PubMed

Int J Mol Sci. 2023 Aug 9;24(16):12613. doi: 10.3390/ijms241612613.ABSTRACTOur understanding of the molecular mechanisms underlying cancer development and evolution have evolved rapidly over recent years, and the variation from one patient to another is now widely recognized. Consequently, one-size-fits-all approaches to the treatment of cancer have been superseded by precision medicines that target specific disease characteristics, promising maximum clinical efficacy, minimal safety concerns, and reduced economic burden. While precision oncology has been very successful in the treatment of some tumors with specific characteristics, a large number of patients do not yet have access to precision medicines for their disease. The success of next-generation precision oncology depends on the discovery of new actionable disease characteristics, rapid, accurate, and comprehensive diagnosis of complex phenotypes within each patient, novel clinical trial designs with improved response rates, and worldwide access to novel targeted anticancer therapies for all patients. This review outlines some of the current technological trends, and highlights some of the complex multidisciplinary efforts that are underway to ensure that many more patients with cancer will be able to benefit from precision oncology in the near future.PMID:37628794 | DOI:10.3390/ijms241612613

Foods. 2023 Aug 20;12(16):3126. doi: 10.3390/foods12163126.ABSTRACTHoneysuckle (the dried flower bud or opening flower of Lonicera japonica Thunb.), a medicinal and edible substance, has is greatly popular among consumers for its remarkable health effects, such as antioxidant, antibacterial, and anti-inflammatory effects. However, due to the influences of processing methods, storage conditions, and other factors, honeysuckles show different colors which can directly reflect the quality and the price on the market. In order to comprehensively compare the quality of different colors, 55 batches of honeysuckle samples were collected and analyzed. Their color parameters, chlorophyll content (chl), total phenol content (TPC), total flavonoid content (TFC), antioxidant activity (AA), main active compounds, and metabolites were measured. As a result, the initial green-white (GW) samples, a kind of highest-quality honeysuckle, had the smallest a* value, largest h*, chl, TPC, TFC, and AA values, and highest content of chlorogenic acid and cynaroside. There was a significant difference between GW samples and a series of discolored samples. As the color darkened or lightened, the quality gradually decreased. The yellow-brown (YB) samples were of the worst quality and were no longer available for clinical and health purposes. A series of differential metabolites, such as quercetin-7-O-glucoside and secologanoside, could be used as important references to evaluate the quality of differently colored samples. The metabolic profile of honeysuckle provided new insights into the process of color change and laid a foundation for further honeysuckle quality control. The correlation results showed that the a* and h* values significantly affect the abovementioned quality indicators and the 10 main active compounds. In other words, the color difference could directly reflect the quality and clinical efficacy. Multiple regression analysis was carried out using combined L*, a*, and b* values to predict the quality of honeysuckle. This is the first time the quality of different color honeysuckle samples on the post-harvest link has been systematically compared and a demonstration of medicinal and edible substances with different colors has been provided.PMID:37628125 | DOI:10.3390/foods12163126

Foods. 2023 Aug 17;12(16):3087. doi: 10.3390/foods12163087.ABSTRACTThe storage process of Baijiu is an integral part of its production (the quality undergoes substantial changes during the aging process of Baijiu). As the storage time extends, the flavor compounds in Baijiu tend to undergo coordinated transformation, thereby enhancing the quality of Baijiu. Among them, long-chain fatty acid ethyl esters (LCFAEEs) were widely distributed in Baijiu and have been shown to have potential contributions to the quality of Baijiu. However, the current research on LCFAEEs in Baijiu predominantly focuses on the olfactory sensation aspect, while there is a lack of systematic investigation into their influence on taste and evaluation after drinking Baijiu during the aging process. In light of this, the present study investigates the distribution of LCFAEEs in Baijiu over different years. We have combined modern flavor sensory analysis with multivariate chemometrics to comprehensively and objectively explore the influence of LCFAEEs on Baijiu quality. The results demonstrate a significant positive correlation between the concentration of LCFAEEs and the fruity aroma (p < 0.05, r = 0.755) as well as the aged aroma (p < 0.05, r = 0.833) of Baijiu within a specific range; they can effectively reduce the off-flavors and spicy sensation of Baijiu. Furthermore, additional experiments utilizing a single variable suggest that LCFAEEs were crucial factors influencing the flavor of Baijiu, with Ethyl Palmitate (EP) being the most notable LCFAEE that merits further systematic investigation.PMID:37628086 | DOI:10.3390/foods12163087

