The plant-specific NAC transcription factor family plays a crucial role in mediating responses to abiotic stress, but the functions of many NAC genes remain poorly characterized. The rice OsNAC29a gene is induced by PEG and abscisic acid (ABA). OsNAC29a exhibits transactivation activity and the region of 248-315 amino acids at its C-terminus is essential for its activation. Over-expression of OsNAC29a enhances drought resistance and ABA sensitivity in transgenic rice. OsNAC29a over-expression modulates physiological indicators related to stress resistance, while RNAi-mediated down-regulation of OsNAC29a results in opposite phenotypes and physiological changes. Under drought conditions, OsNAC29a over-expression significantly up-regulates stress-related genes such as OsP5CS1, OsSRO1c, OsPOD1, OsLEA3, and OsRab16C. Interestingly, OsPOD1 gene expression increases in OsNAC29a over-expression rice under both normal and drought stress conditions, leading to significantly enhanced peroxidase activity. Further research reveals that OsNAC29a binds to the OsPOD1 promoter to drive its expression. Additionally, OsSAPK2 which is a key component of the ABA-dependent drought-tolerance pathway interacts physically with OsNAC29a and enhances its transcriptional activation activity. Collectively, acting as a positive regulator of drought tolerance, OsNAC29a regulates drought resistance in rice by directly or indirectly modulating stress-responsive genes.

Further study of glucocorticoid (GC) -induced osteoblast (OB) apoptosis and its regulatory mechanism is an important direction to explore the therapeutic strategy of steroid-induced osteonecrosis of the femoral head (SONFH) and steroid-induced osteoporosis. The aim of this study is to elucidate the role and mechanism of splicing factors serine/arginine-rich splicing factor 1 (SRSF1) and SRSF2 in GC-induced OB apoptosis. Transcriptome sequencing and bioinformatics prediction showed that the expression of SRSF1 and SRSF2 was significantly down-regulated in GC-treated OB and was related to GC-induced OB apoptosis. RNA immunoprecipitation and RNA-pull down assay further confirmed the interaction between SRSF1 and SRSF2. Moreover, overexpression of SRSF1 or SRSF2 inhibited GC-induced OB apoptosis, on the contrary, knockdown of SRSF1 or SRSF2 increased the rate of GC-induced OB apoptosis. Mechanistically, GC inhibits the expression of SRSF1 and SRSF2 at the same time, and then synergistically up-regulates the expression of pro-apoptotic molecule Bim, activates caspase-9/caspase-3 cascade, and finally leads to OB apoptosis. The aim of this study is to further investigate the GC-induced OB apoptosis and its regulatory mechanism from the direction of splicing factors, and to provide theoretical guidance and experimental basis for the prevention and treatment of SONFH and steroid-induced osteoporosis.

Colorectal cancer (CRC) with hepatic metastasis is associated with poor prognosis. Stereotactic body radiotherapy (SBRT) can provide local control for unresectable hepatic metastases of patients with CRC. However, the mechanisms of responsiveness to SBRT in metastatic CRC (mCRC) remain unclear. We aimed to identify a strategy to enhance the efficacy of SBRT in patients with CRC liver metastases and its mechanisms. Transcriptomic sequencing of CRC cells exposed to SBRT revealed that SBRT inhibited SLC7A11 expression. Downregulation of SLC7A11 enhanced the sensitivity of CRC cells to SBRT via ferroptosis. SBRT diminished the ability of tumor cells to sustain oxidative stress by impeding the phosphorylation of JNK and c-Jun and the transcription of NRF2. Furthermore, sorafenib, which targets SLC7A11, exerted inhibitory effects on tumor growth when used in combination with SBRT. A phase II clinical trial confirmed that sorafenib combined with SBRT overcame the resistance of liver mCRC with high SLC7A11 expression by inducing ferroptosis. The combination of SBRT and sorafenib demonstrated favorable clinical effects and safety, making it a good option for patients with CRC liver metastasis. STATEMENT OF SIGNIFICANCE: A novel strategy using the combination of SBRT and sorafenib for the treatment of patients with CRC hepatic metastasis was investigated. This strategy overcomes the radiation therapy resistance of mCRC by inhibiting SLC7A11 expression and promoting ferroptosis.

