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Methyl jasmonate (MJ) has potential to regulate fruit ripening and quality. 'Yoho' and 'Jiro' persimmons were sprayed with MJ (0, 2, 4, and 6 mM), four weeks before anticipated harvest to evaluate its effects on fruit colour and bioactive compounds. Preharvest MJ application significantly improved fruit colour with increased a*, b*, chroma, and colour index. The MJ 6 mM application had significantly enhanced soluble solids content (SSC), reduced total chlorophyll content in peel and pulp, and soluble and total tannins in persimmons. MJ treatments exhibited higher contents of total phenolics, flavonoids, carotenoids, and antioxidant activities. Additionally, MJ treatments enhanced the activities of shikimate dehydrogenase (SKDH), phenylalanine ammonia-lyase (PAL), catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and lipoxygenase (LOX) enzymes. Overall, pre-harvest MJ application at 6 mM four weeks before anticipated harvest could be useful for advancing colour and improving bioactive compounds in 'Yoho' and 'Jiro' persimmons., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13 C or 14 C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2-4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

High-temperature stress (HTS) affects the growth and production of vegetable crops, including eggplant (Solanum melongena L.). Jasmonic acid (JA) plays key roles in regulating resistance to biotic and abiotic stresses in plants. Nonetheless, reports on the role of JA in heat tolerance in eggplant are rare. Herein, the effects of JA on heat tolerance in eggplant and the functions of the JA biosynthetic genes SmLOX4 and SmLOX5 were analyzed. The results showed that the JA content increased under high-temperature treatment (HTT) and exogenous methyl jasmonate (MeJA) treatment reduced the damage caused by HTT to eggplant. The expression of SmLOX4 and SmLOX5 was induced by HTT and significantly positively correlated with JA biosynthesis. SmLOX4 and SmLOX5 were localized in chloroplasts. The silencing of SmLOX4 and SmLOX5 by virus-induced gene silencing suppressed the heat tolerance of eggplant, whereas the overexpression of SmLOX4 and SmLOX5 enhanced the heat tolerance of Arabidopsis thaliana. JA content and the expression of JA signaling-related genes decreased in the SmLOX4- and SmLOX5-silenced plants but increased in the OE-SmLOX4 and OE-SmLOX5 transgenic plants. These results revealed that SmLOX4 and SmLOX5 improved eggplant heat tolerance by mediating JA biosynthesis and JA signaling pathways., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

The Rhizobium rhizogene-transformed root culture from Physalis peruviana L. (P. peruviana) may be a promising and novel source of valuable phenolics, including caffeoylputrescine (CP), which is known for antioxidant, antidiabetic, insect-resistant, disease-resistant, and neuroprotective properties. In this study, to improve the production efficiency of phytochemical components in P. peruviana hairy root cultures, we optimized various culture conditions, including the inoculum size, liquid volume, culture media type, carbon source, sucrose concentration, initial pH, and application of elicitors, to enhance the total phenolic content and CP yield in these hairy root cultures. The findings indicate that the use of sucrose as carbon source resulted in the highest biomass (13.28 g DW/L), total phenolic content (6.26 mg/g), and CP yield (2.40 mg/L). The White medium excelled in enhancing the total phenolic content (9.35 mg/g), whereas the B5 medium was most effective for the biomass (13.38 g DW/L) and CP yield (6.30 mg/L). A sucrose concentration of 5% was best for the biomass (18.40 g DW/L), whereas a sucrose concentration of 4% was ideal for the CP yield. Optimal culture conditions were as follows: an inoculum size of 0.5 g/100 mL, a liquid volume of 100 mL in a 250-mL flask, B5 medium, 4% sucrose, and a pH of 5.5. Among the tested elicitors, methyl jasmonate (MeJA) at 100 µM significantly increased the biomass (21.3 g/L), total phenolic content (23.34 mg/g), and CP yield (141.10 mg/L), which represent 0.96-, 2.12-, and 13.04-fold increases, respectively, over the control after 8 days. The optimized HR culture of P. peruviana provides a promising system to enhance the production of CP for pharmaceutical applications., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Key Message: The pathogenesis-related 1 gene of watermelon responds to the infection of ZYMV and contributes to the resistance of its host. Zucchini yellow mosaic virus (ZYMV; family Potyviridae) is a single-stranded positive-sense RNA virus that is a serious threat to cucurbits. Previously, we observed a hypersensitivity response (HR) in the systemic leaves of the 938-16-B watermelon line infected with ZYMV, distinct from the typical HR at infected sites. In this study, we confirmed that ZYMV accumulation in 938-16-B was significantly lower than in the susceptible line H1. Upon inoculation, the entry of ZYMV-eGFP into mesophyll cells is restricted into necrotic spots in leaves, indicating that resistance to ZYMV in 938-16-B is linked to the HR. Further, grafting experiments between 938-16-B and susceptible varieties were performed, and revealed an HR induction in susceptible varieties, suggesting the transfer of resistance signal(s) from 938-16-B to susceptible varieties. Through RNA-sequencing and proteomics analyses of the H1 scions on 938-16-B rootstock, a pathogenesis-related 1 (ClPR1) gene was identified. Specifically, ClPR1 expression is unique to ZYMV-infected 938-16-B. Repression of the expression of ClPR1 prevents an HR in 938-16-B. Conversely, overexpression of ClPR1 in susceptible varieties significantly reduces ZYMV accumulation, but an HR was not induced in susceptible line. Besides the virus, jasmonic acid (JA) can also trigger an HR in 938-16-B. Intriguingly, the expression of ClPR1 (Cla97C02G034020) is induced in both of 938-16-B and H1 by MeJA, rather than salicylic acid. These results suggest that HR is associated with the expression of ClPR1 and contributes to resistance to ZYMV in 938-16-B., Competing Interests: Declarations Conflict of interest The authors declare that there are no competing interests associated with this manuscript., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The increase in demand for natural rubber has led to the search for alternative sources. Lactuca serriola is emerging as a promising candidate, as the quality of the natural rubber it produces is comparable to that of the Pará Rubber Plant, Hevea brasiliensis. This study examines the effect of methyl jasmonate (MeJA), a known elicitor, on the expression of key rubber biosynthesis pathway genes (HMGR1, HMGS1, CPT2, and SRPP1) in the latex of L. serriola plants. The expression levels of these genes increased significantly after the foliar application of 200 and 400 µM MeJA. The highest relative expression level for HMGR1, HMGS1, CPT2 and SRPP1 was 3.74, 18.56, 11.91and 16.59 fold respectively. Furthermore, the rubber content in L. serriola showed a significant rise post-treatment compared to the control with increasing the level of MeJA (6.19%, 7.24% and 7.85% which correspond to 0, 200 and 400 µM). Gel permeation chromatography revealed an augmentation in the molecular weight of extracted natural rubber from treated plants. Samples treated with 400 µM of MeJA had the highest molecular weight (1570 kg mol -1 ) compared to control (1186 kg mol -1 ). This study has demonstrated that MeJA, through the regulation of rubber biosynthesis genes, is capable of enhancing the quality and quantity of natural rubber extracted from alternative sources, such as L. serriola., (© 2024. The Author(s).)

