The bZIP transcription factor ABI5 (Abscisic acid insensitive 5) plays a central role in regulating responses to ABA (Abscisic acid) signals during seed germination and early growth. In Arabidopsis thaliana, ABI5 is strongly induced by ABA, and high ABI5 expression inhibits seed germination. Plant MYB (Myeloblastosis) proteins respond to multiple hormonal signals, including ABA. Moreover, many R2R3 MYB transcription factors show functional similarities to ABI5; however, regulation of ABI5 transcriptional activity by R2R3 MYB factors during seed germination remains insufficiently characterized. In this study, we found that BoMYB96 and BoMYB2 bind the BoABI5 promoter and inhibit its transcription. A. thaliana and Brassica napus lines overexpressing BoMYB96 or BoMYB2 exhibited ABA insensitivity when exposed to exogenous ABA, which increased rapeseed germination rates under ABA treatment. These results demonstrate functional conservation of AtMYB96 and AtMYB2 in ABA signaling and expand understanding of ABI5 transcriptional regulation in the genomes of Brassica oleracea and B. napus.

Seed priming with engineered nanoparticles can promote seed germination. Herein, we investigated how priming seeds with antioxidant poly(acrylic acid)-coated cerium oxide nanoparticles (PNC, 0.05 mM) impacts seed germination in cotton (Gossypium hirsutum L.). Seed priming with PNC significantly increased cotton hypocotyl elongation by 13 %-37 %, promoting seed germination in pot experiment. Meanwhile, the emergence rate increased by 15 %-16 % with 0.05 mM PNC-seed priming in the field. Transcriptome analysis identified PNC-induced differentially expressed genes (DEGs) related to the phytohormone, auxin (IAA), and brassinosteroid (BR) biosynthesis (e.g. GhTAA1, GhYUCCA, GhALDH, GhGH3, GhCYPs) and signal transduction (e.g. GhSAUR, GhBZR1). Consistently, PNC priming increased the accumulation of IAA (10 %-25 %) and BR (86 %-100 %) in cotton hypocotyls. In addition, PNC enhanced the expression of the xyloglucan endotransglucosylase/hydrolase (XTHs) genes, regulated by SAUR and BZR1 through IAA and BR signaling pathway and critical for cell elongation. Also, the cell lengths of the epidermis, endodermis, xylem, and pith in cotton hypocotyl increased by 21 %, 17 %, 31 %, and 21 %, respectively upon seed priming with 0.05 mM PNC. The results provide insights into the molecular mechanisms of nanoparticles-seed priming enhancement of plant seed gemination.

Soil alkalinity and heavy metal toxicity are major abiotic stresses that severely limit plant growth and crop productivity. Wild soybean (Glycine soja) exhibits strong alkaline tolerance, making it a valuable genetic resource for improving cultivated soybean. Previous studies identified Gshdz4 and GsNAC019 as key alkaline-tolerant transcription factors, and GsEXPA8 as an alkaline-tolerant expansin protein. This study establishes a hierarchical "nucleus-nucleus-membrane" regulatory model in wild soybean, wherein the nuclear master transcription factor Gshdz4 transcriptionally upregulates GsNAC019, which in turn activates the expression of the plasma membrane-localized expansin GsEXPA8, collectively enhancing alkaline tolerance. We further investigated the role of Gshdz4 in conferring resistance to combined sodium bicarbonate and cadmium chloride stress in soybean. Through integrated RNA-seq and CUT&Tag-seq analyses, we identified Gshdz4 as a direct binder and regulator of diverse stress-responsive genes-including GmDEAH5, GmHSP22.3, GmACR4, and GmATG1c. Under alkaline stress, Gshdz4 modulates GmSLX8, GmSF3, and GmPP4; under cadmium stress, it regulates GmGMFL01 and GmUNC, establishing a broad-spectrum defense mechanism. Additional targets encompass splicing factors, heat shock proteins, ABA signaling components, and ethylene-responsive factors. GO and KEGG enrichment analyses confirmed that Gshdz4 participates in multiple hormonal pathways (ABA, IAA, ET, JA) and stress response signaling. Our findings revealed Gshdz4 as a master transcriptional regulator under multiple stresses and provide a theoretical foundation for molecular breeding strategies to enhance soybean resilience.