Foods. 2023 Aug 17;12(16):3082. doi: 10.3390/foods12163082.ABSTRACTGrafting has a significant impact on the botany properties, commercial character, disease resistance, and productivity of eggplants. However, the mechanism of phenotypic modulation on grafted eggplants is rarely reported. In this study, a widely cultivated eggplant (Solanum. melongena cv. 'Zheqie No.10') was selected as the scion and grafted, respectively, onto four rootstocks of TOR (S. torvum), Sa (S. aculeatissimum), SS (S. sisymbriifolium), and Sm64R (S. melongena cv. 'Qiezhen No. 64R') for phenotypic screening. Physiological and biochemical analysis showed the rootstock Sm64R could improve the fruit quality with the increasing of fruit size, yield, and the contents of total soluble solid, phenolic acid, total amino acid, total sugar, and vitamin C. To further investigate the improvement of fruit quality on Sm64R, a transcriptome and a metabolome between the Sm64R-grafted eggplant and self-grafted eggplant were performed. Significant differences in metabolites, such as phenolic acids, lipids, nucleotides and derivatives, alkaloids, terpenoids, and amino acids, were observed. Differential metabolites and differentially expressed genes were found to be abundant in three core pathways of nutritional qualities, including biosynthesis of phenylpropanoids, phospholipids, and nucleotide metabolism. Thus, this study may provide a novel insight into the effects of grafting on the fruit quality in eggplant.PMID:37628081 | DOI:10.3390/foods12163082

Foods. 2023 Aug 8;12(16):2985. doi: 10.3390/foods12162985.ABSTRACTMushrooms contain multiple essential nutrients and health-promoting bioactive compounds, including the amino acid L-ergothioneine. Knowledge of the chemical composition of different mushroom varieties will aid research on their health-promoting properties. We compared the metabolomes of fresh raw white button, crimini, portabella, lion's mane, maitake, oyster, and shiitake mushrooms using untargeted liquid chromatography mass spectrometry (LC/MS)-based metabolomics. We also quantified amino acid concentrations, including L-ergothioneine, a potential antioxidant which is not synthesized by plants or animals. Among the seven mushroom varieties, more than 10,000 compounds were detected. Principal Component Analysis indicated mushrooms of the same species, Agaricus Bisporus (white button, portabella, crimini), group similarly. The other varieties formed individual, distinct clusters. A total of 1344 (520 annotated) compounds were detected in all seven mushroom varieties. Each variety had tens-to-hundreds of unique-to-mushroom-variety compounds. These ranged from 29 for crimini to 854 for lion's mane. All three Agaricus bisporus varieties had similar amino acid profiles (including detection of all nine essential amino acids), while other varieties had less methionine and tryptophan. Lion's mane and oyster mushrooms had the highest concentrations of L-ergothioneine. The detection of hundreds of unique-to-mushroom-variety compounds emphasizes the differences in chemical composition of these varieties of edible fungi.PMID:37627983 | DOI:10.3390/foods12162985

Bioengineering (Basel). 2023 Aug 17;10(8):972. doi: 10.3390/bioengineering10080972.ABSTRACTAbdominal computed tomography (CT) is a frequently used imaging modality for evaluating gastrointestinal diseases. The detection of colorectal cancer is often realized using CT before a more invasive colonoscopy. When a CT exam is performed for indications other than colorectal evaluation, the tortuous structure of the long, tubular colon makes it difficult to analyze the colon carefully and thoroughly. In addition, the sensitivity of CT in detecting colorectal cancer is greatly dependent on the size of the tumor. Missed incidental colon cancers using CT are an emerging problem for clinicians and radiologists; consequently, the automatic localization of lesions in the CT images of unprepared bowels is needed. Therefore, this study used artificial intelligence (AI) to localize colorectal cancer in CT images. We enrolled 190 colorectal cancer patients to obtain 1558 tumor slices annotated by radiologists and colorectal surgeons. The tumor sites were double-confirmed via colonoscopy or other related examinations, including physical examination or image study, and the final tumor sites were obtained from the operation records if available. The localization and training models used were RetinaNet, YOLOv3, and YOLOv8. We achieved an F1 score of 0.97 (±0.002), a mAP of 0.984 when performing slice-wise testing, 0.83 (±0.29) sensitivity, 0.97 (±0.01) specificity, and 0.96 (±0.01) accuracy when performing patient-wise testing using our derived model YOLOv8 with hyperparameter tuning.PMID:37627857 | DOI:10.3390/bioengineering10080972

