Search Results (303)

The HB (homeobox) transcription factor family plays important roles in plant growth, development, morphogenesis, and stress responses; however, its involvement in longan (Dimocarpus longan Lour.) fruit energy metabolism remains unclear. In this study, 32 DlHB family members were identified in the longan genome, and their physicochemical properties, phylogenetic relationships, gene structures, conserved motifs, conserved domains, tissue-specific expression patterns, promoter cis-acting elements, and collinearity relationships were systematically analyzed. The DlHB family was classified into four subfamilies, HD-ZIP I–IV, with substantial divergence in structural composition, expression patterns, and putative regulatory features. Our previous work showed that 1.5% chitosan (CTS) treatment improved postharvest longan fruit quality through modulation of energy metabolism, and the corresponding CTS-treatment transcriptome was therefore used here to screen energy-metabolism-associated DlHB candidates. DlHB22 was selected as a representative candidate, and its CTS-responsive expression was independently confirmed by qRT-PCR. Exogenous ATP treatment was then used as an independent physiological validation of the relationship between energy metabolism and postharvest storability; ATP-treated fruit showed reduced deterioration together with higher ATP, ADP, and AMP contents and higher activities of H+-ATPase, Ca²+-ATPase, cytochrome c oxidase (CCO), and succinate dehydrogenase (SDH) at 15 d, although adenylate energy charge (AEC) was lower than in the control. DlHB22 localized predominantly to the nucleus. Heterologous overexpression of DlHB22 in tomato accelerated fruit color transition and ripening progression and altered ATP, ADP, and AMP contents, AEC, and the activities of H+-ATPase, Ca²+-ATPase, CCO, and SDH. Transcriptome analysis of DlHB22-overexpressing tomato fruit revealed broad transcriptional changes in pathways associated with central carbon metabolism, energy metabolism, glutathione metabolism, hormone signaling, and MAPK signaling, and qRT-PCR validation of six representative DEGs was consistent with the RNA-seq trends. Because tomato is climacteric whereas longan is non-climacteric, the heterologous tomato results demonstrate the regulatory potential of DlHB22 but do not establish an identical native ripening pathway in longan. Overall, DlHB22 is best regarded as a candidate transcription factor associated with longan fruit energy metabolism, whose native regulatory mechanism requires direct validation in longan. Full article

Lipedema and obesity are often misdiagnosed or clinically confused yet arise via distinct mechanisms, complicating diagnosis and treatment. This review synthesizes evidence differentiating these conditions across genetic, hormonal, inflammatory and mechanical pathways to identify therapeutic targets. Lipedema may involve genetic predisposition (forkhead box C2 [FOXC2], prospero homeobox 1 [PROX1]), hormonal dysregulation with aberrant aromatase activity, and altered adipogenesis (peroxisome proliferator-activated receptor gamma [PPARγ], CCAAT/enhancer-binding protein [C/EBP]). A proinflammatory microenvironment with macrophage M1/M2 imbalance, elevated interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and extracellular matrix remodeling is hypothesized to drive fibrosis. Emerging evidence implicates gut-derived endotoxemia (lipopolysaccharide [LPS]-toll-like receptor 4 [TLR4]-nuclear factor kappa-B [NF-κB]) and mechanotransduction (Yes-associated protein [YAP]/transcriptional coactivator with PDZ-binding motif [TAZ]) in adipocyte hypertrophy and treatment resistance. Obesity involves systemic metabolic dysfunction with visceral adiposity and cardiometabolic comorbidities. Lipedema patients maintain metabolic health, exhibit gluteofemoral fat distribution and experience neuropathic pain via nociceptor sensitization (transient receptor potential vanilloid 1 [TRPV1] and ankyrin 1 [TRPA1]) with central amplification. Weight-loss interventions are ineffective, necessitating targeted strategies. Promising targets include TLR4 antagonism, vascular endothelial growth factor C/vascular endothelial growth factor receptor-3 (VEGF-C/VEGFR3) modulation for lymphatic enhancement, YAP/TAZ inhibition and neuromodulators for pain. Physical therapy functions as a biological modifier targeting inflammation, lymphatic drainage and mechanotransduction. This review highlights promising but largely hypothesis-generating molecular insights and calls for validated biomarkers, rigorous clinical trials, and mechanism-based therapies. Many of the pathways discussed require further confirmation in human studies. Full article

