Search Results (132)

Bacterial stem and root rot (BSRR), caused by Dickeya dadantii, poses a severe threat to global sweetpotato production, yet the genetic architecture underlying resistance remains elusive. To dissect these mechanisms, we conducted a high-resolution genome-wide association study (GWAS) on 135 diverse accessions, integrating two-year field phenotyping with best linear unbiased prediction (BLUP) and 6.8 million single-nucleotide polymorphism (SNP) markers. This approach mapped nine quantitative trait loci (QTLs) exhibiting significant allelic dosage-dependent effects, with the major locus, qBSRR.6.1 was the primary discriminator between resistant and susceptible genotypes. Crucially, transcriptomic profiling within these loci revealed distinct expression patterns: IbTCP5 and IbERF003 (located in qBSRR.5.1 and qBSRR.6.2) were highly expressed in the susceptible cultivar ‘Xinxiang’ but suppressed in the resistant ‘Guangshu87’. Furthermore, BSRR challenge identified IbPUB4, IbKCS5, and IbLig1 as priority candidate genes involved in defense, with expression patterns suggesting roles in ubiquitin-mediated protein turnover, cuticular wax biosynthesis, and DNA repair, respectively. In stark contrast, IbPUB25 was constitutively upregulated in ‘Xinxiang’, potentially acting as a negative regulator of immunity via degradation of target proteins. These findings elucidate the polygenic, dosage-sensitive nature of BSRR resistance and prioritize specific targets for future functional characterization. Pyramiding favorable alleles of positive candidates while silencing potential negative regulators like IbPUB25 offers a promising avenue for developing durable, high-resistance sweetpotato varieties. Full article

Clear-cell renal cell carcinoma (ccRCC) is characterised by constitutive activation of hypoxia-inducible factors (HIFs) following VHL loss, which contributes to tumour progression and therapeutic resistance. Given the limitations of VEGFR-targeted therapies, we investigated the biological and potential therapeutic relevance of the HIF axis in ccRCC. Nuclear and cytoplasmic HIF1A and EPAS1/HIF2A expression were assessed by immunohistochemistry in tumours from 40 patients and correlated with clinicopathological parameters and cancer-specific survival. The functional effects of HIF pathway inhibitors (GN44028, KC7F2, and FM19G11) and sunitinib were analysed in VHL-mutant 786-O and VHL-wild-type Caki-1 cell lines using SRB viability assay, cell cycle analysis, wound closure assay, and RT-qPCR of HIF-related genes, with comparison to non-malignant HK-2 cells. TCGA-ccRCC data from advanced-stage patients (III–IV, n = 185) were analysed as a complementary transcriptomic context. Nuclear, but not cytoplasmic, HIF1A and EPAS1/HIF2A expression was associated with advanced stage and shorter survival in univariable analyses. GN44028 showed the most pronounced antiproliferative effect under tested conditions and was associated with broad suppression of HIF-related transcription, whereas sunitinib was associated with increased expression of selected HIF-related genes. GN44028 did not demonstrate clear selectivity over non-malignant HK-2 cells. Overall, nuclear HIF activation is associated with aggressive ccRCC biology, and broader HIF pathway modulation warrants further experimental investigation; however, the clinical findings remain exploratory, and therapeutic selectivity and translational relevance are not yet established. Full article

