FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.

BACKGROUND: Increased activity of the transcription factor FOXC1 leads to elevated transcription of target genes, ultimately facilitating the progression of various cancer types. However, there are currently no literature reports on the role of FOXC1 in renal cell carcinoma. METHODS: By using RT-qPCR, immunohistochemistry and Western blotting, FOXC1 mRNA and protein expression was evaluated. Gain of function experiments were utilized to assess the proliferation and metastasis ability of cells. A nude mouse model was created for transplanting tumors and establishing a lung metastasis model to observe cell proliferation and spread in a living organism. Various techniques including biological analysis, CHIP assay, luciferase assay, RT-qRCR and Western blotting experiments were utilized to investigate how FOXC1 contributes to the transcription of ABHD5 on a molecular level. FOXC1 was assessed by Western blot for its impact on AMPK/mTOR signaling pathway. RESULTS: FOXC1 is down-regulated in RCC, causing unfavorable prognosis of patients with RCC. Further experiments showed that forced FOXC1 expression significantly restrains RCC cell growth and cell metastasis. Mechanically, FOXC1 promotes the transcription of ABHD5 to activate AMPK signal pathway to inhibit mTOR signal pathway. Finally, knockdown of ABHD5 recovered the inhibitory role of FOXC1 overexpression induced cell growth and metastasis suppression. CONCLUSION: In general, our study demonstrates that FOXC1 exerts its tumor suppressor role by promoting ABHD5 transcription to regulating AMPK/mTOR signal pathway. FOXC1 could serve as both a diagnostic indicator and potential treatment focus for RCC.

Estimating maize evapotranspiration based on hybrid back-propagation neural network models and meteorological, soil, and crop data.

Crop evapotranspiration is a key parameter influencing water-saving irrigation and water resources management of agriculture. However, current models for estimating maize evapotranspiration primarily rely on meteorological data and empirical coefficients, and the estimated evapotranspiration contains uncertainties. In this study, the evapotranspiration data of summer maize were collected from typical stations in Northern China (Yucheng Station), and a back-propagation neural network (BP) model for predicting maize evapotranspiration was constructed based on meteorological data, soil data, and crop data. To further improve its accuracy, the maize evapotranspiration model was optimized using three bionic optimization algorithms, namely the sand cat swarm optimization (SCSO) algorithms, hunter-prey optimizer (HPO) algorithm, and golden jackal optimization (GJO) algorithm. The results showed that the fusion of meteorological, soil moisture, and crop data can effectively improve the accuracy of the maize evapotranspiration model. The model showed higher accuracy with the hybrid optimization model SCSO-BP compared to the stand-alone BP neural network model, with improvements of 2.7-4.8%, 17.2-25.5%, 13.9-26.8%, and 3.3-5.6% in terms of R2, RMSE, MAE, and NSE, respectively. Comprehensively compared with existing maize evapotranspiration models, the SCSO-BP model presented the highest accuracy, with R2 = 0.842, RMSE = 0.433 mm/day, MAE = 0.316 mm/day, NSE = 0.840, and overall global evaluation index (GPI) ranking the first. The results have reference value for the calculation of daily evapotranspiration of maize in similar areas of northern China.

PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer.

Background: Cisplatin (DDP) based combination chemotherapy is a vital method for the treatment of bladder cancer (BLca). Chemoresistance easily occurs in the course of cisplatin chemotherapy, which is one of the important reasons for the unfavorable prognosis of BLca patients. Circular RNAs (circRNAs) are widely recognized for their role in the development and advancement of BLca. Nevertheless, the precise role of circRNAs in DDP resistance for BLca remains unclear. Methods: To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. RT-qPCR assay was utilized to assess the expression levels of circRNA, miRNA and mRNA in BLca tissues and cells. Functional experiments were conducted to assess the function of circATIC in BLca progression and chemosensitivity in vitro. Various techniques such as FISH, Dual-luciferase reporter assay, TRAP, RNA digestion assay, RIP and ChIRP assay were used to investigate the relationships between PTBP1, circATIC, miR-1247-5p and RCC2. Orthotopic bladder cancer model, xenograft subcutaneous tumor model and xenograft lung metastasis tumor model were performed to indicate the function and mechanism of circATIC in BLca progression and chemosensitivity in vivo. Results: In our study, we observed that circATIC expression was significantly enhanced in BLca tissues and cells and DDP resistant cells. Patients with higher circATIC expression have larger tumor diameter, higher incidence of postoperative metastasis and lower overall survival rate. Further experiments showed that circATIC accelerated BLca cell growth and metastasis and induced DDP resistance. Mechanistically, alternative splicing enzyme PTBP1 mediated the synthesis of circATIC. circATIC could enhance RCC2 mRNA stability via sponging miR-1247-5p or constructing a circATIC/LIN28A/RCC2 RNA-protein ternary complex. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Conclusion: Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.