Consensus molecular subtype 4 (CMS4) colorectal cancer (CRC) is associated with an aggressive clinical course and poor survival, yet the biological basis of heterogeneity within this subtype remains incompletely understood. DNA methylation is an epigenetic mechanism involved in transcriptional regulation, cellular differentiation, and colorectal tumorigenesis. Here, we integrated single-cell RNA sequencing (scRNA-seq), bulk data, and promoter DNA methylation data to characterize CMS4-associated cancer cell states and methylation-related features. Using the scAB algorithm, we integrated scRNA-seq with bulk CMS4 data and identified CMS4-related cells distributed across multiple patients. Single-cell analyses of cell–cell communication and transcriptional regulation revealed a CMS4-related cancer cell population characterized by macrophage migration inhibitory factor (MIF)-centered intercellular communication, enhanced caudal type homeobox 1 (CDX1) and Kruppel-like factor 5 (KLF5) regulon activity, and gene modules enriched in differentiation-related pathways. CytoTRACE analysis further stratified CMS4 cancer cells into poorly and well-differentiated states, yielding 802 differentially expressed genes (DEGs). Linking these differentiation-associated DEGs with bulk expression and promoter methylation data identified 218 methylation-associated DEGs showing significant inverse methylation expression correlations, suggesting a link between differentiation-related heterogeneity and promoter methylation. Univariable Cox regression followed by LASSO regression further prioritized eight genes for construction of the methylation and differentiation-related prognostic model (MeDiff-PM). MeDiff-PM consistently stratified overall survival in the TCGA CMS4 cohort and two independent validation cohorts, with cutoff-independent continuous Cox analyses further supporting its prognostic association across cohorts. And MeDiff-PM remained prognostically significant after adjustment for available clinical variables. High MeDiff-PM risk scores were associated with activation of P53, WNT, and ubiquitin-mediated proteolysis pathways and with consistent predicted drug response differences for compounds across three CMS4 cohorts. While individual in silico knockout analysis suggested links between MeDiff-PM genes and metallothionein-related and immune-associated transcriptional responses. Collectively, these findings indicate that methylation-associated differentiation features represent a molecular dimension of intra-CMS4 heterogeneity and provide a biologically informed framework for prognostic stratification within CMS4 CRC. Full article

Background: Homeobox transcription factors regulate developmental programs, cellular plasticity, and tumor progression, yet the role of H2.0-like homeobox (HLX) in prostate cancer (PCa) remains poorly defined. We investigated the clinical significance of HLX and its relationship to the pro-metastatic transcription factor TBX2. Methods: Transcriptomic and clinical datasets from TCGA, MET500, and SU2C/PCF cohorts were analyzed to assess HLX expression, clinicopathologic associations, and its relationship with TBX2. Functional studies in human PCa cell lines included TBX2 gain- and loss-of-function, HLX knockdown, chromatin immunoprecipitation (ChIP), and expression analyses. Shared HLX- and TBX2-associated pathways were evaluated by Reactome enrichment analysis, and Hallmark Gene Set Enrichment Analysis compared castration-resistant prostate cancer (CRPC) bone metastases with high versus low HLX expression (GSE77930; n = 5/group). In vivo relevance was assessed in an orthotopic TBX2 dominant-negative PCa xenograft model. Results: Human PCa datasets showed that HLX expression was elevated in PCa versus normal prostate tissue and associated with higher Gleason grade, lymph node involvement, aggressive molecular subtypes, and shorter disease-free survival. HLX expression also positively correlated with TBX2 across human PCa cohorts. HLX- and TBX2-associated transcriptional programs converged on extracellular matrix organization, cell adhesion, NOTCH, and VEGF-MAPK signaling pathways. Furthermore, HLX-high CRPC bone metastases were enriched for epithelial–mesenchymal transition, NOTCH, TGF-β, inflammatory, angiogenic, hypoxic, and KRAS signaling pathways. Mechanistic studies showed that HLX knockdown suppressed extracellular matrix-associated genes and key NOTCH pathway components. ChIP demonstrated direct TBX2 binding to the HLX promoter, and genetic modulation of TBX2 expression established HLX as a downstream target of TBX2. Consistent with these findings, reduced HLX expression in orthotopic TBX2 dominant-negative xenografts was associated with loss of metastatic progression. Conclusions: HLX is a candidate biomarker of aggressive PCa and a direct transcriptional target of TBX2. These findings identify a previously unrecognized TBX2–HLX regulatory axis associated with metastatic transcriptional programs and aggressive disease in advanced PCa. Full article