Bioengineering (Basel). 2023 Aug 7;10(8):936. doi: 10.3390/bioengineering10080936.ABSTRACTPentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAAs); however, the molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines, and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAAs. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAAs is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAAs.PMID:37627822 | DOI:10.3390/bioengineering10080936

Antibiotics (Basel). 2023 Jul 29;12(8):1250. doi: 10.3390/antibiotics12081250.ABSTRACTAntibiotics are a staple in current medicine for the therapy of infectious diseases. However, their extensive use and misuse, combined with the high adaptability of bacteria, has dangerously increased the incidence of multi-drug-resistant (MDR) bacteria. This makes the treatment of infections challenging, especially when MDR bacteria form biofilms. The most recent antibiotics entering the market have very similar modes of action to the existing ones, so bacteria rapidly catch up to those as well. As such, it is very important to adopt effective measures to avoid the development of antibiotic resistance by pathogenic bacteria, but also to perform bioprospecting of new molecules from diverse sources to expand the arsenal of drugs that are available to fight these infectious bacteria. Filamentous fungi have a large and vastly unexplored secondary metabolome and are rich in bioactive molecules that can be potential novel antimicrobial drugs. Their production can be challenging, as the associated biosynthetic pathways may not be active under standard culture conditions. New techniques involving metabolic and genetic engineering can help boost antibiotic production. This study aims to review the bioprospection of fungi to produce new drugs to face the growing problem of MDR bacteria and biofilm-associated infections.PMID:37627670 | DOI:10.3390/antibiotics12081250

Antioxidants (Basel). 2023 Aug 18;12(8):1631. doi: 10.3390/antiox12081631.ABSTRACTThe benefits of resistant starch on hypoglycemia, obesity prevention, antioxidant status and the alleviation of metabolic syndrome have received considerable attention. In this study, we explored how dietary kelp resistant starch (KRS) enhances intestinal morphology and function through a microbiome-metabolomic analysis. Hybrid snakeheads (initial weight: 11.4 ± 0.15 g) were fed experimental diets for 60 days. Fish were fed a basic wheat starch diet and the KRS diet. Dietary KRS improved intestinal morphology and enhanced intestinal antioxidant and digestive capabilities, as evidenced by decreased intestinal damage and upregulated intestinal biochemical markers. The microbiome analysis showed that KRS administration elevated the proportion of butyrate-producing bacteria and the abundance of beneficial bacteria that increases insulin sensitivity. Furthermore, significant alterations in metabolic profiles were observed to mainly associate with the amino acid metabolism (particularly arginine production), the metabolism of cofactors and vitamins, fat metabolism, glutathione metabolism, and the biosynthesis of other secondary metabolites. Additionally, alterations in intestinal microbiota composition were significantly associated with metabolites. Collectively, changes in intestinal microbiota and metabolite profiles produced by the replacement of common starch with dietary KRS appears to play an important role in the development of intestinal metabolism, thus leading to improved intestinal function and homeostasis.PMID:37627626 | DOI:10.3390/antiox12081631