Purpose: Diabetic macular edema (DME) is the primary cause of vision impairment in diabetic retinopathy (DR) patients. A previous study has shown the efficacy of montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, in a diabetic mouse model. This study aims to understand the CysLTR1 signaling in retinal endothelial cells and the impact of montelukast., Methods: Primary human retinal microvascular endothelial cells (HRECs) challenged with 20 ng/mL TNF-α and 30 mM D-glucose (D-glu) for six to 24 hours served as a model of endothelial activation. HRECs were incubated with L-glucose (L-glu) as an osmotic control. CysLTR1 knockdown and montelukast pretreatment assessed CysLTR1 antagonism. Gene expression, protein expression, and cell-permeable dyes were utilized to measure autophagy and inflammation. Transendothelial electrical resistance (TER) and transendothelial migration of mononuclear leukocytes across HRECs monolayer were measured as a functional assessment of vascular permeability., Results: Endothelial activation induced by hyperglycemia and inflammation increased CysLTR1 expression, triggering autophagy within two to six hours, IL-1β production, loss of junction integrity, decreased TER, and increased leukocyte migration within six to 24 hours. Pretreatment with montelukast effectively alleviated these effects, demonstrating its dependence on CysLTR1., Conclusions: Dysfunctional retinal endothelium initiates a self-reinforcing loop of inflammation, autophagy, and compromised integrity associated with heightened CysLTR1 levels. The antagonistic effect of montelukast against CysLTR1 effectively mitigates these detrimental changes. This study reveals CysLTR1 as a potential therapeutic target in treating DME and offers a novel strategy to mitigate detrimental changes in DR.

Spur-type varieties play an important role in facilitating high-density plantings. However, the underlying mechanisms of internode elongation in spur-type varieties are poorly understood. In this research, we investigated the morphological phenotype of annual shoots in four spur-type varieties ('Miyazak', 'Jinfu 18', 'Yanfu No. 6', and 'Liquan spur') and four standard-type varieties ('Aomorifu', 'Shou Fuji', 'Yanfu No. 10', and 'Yanfu No. 3'). Compared with standard-type varieties, spur-type varieties had a shorter shoot length, an average internode length and a smaller xylem size. The content of Jasmonic acid (JA) and Jasmonic acid isoleucine (JA-Ile) significantly increased in spur-type varieties, accompanied by an increase in the expression of JA biosynthesis and signal transduction genes. Exogenous methyl jasmonate (MeJA) inhibited plant height, xylem size, and vessel area. Additionally, we identified an IAA-Leucine Resistant1-like Hydrolase family member, MdILL6, which was highly expressed in spur-type varieties and mature stems. MdILL6 was mainly expressed in the shoot tips and stem, and its protein was located on the endoplasmic reticulum. Overexpression of MdILL6 in apple inhibited plant height and average internode length by decreasing xylem size and vessel area. Our results revealed a molecular mechanism of spur-type variety development affected by the JA pathway and suggest strategies for genetic improvement and regulation of spur-type varieties., (© 2024 Scandinavian Plant Physiology Society.)

Letermovir and maribavir have demonstrated efficacy in the prevention and treatment, respectively, of immunosuppressed patients with cytomegalovirus (CMV) infection and disease. These patients often have polypharmacy making them at risk for drug-drug interactions. Both letermovir and maribavir can be perpetrators and victims of drug-drug interactions. Letermovir is a moderate inhibitor of CYP3A, CYP2C8 and OATP1B1/3, and a moderate inducer of CYP2C19. It is a substrate of UGT1A1/3, BCRP, P-gp and OATP1B1/3. Maribavir is a moderate CYP2C9 inhibitor and a substrate of CYP3A. Drug-drug interactions between these anti-CMV agents and a number of therapeutic classes, such as immunosuppressants, antifungal agents, and hemato-oncological agents, can have clinical consequences and deserve dose modification or close monitoring. In a number of examples, three-way drug interactions need to be assessed. The objective of this review is to provide clinicians with guidance for drug-drug interaction management, based on existing data from drug-drug interaction studies, and extrapolation to other relevant co-medications that have not (yet) been studied but that are frequently used in these patient populations., Competing Interests: Declarations Funding No funding was received for this publication. Conflicts of Interest D.M.B. is co-founder of Global DDI Solutions and received unrestricted research grants from Gilead, ViiV HealthCare, Pfizer and Merck. All payments were invoiced by the Radboudumc and paid to Radboudumc. J.M. has received research support from Pfizer and Gilead and has served as a consultant or speaker for Gilead, Pfizer, MSD, Cidara, Mundipharma, F2G, Amplyx, Basilea, Shionoghi, Synexis and Takeda. L.H. declares no interest with regards to this work. Outside of this work, he has served as consultant to and has received unrestricted research grants from Astellas Pharma, Chiesi, and Sandoz. All payments were invoiced by the Radboudumc and paid to Radboudumc. R.J.M.B. declares no interest with regards to this work. Outside of this work, he has served as consultant to and has received unrestricted research grants from Astellas Pharma Inc., F2G, Gilead sciences, Merck Sharpe and Dohme Corp., Cidara, Mundipharma Inc. and Pfizer Inc. All payments were invoiced by the Radboudumc and paid to Radboudumc. L.N., M.G., N.B., P.L. and M.C.B. have not declared a conflict of interest. Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Availability of Data and Material Not applicable. Code Availability Not applicable. Author contributions DB performed the initial selection of papers, which were double checked by MG and LN. All authors reviewed draft versions of the paper and the tables, and all authors approved the final version of the paper., (© 2024. The Author(s).)

Background: Hyperglycemia is common after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). More importantly, it is associated with a worse neurological outcome after CA/CPR. Acetate has been proven to be of great value to reprogram glucose metabolism in the whole body. Nevertheless, the impact of acetate on hyperglycemia and neurological outcomes after CA/CPR remains largely unexplored., Methods: Glucose metabolism-related parameters were examined to assess the changes of glucose metabolism in our CA/CPR model. Survival and neurological function were measured after return of spontaneous circulation. Acetate supplementation was achieved by gavage to assess the impact of acetate on CA/CPR-induced hyperglycemia. Proteomics investigation of the changes in proteins of the CA1 region were performed to explore the differences of protein expression. The correlation between acetate supplementation and improvement of neurological outcomes after CA/CPR was elucidated by Serpina3n over-expression and knockdown in CA1 region., Results: CA/CPR induces hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance with upregulation of Serpina3n in CA1 region. Acetate supplementation could attenuate hyperglycemia, reduce protein levels of Serpina3n in CA1 region, and improves neurological outcomes after CA/CPR. Mechanistically, the acetate-dependent improvement of neurological outcomes after CA/CPR and attenuation of CA/CPR-induced hyperglycemia were correlated with the down-regulation of Serpina3n in CA1 region., Conclusions: Our findings suggest that acetate supplementation improves neurological outcomes of CA/CPR mice by maintaining glucose homeostasis in the whole body and suppression of Serpina3n expression in CA1 region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Methyl jasmonate (MeJA), a plant growth regulator, coordinates a diverse array of physiological responses, including the inhibition of seed germination, modulation of secondary metabolite biosynthesis, and activation of defence responses. The external application of MeJA has been demonstrated to effectively diminish the severity of fungal diseases. Here, we unveil a novel mechanism through which exogenous MeJA alleviates Fusarium head blight (FHB) by inhibiting the synthesis of deoxynivalenol (DON) in Fusarium graminearum, rather than by enhancing the wheat resistance response. MeJA treatment reduced the infection by wild-type F. graminearum in wheat coleoptiles, but exhibited no significant influence on that of the DON-deficient mutant strain (∆Tri5). The production of DON in F. graminearum was significantly inhibited both in vitro and in planta. MeJA affected the expression of genes related to DON biosynthesis, without influencing the formation of toxisomes as observed under microscopic analysis. Exogenous MeJA demonstrated a limited impact on the early genes of plant jasmonic acid signalling pathway, in contrast to the wild-type pathogen strain, which induced the upregulation of these genes. The expression levels of defence marker genes induced by MeJA were notably lower compared to those induced by the pathogen. This study elucidates the molecular mechanisms of MeJA in modulating the wheat-F. graminearum interaction, providing new insights into the development of environmentally friendly strategies against fungi., (© 2024 Scandinavian Plant Physiology Society.)