Background: Wild jujube (Ziziphus jujuba var. spinosa) exhibits remarkable tolerance to saline-alkali stress, yet its molecular mechanisms remain poorly understood. 3-ketoacyl-CoA synthase (KCS) is a key enzyme involved in the biosynthesis of very-long-chain fatty acids (VLCFAs), which constitute pivotal precursors for membrane lipids involved in stress adaptation. Methods: Through genome-wide analysis and molecular biology techniques, 20 ZjKCS genes were identified. Results: The ZjKCS genes were grouped into nine subfamilies, exhibiting highly conserved gene structures, motifs, and functional domains within each subfamily. Two pairs of collinear gene pairs were identified, with the ZjKCS12-ZjKCS18 pair retaining core conserved functions despite intense purifying selection. ZjKCS genes are rich in cis-acting elements associated with light transduction, phytohormone responses, and abiotic stress adaptation. Tissue-specific expression patterns of ZjKCS under light, ABA (abscisic acid), and MeJA (methyl jasmonate) treatments were analyzed by quantitative real-time PCR (qRT-PCR). Under saline-alkali stress, ZjKCS genes were significantly upregulated, with most showing strong sustained induction during later treatment stages. Conclusions: These findings indicate that the ZjKCS family participates in saline-alkali stress and abiotic stress adaptation, potentially by enhancing VLCFA synthesis to reinforce and remodel membrane lipid structure. This study provides a foundation for elucidating lipid-mediated stress resistance mechanisms in stress-tolerant fruit trees. Full article

7-ketocholesterol (7-KC) is a bioactive oxysterol generated under oxidative stress and may contribute to bone marrow niche reprogramming in acute myeloid leukemia (AML), thereby promoting stress tolerance and therapeutic resistance Bone marrow mesenchymal stromal cells (MSCs) from healthy donors and AML patients were exposed to subtoxic 7-KC concentrations for 24 h. We evaluated the ABC transporters involved in lipid transport, multidrug resistance and membrane microdomain remodeling; Hedgehog pathway proteins; stress–survival signaling; redox balance by glutathione measurements, and mitochondrial function and dynamics, including membrane potential and gene expression of mitochondrial fission and fusion regulators. Results were integrated using principal component analysis (PCA), heatmaps, and correlation-based networks. Multivariate analyses revealed an integrated, lineage-dependent response. Healthy donor MSCs showed greater plasticity of the efflux and microdomain axis and higher oxidative and mitochondrial vulnerability at high 7-KC doses. AML-MSCs exhibited a basal preconditioned state phenotype and preferentially routed the response toward Hedgehog and stress–survival modules, accompanied by glutathione expansion and adaptive mitochondrial remodeling. 7-KC acts as a broad modulator of several MSC functions, linking sterol homeostasis to Hedgehog signaling, stress–survival pathways, redox balance, and mitochondrial remodeling, potentially supporting a pro-survival, more therapy-tolerant leukemic niche. Full article

The accumulation dynamics and regulatory mechanisms of the alkylamides, the key pungent compounds in the fruits of Sichuan peppers, remain poorly understood. Using fruits of the Zanthoxylum planispinum var. dintanensis (Dintan) harvested at five key developmental stages, we comprehensively mapped the accumulation of numbering compounds and their underlying molecular drivers by integrating HPLC-based metabolite profiling and de novo transcriptomics. Total alkylamide content increased during development, with hydroxyl-α-sanshool (HαSS) being predominant. The contributions of hydroxyl-β-sanshool (HβSS) and hydroxyl-ε-sanshool (HεSS) increased in later stages. Cluster and correlation analyses identified 51 candidate genes strongly correlated (|r| ≥ 0.6) with HαSS accumulation, predominantly enriched in fatty acid and branched-chain amino acid metabolism pathways. The expression patterns of five stearoyl-CoA desaturase (SCD) genes, one long-chain acyl-CoA synthetase (ACSL/fadD), and one S-(hydroxymethyl)glutathione dehydrogenase/alcohol dehydrogenase (frmA) gene closely mirrored HαSS accumulation. In contrast, 3-oxoacyl-[acyl-carrier-protein] synthase II (fabF) and one β-ketoacyl-CoA synthase (KCS) gene exhibited a negative correlation. Accordingly, a positive regulatory network was constructed for HαSS accumulation. These findings revealed key candidate targets for deciphering the molecular basis of its unique flavor and for breeding high-pungency cultivars. Full article