Antioxidants (Basel). 2023 Aug 15;12(8):1615. doi: 10.3390/antiox12081615.ABSTRACTThe appropriate level of dietary lipids is essential for the nutrient requirements, rapid growth, and health maintenance of aquatic animals, while excessive dietary lipid intake will lead to lipid deposition and affect fish health. However, the symptoms of excessive lipid deposition in the liver of freshwater drums (Aplodinotus grunniens) remain unclear. In this study, a 4-month rearing experiment feeding with high-fat diets and a 6-week starvation stress experiment were conducted to evaluate the physiological alteration and underlying mechanism associated with lipid deposition in the liver of A. grunniens. From the results, high-fat-diet-induced lipid deposition was associated with increased condition factor (CF), viscerosomatic index (VSI), and hepatosomatic index (HSI). Meanwhile, lipid deposition led to physiological and metabolic disorders, inhibited antioxidant capacity, and exacerbated the burden of lipid metabolism. Lipid deposition promoted fatty acid synthesis but suppressed catabolism. Specifically, the transcriptome and metabolome showed significant enrichment of lipid metabolism and antioxidant pathways. In addition, the interaction analysis suggested that peroxisome proliferator-activated receptor (PPAR)-mediated 13-S-hydroxyoctadecenoic acid (13 (s)-HODE) could serve as the key target in regulating lipid metabolism and oxidative stress during lipid deposition in A. grunniens. Inversely, with a lipid intake restriction experiment, PPARs were confirmed to regulate lipid expenditure and physiological homeostasis in A. grunniens. These results uncover the molecular basis of and provide specific molecular targets for fatty liver control and prevention, which are of great importance for the sustainable development of A. grunniens.PMID:37627610 | DOI:10.3390/antiox12081615

Antioxidants (Basel). 2023 Aug 1;12(8):1542. doi: 10.3390/antiox12081542.ABSTRACTCurrently, the interest of consumers towards functional foods as source of bioactive compounds is increasing. The sprouts of Raphanus sativus var longipinnatus (Brassicaceae) are "microgreens" popular, especially in gourmet cuisine, for their appealing aspect and piquant flavour. They represent a functional food due to their high nutritional value and health-promoting effects. Herein, the sprouts of daikon were extracted by different solvent mixtures to highlight how this process can affect the chemical profile and the antioxidant activity. An in-depth investigation based on a preliminary LC-ESI/LTQOrbitrap/MS profiling was carried out, leading to the identification of nineteen compounds, including glucosinolates and hydroxycinnamic acid derivatives. An undescribed compound, 1-O-feruloyl-2-O-sinapoyl-β-D-glucopyranoside, was isolated, and its structure was elucidated by NMR spectroscopy. The phenolic content and radical scavenging activity (DPPH and TEAC assays), along with the ability to activate Nrf2 (Nrf2-mediated luciferase reporter gene assay) of polar extracts, were evaluated. The results showed the highest antioxidant activity for the 70% EtOH/H2O extract with a TEAC value of 1.95 mM and IC50 = 93.97 µg/mL in the DPPH assay. Some 50% and 70% EtOH/H2O extracts showed a pronounced concentration-dependent induction of Nrf2 activity. The extracts of daikon sprouts were submitted to 1H NMR experiments and then analyzed by untargeted and targeted approaches of multivariate data analysis to highlight differences related to extraction solvents.PMID:37627537 | DOI:10.3390/antiox12081542

Antioxidants (Basel). 2023 Jul 27;12(8):1505. doi: 10.3390/antiox12081505.ABSTRACTTo assess the effects of microbial fermentation on Gynostemma pentaphyllum leaves (GPL), four probiotics were used to ferment GPL (FGPL) for 7 days. At different stages of fermentation, changes in the active components and biological activities of FGPL were determined. The findings suggest that short-term fermentation with probiotics can enhance both the content and bioactivity of active components in GPL. However, prolonged fermentation may lead to a decline in these aspects. Among them, the best effect was observed with SWFU D16 fermentation for 2 days. This significantly improved the total phenolic and total flavonoid content, antioxidant capacity, and inhibitory ability against α-glucosidase activity with an increase of 28%, 114.82%, 7.42%, and 31.8%, respectively. The high-performance liquid chromatography (HPLC) analysis results also supported this trend. Untargeted metabolomics analysis revealed metabolite changes between GPL and FGPL and the key metabolites associated with these functional activities. These key metabolites are mainly organic acids, flavonoids, carbohydrates, terpenoids, and other substances. KEGG analysis demonstrated that microbial metabolism in diverse environments and carbon metabolism were the most significantly enriched pathways. Among them, 3-(3-hydroxyphenyl) propanoic acid, d-glucose, gallic acid, gluconic acid, l-lactic acid, and l-malic acid were mostly involved in the microbial metabolism of diverse environmental pathways. In contrast, D-glucose, gluconic acid, and l-malic acid were mainly related to the carbon metabolism pathway. This study revealed the positive effect of probiotic fermentation on GPL and its potential metabolism mechanism, which could provide supporting data for further research.PMID:37627500 | DOI:10.3390/antiox12081505