Aims: Tumor fatty acid (FA) metabolic plasticity plays a pivotal role in resistance to therapy and poses limitations to anticancer strategies. In this study, our aim is to uncover the role of acetate metabolism in neurodifferentiation (NED)-mediated castration-resistant prostate cancer (CRPC)., Methods: We conducted analyses using LC-MS/MS on clinical prostate cancer tissue before and after hormone therapy. We established tumor xenograft mouse models, primary tumor cells, and human-derived organoids to detect the novel mechanism of NED and to identify potential therapies., Results: The hormone therapy-induced upregulation of acetate metabolism was mediated by acyl-CoA synthetase short-chain family member 2 (ACSS2), which increased c-MYC expression for NED induction. Notably, combined treatment with an ACSS2 inhibitor and enzalutamide significantly reduced the xenograft tumor volume., Conclusion: Our findings uncovered the critical role of acetate metabolism in NED-mediated CRPC and suggest that ACSS2 inhibitors may represent a novel, low-toxicity strategy when combined with hormone therapy for treating patients with NED-mediated CRPC., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Huan Xu reports financial support was provided by National Natural Science Foundation of China. Huan Xu reports financial support was provided by National Natural Science Foundation of China. Huan Xu reports financial support was provided by Shanghai Sailing Program. Zhong Wang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The economic value of pear is determined by its intrinsic qualities, which are influenced by metabolites produced during the ripening process. Methyl jasmonate (MeJA), a hormone, plays an important role in plant metabolism. To date, few studies have investigated the molecular mechanism underlying the changes in metabolic pathways related to the internal quality of pear fruit after MeJA treatment. In this study, ultrahigh-performance liquid chromatography‒Q Exactive Orbitrap mass spectrometry (UHPLC‒QE‒MS) was used to determine the changes in metabolite contents in pear after MeJA treatment. MeJA treatment primarily activated carbohydrate metabolism and amino acid metabolism pathways. Through combined analysis of UHPLC‒QE‒MS data and whole-transcriptome data, the abovementioned pathways and each metabolite were analysed separately, and competitive endogenous RNA (ceRNA) and microRNA-transcription factor-target (miRNA-TF-target) regulatory networks were constructed. The core nodes of three genes (PEA, Pbr022732.1; GAA, Pbr035655.1; and miR8033-x) and two genes (SDS, Pbr031708.1; and novel-m6796-3p) were associated with the carbohydrate metabolism and amino acid metabolism pathways, respectively. The core mRNA nodes TCONS&#95;00048038 and Pbr019584.1, the core miRNA node miR4993-x, the core lncRNA node TCONS&#95;0004356, the core circRNA node novel&#95;circ&#95;001967 and the core transcription factor node TSO1 (Pbr025407.1) were identified via separate metabolite analyses. These findings elucidate the changes in metabolites related to fruit quality in 'Nanguo' pear and the relationships between the metabolites and genes, reveal the molecular mechanism underlying the response of MeJA treatment in pear fruit, and provide a theoretical basis for improving the internal quality of 'Nanguo' pear., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Histone modifications (HMs) play various roles in growth, development, and resistance to abiotic stress. However, HMs have been systematically identified in a few plants, and identification of HMs in medicinal plants is very rare. Aquilaria sinensis is a typical stress-induced medicinal plant, in which HMs remain unexplored. We conducted a comprehensive study to identify HMs and obtained 123 HMs. To conduct evolutionary analysis, we constructed phylogenetic trees and analyzed gene structures. To conduct functional analysis, we performed promoter, GO, and KEGG analyses and ortholog analyses against AtHMs. Based on the expression profiles of different tissues and different layers of Agar-Wit, some HMs of A. sinensis (AsHMs) were predicted to be involved in the formation of agarwood, and their response to MeJA and NaCl stress was tested by qRT-PCR analysis. By analyzing the enrichment of H3K4me3, H3K27me3, and H4K5ac in the promoter regions of two key sesquiterpene synthase genes, AsTPS13/18, we hypothesized that AsHMs play important roles in the synthesis of agarwood sesquiterpenes. We confirmed this hypothesis by conducting RNAi transgenic interference experiments. This study provided valuable information and important biological theories for studying epigenetic regulation in the formation of agarwood. It also provided a framework for conducting further studies on the biological functions of HMs., Competing Interests: Declaration of competing interest There are no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

TCP (TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1) is a plant-specific transcription factor that has garnered significant attention due to its wide-ranging involvement in the regulation of plant growth or developmental processes. However, the molecular mechanisms through which TCP genes orchestrate leaf senescence have not been extensively elucidated. BpTCP19, a member of the PCF subfamily in Betula platyphylla, and has high homology to AtTCP19. BpTCP19 displayed pronounced downregulation in response to methyl jasmonate (MeJA) and dark treatment. Overexpressing BpTCP19 in Betula platyphylla led to a delay in leaf senescence, resulting in prolonged leaf greenness under both MeJA and dark conditions. Transcriptome analysis revealed that overexpression of BpTCP19 induced alterations in the expression levels of genes linked to cell proliferation, hormone signaling transduction, and leaf senescence, including the early responsive factor BpWRKY53. Furthermore, through Yeast one-hybrid assays and GUS analysis, BpTCP19 was shown to bind to the promoter region of BpWRKY53, suppressing its expression and thereby retarding leaf senescence. This study elucidates the physiological and molecular functions of BpTCP19 as a central transcriptional regulatory module in leaf senescence and provides a potential target gene for delaying leaf senescence by mitigating sensitivity to external aging signals such as Jasmonic acid (JA) and darkness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Salvia miltiorrhiza Bunge, a model plant for medicinal research, is extensively utilized for its dried roots and rhizomes for treatment of various diseases. Soil salinization hinders the large-scale cultivation and industrial production of S. miltiorrhiza by affecting its active compounds. Methyl jasmonate (MeJA) is a crucial plant hormone that regulates plant responses under salt stress. Jasmonate zim domain (JAZ) proteins function as transcriptional repressors in jasmonic acid (JA) signaling pathways. This study explores the interaction between JA and salt stress by using transgenic Arabidopsis thaliana to elucidate the roles of SmJAZ3, SmJAZ4, and SmJAZ8. We found that 2.5 μM MeJA reduced the inhibitory effect of 150 mM NaCl on wild-type seed germination, and this effect was reversed by 15 μM dihydroxyindole-2-carboxylic acid (DIECA). Similar results were observed in transgenic A. thaliana lines overexpressing SmJAZ3/4/8. Inclusion of SmJAZ3/4 enhanced salt resistance by increasing antioxidant enzyme activity, chlorophyll content, proline content, and Na + /K + content, while SmJAZ8 had the opposite effect. These findings suggest that appropriate concentrations of MeJA can alleviate the negative effect of salt stress on plant growth and development. Investigating the salt tolerance of SmJAZ3/4/8 is significant for cultivating high-quality salt-tolerant S. miltiorrhiza., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Quiescence is a reversible cell cycle exit traditionally thought to be associated with a metabolically inactive state. Recent work in muscle cells indicates that metabolic reprogramming is associated with quiescence. Whether metabolic changes occur in cancer to drive quiescence is unclear. Using a multi-omics approach, we found that the metabolic enzyme ACSS2, which converts acetate into acetyl-CoA, is both highly upregulated in quiescent ovarian cancer cells and required for their survival. Indeed, quiescent ovarian cancer cells have increased levels of acetate-derived acetyl-CoA, confirming increased ACSS2 activity in these cells. Furthermore, either inducing ACSS2 expression or supplementing cells with acetate was sufficient to induce a reversible quiescent cell cycle exit. RNA-Seq of acetate treated cells confirmed negative enrichment in multiple cell cycle pathways as well as enrichment of genes in a published G0 gene signature. Finally, analysis of patient data showed that ACSS2 expression is upregulated in tumor cells from ascites, which are thought to be more quiescent, compared to matched primary tumors. Additionally, high ACSS2 expression is associated with platinum resistance and worse outcomes. Together, this study points to a previously unrecognized ACSS2-mediated metabolic reprogramming that drives quiescence in ovarian cancer. As chemotherapies to treat ovarian cancer, such as platinum, have increased efficacy in highly proliferative cells, our data give rise to the intriguing question that metabolically-driven quiescence may affect therapeutic response., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katherine Aird reports financial support was provided by American Cancer Society. Katherine Aird reports financial support was provided by National Cancer Institute. Ronald Buckanovich reports financial support was provided by National Cancer Institute. Allison Sharrow reports financial support was provided by Magee-Womens Research Institute and Foundation. Nathaniel Snyder reports financial support was provided by National Cancer Institute. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Sex pheromones play a crucial role in species recognition and reproductive isolation. Despite being largely species-specific in drosophilids, the mechanisms underlying pheromone detection, production, and their influence on mating behavior remain poorly understood. Here, we compare the chemical profiles of Drosophila bipectinata and D. melanogaster, the mating behaviors in both species, as well as the tuning properties of Or67d receptors, which are expressed by neurons in antennal trichoid sensilla at1. Through single sensillum recordings, we demonstrate that the D. bipectinata Or67d-ortholog exhibits similar sensitivity to cis-vaccenyl acetate (cVA) as compared to D. melanogaster but in addition also responds uniquely to (Z)-11-eicosen-1-yl-acetate (Z11-20:Ac), a compound exclusively produced by D. bipectinata males. Through courtship behavior assays we found that, surprisingly, perfuming the flies with Z11-20:Ac did not reveal any aphrodisiacal or anti-aphrodisiacal effects in mating assays. The behavioral relevance of at1 neuron channels in D. bipectinata compared to D. melanogaster seems to be restricted to its formerly shown function as an aggregation pheromone. Moreover, the non-specific compound cVA affected copulation negatively in D. bipectinata and could potentially act as a premating isolation barrier. As both ligands of Or67d seem to govern different behaviors in D. bipectinata, additional neurons detecting at least one of those compounds might be involved. These results underscore the complexity of chemical signaling in species recognition and raise intriguing questions about the evolutionary implications of pheromone detection pathways in Drosophila species., (© 2024. The Author(s).)

