoid pigments exhibited higher DPPH radical inhibition capacity than other compounds. Total phenolic content (TPC) and phenolic compounds (phenolpolyamides, hydroxycinnamic acids, and hydroxybenzoic acids) were clustered with the ABTS•+ radical inhibition assay. The information obtained is crucial for selecting suitable solvents in the extraction and purification protocols of bioactive compounds. It is also valuable for conducting plant metabolomic analyses and for studies focused on determining the effects of bioactive compounds in food, pharmaceutical, and cosmeceutical applications. PRACTICAL APPLICATION: The results describe the characteristics of the extracts obtained using different solvents. Therefore, the information may be useful for establishing extraction protocols for phytochemical compounds in fruits from Capsicum chinense for various purposes, such as metabolomic analysis, the recovery of specific compounds with antioxidant activity, and food applications.PMID:39731723 | DOI:10.1111/1750-3841.17630

J Food Sci. 2024 Dec 28. doi: 10.1111/1750-3841.17589. Online ahead of print.ABSTRACTMepiquat is a contaminant produced in thermal-processed food. It can induce spleen and liver injury. However, the mechanism that mepiquat induced hepatotoxicity remains unclear. In this study, a ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic analysis of livers in rats was performed to explore metabolic alterations. Our results demonstrated that there were 36 differential metabolites. Eleven major disordered metabolic pathways were found. Network analysis of differential metabolites and metabolic pathways indicated that glutamic acid was a possible key upregulated metabolite. It participated in nine metabolic networks. Glutathione and l-proline may be key downregulated metabolites. They were involved in eight and seven metabolic pathways, respectively. Compared with the control group, serum concentrations of alanine aminotransferase, aspartate aminotransferase, and total bile acid in high dosage group increased significantly. In addition, histopathological analysis showed liver injury in rats with mepiquat exposure. These data were consistent with results of metabolomics. Our results offered new insights for molecular mechanism of liver toxicity induced by mepiquat. PRACTICAL APPLICATION: Mepiquat is a contaminant formed in thermal-processed food. It can induce spleen and liver injury. Our results offered new insights for molecular mechanism of liver toxicity induced by mepiquat. It will provide important information for official limits of mepiquat in foods.PMID:39731714 | DOI:10.1111/1750-3841.17589

J Am Chem Soc. 2024 Dec 28. doi: 10.1021/jacs.4c09582. Online ahead of print.ABSTRACTDiscovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities. Additionally, we demonstrate the use of microcrystal electron diffraction (MicroED) for direct structure elucidation of lead compounds from partially purified mixtures. Using this strategy to screen geographically and phylogenetically diverse microbial metabolites against pseudomyxoma peritonei, a rare and severe cancer, we discovered a new class of leads, aspercyclicins. The aspercyclicins feature an unprecedented tightly packed polycyclic polyketide scaffold that comprises continuous fused, bridged, and spiro rings. The biogenesis of aspercyclicins involves two distinct biosynthetic pathways, leading to formation of chimeric compounds that cannot be predicted by bottom-up approaches mining natural product biosynthetic genes. With comparable potency to some clinically used anticancer drugs, aspercyclicins are active against multiple cancer cell types by inducing immunogenic cell death (ICD), including the release of damage-associated molecular patterns and subsequent phagocytosis of cancer cells. The broad-spectrum ICD-inducing activity of aspercyclicins, combined with their low toxicity to normal cells, represents a new class of potential cancer immunogenic chemotherapeutics and, particularly, the first drug lead for pseudomyxoma peritonei treatment.PMID:39731542 | DOI:10.1021/jacs.4c09582

Virulence. 2025 Dec;16(1):2440541. doi: 10.1080/21505594.2024.2440541. Epub 2024 Dec 28.ABSTRACTAmino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, n = 42; severe, n = 43) and healthy controls (n = 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several amino acids were significantly different between the three groups. Pathway analysis revealed that arginine, proline, and tryptophan metabolism are implicated in the pathogenesis of HFMD. A similar arginine depletion was observed in the brain tissues of CVA6-infected mice. Importantly, L-arginine supplementation improved the survival rate of CVA6-infected mice, inhibited virus multiplication, and reduced pathological autophagy associated with mTOR-autophagy pathway in the brain. Collectively, arginine, as the hub amino acid metabolite of the mammalian target of rapamycin (mTOR) signaling pathway affecting autophagy, plays an important role in the pathogenesis of severe HFMD. L-arginine supplementation may serve as a potential therapeutic option for critical patients with HFMD.PMID:39731500 | DOI:10.1080/21505594.2024.2440541