Cd contamination poses significant ecological risks. Quercus dentata, a tree species of high ecological value, exhibits exceptional tolerance to adverse environmental conditions. This study used Q. dentata as material to investigate its physiological response characteristics and potential molecular mechanisms under different concentrations of Cd stress (0, 200, 400, 600 mg/L). Results showed that with increasing stress concentration, the growth and photosynthesis parameters of Q. dentata continued to decline, while cell membrane permeability parameters, antioxidant enzyme activities, osmoregulatory substances, and Cd accumulation in various tissues continued to increase. Transcriptome sequencing also showed significant enrichment of photosynthesis, oxidative stress, amino acid synthesis, and ion binding-related genes (RBOH, SOS, POD). Based on the transcriptomic analysis, we found that numerous transcription factors (MYB, AP2, and WRKY) and heavy metal transport proteins (MTP, OPT, and HMP) played significant roles in the molecular mechanisms of Q. dentata's response to Cd stress. According to qPCR results, we identified the key gene QdMTP10.3, whose expression was continuously upregulated in different tissues with increasing treatment concentrations, conferring Cd2+, Fe2+, and Mn2+ tolerance to yeast cells. In summary, it is concluded that Q. dentata enhances its tolerance to Cd stress by modulating plasma membrane permeability, osmoregulatory substance content, and antioxidant enzyme system activity, while QdMTP10.3 gene plays a pivotal role in Cd response to heavy metal stress similarly, conferring potential for genetic improvement of heavy metal tolerance in plants.

Cadmium (Cd), a highly toxic element, poses significant constraints on global crop distribution and productivity. A better understanding of the molecular mechanisms underlying the response to Cd stress will help improve plant performance under Cd-exposed conditions. Here, we aimed to elucidate the complex response mechanisms of two oat varieties (CEav5651 and T1402) to Cd stress through integrated metabolomic and transcriptomic analyses. Our findings demonstrated that CEav5651 exhibited superior Cd tolerance compared to T1402. Metabolomic profiling revealed that glutathione and nicotianamine levels were significantly elevated in both varieties under Cd stress, with CEav5651 accumulating substantially higher concentrations of these two metabolites than T1402. This differential accumulation was corroborated by corresponding transcriptomic alterations. Critically, exogenous application of glutathione or nicotianamine markedly enhanced plant Cd tolerance. Heterologous overexpression of AsGS3 and AsNAS17, key genes in glutathione and nicotianamine biosynthesis, respectively, in tobacco (Nicotiana tabacum) elevated endogenous levels of these metabolites and conferred enhanced Cd tolerance. Our findings reveal the pivotal, coordinated role of glutathione and nicotianamine metabolism in Cd tolerance and provide promising genetic targets for breeding resilient crops.

Plants have evolved intricate and sophisticated mechanisms to sense and respond to boron (B) stresses. Alterations to the cell wall and other molecular pathways are strategies that help plants adapt to B stresses by cross-linking with rhamnogalacturonan II (RG-II) to form borate-dimers. However, the molecular mechanism by which cell wall components and organization respond to B stresses is not fully understood in mulberry plants. This study, via conjoint transcriptomics-metabolomics and virus-induced gene silencing analyses, aimed to explore the diverse B stress response mechanisms and functionally characterize the role of MaXTH23 in cell wall remodeling in mulberry leaves subjected to different levels of B, ranging from deficiency (0 mM; T1), sufficiency (0.1 mM; control, CK), moderate deficiency (0.02 mM; T2), toxicity (0.5 and 1.0 mM as T3 and T4, respectively) and cultivated under greenhouse conditions. The analyses identified a total of 6114 and 441 differentially expressed genes (DEGs) and metabolites (DEMs), respectively, in the different KEGG pathways in the separate omics analysis for all treatments. However, our conjoint analysis identified 1120 DEGs associated with 78 DEMs and were significantly co-enriched in 96 different KEGG pathways. Meanwhile, the functional characterization via silencing of MaXTH23 did not nullify its function in cell wall modification and remodeling but concomitantly caused significant increases in total pectin and water-soluble pectin contents, quintessentially promoting pectin cross-linking in the cell wall. This study highlights a novel perspective for identifying and characterizing the regulatory functions of MaXTH23 and the B-induced pathways and tolerance mechanisms employed by mulberry plants.