Nervonic acid (NA), a very-long-chain monounsaturated fatty acid, is known for its benefits in treating neurological diseases and promoting brain health. In this study, we utilized two different receptors, Brassica juncea (B. juncea, rich in erucic acid, C22:1) and Brassica napus (B. napus, high in oleic acid, C18:1), to overproduce NA through systematic metabolic engineering. Two multi-gene vector constructs, Napin-3 and Napin-5 (CgKCS::SLC1-1::DGAT1; CgKCS::SLC1-1::BnFAE1::LdLPAAT::DGAT1), are driven by seed-specific napin promoters. In B. juncea, Napin-3 and Napin-5 expression elevated NA levels to 48.7% and 46.3% in seed oil, respectively, compared to 2.5% in wild types. In B. napus, Napin-3 and Napin-5 expression achieved NA levels of 45% and 39.6%, respectively, while NA is absent in wild types. To our knowledge, this represents the highest NA production in plants to date, with stable oil content and yield, enabling cost-effective NA production. In B. juncea, a significant increase in NA is observed alongside a decrease in C18:1, C20:1, and C22:1 levels; in B. napus, the rise in NA is accompanied by a decrease in C18:1, and an increase in C20:1 and C22:1. These patterns reflect the dynamic equilibrium of fatty acids following NA conversion, influenced by the Dynamic Substrate Tugging (DST) Mechanism, in the form of either an EA-tugging mode or C18:1-tugging mode mechanism, depending on the cellular context. NA is an elongation product derived from C18:1, catalyzed by CgKCS with broad substrate specificity, indicating that plants with high levels of C18:1, similarly to those rich in C22:1, serve as excellent candidates for NA production. This “green factory” for NA production provides strong support for its pharmaceutical, nutraceutical, and industrial applications. The exogenous and the endogenous enzymes coordinate function remodeling of the intra-seed fatty acid elongation flux through the DST strategy, thereby systematically enhancing the synthesis and accumulation efficiency of the target fatty acid. Full article

Background/Objectives: Hypoparathyroidism (HPT) is a disorder caused by the insufficient production of parathyroid hormone (PTH). Its main features include decreased serum calcium, increased serum phosphorus, and abnormal bone modeling. In children, HPT is most commonly due to genetic disorders. Among rare genetic syndromes that can include HPT in their clinical spectrum is Kenny–Caffey syndrome (KCS) type 2. Conventional therapy for HPT primarily consists of oral calcium and active vitamin D metabolites. The major limitation of conventional therapy is hypercalciuria with an increased risk of nephrocalcinosis. However, a subset of patients fails to achieve the desired therapeutic response to conventional treatment; the reasons for this remain incompletely understood in some cases. The failure to achieve therapeutic targets and persistent hypercalciuria are the main indications for considering therapy with recombinant human parathyroid hormone (rhPTH). Methods: In addition to the review of the literature on rhPTH use in pediatric hypoparathyroidism, the first application of rhPTH in the treatment of genetically caused HPT in a child with Kenny–Caffey syndrome type 2 (KCS2) was described. Results: In this paper, we present a two-month-old infant who received rhPTH for 14 months. A heterozygous de novo p.Ser541Pro variant in the FAM111A gene was identified through whole-genome sequencing, indicating a diagnosis of KCS2. A biological mechanism linking FAM111A protein function with a more profound disruption of parathyroid development or function was proposed, suggesting that rhPTH therapy may be particularly beneficial in KCS2 cases. Conclusions: This is the first reported use of rhPTH in a child in Serbia and the first reported use in KCS type 2. By reviewing the literature, we analyzed the conditions in which rhPTH has been used, dosing approaches and durations, requirements for concomitant conventional therapy during rhPTH treatment, and the effects of rhPTH on calciuria. We provide an overview of rhPTH use in children. Additionally, based on the pathogenic genetic variant responsible for KCS2 in our patient, we propose possible etiologic explanations. This work aims to encourage a consideration of rhPTH use in children following its official approval. Full article