Benjakul (BJK) remedy, traditionally used to balance the four elements, has demonstrated clinical efficacy in relieving inflammation and allergic rhinitis (AR) symptoms. This study investigated differential serum peptide expression in AR patients treated with BJK remedy compared to loratadine using MALDI-TOF MS and LC-MS/MS. MALDI-TOF MS revealed four shared mass peptide patterns that were significantly upregulated (p < 0.05) after 3 and 6 weeks of both treatments. Identifying the peptides, 17β-hydroxysteroid dehydrogenase (17β-HSD) and microtubule-actin cross-linking factor 1 (MACF1) were linked to inflammatory suppression and hormonal balance, while zinc finger CCCH-type containing 4 (ZC3H4) and transducin beta-like protein 3 (TBL3) were associated with the relief of pulmonary fibrosis. Conversely, zinc finger homeobox 3 (ZFHX3) and transformation/transcription domain-associated protein (TRRAP) remained elevated after treatment, potentially promoting persistent inflammation via E2F transcription factor 1- (E2F1-) and E2F transcription factor 4- (E2F4-) mediated transcription. Among 1113 peptides identified by LC-MS/MS (selected using a significance threshold of p < 0.05, without a fixed fold-change cutoff), 6-week treatment with BJK remedy significantly downregulated UBQLN1 (4.562-fold; p = 0.016), suppressing toll-like receptor (TLR) activation and B-cell proliferation. It also upregulated Prostaglandin E synthase 2 (PTGES2) and PDZ and LIM domain protein 2 (PDLIM2) (7.841-fold and 8.697-fold, respectively; p = 0.004 and 0.002), while enhancing antioxidant and immunoregulatory responses via ATP-binding cassette subfamily B member 8 (ABCB8) and ADP-ribosylation factor GTPase-activating protein 3 (ARFGAP3). By comparison, 3 weeks loratadine treatment significantly downregulated E2F transcription factor 3 (E2F3) and general transcription factor IIIC subunit 6 (GTF3C6) (p = 0.034 and 0.017) and upregulated CTD small phosphatase like 2 (CTDSPL2), suggesting a distinct but complementary anti-inflammatory mechanism. Together, these findings enhance the understanding of AR pathophysiology and may help to elucidate the mechanisms of BJK remedy and loratadine in treatment, supporting the further development of targeted therapies and biomarkers. Full article