BMC Med. 2023 Aug 25;21(1):323. doi: 10.1186/s12916-023-03032-0.ABSTRACTBACKGROUND: Precocious puberty (PP) in girls is traditionally defined as the onset of breast development before the age of 8 years. The specific biomarkers of premature thelarche (PT) and central precocious puberty (CPP) girls are uncertain, and little is known about their metabolic characteristics driven by perfluorinated compounds (PFCs) and clinical phenotype. This study aimed to screen specific biomarkers of PT and CPP and elucidate their underlying pathogenesis. The relationships of clinical phenotype-serum PFCs-metabolic characteristics were also explored to reveal the relationship between PFCs and the occurrence and development of PT and CPP.METHODS: Nuclear magnetic resonance (NMR)-based cross-metabolomics strategy was performed on serum from 146 PP (including 30 CPP, 40 PT, and 76 unspecified PP) girls and 64 healthy girls (including 36 prepubertal and 28 adolescent). Specific biomarkers were screened by the uni- and multivariate statistical analyses. The relationships between serum PFCs and clinical phenotype were performed by correlation analysis and weighted gene co-expression network analysis to explore the link of clinical phenotype-PFCs-metabolic characteristics in PT and CPP.RESULTS: The disordered trend of pyruvate and butyrate metabolisms (metabolites mapped as formate, ethanol, and 3-hydroxybutyrate) were shared and kept almost consistent in PT and CPP. Eight and eleven specific biomarkers were screened for PT and CPP, respectively. The area under curve of specific biomarker combination was 0.721 in CPP vs. prepubertal, 0.972 in PT vs. prepubertal, 0.646 in CPP vs. prepubertal integrated adolescent, and 0.822 in PT vs. prepubertal integrated adolescent, respectively. Perfluoro-n-heptanoic acid and perfluoro-n-hexanoic acid were statistically different between PT and CPP. Estradiol and prolactin were significantly correlated with PFCs in CPP and PT. Clinical phenotypes and PFCs drive the metabolic characteristics and cause metabolic disturbances in CPP and PT.CONCLUSIONS: The elevation of formate, ethanol, and 3-hydroxybutyrate may serve as the early diagnostic indicator for PP in girls. But the stratification of PP still needs to be further determined based on the specific biomarkers. Specific biomarkers of CPP and PT exhibited good sensitivity and can facilitate the classification diagnosis of CPP and PT. PFC exposure is associated with endocrine homeostasis imbalance. PFC exposure and/or endocrine disturbance directly or indirectly drive metabolic changes and form overall metabolic network perturbations in CPP and PT.PMID:37626398 | DOI:10.1186/s12916-023-03032-0

Nat Chem Biol. 2023 Aug 25. doi: 10.1038/s41589-023-01424-0. Online ahead of print.NO ABSTRACTPMID:37626192 | DOI:10.1038/s41589-023-01424-0

Sci Rep. 2023 Aug 25;13(1):13921. doi: 10.1038/s41598-023-40878-z.ABSTRACTLittle is known about the association of prolonged cough, a common and troublesome symptom, with metabolic pathways. We aimed to clarify this association using data from the Nagahama cohort, a prospective study of participants from the general population. Self-report questionnaires on prolonged cough were collected at baseline and 5-year follow-up assessments. Blood tests at follow-up were used for gas chromatography-mass spectrometry-based metabolomics. The association between metabolites and prolonged cough was examined using the partial least squares discriminant analysis and multiple regression analysis. Among the 7432 participants, 632 had newly developed prolonged cough at follow-up, which was defined as "new-onset prolonged cough". Low plasma citric acid was significantly associated with new-onset prolonged cough, even after the adjustment of confounding factors including the presence of asthma, upper airway cough syndrome (UACS), and gastroesophageal reflux disease (GERD). A similar association was observed for isocitric acid, 3-hydroxybutyric acid, and 3-hydroxyisobutyric acid. The analysis of these four metabolites revealed that citric acid had the strongest association with new-onset prolonged cough. This significant association remained even when the analysis was confined to participants with UACS or GERD at baseline or follow-up, and these associations were also observed in participants (n = 976) who had prolonged cough at follow-up regardless of baseline status. In conclusion, low blood citric acid may be associated with prolonged cough.PMID:37626075 | DOI:10.1038/s41598-023-40878-z