Salvia miltiorrhiza holds significant importance in traditional Chinese medicine. Stress-associated proteins (SAP), identified by A20/AN1 zinc finger structural domains, play crucial roles in regulating plant growth, development, resistance to biotic and abiotic stress, and hormone responses. Herein, we conducted a genome-wide identification of the SAP gene family in S. miltiorrhiza. The expression analysis revealed a significant upregulation of SmSAP4 under methyl jasmonate (MeJA) and salt stress. Overexpressing SmSAP4 in S. miltiorrhiza hairy roots increased tanshinones content while decreasing salvianolic acids content, while RNAi-silencing SmSAP4 had the opposite effect. SmSAP4 overexpression in both Arabidopsis thaliana and S. miltiorrhiza hairy roots decreased their salt stress tolerance, accompanied by increased activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and a hindered ability to maintain the Na +  : K + ratio. Further investigations demonstrated that MeJA alleviated the inhibitory effect of SmJAZ3 on SmSAP4 activation by SmbHLH37 and SmERF73. However, MeJA did not affect the inhibition of SmSAP4 activation by SmJAZ8 through SmbHLH37. In summary, our research reveals that SmSAP4 negatively regulates the accumulation of salvianic acid through the SmJAZs-SmbHLH37/SmERF73-SmSAP4 module and positively impacting the accumulation of tanshinones. Additionally, it functions as a negative regulator under salt stress., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Cyclopamine, a compound found in wild Veratrum has shown promising potential as a lead anti-cancer drug by effectively blocking cancer signaling pathways. However, its complex chemical structure poses challenges for artificial synthesis, thus limiting its supply and downstream drug production. This study comprehensively utilizes induction, system optimization, and transgenic technologies to establish an efficient suspension culture system for the high-yield production of cyclopamine and its precursor, veratramine. Experimental results demonstrate that methyl jasmonate (MeJA) effectively promotes the content of veratramine and cyclopamine in Veratrum californicum var. callus tissue, while yeast extract (YE) addition significantly increases cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg after synergistic treatment of suspension system with these two elicitors. And the content of the two substances was further increased to 0.0827 mg after the optimization by response surface methodology. Subsequently, a genetic transformation system for V. californicum callus was established and a crucial enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was screened and identified for genetic transformation. Combined suspension culture and synergistic induction system, the total content of the two substances in transgenic suspension system was further increased to 0.1228 mg, representing a 276.69% improvement compared to the initial culture system. This study proposes a complete and effective genetic transformation and cultivation scheme for V. californicum tissue cells, achieving milligram-level production of the anticancer agent cyclopamine and its direct precursor veratramine for the first time. It provides a theoretical basis for the industrial-scale production of these substances., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Gut microbiota dysbiosis induces intestinal barrier damage during parenteral nutrition (PN). However, the underlying mechanisms remain unclear. This study aimed to investigate gut microbiota dysbiosis, luminal short-chain fatty acids, and autophagy in a mouse model and how these short-chain fatty acids regulate autophagy., Methods: Eight-week-old male specific-pathogen-free mice were randomly divided into a Chow group (standard diet and intravenous normal saline infusion) and a PN group (continuous infusion of PN nutrient solution) for 7 days. Caco-2 cells were also treated with intestinal rinse solutions from Chow and PN mouse models., Results: Compared with the Chow group, the PN group exhibited increased Proteobacteria and decreased Firmicutes, correlating with decreased propyl acetate. In the PN group, intestinal tissue exhibited elevated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, LC3II protein levels, and Atg3 and Atg7 messenger RNA levels. P62 protein levels were decreased, indicating an increase of autophagy flux in the PN group. In the Caco-2 cell model, cells treated with PN solution plus propyl acetate exhibited increased Claudin-1 and occluding along with decreased interleukin-6 and tumor necrosis factor α compared with those treated with PN solution alone. Propyl acetate addition inhibited the AMPK-mammalian target of rapamycin (mTOR) pathway, mitigating the excessive autophagy induced by the PN intestinal rinse solution in Caco-2 cells., Conclusion: PN led to a significant reduction in propyl acetate levels in the intestine, excessive activation of autophagy, and barrier dysfunction. Propyl acetate inhibited excessive autophagy via the AMPK/mTOR signaling pathway and protected the intestinal barrier during PN., (© 2024 American Society for Parenteral and Enteral Nutrition.)

Inflammation management presents a critical challenge in modern medicine, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a widely used therapeutic option. However, their efficacy is often accompanied by significant gastrointestinal adverse effects, necessitating the exploration of safer alternatives, particularly through the investigation of cyclooxygenase-2 (COX-2) inhibitors. This study endeavors to address this imperative through the synthesis and evaluation of pyrazoline-phenoxyacetic acid derivatives. Among the synthesized compounds, 6a and 6c emerged as promising candidates, demonstrating potent COX-2 inhibition with IC 50 values of 0.03 µM for both and selectivity index = 365.4 and 196.9, respectively. Furthermore, these compounds exhibited efficacy in mitigating formalin-induced edema in male Wistar rats, accompanied by favorable safety profiles upon histological examination of vital organs. Comprehensive safety assessments, including evaluation of creatinine, AST, and ALT enzymatic as well as troponin T and creatine kinase-MB levels, further reinforce the promising attributes of the synthetic candidates. Molecular docking studies endorsed by molecular dynamic simulations corroborate the biological findings, elucidating significant protein-ligand interactions at COX-2 active sites indicative of therapeutic potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Terpene synthases (TPSs) play a crucial role in the synthesis of terpenoids that contribute to the scent profiles of flowers. However, few studies report the genome-wide analysis of TPS s gene in Jasminum sambac var. Fuzhou bifoliatum and their expression pattern in response to methyl jasmonate (MeJA). In this study, we employed bioinformatics tools for genome-wide analysis of the J . sambac TPS (DJTPS) gene family and determined the physical and chemical properties, subcellular location, protein-protein interactions, phylogenetic relationship, subfamily classification, chromosomal location and collinearity, gene structure, conserved motifs, and promoter cis -acting elements. The expression patterns of DJTPS s in different tissues and in response to MeJA treatment were analyzed based on the transcriptome data combined with quantitative real-time PCR (qRT-PCR). We identified 32 intact DJTPS genes in the genome of J . sambac , which presented uneven distribution across nine chromosomes. All the deduced proteins were hydrophilic, predominantly localized in the cytoplasm. The phylogenetic analysis classified the DJTPS genes into five subfamilies: TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g. The results of the collinearity analysis showed a total of 10 sets of replication events in DJTPS s, most of which underwent purifying selection. A comparative analysis of TPS homologous gene pairs was performed among J . sambac var. Fuzhou bifoliatum and other six species, which revealed different number of homologous gene pairs. The number of exons and motifs was conserved within the same subfamily. DJTPS genes carried multiple elements that may be involved in the response to MeJA. In addition, the transcriptome and qRT-PCR data unveiled that several TPS genes exhibited tissue-specific expression patterns, and the genes with specific expression in flowers were the most. Upon exposure to MeJA, 14 TPS genes showcased upregulated expression 5 h or 6 h post-treatment, and DJTPS03 , DJTPS04 and DJTPS21 showed significantly increased expression levels after MeJA treatment. This study provides preliminary evidence that MeJA possesses the ability to enhance the expression of DJTPS genes during the critical flowering stage, which will facilitate the synthesis of terpenoids and improve the quality of floral fragrance.