J Orthop Res. 2024 Dec 27. doi: 10.1002/jor.26030. Online ahead of print.ABSTRACTExercise influences clinical Achilles tendon health in humans, but animal models of exercise-related Achilles tendon changes are lacking. Moreover, previous investigations of the effects of treadmill running exercise on rat Achilles tendon demonstrate variable outcomes. Our objective was to assess the functional, structural, cellular, and biomechanical impacts of treadmill running exercise on rat Achilles tendon with sensitive in and ex vivo approaches. Three running levels were assessed over the course of 8 weeks: control (cage activity), moderate-speed (treadmill running at 10 m/min, no incline), and high-speed (treadmill running at 20 m/min, 10° incline). We hypothesized that moderate-speed treadmill running would beneficially impact tendon biomechanics through increased tenocyte cellularity, metabolism, and anabolism whereas high-speed treadmill running would cause a tendinopathic phenotype with compromised tendon biomechanics due to pathologic tenocyte differentiation, metabolism, and catabolism. Contrary to our hypothesis, treadmill running exercise at these speeds had a nominal effect on the rat Achilles tendon. Treadmill running modestly influenced tenocyte metabolism and nuclear aspect ratio as well as viscoelastic tendon properties but did not cause a tendinopathic phenotype. These findings highlight the need for improved models of exercise- and loading-related tendon changes that can be leveraged to develop strategies for tendinopathy prevention and treatment.PMID:39731286 | DOI:10.1002/jor.26030

Virol J. 2024 Dec 27;21(1):336. doi: 10.1186/s12985-024-02603-8.ABSTRACTBACKGROUND: Canine adipose-derived mesenchymal stem cells (cAD-MSCs) demonstrate promising tissue repair and regeneration capabilities. However, the procurement and preservation of these cells or their secreted factors for therapeutic applications pose a risk of viral contamination, and the consequences for cAD-MSCs remain unexplored. Consequently, this research sought to assess the impact of canid alphaherpesvirus 1 (CHV) on the functional attributes of cAD-MSCs, including gene expression profiles and secretome composition.METHODS: To this end, abdominal adipose tissue from 12 healthy dogs was harvested to isolate cAD-MSCs. These samples were tested for CHV contamination before introducing a wild-type CHV strain via serial passages. Following CHV infection, real-time reverse transcription-polymerase chain reaction array and liquid chromatography with tandem mass spectrometry assessments enabled analyses of gene expression and secretome's proteomic profile, respectively.RESULTS: This study showed that the initial cAD-MSC populations were devoid of CHV. cAD-MSCs showed susceptibility to infection with wild-type CHV, leading to notable modifications in gene expression and secretome profile. The observed genomic variations in gene expression indicate potential impacts on the stemness, migration, and other functional properties of cAD-MSCs, highlighting the need for further studies to evaluate their functional capacity post-infection. Moreover, gene expression and secretome analyses suggest a shift in stem cell differentiation toward an adipogenic phenotype.CONCLUSION: To the best of our knowledge, this is the first study of the effects of virus infection on gene expression and secretome composition in cAD-MSCs. The outcomes of our study underscore the imperative of routine viral screening prior to the therapeutic use of cAD-MSCs. Moreover, these findings provide novel insights into the pathogenic mechanisms of CHV and pave the way for future canine stem cell and virus research.PMID:39731173 | DOI:10.1186/s12985-024-02603-8