Anti-CD38 antibodies (Abs) are promising immunotherapeutics for hematologic malignancies, but their efficacy in leukemias often requires pharmacologic upregulation of CD38. Immuno-PET provides a noninvasive strategy to evaluate such target modulation in vivo. Cysteine site-specific 89Zr labeling of anti-CD38 Abs was performed using deferoxamine-maleimide. CD38-specific target binding was confirmed in three human myeloma and two leukemia cell lines. Total and surface expressed CD38 levels were assessed by Western blotting and flow cytometry. Immuno-PET imaging and biodistribution studies were conducted in murine leukemia models. All-trans retinoic acid (ATRA) was used to stimulate CD38 expression. Myeloma and MOLT4 leukemia cells showed variable baseline CD38, while HL60 cells exhibited negligible levels. All tumor cells demonstrated 89Zr-OKT10 IgG and 89Zr-daratumumab (Fc-silenced) binding that paralleled surface CD38 expression. ATRA upregulated CD38 in all tested cells, including a marked induction in HL60 cells, all accompanied by corresponding elevations in 89Zr-CD38 Ab binding. On 89Zr-OKT10 IgG PET, MOLT4 tumors showed high uptake that was reduced by 67.9% with unlabeled Ab, but HL60 tumors showed low uptake and high liver accumulation, limiting ATRA assessment. 89Zr-daratumumab produced lower liver uptake and improved MOLT4 and HL60 tumor visualization; ATRA modestly increased MOLT4 tumor uptake and substantially enhanced HL60 tumor uptake from 8.0 ± 1.7 %ID/g to 14.7 ± 3.1 %ID/g (83.8% increase; P < 0.005). Mechanistic studies demonstrated ATRA-induced ERK1/2 activation in HL60 cells that was abolished by the MAPK inhibitor U0126; U0126 also suppressed CD38 induction and 89Zr-CD38 Ab uptakes in all tested tumor cells. Furthermore, U0126 blocked ATRA-induced HL60 tumor 89Zr-daratumumab uptake in vivo. Western blots and immunohistochemistry confirmed ATRA-induced HL60 tumor CD38 elevation, which was partly reversed by U0126. Thus, 89Zr immuno-PET enables noninvasive monitoring of ATRA-driven CD38 upregulation via MAPK signaling and supports its potential utility for optimizing combination strategies in leukemias.

In an attempt to identify markers that better characterize microglial states and to search for potential therapeutic targets, we performed a study using the IMG cell line as an in vitro microglial model. Specifically, we tested its response to several pro-inflammatory stimuli (lipopolysaccharide, interferon gamma, and tumor necrosis factor) and an anti-inflammatory stimulus (Interleukin-4) after 12 and 24 h of incubation. We performed RNA sequencing to identify genes modified at both incubation times (i.e., genes with sustained changes in the window between 12 and 24 h) that could reflect sustained microglial transcriptional responses. We also used Gene Ontology (GO) analysis to identify the most relevant pathways modified by these stimuli. RNA sequencing revealed four gene sets: (1) common genes that respond similarly to IL-4 and LPS, (2) specific LPS responders, (3) specific IL-4 responders, and (4) genes that exhibit LPS-induced upregulation and IL-4-induced downregulation, and vice versa (opposite responders). We hypothesize that the common gene set represents a general microglia response to pathological conditions, while the LPS- and IL-4-responder gene sets define specific microglial states under pro- and anti-inflammatory stimuli, respectively. We further propose that opposite responder genes act as metabolic switches between certain microglial states. The GO analysis indicated that LPS strongly upregulates biological processes related to the innate immune response, while IL-4 upregulates pathways related to repair, metabolic reprogramming, and cellular cooperation. Finally, the transcriptional response of IMG cells closely mirrored that of primary microglia, revealing highly similar gene expression and GO term profiles under LPS stimulation.

