The defense response of peach (Prunus persica) to insect attack involves changes in gene expression and metabolites. Piercing/sucking insects such as green peach aphid cause direct damage by obtaining phloem nutrients and indirect damage by spreading plant viruses. To investigate the response of peach trees to aphids, the leaf transcriptome and metabolome of two genotypes with different sensitivities to green peach aphid (GPA, Myzus persicae) were studied. The transcriptome analysis of infected peach leaves showed two different response patterns. The gene expression of aphid-susceptible peach plants infected by aphids was more similar to that of the control plants, while the gene expression of aphid-resistant peach plants infected by aphids showed strongly induced changes in gene expression compared with the response in the control plants. Furthermore, gene transcripts in defense-related pathways, including plant-pathogen interaction, MAPK signaling, and several metabolic pathways, were more strongly enriched upon aphid infestation. Untargeted secondary metabolite profiling confirmed that aphid treatment induced larger changes in aphid-resistant peaches than in aphid-susceptible peaches. Consistent with transcriptomic alterations, nine triterpenoids showed extremely significant GPA-induced accumulation in aphid-resistant peaches, whereas triterpenoid abundance remained predominantly unchanged or undetected in aphid- susceptible peaches. Furthermore, some types of transcription factors (including WRKYs, ERFs, NACs, etc.) were more strongly induced upon GPA infestation in aphid-resistant peaches but not in aphid-susceptible peaches. Aphid feeding-dependent transcriptome and metabolite profiles provide the foundation for understanding the molecular mechanisms underlying the response of peach to aphid infestation. These results suggested that accumulation of specialized triterpenoids and the corresponding pathway transcripts may play a key role in peach GPA resistance.

White pepper, used both as a seasoning in people\'s daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.

Social wasps exhibit a unique nutritional cycle in which adults feed larvae with prey, and larvae provide adults with larval secretions (LS). LS serves as a vital nutritional source for adults, contributing to the colony\'s health and reproductive success. The LS nutrient composition has been previously reported in various wasp species, yet these analyses focused solely on worker-destined larvae, overlooking the potential caste designation effects on LS composition. Using metabolomics techniques, we analysed and compared the metabolite and nutrient composition in LS of queen- and worker-destined larvae of the Oriental hornet. We found that queen-destined LS (QLS) contain greater amounts of most metabolites, including amino acids, and smaller amounts of sugars compared to worker-destined LS (WLS). The amino acid-to-sugar ratio in QLS was approximately tenfold higher than in WLS. Thus, as the colony transitions from the production of workers to the production of reproductives, it gradually experiences a nutritional shift that may influence the behaviour and physiology of the adult nest population. This caste-specific metabolite profile and nutrient composition of LS reflect the differences in the diet and physiological requirements of worker- and queen-destined larvae and may play a critical role in caste determination in social wasps.

In China and Southeast Asia, pre-fermented coconut water is commonly used for the production of nata de coco, a jelly-like fermented food that consists of bacterial cellulose (BC). The inherent natural fermentation process of coconut water introduces uncontrollable variables, which can lead to unstable yields during BC production. This study involved the collection of spontaneously pre-fermented coconut water over a five-month production cycle. The aim was to evaluate the microbiota and metabolite profile, as well as determine its impact on BC synthesis by Komagataeibacter nataicola. Significant variations in the microbial community structure and metabolite profile of pre-fermented coconut water were observed across different production months, these variations had significant effects on BC synthesis by K. nataicola. A total of 52 different bacterial genera and 32 different fungal genera were identified as potential biotic factors that can influence BC production. Additionally, several abiotic factors, including lactate (VIP = 4.92), mannitol (VIP = 4.22), ethanol (VIP = 2.67), and ascorbate (VIP = 1.61), were found to be potential driving forces affecting BC synthesis by K. nataicola. Upon further analysis, the correlation network indicated that 14 biotic factors had a significant contribution to BC production in three strains of K. nataicola. These factors included 8 bacterial genera, such as Limosilactobacillus and Lactiplantibacillus, and 6 fungal genera, such as Meyerozyma and Ogataea. The abiotic factors lactate, mannitol, and ethanol showed a positive correlation with the BC yield. This study provides significant insights into controlling the fermentation processes of pre-fermented coconut water in industrial settings.

Du-Zhi pill (DZP) is widely used as a Chinese medicine in treating cerebral ischemia. UHPLC-Q-TOF-MS/MS techniques were used to detect and identify the metabolites in rat brain samples of normal and middle cerebral artery occlusion (MCAO) model rats administered with DZP. It was tentatively found that 43 prototypes and 93 metabolites could be identified in rat brain samples. Normal and MCAO model rat brain samples contained 19 prototype components. Eight prototype components were only detected in normal rat brain samples, while 16 were found only in MCAO model rat brain samples. It was determined that 47 metabolites had been identified in the normal rats, while 86 had been placed in MCAO model rats. There were 40 common metabolites in both normal and MCAO model rat brain samples. Seven metabolites were only detected in normal rat brain samples, while 46 were found only in MCAO rat brain samples. The comparison of metabolites in brain samples of normal and MCAO rats showed apparent differences. It was discovered that glucuronidation, methylation, acetylation, and sulfation are phase II metabolic routes of DZP, while hydrogenation, hydroxylation, and dehydroxylation are phase I metabolic routes. Moreover, hydrogenation, glucuronidation, hydroxylation, and methylation were the main metabolic pathways because of the number of metabolites identified in these metabolic pathways. The results provide a valuable reference for further research into effective substances of DZP for treating cerebral ischemia.