Background/Objectives: The 3-ketoacyl-CoA synthase (KCS) enzyme is a key and rate-limiting component in the biosynthesis of very long-chain fatty acids (VLCFAs). Through controlling VLCFA production, KCS plays an essential role in plant cuticle formation. The necrotrophic fungus Botrytis cinerea can infect all aboveground parts of rose plants (flowers, leaves, and stems), causing severe economic losses. KCS restricts pathogen invasion by influencing cuticle formation and enhances tolerance to environmental stresses. While the KCS gene family has been well-studied in some plants, it remains unexplored in rose (Rosa × hybrida Hort.), a species of significant ornamental and economic value. Methods: In this study, we conducted a genome-wide analysis of the RcKCS gene family in rose, identifying 18 non-redundant genes. Phylogenetic, structural, and synteny analyses were performed to investigate the evolutionary relationships, gene architecture, and duplication events. The expression patterns of RcKCS genes in rose petals during B. cinerea infection were examined, and transient overexpression and silencing of RcKCS6 were used to study its function. Results: RcKCS6 was found to be upregulated during gray mold infection, and transient overexpression reduced lesion size on infected petals. Conclusions: Our study provides the first comprehensive analysis of the RcKCS gene family in rose and highlights RcKCS6 as a potential candidate for improving resistance to gray mold in rose through molecular breeding. Full article

This study aimed to systematically identify the active constituents of Kadsura coccinea (Lem.) A. C. Smith (KC) and elucidate their potential mechanisms in treating rheumatoid arthritis (RA) using an integrated analytical and computational approach. Chemical profiling of KC root extract was performed by UPLC-Q-TOF-MS/MS. Active compounds and their targets were predicted using the SwissTargetPrediction database, while RA-related genes were retrieved from OMIM, GeneCards, and DisGeNET. A compound–target network was constructed and analyzed via Cytoscape. Functional enrichment analyses and protein–protein interaction (PPI) clustering were conducted to identify key pathways. Molecular docking was employed to validate interactions between core compounds and key RA targets. A total of 90 compounds were identified, primarily 36 lignans and 29 triterpenoids. Network analysis revealed 145 overlapping targets between KC and RA. These targets were further associated with 65 compounds derived from KC. Key compounds such as kadcoccinone F, kadsuralignan I and schisantherin M were linked to hub targets including MAPK14, MMPs, and JAKs, which are involved in inflammatory signaling, matrix degradation, and immune regulation. Molecular docking confirmed strong binding affinities (ΔG < −5.0 kcal/mol) between representative KC compounds and targets like MMP1, MMP2, JAK2 and JAK3, supported by analyses of hydrogen bonding, hydrophobic, and π-interactions. These results suggest that KC exerts anti-RA effects through multi-component, multi-target mechanisms, primarily modulating inflammatory signaling, immune cell recruitment, and tissue-destructive pathways. This study provides a pharmacological basis for the traditional use of KC in RA management and supports its potential as a complementary therapeutic agent. Full article

Background: Keratoconus (KC) is a progressive corneal ectasia and a leading cause of corneal transplantation in young adults. Once regarded as a biomechanical disorder, KC is now recognized as a complex disease driven by genetic predisposition, epigenetic modulation, and environmental triggers. Advances in genomics and transcriptomics have begun to elucidate the molecular mechanisms underlying corneal thinning and ectasia. Objectives: This review synthesizes two decades of evidence on the genetic and epigenetic architecture of keratoconus, highlights key molecular pathways implicated by these findings, and discusses translational implications for early diagnosis, risk prediction, and novel therapeutic strategies. Methods: A narrative review was conducted of peer-reviewed human, animal, and in vitro studies published from 2000 to 2025, with emphasis on genome-wide association studies (GWAS), sequencing data, methylation profiling, and non-coding RNA analyses. Findings were integrated with functional studies linking genetic variation to molecular and biomechanical phenotypes. Results: Genetic studies consistently implicate loci such as ZNF469, COL5A1, LOX, HGF, FOXO1, and WNT10A, alongside rare variants in Mendelian syndromes (e.g., brittle cornea syndrome, Ehlers–Danlos spectrum). Epigenetic research demonstrates altered DNA methylation, dysregulated microRNAs (e.g., MIR184, miR-143, miR-182), and aberrant lncRNA networks influencing extracellular matrix remodeling, collagen cross-linking, oxidative stress, and inflammatory signaling. Gene–environment interactions, particularly with eye rubbing and atopy, further shape disease expression. Translational progress includes polygenic risk scores, tear-based biomarkers, and early preclinical studies using RNA-based approaches (including siRNA and antisense oligonucleotides targeting matrix-degrading and profibrotic pathways) and proof-of-concept gene-editing strategies demonstrated in corneal cell and ex vivo models. Conclusions: Keratoconus arises from the convergence of inherited genomic risk, epigenetic dysregulation, and environmental stressors. Integrating multi-omic insights into clinical practice holds promise for earlier detection, precision risk stratification, and development of targeted therapies that move beyond biomechanical stabilization to disease modification. Full article