In patients with sepsis, neutrophil apoptosis tends to be inversely proportional to the severity of sepsis, but its mechanism is not yet clear. This study aimed to explore the mechanism of fatty acid binding protein 4 (FABP4) regulating neutrophil apoptosis through combined analysis of gut microbiota and short-chain fatty acids (SCFAs) metabolism. First, neutrophils from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced acute respiratory distress syndrome (ARDS) were purified and isolated RNA was applied for sequencing. Then, the cecal ligation and puncture (CLP) method was applied to induce the mouse sepsis model. After intervention with differential SCFAs sodium acetate, neutrophil apoptosis and FABP4 expression were further analyzed. Then, FABP4 inhibitor BMS309403 was used to treat neutrophils. We found CLP group had increased lung injury score, lung tissue wet/dry ratio, lung vascular permeability, and inflammatory factors IL-1β, TNF-α, IL-6, IFN-γ, and CCL3 levels in both bronchoalveolar lavage fluid and lung tissue. Additionally, FABP4 was lower in neutrophils of ARDS patients and mice. Meanwhile, CLP-induced dysbiosis of gut microbiota and changes in SCFAs levels were observed. Further verification showed that acetic acids reduced neutrophil apoptosis and FABP4 expression via FFAR2. Besides, FABP4 affected neutrophil apoptosis through endoplasmic reticulum (ER) stress, and neutrophil depletion alleviated the promotion of ARDS development by BMS309403. Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage., (© 2024. The Author(s).)

DpAP2 is a transcription factor regulating carotenoid biosynthesis pathway. It was speculated that MeJA significantly decreased expression of DpAP2 gene, then the decreasing DpAP2 expression significantly inhibited expression of some key enzyme genes such as PSY, PDS and GGPS in carotenoid biosynthesis pathway. In contrast, it was speculated that GA3 significantly increased expression of DpAP2 gene, then the increasing DpAP2 expression significantly increased expression of some key enzyme genes such as PDS and GGPS in carotenoid biosynthesis pathway. To increase the content of carotenoid, we evaluated the effect of DpAP2 overexpression on carotenoid accumulation in D. parva. Transgenic D. parva showed a higher carotenoid content (3.18 mg/g DW) compared with control group (2.13 mg/g DW) at 9 d. The dosage effects of exogenous hormones MeJA and GA3 were found in D. parva cells treated with different concentrations of MeJA (10, 20, 50, 100 μM) and GA3 (10, 20, 50, 100 μM). The high concentrations of MeJA (10-100 μM) inhibited the accumulation of carotenoid, and the relative expression of DpAP2, PSY, PDS and GGPS decreased significantly. On the contrary, the relative expression of DpAP2, PDS and GGPS increased significantly when D. parva was treated with 10, 20, 50 and 100 μM GA3, which promoted the biosynthesis of carotenoid. Therefore, we inferred that there was a hierarchical regulation from hormone, transcription factor, key enzyme gene to carotenoid accumulation in carotenoid biosynthesis. Carotenoid biosynthesis was enhanced by DpAP2 overexpression (1.4930 fold of control) and exogenous substances such as GA3 (1.5889 fold of control), which laid a foundation for massive accumulation of carotenoids in microalgae. In the future, further studies were required to demonstrate the complex regulatory network., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ruan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

(1) Background: Methyl jasmonate-treated D. morbifera adventitious root extract (MeJA-DMARE), enriched with phenolics, has enhanced bioactivities. However, phenolics possess low stability and bioavailability. Substantial evidence indicates that plant extract-phospholipid complex assemblies, known as phytosomes, represent an innovative drug delivery system. (2) Methods: The phytosome complex was created by combining MeJA-DMARE with Soy-L-α-phosphatidylcholine (PC) using three different ratios through two distinct methods (co-solvency method: A1, A2, and A3; thin-layer film method: B1, B2, and B3). (3) Results: Initial evaluation based on UV-Vis, entrapment efficiency (EE%), and loading content (LC%) indicated that B2 exhibited the highest EE% (79.98 ± 1.45) and LC% (69.17 ± 0.14). The phytosome displayed a spherical morphology with a particle size of 210 nm, a notably low polydispersity index of 0.16, and a superior zeta potential value at -25.19 mV. The synthesized phytosome exhibited superior anti-inflammatory activities by inhibiting NO and ROS production (reduced to 8.9% and 55.1% at 250 μg/mL) in RAW cells and adjusting the expression of related inflammatory cytokines; they also slowed lung tumor cell migration (only 2.3% of A549 cells migrated after treatment with phytosomes at 250 μg/mL), promoting ROS generation in A549 cell lines (123.7% compared to control) and stimulating apoptosis of lung cancer-related genes. (4) Conclusions: In conclusion, the MeJA-DMARE phytosome offers stable, economically efficient, and environmentally friendly nanoparticles with superior inflammation and lung tumor inhibition properties. Thus, the MeJA-DMARE phytosome holds promise as an applicable and favorable creation for drug delivery and lung cancer treatment.

The effect of methyl jasmonate (MeJA) foliar spray on the activity of antioxidant enzymes-Superoxide dismutase (SOD), Catalase (CAT), Ascorbate peroxidase (APX), and Guaiacol peroxidase (GPX)-along with assessments of total phenolic and flavonoid contents and antioxidant activity (IC50), was examined in Prickly lettuce (Lactuca serriola L.). The study involved treating plants with three MeJA solutions (0, 200, and 400 µM) and harvesting samples at four distinct time intervals. Varied MeJA concentrations and time intervals resulted in a substantial increase in the activity of all the antioxidant enzymes investigated in this study. Both concentration levels and time courses exhibited progressive outcomes. Moreover, MeJA treatment led to elevated levels of total phenolic and flavonoid contents, reaching peaks of 17.02 (mg GAL/g DW) and 8.3 (mg QUE/g DW), respectively, particularly in response to the 400 µM concentration. However, the total flavonoid content did not show any significant variation between the two concentrations. Based on the half-maximal inhibitory concentration (IC50) values, the antioxidant activity in MeJA-treated plants was found to be lower compared to the controls. However, our findings suggest that, under specific conditions discussed in this study, MeJA has the potential to enhance the nutritional value of L. serriola.