Decabromodiphenyl ethane (DBDPE), an emerging ubiquitous contaminant, enters the food chain through crop bioaccumulation, threatening food safety. This study investigated the bioaccumulation, toxicity, and tolerance mechanisms of DBDPE in sugar beet. The results showed that DBDPE was absorbed by roots and transported to leaves in a constant proportion, with greater toxicity in leaves than in roots. Physiological analyses revealed that DBDPE induced chloroplastic dysfunction and oxidative stress in a concentration-dependent manner. The antioxidant system in response to DBDPE varied with exposure levels. Integrated transcriptomic, proteomic, and metabolomic analyses revealed that remodeling of jasmonic acid (JA) biosynthesis and consequent activation of JA signaling were critical for DBDPE tolerance. Exogenous JA and JA-Ile (active JA) maintained photosynthetic activity by protecting chloroplasts and mitigated oxidative damage by enhancing antioxidant system activity, thereby improving DBDPE tolerance. This study provides an insight into the development of effective mitigation strategies against DBDPE toxicity in crops.

Triclosan (TCS), a widely used antimicrobial, has emerged as a concerning aquatic pollutant, especially post-COVID-19 due to increased disinfectant use. The study aimed to investigate the toxic impacts of TCS on Labeo rohita, revealing a 96-h LC50 of 0.742 mg/L. Well-acclimatized fish were categorised into three groups: one control and two treatment (T1 and T2) that were exposed to 1/10th and 1/5th of 96-h LC50 i.e., 0.0742 mg/L and 0.148 mg/L, respectively for 6 weeks under semi-static condition. Significantly (p < 0.05) elevated extents of reactive oxygen species (ROS) in the liver indicated enhanced oxidative stress. The activities of enzymatic antioxidants viz. superoxide dismutase (SOD) and catalase (CAT) were significantly (p < 0.05) increased while the reduced glutathione (GSH) levels were significantly (p < 0.05) decreased in a dose- and duration-dependent manner. A significant (p < 0.05) increase was observed in the lipid peroxidation (LPO) rate, which coincided with disruptions in the histological structure of the liver. Significant (p < 0.05) induction in Micronuclei frequency validated genomic instability. Furthermore, Endoplasmic Reticulum (ER) stress was marked by the increased intracellular calcium levels and elevated expression of grp78, chop, atf4, perk, eIF2α and gadd34 in TCS-exposed groups. Moreover, the consequent activation of bax, caspase-3, caspase-9, apaf-1 and the regulation of bcl-2 due to ER-stress, ultimately resulted in apoptosis of hepatocytes. Pearson correlation matrix and Principal Component Analysis (PCA) further underscored key interactions among parameters. Our findings demonstrate that the TCS, at its sub-lethal concentrations, is causing severe anomalies and even cell-death via triggering ER-stress-mediated apoptotic pathway in the fish liver.

Peptidylarginine deiminases (PAD1-4) are calcium dependent enzymes responsible for protein citrullination, a post-translational modification converting arginine residues to citrulline. Elevated levels of citrullinated proteins have been associated with rheumatoid arthritis, neurodegenerative diseases, and cancers. Though highly selective PAD4 inhibitors have been described, inhibitors to the broader family currently are limited to covalent substrate analogs. Herein, we describe an allosteric binding pocket common to PAD1-4 suitable for the identification of potent, non-covalent enzyme inhibitors. A ligand-based virtual screen is utilized to identify a PAD4 inhibitor for which surface plasmon resonance confirms target binding but non-competitively with a known PAD4 ligand. We further show through co-crystal structure analysis that the ligand binds PAD4 at an allosteric pocket resulting in stabilization of a catalytically inactive, calcium-deficient enzyme conformation. A ligand designed based on this site potently inhibits all four PAD isozymes and prevents protein citrullination in neutrophils with a broader protein repertoire than observed with a PAD4-selective inhibitor.