Clin Gastroenterol Hepatol. 2023 Sep;21(10S):S1-S10. doi: 10.1016/j.cgh.2023.04.034.ABSTRACTHepatorenal syndrome is a complication of liver cirrhosis with ascites that results from the complex interplay of many pathogenetic mechanisms. Advanced cirrhosis is characterized by the development of hemodynamic changes of splanchnic and systemic arterial vasodilatation, with paradoxical renal vasoconstriction and renal hypoperfusion. Cirrhosis is also an inflammatory state. The inflammatory cascade is initiated by a portal hypertension-induced increased translocation of bacteria, bacterial products, and endotoxins from the gut to the splanchnic and then to the systemic circulation. The inflammation, whether sterile or related to infection, is responsible for renal microcirculatory dysfunction, microthrombi formation, renal tubular oxidative stress, and tubular damage. Of course, many of the bacterial products also have vasodilatory properties, potentially exaggerating the state of vasodilatation and worsening the hemodynamic instability in these patients. The presence of cardiac dysfunction, related to cirrhotic cardiomyopathy, with its associated systolic incompetence, can aggravate the mismatch between the circulatory capacitance and the circulation volume, worsening the extent of the effective arterial underfilling, with lower renal perfusion pressure, contributing to renal hypoperfusion and increasing the risk for development of acute kidney injury. The presence of tense ascites can exert an intra-abdominal compartmental syndrome effect on the renal circulation, causing renal congestion and hampering glomerular filtration. Other contributing factors to renal dysfunction include the tubular damaging effects of cholestasis and adrenal dysfunction. Future developments include the use of metabolomics to identify metabolic pathways that can lead to the development of renal dysfunction, with the potential of identifying biomarkers for early diagnosis of renal dysfunction and the development of treatment strategies.PMID:37625861 | DOI:10.1016/j.cgh.2023.04.034

Environ Pollut. 2023 Aug 23:122438. doi: 10.1016/j.envpol.2023.122438. Online ahead of print.ABSTRACTExcessive amounts of iron (Fe), zinc (Zn), and copper (Cu) can be toxic to neuronal cells, even though these are essential trace elements for animals and humans. However, the precise mechanisms underlying the neurotoxicity of exposure to mixtures of Fe, Zn, and Cu are still mostly unclear. The research aimed to investigate the influence of co-exposure to iron, zinc and copper and the related mechanisms in HT22 murine hippocampal neuronal cells. Intracellular metal content, markers of oxidative damage, and biomarkers of ferroptosis were respectively detected. Afterward, metabolomic analyses were performed to obtain a comprehensive understanding of the metal mixtures on metabolism, and the functions of key enzymes on metabolic pathways were validated. The results showed that metal co-exposure resulted in cellular iron overload and increased lipid peroxidation, accompanied by significant pathological damage and mitochondrial abnormalities in HT22 cells. Meanwhile, it was found that GSH depletion, decreased GPX4, and increased expression of the lipid metabolism gene ACSL4 play important roles in ferroptosis induced by metal mixture. Further, metabolomic analysis revealed metal co-exposure induced significant alterations in metabolite levels, especially in the glycerophospholipid metabolism pathway and the arachidonic acid metabolism pathway. The levels of cPLA2 and its metabolite, arachidonic acid, were significantly increased after metal co-exposure. Then, inhibition of cPLA2 decreased the level of arachidonic acid and attenuated ferroptosis in neuronal cells. Collectively, our findings unveiled ferroptosis induced by metal co-exposure associated with crucial molecular changes in neuronal cells, providing a novel perspective on the comprehensive toxicity risk assessment of metal mixtures.PMID:37625769 | DOI:10.1016/j.envpol.2023.122438