Somatic embryogenesis (SE) is an indispensable biotechnological platform for plant regeneration, micropropagation and genetic modification. Members of WUSCHEL-related homeobox (WOX) transcription factor family are key regulators in SE, yet their roles in Catalpa bungei remain largely unexplored. C. bungei is a high-quality ornamental tree species endemic to China with prominent horticultural ornamental value. Here, we present the first genome-wide identification and expression profiling of the CbWOX gene family during SE in C. bungei. Fourteen CbWOX genes were identified and phylogenetically classified into three major clades. These genes are distributed across the 11 chromosomes of C. bungei, and their promoter regions are enriched with cis-regulatory elements associated with phytohormone response, stress adaptation, and growth/development. Integrated transcriptome and quantitative real-time PCR (qPCR) data indicated that CbWOX2, CbWOX5, CbWOX8, and CbWOX9 were highly expressed in embryogenic callus (EC), while CbWOX1.1 and CbWOX13 were predominantly expressed in non-embryogenic callus (NEC). Notably, only eight of the fourteen CbWOX genes were significantly expressed during SE, with distinct expression profiles across developmental stages. CbWOX4.1 and CbWOX4.2 were specifically associated with yellow-green hypocotyl callus development, while CbWOX2 and CbWOX8 were highly expressed at the EC stage. During later SE stages, CbWOX1.2, CbWUS, CbWOX5, and CbWOX13 showed significant expression at the globular embryo (GE) stage, while CbWOX1.3 was specifically upregulated at the cotyledon embryo (CE) stage. Our study provides a comprehensive genomic and transcriptomic foundation for the CbWOX family in C. bungei and reveals candidate genes with stage-specific expression during SE. These findings lay a solid basis for subsequent functional research to boost SE efficiency and advance the large-scale propagation of this precious ornamental tree. Full article

Triple negative breast cancer (TNBC) continues to have a poor prognosis relative to other forms of this disease. Previous studies have shown that the HOX family of transcription factors generally show increased expression in breast cancer and may have a primarily pro-oncogenic role. In this study, we assessed the sensitivity of a range of TNBC-derived cell lines to an inhibitor of HOX protein function, HTL-001, which blocks the interaction between HOX proteins and the Pre-B-cell Leukaemia Homeobox (PBX) cofactor. The sensitivity of cell lines was measured by MTS viability assays, and gene expression by RT-qPCR. Combination studies were performed with epigenetic modifiers (5-azacytidine (5-aza), Trichostatin A (TSA)) and standard-of-care chemotherapeutic drugs including Paclitaxel. A mouse tumour flank model of MDA-MB-231 cells was used to assess response to HTL-001, paclitaxel, or combination therapy. All the cell lines exhibited high levels of HOX dysregulation compared to an immortalised line derived from normal breast cells, and greater sensitivity to HTL-001-induced apoptosis. Epigenetic changes have previously been shown to be key modulators of HOX expression and, correspondingly, we show that reversing epigenetic changes in these cell lines significantly alters HOX expression and generally reduces sensitivity to HTL-001. In addition, HTL-001 shows synergistic interactions with several established chemotherapeutic agents in vitro. We further demonstrate that HTL-001 can significantly reduce tumour growth in a mouse model of TNBC. Our findings indicate that HOX/PBX dimers are a potential therapeutic target in this cancer. Full article

Background and Objectives: Male factors account for approximately 30–50% of subfertile couples. Teratozoospermia is one of the major causes of male infertility; however, the genetic factors underlying many cases remain incompletely understood. This study aimed to identify potential genetic variants associated with teratozoospermia and to investigate the possible involvement of Caudal-Type Homeobox 4 (CDX4) in sperm morphogenesis. Materials and Methods: Whole-exome sequencing was performed in 44 individuals with teratozoospermia. A rare CDX4 variant (NM_005193.2, c.103G>T; NP_005184.1, Gly35Cys) was identified and confirmed by Sanger sequencing. Because CDX4 is located on the X chromosome, this variant was interpreted as hemizygous in the male patient. Sperm morphology, CDX4 localization, public GEO transcriptomic data (GSE6969), and CDX4 expression during murine spermiogenesis were analyzed. Results: The CDX4 p.Gly35Cys variant is located within the Caudal-like transactivation domain, a conserved region involved in transcriptional regulation. Spermatozoa from the patient carrying this variant exhibited severe morphological abnormalities, predominantly involving sperm-head defects, together with aberrant CDX4 localization along the midpiece and tail, in contrast to the neck- and annulus-enriched distribution observed in control spermatozoa. Reanalysis of the GEO dataset showed increased CDX4 transcript levels in teratozoospermic samples compared with normozoospermic controls. During murine spermiogenesis, CDX4 was detected in the nuclei of spermatogonia and spermatocytes and subsequently localized to the sperm head and neck/tail regions during sperm morphogenesis. Conclusions: CDX4 c.103G>T (p.Gly35Cys) is a rare hemizygous X-linked candidate variant associated with severe teratozoospermia in a single patient. Further cohort-based, segregation, and functional studies are required to clarify its role in sperm morphogenesis. Full article

