DataSheet_1_Cost-effectiveness analysis of amivantamab plus chemotherapy versus chemotherapy alone in NSCLC with EGFR Exon 20 insertions.docx

ObjectiveAmivantamab plus chemotherapy has been proved to be an efficient treatment strategy for non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertions. The aim of this study was to conduct the cost-effectiveness analysis of amivantamab-chemotherapy compared with chemotherapy alone in NSCLC harboring EGFR exon 20 insertion mutations.MethodsWe constructed a Markov model based on the data derived from the PAPILLON trial. We evaluated the cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were used to evaluate the influence of different parameters on this model.ResultsCompared with chemotherapy alone, amivantamab combined with chemotherapy treatment gained an incremental effectiveness of 0.473 QALYs and an incremental cost of $361,950.952, which resulted in an ICER of$765,224/QALY. The ICER was much higher than the willingness-to-pay threshold of 15,0000/QALY. One-way sensitivity analysis revealed that amivantamab cost was the leading influential factor in the model.ConclusionsCompared with chemotherapy alone, amivantamab plus chemotherapy is not a cost-effective first-line treatment choice for NSCLC patients with EGFR exon 20 insertions. The costly price of amivantamab is one of the major reasons for the high cost of this combined treatment strategy. Therefore, it is imperative to take into account the high cost of amivantamab in the subsequent clinical application and strive to attain a relative equilibrium between its significant clinical benefit and economic encumbrance.</p

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Urolithin A Produced by Novel Microbial Fermentation Possesses Anti-aging Effects by Improving Mitophagy and Reducing Reactive Oxygen Species in Caenorhabditis elegans

Urolithin, intestinal microbiota metabolites of ellagitannin-rich foods, exhibit anti-aging activities. However, urolithin A is significantly superior to other types of urolithin with regard to this anti-aging function. This study aimed to screen edible urolithin A-producing strains of bacteria and explore the corresponding anti-aging efficacy of fermented products produced by these strains using Caenorhabditis elegans as a model. Our results showed that the Lactobacillus plantarum strains CCFM1286, CCFM1290, and CCFM1291 converted ellagitannin to produce urolithin A; the corresponding yields of urolithin A from these strains were 15.90 ± 1.46, 24.70 ± 0.82, and 32.01 ± 0.97 μM, respectively. Furthermore, it was found that the pomegranate juice extracts fermented by the CCFM1286, CCFM1290, and CCFM1291 strains of L. plantarum could extend lifespan by 26.04 ± 0.12, 32.05 ± 0.14, and 46.33 ± 0.12%, respectively, by improving mitochondrial function and/or reducing reactive oxygen species levels. These findings highlight the potential application of this fermentation in the subsequent development of anti-aging products

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Table_1_Comparative Analysis of Cuticular Wax in Various Grape Cultivars During Berry Development and After Storage.XLSX

Cuticular wax covering the surface of fleshy fruit is closely related to fruit glossiness, development, and post-harvest storage quality. However, the information about formation characteristics and molecular mechanisms of cuticular wax in grape berry is limited. In this study, crystal morphology, chemical composition, and gene expression of cuticular wax in grape berry were comprehensively investigated. Morphological analysis revealed high density of irregular lamellar crystal structures, which were correlated with the glaucous appearances of grape berry. Compositional analysis showed that the dominant wax compounds were triterpenoids, while the most diverse were alkanes. The amounts of triterpenoids declined sharply after véraison, while those of other compounds maintained nearly constant throughout the berry development. The amounts of each wax compounds varied among different cultivars and showed no correlation with berry skin colors. Moreover, the expression profiles of related genes were in accordance with the accumulation of wax compounds. Further investigation revealed the contribution of cuticular wax to the water preservation capacity during storage. These findings not only facilitate a better understanding of the characteristics of cuticular wax, but also shed light on the molecular basis of wax biosynthesis in grape.</p

Data_Sheet_1_Comparative Analysis of Cuticular Wax in Various Grape Cultivars During Berry Development and After Storage.PDF

Cuticular wax covering the surface of fleshy fruit is closely related to fruit glossiness, development, and post-harvest storage quality. However, the information about formation characteristics and molecular mechanisms of cuticular wax in grape berry is limited. In this study, crystal morphology, chemical composition, and gene expression of cuticular wax in grape berry were comprehensively investigated. Morphological analysis revealed high density of irregular lamellar crystal structures, which were correlated with the glaucous appearances of grape berry. Compositional analysis showed that the dominant wax compounds were triterpenoids, while the most diverse were alkanes. The amounts of triterpenoids declined sharply after véraison, while those of other compounds maintained nearly constant throughout the berry development. The amounts of each wax compounds varied among different cultivars and showed no correlation with berry skin colors. Moreover, the expression profiles of related genes were in accordance with the accumulation of wax compounds. Further investigation revealed the contribution of cuticular wax to the water preservation capacity during storage. These findings not only facilitate a better understanding of the characteristics of cuticular wax, but also shed light on the molecular basis of wax biosynthesis in grape.</p

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products

Additional file 3 of “The PLCP gene family of grapevine (Vitis vinifera L.): characterization and differential expression in response to Plasmopara Viticola”

Additional file 3: Figure S1: Predict the conservative motif of PLCPs by online MEME website

Integrative Analyses of Metabolomes and Transcriptomes Provide Insights into Flavonoid Variation in Grape Berries

Flavonoids in grapes contribute the quality of the berry, but the flavonoid diversity and the regulatory networks underlying the variation require a further investigation. In this study, we integrated multi-omics data to systematically explore the global metabolic and transcriptional profiles in the skins and pulps of three grape cultivars. The results revealed large-scale differences involved in the flavonoid metabolic pathway. A total of 133 flavonoids, including flavone and flavone C-glycosides, were identified. Beyond the visible differences of anthocyanins, there was large variation in other sub-branched flavonoids, most of which were positively correlated with anthocyanins in grapes. The expressions of most flavonoid biosynthetic genes and the major regulators MYBA1 were strongly consistent with the changes in flavonoids. Integrative analysis identified two novel transcription factors (MYB24 and MADS5) and two ubiquitin proteins (RHA2) as promising regulatory candidates for flavonoid biosynthesis in grapes. Further verification in various grape accessions indicated that five major genes including flavonol 3′5′-hydroxylase (F3′5′H), UDP-glucose:flavonoid 3-O-glycosyl-transferase, anthocyanin O-methyltransferase, acyltransferase (3AT), and glutathione S-transferase (GST4) controlled flavonoid variation in grape berries. These findings provide valuable information for understanding the mechanism of flavonoid biosynthesis in grape berries and the further development of grape health products