Microbiome. 2024 Dec 28;12(1):274. doi: 10.1186/s40168-024-01987-7.ABSTRACTBACKGROUND: Studies have reported clinical heterogeneity between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). However, none of these studies used multi-omics analysis combining genetic regulation, microbiota, and metabolites to explain the site-specific difference.METHODS: Here, 494 participants from a 16S rRNA gene sequencing cohort (50 RCC, 114 LCC, and 100 healthy controls) and a multi-omics cohort (63 RCC, 79 LCC, and 88 healthy controls) were analyzed. 16S rRNA gene, metagenomic sequencing, and metabolomics analyses of fecal samples were evaluated to identify tumor location-related bacteria and metabolites. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) were conducted to obtain the mutation burden and genomic expression pattern.RESULTS: We found unique profiles of the intestinal microbiome, metabolome, and host genome between RCC and LCC. The bacteria Flavonifractor plautii (Fp) and Fusobacterium nucleatum, the metabolites L-phenylalanine, and the host genes PHLDA1 and WBP1 were the key omics features of RCC; whereas the bacteria Bacteroides sp. A1C1 (B.A1C1) and Parvimonas micra, the metabolites L-citrulline and D-ornithine, and the host genes TCF25 and HLA-DRB5 were considered the dominant omics features in LCC. Multi-omics correlation analysis indicated that RCC-enriched Fp was related to the accumulation of the metabolite L-phenylalanine and the suppressed WBP1 signal in RCC patients. In addition, LCC-enriched B.A1C1 was associated with the accumulation of the metabolites D-ornithine and L-citrulline as well as activation of the genes TCF25, HLA-DRB5, and AC079354.1.CONCLUSION: Our findings identify previously unknown links between intestinal microbiota alterations, metabolites, and host genomics in RCC vs. LCC, suggesting that it may be possible to treat colorectal cancer (CRC) by targeting the gut microbiota-host interaction. Video Abstract.PMID:39731152 | DOI:10.1186/s40168-024-01987-7

Microb Cell Fact. 2024 Dec 27;23(1):347. doi: 10.1186/s12934-024-02605-9.ABSTRACT17β-estradiol (E2) is an endocrine disruptor, and even trace concentrations (ng/L) of environmental estrogen can interfere with the endocrine system of organisms. Lignin holds promise in enhancing the microbial degradation E2. However, the mechanisms by which lignin facilitates this process remain unclear, which is crucial for understanding complex environmental biodegradation in nature. In this study, we conducted a comprehensive analysis using cellular and lipidomics approaches to investigate the relationship between E2-degrading strain, Rhodococcus sp. RCBS9, and lignin. Our findings demonstrate that lignin significantly enhances E2 degradation efficiency, reaching 94.28% within 5 days with the addition of 0.25 mM lignin. This enhancement is associated with increased microbial growth and activity, reduced of membrane damages, and alleviation of oxidative stress. Fourier Transform Infrared Spectroscopy (FTIR) results indicate that lignin addition alters lipid peaks. Consequently, by analyzing lipid metabolism changes, we further elucidate how lignin addition promotes E2 degradation.PMID:39731085 | DOI:10.1186/s12934-024-02605-9

BMC Microbiol. 2024 Dec 27;24(1):541. doi: 10.1186/s12866-024-03688-5.ABSTRACTBACKGROUND: Smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). This study aimed to investigate the effects of smoking on the pancreatic microbiome and metabolome in resectable and unresectable male PDAC patients.METHODS: The pancreatic tissue samples were collected from resectable PDACs via surgery and unresectable PDACs via endoscopic ultrasound fine needle aspiration (EUS-FNA). Surgical samples obtained from 10 smoking and 6 non-smoking PDACs were measured by 16S ribosomal RNA (16S rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC/MS). Fine needle aspiration (FNA) samples obtained from 20 smoking and 14 non-smoking PDACs were measured by 16S rRNA gene sequencing.RESULTS: From resectable to unresectable patients, the dominant genus in the pancreas changed from Achromobacter to Delftia. Smoking further altered the abundance of specific bacteria, mainly manifested as an increase of Slackia in surgical tumor tissue of the smoking group, and an enrichment of Aggregatibacter and Peptococcus in FNA samples of the smoking group. In tumor tissue, smoking caused an enrichment of the cancer-promoting cAMP signaling pathway and L-lactic acid. In paracancerous tissue, smoking also induced a detrimental disturbance in the pancreatic microbiome and metabolome, including an enrichment of Veillonella, Novosphingobium, Deinococcus, and 3-hydroxybutanoic acid, and a reduction of linoleic acid. Besides, the cancer-promoting L-lactic acid was negatively correlated with Faecalibacterium in tumor tissue based on the correlation analysis.CONCLUSION: There were differences in the pancreatic microbiome of PDAC patients at different stages, and smoking can further disrupt the pancreatic microbiome and metabolism in PDAC.PMID:39731043 | DOI:10.1186/s12866-024-03688-5