As a vital appearance quality trait of broccoli, curd-surface wax powder not only affects its commercial value but also plays a key role in plant resistance to abiotic stresses. However, its formation mechanism remains unclear. Using low-wax variety CK (‘QH18’) and high-wax variety T1 (‘QHMS4’) as materials, this study systematically elucidated the molecular mechanism of wax powder formation via physiological indexes, scanning electron microscopy (SEM), targeted metabolomics, and transcriptomics. Determination of fatty acid (FA) content in broccoli flower bud tissue showed a close association between FA content and wax deposition. SEM observation revealed that T1 had significantly denser wax crystals, mainly granular, than CK. Targeted metabolomics identified 25 fatty acids in the two varieties. And the linolenic and palmitic acids, with high content and significant differences, may be key metabolites regulating wax synthesis. Integrated transcriptomics and metabolomics indicated that BolfabG, BolLACS, BolKCS1, BolKCS2 and BolMAH1 genes are involved in wax biosynthesis. Moreover, AP2/ERF-ERF transcription factor (TF)-encoding genes (BolERF018, BolERF1F.1, BolERF1F.2 and BolERF1C) played the primary role in regulating wax biosynthesis, followed by NAC (BolNAC62.1), MYB (BolMYB44), and MADS-MIKC(BolPISTILLATA). These TFs may regulate BolfabG, BolLACS, BolKCS1, BolACOX2 and BolACAA1 to affect linolenic and palmitic acid balance, altering wax precursor synthesis and accumulation, and finally leading to differences in wax morphology and content. This study reveals a “Transcription Factors–Differentially Expressed Genes–Differentially Accumulated Metabolites–Fatty Acids” (TFs-DEGs-DAMs-FA) network, providing a basis for understanding broccoli wax formation. Full article

Glossy appearance is a critical trait that affects the appearance quality and marketability of leafy vegetables, including Chinese cabbage. The glossy trait is primarily associated with cuticular wax. Although several genes involved in cuticular wax biosynthesis have been characterized in Chinese cabbage, the regulatory relationships among them remain unclear. In this study, we identified a glossy mutant, glossy leaf4 (gl4), and cuticular wax crystals in the gl4 mutant were obviously reduced. Genetic analysis indicated that the glossy phenotype in the gl4 mutant appears to be controlled by a single recessive gene. Using a bulked segregant analysis coupled with next-generation sequencing (BSA-seq) and map-based cloning methods, the AtCER2 homologous gene BrCER2 was identified as the candidate gene. BrCER2 was expressed in various tissues, and BrCER2-GFP was localized in the endoplasmic reticulum (ER). Furthermore, BrCER2 could interact with BrKCS6 in the ER, and the expression levels of some wax biosynthesis-related genes were decreased in the gl4 mutant. Our overall results provide insights about the role of BrCER2 in wax biosynthesis through ER localization and interaction with BrKCS6 in Chinese cabbage. Full article