Background: The Proline Rich Homeodomain/Haematopoietically Expressed Homeobox (PRH/HHEX) transcription factor down-regulates the proliferation of prostate cells, and it has been suggested that this protein acts as a tumour suppressor in prostate epithelial cells. Results: Here, we show that the HHEX gene encoding PRH, located at chromosome 10q23, is often deleted in prostate cancer cells. Moreover, the gene encoding PRH displays increased CpG methylation in prostate cancer cells, and PRH mRNA levels and protein levels are decreased in high Gleason grade prostate tumours. Using a doxycycline-inducible model, we show that over-expression of PRH in prostate cancer cells reduces cell proliferation and cell migration in vitro and inhibits tumour growth and tumour initiation in a mouse xenograft model. Similarly, PRH over-expression in a syngeneic mouse model reduces tumour growth. Interestingly, the inhibition of Protein Kinase CK2 in this model results in increased PRH protein levels in vitro, decreased cell viability, and reduced tumour growth in vivo. Conclusions: PRH acts as a tumour suppressor protein in prostate cancer cells and the re-establishment of PRH activity in these cells through the inhibition of PRH phosphorylation, or through other means, could be a useful approach to prostate cancer treatment. Full article

Class I KNOX1 (KNOTTED1-like homeobox 1) transcription factors integrate gibberellin (GA), cytokinin (CK), and auxin (IAA) signaling to maintain shoot apical meristem identity and coordinate plant organogenesis. This review examines the structural conservation, evolutionary dynamics, and regulatory architecture of KNOX1 genes across horticultural crops, drawing essential mechanistic context from model species. We synthesize KNOX1 functions in six agronomic domains, including plant architecture and branching, leaf morphogenesis and ornamental traits, floral development and sex determination, fruit formation and quality, storage organ specification, and abiotic stress resilience. Particular attention is given to recent breakthroughs in cucurbit inferior ovary development, tomato chloroplast patterning, and potato tuber morphogenesis. We identify critical bottlenecks constraining translation, including fragmented regulatory networks, recalcitrant transformation systems in woody perennials, uneven taxonomic coverage favoring annual vegetables over ornamentals and medicinal species, and a near-complete absence of multi-environment field validation. We propose four strategic priorities to bridge this gap: (i) construction of spatiotemporal expression atlases using single-cell and spatial transcriptomics; (ii) tissue-specific and promoter-engineered CRISPR/Cas9 editing to circumvent pleiotropic penalties; (iii) cross-species comparative evo–devo analysis of lineage-specific innovations (compound leaves, inferior ovaries, tubers); and (iv) integrated field trials assessing genotype-by-environment interactions and trait stability. This framework aims to accelerate KNOX1-directed molecular design breeding in horticultural crops. Full article