Pancreatic cancer is characterized by high rates of metastasis, recurrence, and chemoresistance, contributing to its poor prognosis. Transforming growth factor-β2 (TGF-β2), a member of the TGF-β family, plays a pivotal role in promoting cancer cell metastasis and mediating chemoresistance, particularly in advanced stages of tumor progression. However, the precise role of TGF-β in chemoresistance and metastasis in pancreatic cancer has not been studied yet. In the current study, we investigated the potential of human TGF-β2 antisense oligonucleotides (TGF-β2i) to enhance the chemosensitivity to gemcitabine in pancreatic cancer, using human pancreatic cancer cell lines (hPCCs; PANC-1, MIA PaCa-2, and AsPC-1), a co-culture model with human pancreatic stellate cells (hPSCs), a cancer-associated fibroblast-integrated pancreatic cancer organoid model (CIPCO), and an orthotopic xenograft mouse model. TGF-β2i decreased cell proliferation, migration, and viability in hPCCs, and its combination with gemcitabine exhibited a synergistic effect in PANC-1 and MIA PaCa-2 cells. Flow cytometry demonstrated a decrease in CD44 +CD24 +EpCAMHigh cancer stem-like cell populations following TGF-β2i treatment. In co-culture models, hPSCs-induced enhancement of hPCCs migration was attenuated by TGF-β2i. In the CIPCOs, TGF-β2i suppressed the gemcitabine-induced expression of extracellular matrix components such as COL1A1 and VIM. Furthermore, in an orthotopic mouse model generated by co-inoculating hPCCs and hPSCs into the pancreatic wall, co-treatment of TGF-β2i with gemcitabine significantly delayed tumor growth and metastasis to the liver compared to vehicle control. These findings suggest that TGF-β2i enhances chemosensitivity and suppresses metastatic properties by regulating both tumor-intrinsic and -extrinsic factors, indicating that targeting TGF-β2 could be a promising strategy for managing pancreatic cancer.

Glioblastomas utilize malignant gene expression pathways to drive growth. Many of these gene pathways are not directly accessible with molecularly targeted pharmacological agents. Chromatin-modifying compounds can alter gene expression and target glioblastoma growth pathways. In this study, we utilize a systematic screen of chromatin-modifying compounds on a panel of patient-derived glioblastoma lines to identify promising compounds and their associated gene targets.

Chitinase 3-like 1 (CHI3L1) has been implicated in the pathogenesis of various diseases, including cancer. In our previous study, we found that anti-CHIL1 antibody inhibited lung tumorigenesis. It has been reported that CHI3L1 is highly overexpressed in colon cancer tissue compared with normal tissue, and high levels of serum CHI3L1 have been associated with worse colon cancer prognosis. We investigated the anticancer effect of an anti-CHI3L1 antibody on colon cancer cells. The anti-CHI3L1 antibody inhibited the cell growth of colon cancer cells in a concentration-dependent manner. The anti-CHI3L1 antibody also reduced the migration but increased apoptotic cell death in colon cancer cells. Using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), we identified an association between VEGFA and CHI3L1 in colon cancer. We confirmed interaction between VEGFA and CHI3L1 through immunoprecipitation. Furthermore, the combination treatment of the anti-CHI3L1 antibody and VEGFA siRNA inhibited cell growth but increased apoptotic cell death. Additionally, using the Human Base database, we found that CHI3L1 and VEGFA are associated with nicotinamide phosphoribosyltransferase (NAMPT). Furthermore, combining the anti-CHI3L1 antibody and NAMPT siRNA more effectively reduced cell growth and the expression of CHI3L1, VEGFA, and cell growth-related proteins, but significantly increased apoptosis-related proteins. The combination of VEGFA siRNA and NAMPT siRNA more effectively inhibited cell growth. Anti-CHI3L1 antibody inhibited the production of ATP and NADH in colon cancer and had a higher inhibitory effect on these levels when combined with NAMPT siRNA These data demonstrated that anti-CHI3L1 antibody is useful as a potential therapy for colon cancer by inhibiting NAMPT-dependent VEGFA expression and ATP and NADH levels.