GATA6 promotes epithelial phenotypes and limits epithelial-to-mesenchymal (EMT) transition in pancreatic ductal adenocarcinoma (PDAC). Here we show that GATA6 defines a tumor cell state that induces MHCI expression and anti-tumor cytotoxicity upon therapy. In human PDAC, GATA6 expression correlates with immune cell infiltration, and spatial analysis reveals interaction between GATA6+ tumor cells and CD8+ T cells. In murine PDAC, MEK inhibition (MEKi) enriches antigenicity-related gene sets in GATA6high cells, while GATA6 knockout or degradation impairs MEKi-induced MHCI upregulation. High-GATA6 tumors respond to MEKi with increased MHCI, enhancing T-cell cytotoxicity, whereas GATA6 loss abolishes this effect. Treatment-induced EMT reduces GATA6+ populations and MHCI expression, which is restored by combining MEKi with HDAC inhibitors, enhancing GATA6+ tumor cells, MHCI, CD8+ T cell infiltration, tumor suppression, and survival. These findings suggest that therapeutic strategies promoting a GATA6-driven tumor cell state improve immune recognition of PDAC cells and potentiate anti-tumor cytotoxic effects.

Piperine is a common anti-ischemic compound and an active ingredient of herbal medicine for various ailments. It is widely sourced and affordable. However, its bioactivity and anti-ischemic effects on retinal ischemic injury are unknown. The chemical-gene interactions of piperine were analyzed using data from "SwissTargetPrediction," "Binding DB", and "TargetNet" databases. Gene expression data from GSE43671 dataset and the Kyoto encyclopedia of genes and genomes (KEGG) were used for differential gene and ontology analyses. To evaluate the activation of disease pathways, by analyzing gene sets and applying weighted gene co-expression networks to differential gene interaction data. Additionally, molecular complex detection analyses of retinal ischemia and control samples were performed to determine which genes are affected by piperine, to compare gene expression differences, and to map receiver operator characteristic data. Utilizing network pharmacology and transcriptome sequencing, this study elucidates the targets and pathways affected by pharmacological interventions involving piperine in retinal ischemia injury. 176 target genes connected to piperine were identified and retrieved. Screening of 8 hub genes using machine learning. Through screening, we detected disease-associated genes, differential genes, and drug targets, and pinpointed two biomarker genes, Aoc3 and Gabra3. We found that piperine may have a protective effect on retinal ischemic injury. Consequently, piperine may modulate retinal ischemic injury through specifically targeting Aoc3 and Gabra3 for retinal protection.

Menin inhibitors disrupt oncogenic transcription in KMT2A-rearranged leukemias, but responses are heterogeneous. A previous study highlighted the role of nongenetic resistance driven by altered chromatin context, including loss of KMT2C/D-UTX activity, underscoring the need for broader epigenetic profiling to guide therapy timing and combination strategy selection.