Environ Res. 2023 Aug 23:116974. doi: 10.1016/j.envres.2023.116974. Online ahead of print.ABSTRACTThe wide use of antibiotics in aquaculture has triggered global ecological security issue. Microalgal bioremediation is a promising strategy for antibiotics elimination due to carbon recovery, detoxification and various ecological advantages. However, a lack of understanding with respect to the corresponding regulation mechanism towards antibiotic stress may limit its practical applicability. The microalga Scenedesmus obliquus was shown to be capable of effectively eliminating ciprofloxacin (CIP), which is a common antibiotic used in aquaculture. However, the corresponding transcriptional alterations require further investigation and verification at the metabolomic level. Thus, this study uncovered the metabolomic profiles and detailed toxic and defense mechanisms towards CIP in S. obliquus using untargeted metabolomics. The enhanced oligosaccharide/polyol/lipid transport, up-regulation of carbohydrate and arachidonic acid metabolic pathways and increased energy production via EMP metabolism were observed as defense mechanisms of microalgal cells to xenobiotic CIP. The toxic metabolic responses included: (1) down-regulation of parts of mineral and organic transporters; (2) electrons competition between antibiotic and NAD during intracellular CIP degradation; and (3) suppressed expression of the hem gene in chlorophyll biosynthesis. This study describes the metabolic profile of microalgae during CIP elimination and reveals the key pathways from the perspective of metabolism, thereby providing information on the precise regulation of antibiotic bioremediation via microalgae.PMID:37625537 | DOI:10.1016/j.envres.2023.116974

J Exp Bot. 2023 Aug 25:erad338. doi: 10.1093/jxb/erad338. Online ahead of print.ABSTRACTGreen leaf volatiles (GLVs), volatile organic compounds released by plants upon tissue damage, are key signaling molecules in plant immunity. The ability of exogenous GLV application to trigger an induced resistance (IR) phenotype against arthropod pests has been widely reported, but its effectiveness against plant pathogens is less well-understood. In this study, we combined mRNA sequencing-based transcriptomics and phytohormone measurements with multispectral imaging-based precision phenotyping to gain insights into the molecular basis of Z-3-hexenyl acetate induced resistance (Z-3-HAC-IR) in rice. Furthermore, we evaluated the efficacy of Z-3-HAC-IR against a panel of economically significant rice pathogens: Pyricularia oryzae, Rhizoctonia solani, Xanthomonas oryzae pv. oryzae, Cochliobolus miyabeanus and Meloidogyne graminicola. Our data revealed rapid induction of jasmonate metabolism and systemic induction of plant immune responses upon Z-3-HAC exposure, as well as a transient allocation cost due to accelerated chlorophyll degradation and nutrient remobilization. Z-3-HAC-IR proved effective against all tested pathogens except for C. miyabeanus, including against the (hemi)biotrophs M. graminicola, X. oryzae pv. oryzae and P. oryzae. The Z-3-HAC-IR phenotype was lost in the jasmonate-deficient hebiba mutant, which confirms the causal role of JA in Z-3-HAC-IR. Together, our results show that GLV exposure in rice induces broad-spectrum, JA-mediated disease resistance with limited allocation costs, and may thus be a promising alternative crop protection approach.PMID:37624920 | DOI:10.1093/jxb/erad338

Sci Adv. 2023 Aug 25;9(34):eade8984. doi: 10.1126/sciadv.ade8984. Epub 2023 Aug 25.ABSTRACTSpecialized metabolite (SM) diversification is a core process to plants' adaptation to diverse ecological niches. Here, we implemented a computational mass spectrometry-based metabolomics approach to exploring SM diversification in tissues of 20 species covering Nicotiana phylogenetics sections. To markedly increase metabolite annotation, we created a large in silico fragmentation database, comprising >1 million structures, and scripts for connecting class prediction to consensus substructures. Together, the approach provides an unprecedented cartography of SM diversity and section-specific innovations in this genus. As a case study and in combination with nuclear magnetic resonance and mass spectrometry imaging, we explored the distribution of N-acylnornicotines, alkaloids predicted to be specific to Repandae allopolyploids, and revealed their prevalence in the genus, albeit at much lower magnitude, as well as a greater structural diversity than previously thought. Together, the data integration approaches provided here should act as a resource for future research in plant SM evolution.PMID:37624884 | DOI:10.1126/sciadv.ade8984