Self-incompatibility (SI) poses a significant reproductive barrier, severely impacting the yield, quality, and economic value of Camellia oleifera . In this study, methyl jasmonate (MeJA) was employed as an exogenous stimulus to alleviate SI in C. oleifera . The research findings revealed that an exogenous dose of 1000 μmol·L -1 MeJA enhanced the germination and tube growth of C. oleifera self-pollen and greatly improved ovule penetration (18.75%) and fertilization (15.81%), ultimately increasing fruit setting (18.67%). It was discovered by transcriptome analysis that the key genes ( CAD , C4H ) involved in the lignin production process exhibited elevated expression levels in self-pistils treated with MeJA. Further analysis showed that the lignin concentration in the MeJA-treated pistils was 31.70% higher compared with the control group. As verified by pollen germination assays in vitro, lignin in the appropriate concentration range could promote pollen tube growth. Gene expression network analysis indicated that transcription factor bHLH may be pivotal in regulating lignin biosynthesis in response to MeJA, which in turn affects pollen tubes. Further transient knockdown of bHLH ( Co&#95;33962 ) confirmed its important role in C. oleifera pollen tube growth. In summary, the application of MeJA resulted in the stimulation of self-pollen tube elongation and enhanced fruit setting in C. oleifera , which could be associated with the differential change in genes related to lignin synthesis and the increased lignin content.

Deep sowing, as a method to mitigate drought and preserve soil moisture and seedlings, can effectively mitigate the adverse effects of drought stress on seedling growth. The elongation of the hypocotyl plays an important role in the emergence of maize seeds from deep-sowing stress. This study was designed to explore the function of exogenous methyl jasmonate (MeJA) in the growth of the maize mesocotyl and to examine its regulatory network. The results showed that the addition of a 1.5 μ mol L -1 MeJA treatment significantly increased the mesocotyl length (MES), mesocotyl and coleoptile length (MESCOL), and seedling length (SDL) of maize seedlings. Transcriptome analysis showed that exogenous MeJA can alleviate maize deep-sowing stress, and the differentially expressed genes (DEGs) mainly include ornithine decarboxylase, terpene synthase 7, ethylene responsive transcription factor 11, and so on. In addition, candidate genes that may regulate the length of maize hypocotyls were screened by Weighted Gene Co-expression Network Analysis (WGCNA). These genes may be involved in the growth of maize hypocotyls through transcriptional regulation, histones, ubiquitin protease, protein binding, and chlorophyll biosynthesis and play an important role in maize deep-sowing tolerance. Our research findings may provide a theoretical basis for determining the tolerance of maize to deep-sowing stress and the mechanism of exogenous hormone regulation of deep-sowing stress.

Jasmonic acid (JA), an important plant hormone, plays a crucial role in defending against herbivorous insects. In this study, we have identified a new Bowman-Birk type protease inhibitor (BBTI) protein in maize that is regulated by the JA pathway and exhibits significant antifeedant activity, which is notably induced by exogenous Methyl Jasmonate and Ostrinia furnacalis feeding treatments. Bioinformatics analysis revealed significant differences in the BBTI protein among different maize inbred lines, except for the conserved domain. Prokaryotic and eukaryotic expression systems were constructed and expressed, and combined with bioassays, it was demonstrated that the antifeedant activity of BBTI is determined by protein modifications and conserved domains. Through RT-qPCR detection of BBTI and JA regulatory pathway-related genes' temporal expression in different maize inbred lines, we identified the regulatory mechanism of BBTI synthesis under the JA pathway. This study successfully cloned and identified the MeJA-induced anti-feedant activity gene BBTI and conducted functional validation in different maize inbred lines, providing valuable insights into the response mechanism of insect resistance induced by the plant JA pathway. The increased expression of the anti-feedant activity gene BBTI through exogenous MeJA induction may offer a potential new strategy for mediating plant defense against Lepidoptan insects., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

In natural environments, general plant volatiles and herbivore-induced plant volatiles (HIPVs) serve as critical clues for predatory natural enemies in the search for prey. The insect olfactory system plays a vital role in perceiving plant volatiles including HIPVs. In this study, we found that HIPV ( E , E )-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT) and the plant volatile geranyl acetate (GA), two structurally similar chemicals, displayed electrophysiological activities on the antennae of the ladybird Hippodamia variegata , but were only attractive to adult females in behavior. Moreover, mated female ladybirds laid a significantly higher number of eggs on TMTT-treated and GA-treated cotton leaves compared to controls. Screening of female-biased odorant receptors (ORs) from the antennal transcriptomes, performing Xenopus oocytes expression coupled with two-electrode voltage clamp recordings, suggested that HvarOR28 specifically tuned to TMTT and GA. Molecular docking and site-directed mutagenesis revealed that the amino acid residues Tyr143 and Phe81 of HvarOR28 are the key site for binding with TMTT and GA. Furthermore, RNA interference (RNAi) assay demonstrated that HvarOR28 -silenced individuals demonstrated a notable decrease in electrophysiological responses, even female adults almost lost behavioral preference for the two compounds. Thus, it could be concluded that HvarOR28 in H. variegata contributes to facilitating egg laying through the perception of TMTT and GA. These findings may help to develop new olfactory modulators based on the behaviorally active ligands of HvarOR28.

The hydrolysis of cellulose generates inhibitors like acetate, suppressing fermentation performance. Here, 25SrRNA methyltransferase CgBMT5 from stress-tolerant yeast Candida glycerinogenes was used as an anti-stress gene element in Saccharomyces cerevisiae and Yarrowia lipolytica. Expression of CgBMT5 in S. cerevisiae increased cell tolerance to acetate, high osmolarity, and heat stress and rescued the delay in cell growth under acetate stress. Ethanol productivity was improved from 0.52 g·(L/h) to 0.69 g·(L/h). CgBMT5 improved GFP expression. The transcription factor ARG81 binds to the promoter of CgBMT5. CgBMT5 upregulated HOG1, GPD1, HAA1, and PMA1 and reduced ROS level, thereby improving cell resistance to acetate. CgBMT5 also improved resistance of Y. lipolytica Po1g to multiple-stress. The lipid titer was improved by 37% in the typical medium. Y. lipolytica-CgBMT5 produced 94 mg/L lipid in the undetoxified cellulose hydrolysate., (© 2024 Wiley‐VCH GmbH.)