BMC Plant Biol. 2024 Dec 28;24(1):1269. doi: 10.1186/s12870-024-05999-1.ABSTRACTBACKGROUND: Yellow nutsedge (Cyperus esculentus, known as 'YouShaDou' in China, YSD) and purple nutsedge (Cyperus rotundus, known as 'XiangFuZi' in China, XFZ), closely related Cyperaceae species, exhibit significant differences in triacylglycerol (TAG) accumulation within their tubers, a key factor in carbon flux repartitioning that highly impact the total lipid, carbohydrate and protein metabolisms. Previous studies have attempted to elucidate the carbon anabolic discrepancies between these two species, however, a lack of comprehensive genome-wide annotation has hindered a detailed understanding of the underlying molecular mechanisms.RESULTS: This study utilizes transcriptomic analyses, supported by a comprehensive YSD reference genome, and metabolomic profiling to uncover the mechanisms underlying the major carbon perturbations between the developing tubers of YSD and XFZ germplasms harvested in Yunnan province, China, where the plant biodiveristy is renowned worldwide and may contain more genetic variations relative to their counterparts in other places. Our findings indicate distinct expression patterns of key regulatory genes involved in TAG biosynthesis and lipid droplet formation, including transcriptional factors and structural genes such as ABI3 transcriptional factor, rate-limiting enzymes GPAT3/6/9 and DGAT2/3, and oleosin and caleosin homologs. Furthermore, our omics data suggest that these differences in gene expression are not the sole contributors to the diverse tuber compositions. Instead, complex interactions among highly regulated catalytic reactions, governing carbohydrate, protein, and species-specific metabolite metabolisms, such as starch and sucrose metabolic pathways, flavonoid and amino acids biosynthetic pathways, collectively contribute to the pronounced carbon anabolic differentiation primarily evident in TAG accumulation, as well as the starch properties in mature tubers.CONCLUSION: This study offers new metabolic insights into the high-value underground non-photosynthetic tissues of Cyperaceae species, which harbors not only high biomass productivity but also abundant nutrients as favorable food or industrial sources in the modern agriculture. The detailed omics analyses aim to deepen our understanding of the Cyperaceae species, which may potentially broaden their application values and facilitate the molecular breeding of better varieties to ameliorate the food safety problem.PMID:39731027 | DOI:10.1186/s12870-024-05999-1

BMC Plant Biol. 2024 Dec 27;24(1):1263. doi: 10.1186/s12870-024-05991-9.ABSTRACTBACKGROUND: Lavandula angustifolia Mill., a valuable aromatic plant, often encounters low temperature stress during its growth in Northeast China. Understanding the mechanisms behind its resistance to low temperatures is essential for enhancing this trait. Flavonoids play a vital role as stress-resistant compounds, significantly contributing to plants' responses to low-temperature stress. However, the molecular mechanism governing flavonoid biosynthesis in L. angustifolia under low-temperature stress is remains inadequately understood.RESULTS: In this study, the physiological indexes, metabolome, and transcriptome of L. angustifolia were studied under temperatures of 30 °C, 20 °C, 10 °C, and 0 °C. The activities of peroxidase (POD) and superoxide dismutase (SOD) were notably the highest at 0 ℃, demonstrating optimal scavenging of reactive oxygen species (ROS). Among the 1150 metabolites analyzed, 52 flavonoid differential expression metabolites (DEMs) significantly increased at 10 °C and 0 °C. Furthermore, 55 differential expression genes (DEGs) involved in the flavonoid biosynthesis pathway showed significant up-regulation as the temperature dropped from 30 °C to 0 °C, indicating their role in positively regulating flavonoid biosynthesis under low temperatures. The flavonoid biosynthetic pathway was established based on key DEGs, including LaPAL-5, LaPAL-11, LaC4H-2, LaHCT, LaC3'H-4, LaCHS, LaF3PH-3, LaCCoAOMT-2, LaCCoAOMT-3, and LaDFR. Conserved domains predicted in 10 key proteins were identified as being responsible for catalytic functions that promote flavonoid biosynthesis under low temperatures. The synergistic enhancement between flavonoid DEMs and antioxidant enzymes was found to significantly contribute to the cold resistance of L.angustifolia.CONCLUSIONS: The findings of this study provide a valuable reference for understanding the molecular regulation of L. angustifolia in response to low temperatures, laying a crucial foundation for future molecular breeding efforts aimed at developing cold-resistant varieties.PMID:39731022 | DOI:10.1186/s12870-024-05991-9