High-glucose exposure impairs intestinal metabolic homeostasis and barrier integrity in fish, but the transcriptional responses associated with high-glucose adaptation in fish intestinal epithelial cells remain incompletely understood. This study investigated whether exogenous 5-methylcytosine (5MC) alleviates high-glucose-induced metabolic and epithelial stress in grass carp (Ctenopharyngodon Idella) intestinal epithelial cells and whether these responses are associated with changes in DNA methyltransferase 3 beta (dnmt3b) expression and Caudal type homeobox 1b (cdx1b)/Sodium-glucose cotransporter 1 (sglt1)-related transcriptional responses. As exploratory in silico information, molecular docking predicted candidate complex conformations of DNMT3B with CDX1B and SGLT1, with binding energies of −37.2 and −25.9 kcal/mol, respectively. Functionally, dnmt3b knockdown significantly reduced dnmt3b, Interleukin 6 (il6), and Nuclear factor kappa B (nfκb) expression, while increasing cdx1b, sglt1, Solute carrier family 2 member 3a (slc2a3a), 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4a (pfkfb4a), and Amine oxidase copper containing 1 (aoc1) expression (p < 0.05). CDX2/CDX1B-like immunoreactive protein and SGLT1 protein levels were also increased after dnmt3b knockdown (p < 0.05). Under high-glucose stress, exogenous 5MC exerted concentration-dependent effects. Specifically, 6 mM 5MC significantly reduced residual extracellular glucose, lactate dehydrogenase and diamine oxidase activities, and malondialdehyde content, while increasing glutathione content, cell viability, and cell migration (p < 0.05). These effects remained detectable after replacement with high-glucose medium for an additional 12 h. By contrast, 24 mM 5MC markedly increased lactate dehydrogenase activity and reduced cell viability, suggesting potential cytotoxicity (p < 0.05). S-adenosylmethionine (SAM) levels were significantly lower in the NC and 6 mM groups than in the HG, 12 mM, and 24 mM groups, suggesting changes in SAM-related one-carbon metabolic status rather than direct evidence of altered DNA methylation (p < 0.05). Exogenous 5MC, particularly at 6 mM, alleviated high-glucose-induced metabolic and epithelial stress in grass carp intestinal epithelial cells. These effects were accompanied by changes in several glucose metabolism- and inflammation-related genes. However, the cellular uptake, metabolic fate, DNA incorporation, methylation consequences, and causal roles of these gene-expression changes remain to be further verified. Full article

Polygonatum cyrtonema is a medicinally and edible perennial herb, yet functional studies in this species are constrained by limited knowledge of regeneration-associated developmental regulators. Here, we performed a genome-wide characterization of the WUSCHEL-related homeobox (WOX) gene family in P. cyrtonema. Eleven PcWOX genes were identified and classified into the ancient, intermediate, and modern/WUS clades. Comparative phylogenetic, syntenic, structural, and chromosomal analyses indicated that the PcWOX family retains a conserved evolutionary framework but also exhibits clear lineage-specific diversification. Tissue- and stage-specific expression profiling, promoter cis-element analysis, and subcellular localization further supported functional differentiation among PcWOX members, particularly between PcWOX5 and PcWUS. Weighted gene co-expression network analysis identified 33 co-expression modules, including six key modules strongly associated with PcWOX abundance patterns, and prioritized 49 candidate transcription factors (TFs) to construct PcWOX-centered regulatory networks. These TFs showed marked tissue- and stage-dependent heterogeneity. Heterologous assays in Nicotiana benthamiana showed that both PcWUS and PcWOX5 enhanced regeneration competence but produced distinct developmental outputs. These findings support PcWUS and PcWOX5 as promising candidate morphogenic regulators and provide a useful framework for future mechanistic studies, homologous validation, and regeneration improvement in P. cyrtonema. Full article