Nutrient imbalances, such as high boron (B) stress, occur within, as well as across, agricultural systems worldwide and have become an important abiotic factor that reduces soil fertility and inhibits plant growth. Sugar beet is a B-loving crop and is better suited to be grown in high B environments, but the methods and mechanisms regarding the enhancement of high-B stress tolerance traits are not clear. The main objective of this research was to elucidate the effects of the alone and/or combined foliar spraying of zinc sulfate (ZnSO 4 ) and methyl jasmonate (MeJA) on the growth parameters, tolerance, and photochemical performance of sugar beet under high-B stress. Results demonstrated that the photosynthetic performance was inhibited under high-B stress, with a reduction of 11.33% in the net photosynthetic rate (Pn) and an increase of 25.30% in the tolerance index. The application of ZnSO 4 , MeJA, and their combination enhanced sugar beet's adaptability to high-B stress, with an increase in Pn of 9.22%, 4.49%, and 2.85%, respectively, whereas the tolerance index was elevated by 15.33%, 8.21%, and 5.19%, respectively. All three ameliorative treatments resulted in increased photochemical efficiency (F v /F m ) and the photosynthetic performance index (PI ABS ) of PSII. Additionally, they enhanced the light energy absorption (ABS/RC) and trapping capacity (DI O /RC), reduced the thermal energy dissipation (TR O /RC), and facilitated the Q A to Q B transfer in the electron transport chain (ETC) of PSII, which collectively improved the photochemical performance. Therefore, spraying both ZnSO 4 and MeJA can better alleviate high-B stress and promote the growth of sugar beet, but the combined spraying effect of ZnSO 4 and MeJA is lower than that of individual spraying. This study provides a reference basis for enhancing the ability of sugar beet and other plants to tolerate high-B stress and for sugar beet cultivation in high B areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bioactive secondary metabolites from fungi, including Trichoderma, are an excellent source of plant biostimulants. Although production of novel biostimulants from known microbes is critical, challenging them may produce novel bioactive compounds. With this hypothesis, the study used live Fusarium chlamydosporum (FOL7) culture as the inducer during T. harzianum (IF63) growth in broth. Plate assays and gas chromatography-mass spectrometry (GC-MS) analysis were used to characterise the metabolites. Microscopy, pot experiments and, biochemical estimations of the defence-related enzymes in tomato plants established the biostimulant activity of the induced Trichoderma metabolites. Fungal crude metabolites (FCM) obtained from IF63+FOL7 extracts (TF.ex) showed increased antimicrobial activity. TF.ex at 50 μg mL -1 , inhibited the FOL7 growth by 68.33% compared to the Trichoderma alone extract. Scanning electron microscopy (SEM) revealed morphological disruption of FOL7 mycelia by TF.ex. GC-MS analysis of the extracts revealed the presence of approximately 64 compounds, of which at least 13 were detected explicitly in TF.ex. Methyl (3-oxo-2-pentylcyclopentyl) acetate (Methyl dihydrojasmonate), a lipid functionally related to jasmonic acid, was the major metabolite (∼21%) present in TF.ex. Tomato seed dressing with TF.ex promoted plant growth and induced systemic resistance against FOL7 compared to alone Trichoderma and Fusarium extracts. The TF.ex treatment increased the superoxide dismutase (33%) and catalase activity by 2.5-fold in tomato plants. The study concludes that fungal secondary metabolites may be modulated by providing appropriate challenges to produce effective metabolite-based biostimulants for agricultural applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In large groups of vertebrates and invertebrates, aggregation can affect biological characters such as gene expression, physiological, immunological and behavioral responses. The insect cuticle is covered with hydrocarbons (cuticular hydrocarbons; CHCs) which reduce dehydration and increase protection against xenobiotics. Drosophila melanogaster and D. simulans flies also use some of their CHCs as contact pheromones. In these two sibling species, males also produce the volatile pheromone 11-cis-Vaccenyl acetate (cVa). To investigate the effect of insect density on the production of CHCs and cVa we compared the level of these male pheromones in groups of different sizes. These compounds were measured in six lines acclimated for many generations in our laboratory - four wild-type and one CHC mutant D. melanogaster lines plus one D. simulans line. Increasing the group size substantially changed pheromone amounts only in the four D. melanogaster wild-type lines. To evaluate the role of laboratory acclimation in this effect, we measured density-dependent pheromonal production in 21 lines caught in nature after 1, 12 and 25 generations in the laboratory. These lines showed varied effects which rarely persisted across generations. Although increasing group size often affected pheromone production in laboratory-established and freshly-caught D. melanogaster lines, this effect was not linear, suggesting complex determinants., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nymphaea candida Presl (NC), traditionally used in medicine for heat syndrome-related ailments, possesses antioxidative, anti-inflammatory, hepatoprotective, and neuroprotective properties. This research investigates the antidepressant and neuroprotective effects and mechanisms of Nymphaea candida Presl ethyl acetate (NCEA). Primary components of NCEA were identified as phenolic acids and flavonoids through UPLC-MS/MS analysis. The depression mouse model was induced via intracerebroventricular injection of Lipopolysaccharide (LPS), followed by oral administration of fluoxetine and NCEA for one week. Biochemical assays and HE staining confirmed NCEA's non-toxicity and protective effects on the liver and lungs. NCEA administration mitigated LPS-induced depressive behaviors, decreased IL-1β, TNF-α levels in the hippocampus, suppressed microglial activation, reduced Iba-1 expression, and increased NA, brain-derived neurotrophic factor (BDNF), and dendritic spine density in the hippocampus. Furthermore, NCEA enhanced cell viability in a CORT-induced PC12 cell model, decreased lactate dehydrogenase (LDH) release rate, total superoxide dismutase (SOD) inhibition rate, intracellular nitric oxide (NO) release, and reduced reactive oxygen species (ROS) production. Our research findings suggest that NCEA exhibits significant antidepressant effects, which may be attributed to its reduction of neuroinflammation, improvement in neurotransmitter levels, neuronal protection, and antioxidative stress properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Viticulture has adapted foliar applications of biostimulants as a tool to improve crop quality. Recently, nanotechnology has been incorporated as a strategy to reduce the loss of biostimulants and treat nutrient deficiencies. Therefore, the present study aimed to investigate the effect of foliar applications of amorphous calcium phosphate nanoparticles (ACP) doped with methyl jasmonate (ACP-MeJA) and urea (ACP-Ur), individually or together (ACP-MeJA+Ur), on the content of volatile compounds in 'Tempranillo' grapes, compared to the conventional application of MeJA and Ur, individually or in combination (MeJA+Ur)., Results: The results showed that nanoparticle treatments reduced the total C6 compounds and some carbonyl compounds in the grape musts. This is of novel interest because their presence at high levels is undesirable to quality. In addition, some aroma-positive compounds such as nerol, neral, geranyl acetone, β-cyclocitral, β-ionone, 2-phenylethanal and 2-phenylethanol increased, despite applying MeJA and Ur at a lower dose., Conclusion: Consequently, although few differences in grape volatile composition were detected, nanotechnology could be an option for improving the aromatic quality of grapes, at the same time as reducing the required doses of biostimulants and generating more sustainable agricultural practices. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Plants perceive the presence and defence status of their neighbours through light and volatile cues, but how plants integrate both stimuli is poorly understood. We investigated if and how low Red to Far red light (R:FR) ratios, indicative of shading or canopy closure, affect maize (Zea mays) responses to herbivore-induced plant volatiles (HIPVs), including the green leaf volatile (Z)-3-hexenyl acetate. We modulated light signalling and perception by using FR supplementation and a phyB1phyB2 mutant, and we determined volatile release as a response readout. To gain mechanistic insights, we examined expression of volatile biosynthesis genes, hormone accumulation, and photosynthesis. Exposure to a full blend of HIPVs or (Z)-3-hexenyl acetate induced maize volatile release. Short-term FR supplementation increased this response. In contrast, prolonged FR supplementation or constitutive phytochrome B inactivation in phyB1phyB2 plants showed the opposite response. Short-term FR supplementation enhanced photosynthesis and stomatal conductance and (Z)-3-hexenyl acetate-induced JA-Ile levels. We conclude that a FR-enriched light environment can prompt maize plants to respond more strongly to HIPVs emitted by neighbours, which might be explained by changes in photosynthetic processes and phytochrome B signalling. Our findings reveal interactive responses to light and volatile cues with potentially important consequences for plant-plant and plant-herbivore interactions., (© 2024 The Author(s). Plant, Cell & Environment published by John Wiley & Sons Ltd.)

Heavy metal toxicity adversely affects plants by changing physiological, biochemical, and molecular mechanisms. Lead (Pb) is one of the most common heavy metal pollutants. Hence this study investigated changes caused by exogenous methyl jasmonate (MeJA; 20 and 100 µM) and salicylic acid (SA; 2 and 20 mM) elicitors in local Karacadağ rice exposed to Pb stress (0, 100, and 400 ppm). The effects of elicitors on photosynthetic pigment content (chlorophyll a, chlorophyll b, and total carotenoid), proline, malondialdehyde (MDA), total phenolic and flavonoid, Pb, and total protein contents in stressed plants were evaluated. All parameters studied increased and decreased at varying rates in the treatment groups compared to the Pb-free group (control), indicating that rice plants were affected by Pb stress. The elicitors (MeJA, SA, and MeJA + SA) were applied by foliar spraying. The elicitor treatments increased photosynthetic pigment content, total protein, proline, total flavonoid, and phenolic contents depending on the elicitor type and concentration. MDA and Pb contents, increasing with Pb toxicity, decreased with elicitor treatments, and the stress degree was reduced. When the elicitors were compared, SA was more effective than MeJA in total flavonoid content at 400 ppm Pb toxicity. However, MeJA was more effective in photosynthetic pigment contents, MDA, total protein, Pb, total phenolic, and proline contents. The best results for all parameters examined in rice plants exposed to Pb toxicity were obtained from the 400 ppm Pb + 2 mM SA + 20 µM MeJA treatment group. In conclusion, this study showed that the combined application of MeJA + SA alleviated the harmful effects of Pb by reducing MDA and increasing photosynthetic pigments, total protein, proline, and secondary metabolites, especially at high Pb concentrations. Consequently, this study demonstrated that the combined use of MeJA and SA in rice plants eliminated the negative effects of stress quite effectively, even at high Pb concentrations. Therefore, future studies should focus on the synergistic application of different elicitors to better understand the effects of heavy metal toxicity on plant growth and development., (© 2024. The Author(s).)