Plants have evolved complex defense mechanisms against biotic stressors, such as insect pests, involving chemical, physical, and molecular responses. These mechanisms, including producing secondary metabolites and activating specific signaling pathways, help mitigate damage and ensure survival under pest pressure. Many plants defense-related genes that play crucial roles in regulating defense responses have been identified in common bean. Phosphatidic acid (PA) is a vital lipid signaling molecule in plant stress responses, with diacylglycerol kinases (DGKs) play a key role in its production. In this study, we investigated the role of the PvDGK gene family in common bean under control, wounding, methyl jasmonate (MeJA, 100 µM), Helicoverpa armigera infestation, MeJA x wounding interaction and MeJA x H. armigera interaction. The larvae of H. armigera were reared under controlled conditions and used for infestation when they reached the fifth instar (L5). Expression levels of PvDGK1, PvDGK2, PvDGK3, PvDGK5a, PvDGK5b, and PvDGK6 genes were analyzed through qRT-PCR in leaves tissues. All PvDGK genes were upregulated in response to MeJA x H. armigera interaction. Notably, PvDGK2 was the most upregulated gene in the interaction of MeJA x H. armigera interaction, indicating its potential role in defense signaling. These findings provide the first evidence the importance of PvDGK genes in stress adaptation mechanisms in common bean and highlight their potential as targets for improving insect resistance. Future functional studies are crucial to fully elucidating the mechanisms through which these genes contribute to stress resilience and enhance our understanding of lipid signaling pathways in plant defense.

Synthetic developmental biology uses engineering approaches to understand multicellularity with goals ranging from recapitulating development to building synthetic organisms. Current approaches include engineering multicellular patterning, controlling differentiation and implementing cooperative cellular behaviors in model systems. Synthetic biology enables these pursuits by providing tools to control cell behavior. Mouse embryonic stem cells (mESCs) offer a well-studied and genetically tractable pluripotent model for pursuing synthetic development questions. However, there is minimal characterization of existing synthetic biology tools in mESCs. Here, we characterize three small molecule- and two cell contact-inducible systems for gene expression in and differentiation of mESCs. We show that small molecule- and cell contact-inducible systems work reliably and efficiently for controlling expression of arbitrary genetic payloads. We identify how these systems function differently across model differentiations. Furthermore, we show that these systems can drive direct differentiation of mESCs into neurons. Each of these systems can be used on their own or in combination, raising many possibilities for studying developmental principles with high precision.

Chaetocin, a fungal metabolite, exerts notable antiproliferative effects against solid tumors by triggering apoptosis; however, the mechanisms underlying its effects remain unclear. As tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) promotes apoptosis in certain types of tumor, the present study aimed to explore the sensitizing effects of chaetocin in TRAIL‑induced apoptosis in human glioblastoma cells and the underlying mechanism. Human glioblastoma cells (U343MG, U87MG, U251MG, and T98G) and embryonic kidney cells (HEK293) were co‑treated with chaetocin and TRAIL, followed by assessment of cell viability. The results from viability and apoptosis assays demonstrated a significant increase in caspase-dependent apoptosis in glioblastoma cells, but not in HEK293 cells, upon co-treatment with chaetocin and TRAIL. Additionally, death receptor 5 (DR5) expression analysis demonstrated that co‑treatment with chaetocin and TRAIL upregulated DR5 expression in a dose‑ and time‑dependent manner by increasing the stability of DR5 on the cell surface. In glioblastoma cells, small interfering RNA‑mediated DR5 knockdown markedly suppressed chaetocin/TRAIL‑induced apoptosis. Moreover, chaetocin enhanced reactive oxygen species (ROS) production, which facilitated TRAIL‑mediated apoptosis by enhancing DR5 upregulation. Thus, chaetocin sensitized the human glioblastoma cell lines U87MG and T98G to TRAIL‑mediated apoptosis by upregulating DR5 expression through ROS-mediated mechanisms. The present findings underscore chaetocin as a potential novel therapeutic agent for glioblastoma.