This study explores the bioactivity and intestinal absorption of peptides from Acheta domesticus (house cricket), emphasizing their potential health benefits and relevance to sustainable protein sources. Six peptides (DVW, AVQPCF, QIVW, CAIAW, PIVCF, and IIIGW) obtained from the simulated gastrointestinal digestion of the A. domesticus proteins acyl-CoA Delta12-desaturase, acyl-CoA Delta-9 desaturase and diuretic hormone receptor were assessed for their effects on gene expression markers related to diabetes (DPP-4, SGLT1) and hypertension (sACE, ACE2). Using Caco-2 cells to model intestinal absorption, the peptides were evaluated for transport, cytotoxicity, and impact on barrier integrity. All peptides were non-cytotoxic up to 2 mM; however, DVW and PIVCF disrupted epithelial integrity. Only DVW crossed the epithelium intact. While none of the peptides significantly affected sACE or ACE2 expression, DVW and PIVCF notably downregulated SGLT1 expression (to 0.42- and 0.52-fold, respectively), suggesting potential antidiabetic effects through reduced glucose absorption.

Choroidal neovascularization (CNV) is a leading cause of central vision impairment with limited treatment options. Ethyl ferulate is a natural compound with antioxidant and anti-angiogenic properties; however, its application for treating CNV and the underlying mechanisms remain largely unexplored.

Sepsis, driven by dysregulated host inflammation, remains a leading cause of global mortality and lacks sufficiently effective therapies. Phillyrin (PHN), a lignan glycoside from Forsythia suspensa (Thunb.) Vahl (Oleaceae), exhibits anti-inflammatory and antimicrobial properties. However, its molecular mechanism in sepsis remains poorly understood.

Bevacizumab (Bev) resistance limits therapeutic efficacy in ovarian cancer (OC) patients. We identified ESM1 as a key gene in Bev-resistant OC. ESM1 secreted by OC-resistant cell lines activates the ITGB1/FAK axis to induce neovascularization and Bev resistance. Additionally, ESM1 overexpression promoted the growth and Bev resistance of OC, lung, intestinal, and hepatocellular carcinoma tumors. Then, we identified TRIM28 as an upstream regulator that stabilizes ESM1 by promoting SUMOylation, inhibiting its proteasomal degradation. In OC mice, TRIM28 overexpression promotes angiogenesis and Bev resistance via ESM1-mediated ITGB1/FAK activation. This work unveils a new molecular pathway underlying Bev resistance in OC and proposes TRIM28 and ESM1 as potential therapeutic targets.

Soil contamination by bisphenol A (BPA) has raised considerable ecological and environmental concerns, particularly due to its potential impact on plant growth. However, the interactive effects of BPA and different soil types on soil-plant systems remain poorly understood. Capsicum annuum L., a widely cultivated vegetable crop, was used as a model to systematically investigate the mechanisms of BPA uptake, translocation, and metabolic disruption in roots under varying soil types and BPA dose. Greenhouse experiments showed that BPA accumulation in pepper roots was highest in viscous soil, significantly greater than in sandy or loamy soils. When BPA dose exceeded 10 mg kg-1, root elongation and vitality were markedly suppressed, accompanied by enhanced antioxidant enzyme activity and elevated malondialdehyde content, indicating phytotoxicity was linked to increased oxidative stress. Integrated transcriptomic and metabolomic analyses identified 995 differentially expressed genes and revealed significant disruptions in root metabolic processes. BPA exposure altered the expression of genes related to the biosynthesis of phytohormone precursors and branched metabolites. Key pathways, including indole-3-acetic acid biosynthesis and phytohormone signal transduction, were significantly affected. These findings clarify the soil-dependent uptake and translocation patterns of BPA in pepper roots and provide important molecular insights into the plant's adaptive and defense responses to BPA-induced stress.