Backgrounds & Aim: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats., Materials and Methods: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1β (IL-1β), and cleaved caspase-3 immuno-expressions were also evaluated., Results: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1β and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1β), and apoptotic (caspase-3) parameters., Conclusion: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1β signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Key Message: This study described the biosynthesis of 4-hydroxydihydrocinnamaldehyde sharing with monolignol pathway and supplemented the biosynthesis of colchicine in G. superba, 4-hydroxydihydrocinnamaldehyde produced in tobacco BY2 cells provided an important stepstone. The precursor, 4-hydroxydihydrocinnamaldehyde (4-HDCA), participates in the biosynthesis of the carbon skeleton of colchicine, which is derived from L-phenylalanine. However, one hypothesis proposed that 4-HDCA is synthesized by sharing the early part of the monolignol pathway in G. superba. In this study, we validated this prediction and identified the enzymatic functions involved in this pathway. GsDBR1 is a crucial enzyme to illustrate 4-HDCA diverging from monolignol pathway, we first confirmed its reductase activity on 4-coumaraldehyde, an important intermediate compound in monolignol biosynthesis. Then, the biochemical function of recombinant enzymes belonging to the other four families were verified to elucidate the entire process of 4-HDCA biosynthesis from L-phenylalanine. After reconstruction, the 4-HDCA was 78.4 ng/g with fresh weight (FW) of transgenic tobacco cells, and the yield increased to 168.22 ng/g·FW after improved treatment with methyl jasmonate (MeJA). The elucidation of 4-HDCA biosynthesis sharing the monolignol pathway supplemented the biosynthesis of colchicine in G. superba, and the production of 4-HDCA in tobacco cells provides an important step in the development of plant cell cultures as heterologous bio-factories for secondary metabolite production., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A series of seleno-containing polyfunctionalized compounds was synthesized exploring cyanohydrin chemistry, including α-hydroxy esters, α-hydroxy acids, 1,2-diols, and 1,2-diacetates, with yields ranging from 26 up to 99 %. The cytotoxicity of all synthesized compounds was then evaluated using a non-tumor cell line (BALB/3T3 murine fibroblasts), and those deemed non-cytotoxic had their anti-melanoma activity evaluated using B16-F10 murine melanoma cells. These assays identified two compounds with selective cytotoxic activity against the tested melanoma cell line, showing a potential anti-melanoma application., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leandro Piovan reports financial support was provided by Federal University of Parana. Leandro Piovan reports a relationship with Federal University of Parana that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Root exudates are known signaling agents that influence legume root nodulation, but the molecular mechanisms for nonflavonoid molecules remain largely unexplored. The number of soybean root nodules during the initial growth phase shows substantial discrepancies at distinct developmental junctures. Using a combination of metabolomics analyses on root exudates and nodulation experiments, we identify a pivotal role for certain root exudates during the rapid growth phase in promoting nodulation. Phenoxyacetic acid (POA) was found to activate the expression of GmGA2ox10 and thereby facilitate rhizobial infection and the formation of infection threads. Furthermore, POA exerts regulatory control on the miR172c-NNC1 module to foster nodule primordia development and consequently increase nodule numbers. These findings collectively highlight the important role of POA in enhancing nodulation during the accelerated growth phase of soybeans., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown., Results: We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation., Conclusions: Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima., (© 2024. The Author(s).)

Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation., Competing Interests: Dr Raymund Razonable reports grants from Gilead, grants from Roche, grants from Regeneron, personal fees from Allovir, personal fees from Novartis, outside the submitted work. The author reports no other conflicts of interest in this work., (© 2024 Razonable.)

While the placenta regulates nutritional exchange between mother and fetus, Yu et al. reveal that human placental development is itself nutrient-sensitive. They elucidate entwined metabolic and epigenetic transitions driving syncytialization and pinpoint a requirement for the metabolite acetyl-CoA, which is sensitive to glucose metabolism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cysteinyl leukotrienes (CysLTs) are central to the pathophysiology of asthma and various inflammatory disorders. Leukotriene receptor antagonists (LTRAs) effectively treat respiratory conditions by targeting cysteinyl leukotriene receptors, CysLT 1 and CysLT 2 subtypes. This review explores the multifaceted effects of LTs, extending beyond bronchoconstriction. CysLT receptors are not only present in the respiratory system but are also crucial in neuronal signaling pathways. LTRAs modulate these receptors, influencing downstream signaling, calcium levels, inflammation, and oxidative stress (OS) within neurons hinting at broader implications. Recent studies identify novel molecular targets, sparking interest in repurposing LTRAs for therapeutic use. Clinical trials are investigating their potential in neuroinflammation control, particularly in Alzheimer's disease (AD) and Parkinson's diseases (PD). However, montelukast, a long-standing LTRA since 1998, raises concerns due to neuropsychiatric adverse drug reactions (ADRs). Despite widespread use, understanding montelukast's metabolism and underlying ADR mechanisms remains limited. This review comprehensively examines LTRAs' diverse biological effects, emphasizing non-bronchoconstrictive activities. It also analyses plausible mechanisms behind LTRAs' neuronal effects, offering insights into their potential as neurodegenerative disease modulators. The aim is to inform clinicians, researchers, and pharmaceutical developers about LTRAs' expanding roles, particularly in neuroinflammation control and their promising repurposing for neurodegenerative disease management., Competing Interests: Declaration of competing interest We confirm that the paper has been seen and reviewed by co-authors, approved the submission to the journal. We confirm that there are no conflicts of interest in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Rosa damascena Mill., commonly known as the King Flower, is a fragrant and important species of the Rosaceae family. It is widely used in the perfumery and pharmaceutical industries. The scent and color of the flowers are significant characteristics of this ornamental plant. This study aimed to investigate the relative expression of MYB1, CCD1, FLS, PAL, CER1, GT1, ANS and PAR genes under two growth stages (S1 and S2) in two morphs. The CCD1 gene pathway is highly correlated with the biosynthesis of volatile compounds. The results showed that the overexpression of MYB1, one of the important transcription factors in the production of fragrance and color, in the Hot pink morph of sample S2 increased the expression of PAR, PAL, FLS, RhGT1, CCD1, ANS, CER1, and GGPPS. The methyl jasmonate (MeJA) stimulant had a positive and cumulative effect on gene expression in most genes, such as FLS in ACC.26 of the S2 sample, RhGT1, MYB1, CCD1, PAR, ANS, CER1, and PAL in ACC.1. To further study, a comprehensive analysis was performed to evaluate the relationship between the principal volatile compounds and colors. Our data suggest that the rose with pink flowers had a higher accumulation content of flavonoids and anthocyanin. To separate essential oil compounds, GC/MS analysis identified 26 compounds in four samples. The highest amount of geraniol, one of the main components of damask rose, was found in the Hot pink flower, 23.54%, under the influence of the MeJA hormone., (© 2024. The Author(s).)

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or astrocyte-specific Acss1 deletion to elevate acetate levels, we observed mitigated metabolic and cognitive impairments in SF mice. Mechanistically, acetate binds and activates pyruvate carboxylase, thereby restoring glycolysis and the tricarboxylic acid cycle. Among individuals most commonly affected by SF, patients with obstructive sleep apnea exhibited elevated acetate levels when coupled with type 2 diabetes. Our study uncovers the protective effect of acetate against sleep-induced metabolic and cognitive impairments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)