Triple‑negative breast cancer (TNBC) exhibits a high degree of malignancy and a propensity for metastasis, ultimately resulting in unfavorable patient outcomes. Curcuma phaeocaulis Valeton is a common herb used in traditional Chinese medicine to treat TNBC. Curcumenol (Cur) is a natural compound derived from C. phaeocaulis Valeton, the effects of which on breast cancer remain under‑reported. The present study elucidated that Cur could effectively inhibit the survival ability of TNBC cells and enhance their sensitivity to paclitaxel. Western blotting (WB) further revealed that Cur modulated apoptosis and epithelial‑mesenchymal transition (EMT) in TNBC. Findings from animal experiments further validated these observations. In the established TNBC mouse model, Cur was shown to exert an inhibitory effect on tumor growth, effectively attenuate EMT and substantially reduce the incidence of lung metastasis. Integrated analyses using RNA sequencing, WB and reverse transcription‑quantitative polymerase chain reaction demonstrated that Cur markedly downregulated the expression levels of solute carrier family 7 member 11 (SLC7A11), phosphorylated‑NF‑κB and TGF‑β. Molecular docking studies further validated that Cur can establish stable interactions with SLC7A11. In‑depth bioinformatics analysis revealed a positive association between high SLC7A11 expression and reduced disease‑free survival in patients with breast cancer. Additionally, in TNBC cells, Cur was revealed to reduce the mitochondrial membrane potential and promote the accumulation of lipid reactive oxygen species. Subsequent experimental investigations demonstrated that Cur can counteract the inhibitory influence of ferrostatin‑1 on ferroptosis. These findings strongly implied a potential underlying mechanism, suggesting that Cur may impede the malignant progression of TNBC via the modulation of ferroptosis. In conclusion, the findings of the present study underscore the marked efficacy of Cur in hampering the progression of TNBC by suppressing the SLC7A11/NF‑κB/TGF‑β signaling pathway.

The centrosome, a vital component in mitosis in eukaryotes, plays a pivotal role in cancer progression by influencing the proliferation and differentiation of malignant cells, making it a significant therapeutic target. We collected genes associated with centrosomes from existing literature and established a prognostic model for 85 osteosarcoma patients from the TARGET database. Genes associated with prognosis were identified through univariate Cox regression. We then mitigated overfitting by addressing collinearity using LASSO regression. Ultimately, a set of five genes was selected for the model through multivariable Cox regression. Model performance was assessed using ROC curves, which yielded a training set AUC of 0.965 and a validation set AUC of 0.770, indicating satisfactory model performance. We further identified genes with differential expression in high and low-risk groups and conducted functional enrichment analysis using KEGG, GO, Progeny, GSVA, and GSEA. Results revealed significant variances in various immune-related pathways between high and low-risk cohorts. Analysis of the immune microenvironment using ssGSEA and ESTIMATE indicated that individuals with unfavorable prognoses had lower immune scores, stromal scores, and ESTIMATE scores, coupled with higher tumor purity. This suggests that high-risk individuals have compromised immune microenvironments, potentially contributing to their unfavorable prognoses. Additionally, drug sensitivity and molecular docking analysis revealed increased responsiveness to paclitaxel in high-risk individuals, implying its prognostic value. The JTB-encoded protein exhibited a negative binding energy of - 5.5 kcal/mol when interacting with paclitaxel, indicating its potential to enhance the patient's immune microenvironment. This framework enables patient prognosis prediction and sheds light on paclitaxel's mechanism in osteosarcoma treatment, facilitating personalized treatment approaches.

Metformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI > 25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1, MT-RNR2, EGFL6 and FDCSP expression to be differentially expressed in breast tissues from metformin-treated postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that postmenopausal breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors.Trial registration: MetBreCs trial is registered at European Union Clinical Trials Register (EudraCT Protocol # 2015-001001-14) on 07/10/2015.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, posing a significant threat to human health. Recently, gambogic acid (GA) has garnered attention for its anticancer properties in GC. However, it remains unclear whether GA can regulate other forms of cell death beyond apoptosis. In this study, we found that GA inhibited proliferation and induced ferroptosis in GC cells. Western blot analysis was employed to assess ferroptosis and endoplasmic reticulum (ER) stress-related proteins, as well as forkhead box A2 (FOXA2) expression. Additionally, malondialdehyde (MDA) and glutathione (GSH) levels were measured following GA treatment, and quantitative real-time polymerase chain reaction (RT-qPCR) was used to evaluate miR-1291 expression. Our findings revealed that GA treatment elevated reactive oxygen species (ROS) levels and promoted intracellular Fe[Formula: see text], MDA, and GSH accumulation. Furthermore, GA upregulated SLC7A11 and ferritin expression while suppressing glutathione peroxidase 4 (GPX4) in AGS and HGC27 cells, suggesting its role in ferroptosis induction. Notably, GA increased miR-1291 levels and downregulated FOXA2 expression. Subsequent analyses showed FOXA2 as a direct target of miR-1291. Functional experiments involving miR-1291 and FOXA2 knockdown or overexpression further suggested that the miR-1291/FOXA2 axis mediates ferroptosis. Finally, tumor xenograft models showed that GA effectively inhibited tumor growth by inducing ferroptosis. In conclusion, our study provides compelling evidence that GA induces ferroptosis in GC through the miR-1291/FOXA2 axis, highlighting its potential as a novel therapeutic strategy and preventive target for gastric cancer treatment.

Transcriptomics has become a useful tool for comparing the levels of gene expression in healthy and malignant cells, holding potential for the discovery of new cancer therapies. This study used RNA-sequencing and transcriptome analysis on the PA1 ovarian cancer cell line to examine the potential of Cadmium Sulfide Nanoparticles (CdSNPs) as a therapeutic agent. A total of 5.42 Gb of high-quality reads was estimated based on the findings of gene expression techniques, comprising 2.25 Gb of treated PA1 cells and 3.17 Gb of control cells. Of these, 1641 genes with padj<0.001 and log2 foldchange >2 were found to be significantly regulated DEGs (differentially expressed genes). Analysis of gene ontology (GO) assays demonstrates the molecular mechanism behind CdSNPs anticancer effects. GO:0006915, GO:0012501, GO:1903561, and GO:0070588 are a few significant highlights of elevated GO (enriched DEGs) that are involved in apoptotic pathways, extracellular vesicles, programmed cell death, and Ca++ signaling. KEGG analysis elucidated that up and downregulated DEGs were enriched in a few pathways: calcium signaling pathway, Apoptosis, and TNF signaling pathway. Important pathways like MAP kinase, JAK/STAT, cAMP, and folate biosynthesis, showed inhibitory effects on ovarian cancer cell proliferation. The results of this work provide insight into possible therapeutic approaches employing CdSNPs and encourage additional research using a variety of cell lines and in vivo models to improve ovarian cancer treatment.