Mol Med. 2024 Dec 27;30(1):279. doi: 10.1186/s10020-024-01019-y.ABSTRACTMetabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes. Insulin, a vital peptide hormone, regulates glucose metabolism throughout the body. When cells become resistant to insulin's effects, it disrupts various molecular pathways, leading to IR. This condition is linked to a range of disorders, including obesity, diabetes, fatty liver disease, cardiovascular disease, and polycystic ovary syndrome. Atherogenic dyslipidemia is characterized by three key factors: high levels of small, low-dense lipoprotein (LDL) particles and triglycerides, alongside low levels of high-density lipoprotein (HDL), the "good" cholesterol. Such a combination is a major player in MetS, where IR is a driving force. Atherogenic dyslipidemia contributes significantly to the development of atherosclerosis, which can lead to cardiovascular disease. On top of that, genetic alteration and lifestyle factors such as diet and exercise influence the complexity and progression of MetS. To enhance our understanding and consciousness, it is essential to understand the fundamental pathogenesis of MetS. This review highlights current advancements in MetS research including the involvement of gut microbiome, epigenetic regulation, and metabolomic profiling for early detection of Mets. In addition, this review emphasized the epidemiology and fundamental pathogenesis of MetS, various risk factors, and their preventive measures. The goal of this effort is to deepen understanding of MetS and encourage further research to develop effective strategies for preventing and managing complex metabolic diseases.PMID:39731011 | DOI:10.1186/s10020-024-01019-y

Sci Rep. 2024 Dec 28;14(1):30978. doi: 10.1038/s41598-024-82047-w.ABSTRACTHigh-altitude pulmonary edema (HAPE) is a life-threatening altitude sickness afflicting certain individuals after rapid ascent to high altitude above 2500 m. In the setting of HAPE, an early diagnosis is critical and currently based on clinical evaluation. The aim of this study was to utilize the metabolomics to identify the altered metabolic patterns and potential biomarkers for HAPE. Serum samples from HAPE patients (n = 24) and healthy controls (n = 21) were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) to profile differential metabolites and explore dysregulated metabolic pathways. The correlation analysis and receiver operating characteristic (ROC) curve analysis were further performed to screen biomarkers for HAPE. A total of 119 differential metabolites between the control and HAPE groups were identified. Top dysregulated pathways included pyrimidine metabolism, citrate cycle, sulfur metabolism, phenylalanine metabolism and purine metabolism. After correlation analysis with clinical indices, 39 differential metabolites were obtained as potential biomarkers related to HAPE. Finally, 7 biomarkers, specifically S-nitroso-N-acetylcysteine, aminocaproic acid, emodin, threo-hydroxyaspartic acid, 6-hydroxynicotinic acid, 3-acetylphenol sulfate and cis-aconitic acid, were screened out through ROC analysis, which displayed high diagnostic accuracy for HAPE. Taken together, the altered serum metabolic profile is associated with the occurrence of HAPE. Diagnostic tests based on the biomarkers from metabolomics may hold promise as a strategy for early detection of HAPE.PMID:39730680 | DOI:10.1038/s41598-024-82047-w