Breast cancer is a global health challenge for women and chemoresistance is a major contributor to its high mortality rates. Quercetin (Que), a flavonoid with antioxidant, antiviral, anti‑tumor and anti‑inflammatory properties, sensitizes cancer cells to chemotherapy. The present study investigated the mechanism by which Que regulates ATP‑binding cassette (ABC) transporter expression in MCF‑7 cells using a PTEN overexpression plasmid and the PI3K inhibitor LY294002. The present study assessed cell viability via Cell Counting Kit‑8 and Hoechst 33342 staining and analyzed mRNA and protein expression levels by reverse transcription‑quantitative PCR and western blotting. Apoptosis was evaluated by flow cytometry and ABCG2 expression was detected by immunofluorescence. Furthermore, the present study determined the effect of Que on drug uptake using a Rhodamine 123 accumulation assay. The results of the present study demonstrated that Que suppresses cell viability and induces apoptosis in MCF‑7 cells. Moreover, it enhances intracellular drug accumulation and downregulates ABC transporter expression by modulating the PTEN/PI3K/AKT signaling pathway.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the statistical analysis in this study may not have employed the most appropriate statistical tests; namely, the paired Student's t‑test was used for comparisons between independent groups, which the reader considered may have inflated the statistical significance. Neither may the paired Student's t‑test have been the most appropriate test to have been selected for various of the migration and invasion assay experiments, wherein at least three groups were being compared. Owing to the fact that the Editorial Office has been made aware of the possibility of inappropriate statistics handling in this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Molecular Medicine Reports 1: 641‑646, 2008; DOI: 10.3892/mmr_00000005].

High concentrations of manganese (Mn) ions in the soil of facility-based cultivation significantly restrict the development of the cucumber industry. However, the genetic mechanisms governing Mn accumulation in crops are still not well comprehended. Through the comprehensive integration of molecular biology, epigenetic modification analysis combined with genetic analysis, we functionally characterized a novel regulatory module. Consisting of a long non-coding RNA (lncRNA, asCsMTP6) and its mitochondria-localized target Metal Tolerance Protein 6 (MTP6), it coordinately regulates Mn accumulation in cucumber. CRISPR-CsMTP6 or asCsMTP6-OE mimics toxicity, whereas CsMTP6-OE or asCsMTP6 knockdown enhances tolerance, confirming that asCsMTP6 negatively regulates CsMTP6 transcription. Additionally, the H3K27me3 methylation marks surrounding the CsMTP6 genome are reduced under Mn stress, and the inhibited expression of asCsMTP6 results in a lower level of H3K27me3 methylation in the CsMTP6 gene body and 3'UTR region, thereby facilitating the expression of CsMTP6 for tolerance to Mn stress. Furthermore, virus-induced silencing of histone methyltransferases SWN and CLF also reduces H3K27me3 methylation in the CsMTP6 genomic region, thus releasing the expression of CsMTP6. Taken together, this study demonstrates the epigenetic regulation of lncRNAs in response to Mn stress, providing new insights into the potential for developing cucumber varieties with improved tolerance to manganese-contaminated soils.

Avena fatua L. is a major grass weed infesting wheat fields worldwide, with the ACCase-inhibiting herbicide fenoxaprop-P-ethyl serving as the primary chemical control agent. However, prolonged and widespread use has resulted in the evolution of resistance in A. fatua, posing a serious threat to effective weed management in wheat production. This study investigates the resistance level and elucidates the underlying mechanisms in a fenoxaprop-P-ethyl-resistant A. fatua population (HZXH-R) collected from China. Whole-plant bioassays demonstrated that the HZXH-R population exhibited a 21.3-fold resistance to fenoxaprop-P-ethyl compared with sensitive population. Sequencing of the ACCase gene detected no known target-site mutations, thereby excluding target-site mutation-mediated resistance. Treatment with cytochrome P450 inhibitors (piperonyl butyl ether [PBO], malathion, and 1-aminobenzotriazole [ABT]) significantly reduced resistance in HZXH-R, implicating P450 monooxygenases in resistance regulation. Transcriptome sequencing identified six genes that were significantly upregulated and two that were downregulated. RT-qPCR validation confirmed that the P450 gene CYP710A8B showed the highest relative expression in the resistant population. This study demonstrates that the A. fatua population HZXH-R exhibits high-level resistance to fenoxaprop-P-ethyl, with the upregulation of CYP710A8B identified as a potential factor in resistance development. These findings provide a foundation for elucidating the evolutionary mechanisms underlying resistance to ACCase-inhibiting herbicides and for guiding the development of more effective, science-based weed management strategies.