Vibrio campbellii is a significant pathogen in shrimp aquaculture, causing luminous vibriosis and leading to considerable declines in productivity and quality. The rapid emergence of multi-drug and detergent-resistant strains presents a major challenge in controlling this pathogen. This study investigates the inhibitory effects of rambutan peel extract (RPE) on quorum sensing (QS) systems, biofilm formation, and virulence-related traits in V. campbellii. The minimum inhibitory concentration (MIC) of RPE was found to be 2048 μg/ml for the pathogenic strain V. campbellii HY01 and 1024 μg/ml for the non-pathogenic QS reporter strains. Sub-inhibitory concentrations significantly reduced bioluminescence in V. campbellii, indicating interference with QS systems, particularly harveyi autoinducer-1 (HAI-1) and autoinducer-2 (AI-2). RPE disrupted autoinducer detection, down-regulated the expression of QS sensor genes, inhibited phosphorylation, and affected the transcription of QS regulator AphA. Additionally, RPE reduced biofilm formation, swimming motility, caseinase production, and virulence gene expression in the shrimp pathogenic strain HY01. These findings demonstrate the strong anti-QS activity of RPE against V. campbellii by targeting QS systems, phosphorylation pathways, and the master QS regulator. The study highlights the potential of RPE as a sustainable approach to control luminous vibriosis, offering a promising strategy for managing disease outbreaks and improving shrimp health in aquaculture.

The various components of the auxin signal transduction pathways, including auxin receptors, signal transduction processes, and physiological reactions (such as the overproduction of ethylene and abscisic acid, ABA), contribute to weed resistance to synthetic auxin herbicides. Auxin receptors and their physiological reactions have been well documented; however, research on signal transduction processes associated with herbicide resistance remains limited. In this study, we identified the candidate gene EcARF3, a transcription factor that is upregulated following treatment with florpyrauxifen-benzyl in the susceptible (S) population of Echinochloa crus-galli, whereas its expression remained relatively unchanged in the resistant (R) population. Additionally, key genes in ethylene and ABA biosynthesis, EcACS-like and EcNCED5, were similarly induced and upregulated by florpyrauxifen-benzyl in the S population. Furthermore, protein-DNA binding assays demonstrated that EcARF3 directly binds to the promoters of EcACS-like and EcNCED5, activating their expression. CRISPR-Cas9-mediated knockout of the rice ARF3 ortholog decreased sensitivity to florpyrauxifen-benzyl and quinclorac, whereas overexpression increased it. Moreover, OsARF3 directly binds to the AuxRE element in OsACS7, OsACS7-like, and OsNCED5 promoters, activating their expression, and regulating ethylene and ABA biosynthesis in rice. The role of the ARF3 transcription factor in auxin signal transduction pathways provides new insights into resistance to synthetic auxin herbicide.

DJ-1 is a multifunctional protein involved in diverse cellular processes, including defense against oxidative stress, regulation of gene transcription, and maintenance of mitochondrial function. Mutations in the DJ-1 gene are closely associated with early-onset Parkinson's disease, and loss of DJ-1 function increases the susceptibility of dopaminergic neurons to oxidative damage, potentially driving neurodegeneration. Therefore, DJ-1 represents an attractive therapeutic target for PD. In this study, we screened a library of blood-brain barrier-permeable small molecules to identify compounds that modulate DJ-1 expression in the mouse brain. Through molecular docking, we discovered that URB597, a selective fatty acid amide hydrolase inhibitor, binds to DJ-1 and forms a stable complex. URB597 treatment markedly reduced DJ-1 protein levels in SH-SY5Y cells, leading to decreased cell survival and impaired mitochondrial function under oxidative stress conditions. In addition, URB597-treated mice exhibited motor deficits and dopaminergic neuron loss, indicating that suppressing DJ-1 expression may adversely affect neuronal function. Gene expression and pathway enrichment analyses revealed that URB597 targets DJ-1 in the mouse striatum and regulates the expression of genes involved in protein acetylation. Collectively, these findings underscore the critical role of DJ-1 in protecting dopaminergic neurons from oxidative damage and uncover its potential implications in regulating protein acetylation.