Pritelivir is a helicase-primase inhibitor active against HSV. Two human mass balance trials (a multiple-dose trial and a single-dose trial) were performed to characterize the absorption, distribution, metabolism, and excretion of 100 mg oral pritelivir combined with a single microdose of 14C-pritelivir. Blood, urine, and feces samples were collected up to 26 days postdose. The plasma half-life of pritelivir was 63-67 hours. Overall, 92% and 66% of the administered dose was recovered in the multiple and single dose trials, respectively. The low recovery after the single dose (66%) was most likely related to the formulation used. The major metabolic pathway was amide hydrolysis leading to amino thiazole sulfonamide (ATS) and pyridinyl phenyl acetic acid (PPA). In plasma, pritelivir, ATS, PPA, and PPA-acyl glucuronide accounted for 40.6%, 9.4%, 5.1%, and 0.2% of total radioactivity. More than 90% of drug-related material was eliminated 624 hours postdose. The majority was excreted in urine (75% and 77%), followed by feces (16% and 23%). The main components in urine were PPA-acyl glucuronide (and its isomers), ATS, and its N-demethylated isomers. Only minor metabolites were observed in feces. In conclusion, the major metabolic pathways of pritelivir have been identified with the primary excretion route being renal.

Saliva, which contains molecular information that may reflect an individual\'s health status, has become a valuable tool for discovering biomarkers of oral and general diseases. Due to the high vascularization of the salivary glands, there is a molecular exchange between blood and saliva. However, the composition of saliva is complex and influenced by multiple factors. This study aimed to investigate the possible relationships between the salivary and serum metabolomes to gain a comprehensive view of the metabolic phenotype under physiological conditions. Using 1H-NMR spectroscopy, we obtained the serum metabolite profiles of 20 healthy young individuals and compared them with the metabolomes of parotid, submandibular/sublingual, and whole-saliva samples collected concurrently from the same individuals using multivariate and univariate statistical analysis. Our results show that serum is more concentrated and less variable for most of the shared metabolites than the three saliva types. While we found moderate to strong correlations between serum and saliva concentrations of specific metabolites, saliva is not simply an ultrafiltrate of blood. The intense oral metabolism prevents very strong correlations between serum and salivary concentrations. This study contributes to a better understanding of salivary metabolic composition, which is crucial for utilizing saliva in laboratory diagnostics.

The successful choice of hit compounds during drug development programs involves the integration of structure-activity relationship (SAR) studies with pharmacokinetic determinations, including metabolic stability assays and metabolite profiling. A panel of nine ruthenium-cyclopentadienyl (RuCp) compounds with the general formula [Ru(η5-C5H4R)(PPh3)(bipyR\')]+ (with R = H, CHO, CH2OH; R\' = H, CH3, CH2OH, CH2Biotin) has been tested against hormone-dependent MCF-7 and triple negative MDA-MB-231 breast cancer cells. In general, all compounds showed important cytotoxicity against both cancer cell lines and were able to inhibit the formation of MDA-MB-231 colonies in a dose-dependent manner, while showing selectivity for cancer cells over normal fibroblasts. Among them, four compounds stood out as lead structures to be further studied. Cell distribution assays revealed their preference for the accumulation at cell membrane (Ru quantification by ICP-MS) and the mechanism of cell death seemed to be mediated by apoptosis. Potential structural liabilities of lead compounds were subsequently flagged upon in vitro metabolic stability assays and metabolite profiling. The implementation of this integrated strategy led to the selection of RT151 as a promising hit compound.

Plant and soil biodiversity can have significant effects on herbivore resistance mediated by plant metabolites. Here, we disentangled the independent effects of plant diversity and soil legacy on constitutive and herbivore-induced plant metabolomes of three plant species in two complementary microcosm experiments. First, we grew plants in sterile soil with three different plant diversity levels. Second, single plant species were grown on soil with different plant diversity-induced soil legacies. We infested a subset of all plants with Spodoptera exigua larvae, a generalist leaf-chewing herbivore, and assessed foliar and root metabolomes. Neither plant diversity nor soil legacy had significant effects on overall foliar, root, or herbivore-induced metabolome composition. Herbivore-induced metabolomes, however, differed from those of control plants. We detected 139 significantly regulated metabolites by comparing plants grown in monocultures with conspecifics growing in plant or soil legacy mixtures. Moreover, plant-plant and plant-soil interactions regulated 141 metabolites in herbivore-induced plants. Taken together, plant diversity and soil legacy independently alter the concentration and induction of plant metabolites, thus affecting the plant\'s defensive capability. This is a first step toward disentangling plant and soil biodiversity effects on herbivore resistance, thereby improving our understanding of the mechanisms that govern ecosystem functioning.