Collagen types I and III are primary structural proteins that maintain human skin integrity, and their ratio is disrupted during aging. In this study, we developed a biomimetic 3D skin model with vascularization potential to evaluate the effects of nano-zinc oxide (nano-ZnO) in a physiologically relevant context. The model used methacrylated recombinant human collagen (RHC-MA) bioinks with tunable collagen I/III ratios that mimic the skin of children and adults. The bioinks exhibited excellent printability and mechanical properties that enabled the 3D bioprinting of full-thickness skin products, including dermal layers with human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as epidermal layers with keratinocytes (KCs). The model recapitulated native skin architecture, and key markers such as keratin 10 (K10), keratin 14 (K14), and cluster of differentiation 31 (CD31) were determined. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that nano-ZnO significantly modulated genes associated with apoptosis, inflammation, and oxidative stress in skin cells. Full article

Seed physical dormancy, also known as hard-seededness, is a characteristic commonly found in higher plants, which functions to prevent water and oxygen from passing through the impermeable seed coat. Background: Notably, seed dormancy has emerged as a critical factor in the domestication of leguminous plants. Alfalfa (Medicago sativa L.) is a globally cultivated high-quality legume forage crop, while the seeds from different varieties maintain varying degrees of hard-seededness. However, the molecular mechanisms underlying physical dormancy in alfalfa seeds remain poorly understood. In particular, the regulatory mechanisms at the transcriptomic level remain unclear, which has hindered the breeding process of varieties with low hard-seededness. Methods: In this study, we performed global transcriptome analysis to discover the genes specifically expressed in the alfalfa seed coat and provide insights into alfalfa seeds’ physical dormancy domestication traits. RNA sequencing was performed on various alfalfa tissues, including roots, stems, leaves, flowers, and seed coats. Results: This analysis led to the identification of 4740 seed coat-specific expressed genes, including key genes such as KNOX4 (a class II KNOTTED-like homeobox gene), qHs1 (encoding endo-1,4-β-glucanase), GmHs1-1 (encoding a calcineurin-like metallophosphoesterase), and KCS12 (β-ketoacyl-CoA synthase). In addition, several seed coat-specific transcription factor families were identified, including ERF, B3, and NAC, among others. Furthermore, a comparison of gene expression profiles between seeds with and without physical dormancy revealed 60 upregulated and 197 downregulated genes associated with physical dormancy. Crucially, functional enrichment analysis demonstrated that these genes are predominantly associated with lipid metabolism pathways, particularly those involved in the formation of “monolayer-surrounding lipid storage bodies.” Conclusions: This key finding suggests that the establishment of physical dormancy is closely linked to the biosynthesis and deposition of specialized lipid-based layers in the seed coat, which likely constitute the primary barrier to water penetration. Our study thus provides fundamental insights and a valuable genetic resource for future functional studies aimed at deciphering and manipulating physical dormancy in alfalfa. Full article

A high salt environment seriously affects the physiological metabolism and yield of plants. Hordeum brevisubulatum (Trin.) Link has high biomass and important ecological, feeding and economic values, but its growth conditions have serious saline-alkali effects. The NHX gene family plays a vital role in regulating intracellular Na⁺/K⁺ balance, pH homeostasis, and vesicle and protein transport in plants. In this study, the HbNHX2 gene was cloned from Hordeum brevisubulatum and functionally characterized through phenotypic, physiological, and molecular analyses in transgenic tobacco. Expression profiling revealed that HbNHX2 was most abundant in spikes and least abundant in root tips, and the expression level was significantly induced under salt stress. Overexpression of HbNHX2 led to decreased malondialdehyde (MDA) and superoxide anion (O²⁻) levels, while it enhanced the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Additionally, the levels of glutathione (GSH), soluble proteins, proline, and chlorophyll were also increased. Several stress-responsive genes, including CBL1, ERF2, BI-1, Cu/Zn-SOD, Mn-SOD, POD, GR1, KC1, TPK1, TIP, P5CS, BAS1, STN7 and LTP1, were significantly upregulated, while SERK3B was downregulated. These findings suggest that HbNHX2 enhances plant salt tolerance by maintaining osmotic balance, scavenging reactive oxygen species (ROS), and regulating stress-responsive gene expression. This study provides new insights into the molecular mechanism of salt tolerance in Hordeum brevisubulatum and lays a foundation for breeding salt-tolerant forage crops. Full article