Background: MEIS proteins are essential homeobox transcription factors that play critical roles in development and have been increasingly implicated in oncogenesis, including breast cancer. Methods: In this study, we identified and characterized novel small-molecule MEIS2 inhibitors through in silico docking targeting the active region of the human MEIS2 homeobox domain. Lead candidates MEISi-2E, MEISi-3, and MEISi-4 were identified with binding energies ranging from −3.0 to −3.90 kcal/mol. The inhibitory potential of these molecules was validated in vitro using a species-conserved MEIS-Luciferase Reporter construct containing the TGACAG targeted locus. Results: Our results demonstrate that MEISi-2E, MEISi-3, and MEISi-4 significantly suppress MEIS-driven luciferase activity and downregulate the expression of Meis1, Meis2, and downstream genes such as IL17RB, CDH1, EGR2, PAX6, and SERPINE1 while upregulating negative regulator TGIF1 and SOX3. In breast cancer cell lines, these inhibitors exhibited potent growth inhibition, with MEISi-3 showing an exceptional IC50 as low as 0.1 μM in SK-BR-3 cells. Mechanistic studies using flow cytometry revealed that these inhibitors induce dose-dependent apoptosis and necrosis. Importantly, the novel inhibitors showed minimal toxicity to healthy human dermal and MRC5 fibroblasts, suggesting a favorable safety profile. Conclusions: These findings establish these small molecules as promising therapeutic candidates for targeting MEIS2-dependent pathways in breast cancer. Full article

Catecholamines are crucial signaling molecules that initiate thermogenesis in adipocytes through beta-adrenergic receptors (ADRBs). Adipocyte catecholamine resistance is a common feature of pediatric obesity, often impeding weight loss and the maintenance of a healthy body fat percentage. Our aim was to identify possible mechanisms that may be responsible for the development of catecholamine resistance in adipocytes. We demonstrate that Lim homeobox 8 (LHX8), a transcription factor previously known for its role in gametogenesis, is essential for catecholamine-induced thermogenesis in human adipocytes. LHX8 is expressed in developing human adipocytes throughout intrauterine and perinatal life, as well as in adulthood, and its expression levels positively correlate with the expression of key thermogenesis genes. Pediatric obesity diminished adipocyte expression of LHX8. Functionally, ADRB stimulation failed to induce thermogenesis in both mouse and human adipocytes when LHX8 was absent. Conversely, LHX8 overexpression enhanced thermogenesis in murine adipocytes. Mechanistically, LHX8 stimulated adipocyte interleukin-33 (IL-33) synthesis in response to ADRB activation, which subsequently increased thermogenic gene expression in both human and mouse adipocytes. In conclusion, adipocyte LHX8 is indispensable for catecholamine-responsive thermogenesis and represents a promising novel therapeutic target to overcome catecholamine resistance and promote effective weight management. Full article

Heat stress (HS), increasingly intensified by climate change, severely restricts tomato growth and productivity. Although core heat shock factor-mediated transcriptional networks have been extensively characterized, how lipid metabolic reprogramming is transcriptionally coordinated during thermotolerance remains unclear. Using SlHDZ19 overexpression and mutant lines together with transcriptomic, biochemical, promoter-binding, and gene-silencing analyses, we show that the homeobox-leucine zipper transcription factor SlHDZ19 promotes tomato (Solanum lycopersicum) thermotolerance by activating a PLA2-dependent lipid-metabolic transcriptional program in leaves. SlHDZ19 overexpression generally improved heat-stress performance, while SlHDZ19 mutant lines exhibited heightened sensitivity, including more severe wilting, higher electrolyte leakage, and reduced proline accumulation and CAT activity under heat stress. Transcriptomic analysis revealed that SlHDZ19 is required for the full induction of canonical heat-responsive genes and that the linoleic acid metabolism pathway was repeatedly implicated in SlHDZ19-dependent transcriptional changes. SlHDZ19 binds to and activates the promoters of SlPLA_2α, which encodes a phospholipase A2 involved in releasing linoleic acid from membrane lipids, and three lipoxygenase genes (SlLox7, SlLox8, and SlLoxC), accompanied by elevated overall PLA2 and LOX activities in SlHDZ19-overexpressing plants. Moreover, genetic silencing of SlPLA_2α in both wild-type and SlHDZ19-overexpressing backgrounds supported its functional requirement downstream of SlHDZ19 in thermotolerance. Collectively, our findings support a thermotolerance module in which SlHDZ19 transcriptionally regulates PLA2- and LOX-associated steps of linoleic acid metabolism, potentially linking lipid-associated signaling and membrane remodeling with heat stress adaptation in tomato. Full article