Glutathione is required for nitric oxide-induced chilling tolerance by synergistically regulating antioxidant system, polyamine synthesis, and mitochondrial function in cucumber (Cucumis sativus L.).

In this paper, we discussed the physiological mechanism of enhanced chilling tolerance with combined treatment of nitric oxide (NO) and reduced glutathione (GSH) in cucumber seedlings. With prolonged low temperature (10 °C/6 °C), oxidative stress improved, which was manifested as an increase the hydrogen peroxide (H2O2) and malondialdehyde (MDA), causing cell membrane damage, particularly after 48 h of chilling stress. Exogenous sodium nitroprusside (SNP, NO donor) enhanced the activity of nitric oxide synthase NOS-like, the contents of GSH and polyamines (PAs), and the cellular redox state, thus regulating the activities of mitochondrial oxidative phosphorylation components (CI, CII, CIV, CV). However, buthionine sulfoximine (BSO, a GSH synthase inhibitor) treatment drastically reversed or attenuated the effects of NO. Importantly, the combination of SNP and GSH treatment had the best effect in alleviating chilling-induced oxidative stress by upregulating the activities of antioxidant enzyme, including superoxidase dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) and improved the PAs content, thereby increased activities of CI, CII, CIII, CIV, and CV. This potentially contributes to the maintenance of oxidative phosphorylation originating from mitochondria. In addition, the high activity of S-nitrosoglutathione reductase (GSNOR) in the combined treatment of SNP and GSH possibly mediates the conversion of NO and GSH to S-nitrosoglutathione. Our study revealed that the combined treatment with NO and GSH to synergistically improve the cold tolerance of cucumber seedlings under prolonged low-temperature stress.

Reactive oxygen species signaling in melatonin-mediated plant stress response.

Reactive oxygen species (ROS) are crucial signaling molecules in plants that play multifarious roles in prompt response to environmental stimuli. Despite the classical thoughts that ROS are toxic when accumulate in excess, recent advances in plant ROS signaling biology reveal that ROS participate in biotic and abiotic stress perception, signal integration, and stress-response network activation, hence contributing to plant defense and stress tolerance. ROS production, scavenging and transport are fine-tuned by plant hormones and stress-response signaling pathways. Crucially, the emerging plant hormone melatonin attenuates excessive ROS accumulation under stress, whereas ROS signaling mediates melatonin-induced plant developmental response and stress tolerance. In particular, RESPIRATORY BURST OXIDASE HOMOLOG (RBOH) proteins responsible for apoplastic ROS generation act downstream of melatonin to mediate stress response. In this review, we discuss promising developments in plant ROS signaling and how ROS might mediate melatonin-induced plant resilience to environmental stress.

Epigallocatechin-3-gallate-induced tolerance to cadmium stress involves increased flavonoid synthesis and nutrient homeostasis in tomato roots.

Cadmium (Cd) is a toxic heavy metal, increasingly accumulating in the environment and its presence in various environmental compartments represents a significant risk to human health via the food chain. Epigallocatechin-3-Gallate (EGCG) is a prominent secondary metabolite, which can safeguard plants from biotic and abiotic stress. However, the role of EGCG in flavonoid synthesis, nutrient acquisition and reactive oxygen species (ROS) metabolism under Cd stress remains unclear. Here, we examined the effects of EGCG and Cd treatment on leaf photochemical efficiency, cell ultrastructure, essential element acquisition, antioxidant system, and secondary metabolism in tomato (Solanum lycopersicum L.). The results showed that O2•-, H2O2, and malondialdehyde levels increased after Cd treatment, but Fv/Fm decreased significantly, suggesting that Cd induced oxidative stress and photoinhibition. However, EGCG mitigated the adverse effects of Cd-induced phytotoxicity in both the roots and leaves. A decrease in ROS accumulation under EGCG + Cd treatment was mainly attributed to the significant enhancement in antioxidant enzyme activity, flavonoid content, and PHENYLALANINE AMMONIA-LYASE expression in roots. Moreover, EGCG reduced Cd content but increased some essential nutrient contents in tomato plants. Transmission electron microscopy-based observations revealed that EGCG treatment safeguards leaf and root cell ultrastructure under Cd stress. This implies that tomato plants subjected to Cd stress experienced advantageous effects upon receiving EGCG treatment. The present work elucidated critical mechanisms by which EGCG induces tolerance to Cd, thereby providing a basis for future investigations into environmentally sustainable agricultural practices in areas contaminated with heavy metals, for utilizing naturally occurring substances found in plants.

Cytochrome P450 CYP736A12 is crucial for Trichoderma asperellum-induced alleviation of phoxim phytotoxicity and reduction of pesticide residue in tomato roots.

Trichoderma can enhance the metabolism of organophosphate pesticides in plants, but the mechanism is unclear. Here, we performed high-throughput transcriptome sequencing of roots upon Trichoderma asperellum (TM) inoculation and phoxim (P) application in tomato (Solanum lycopersicum L.). A total of 4059 differentially expressed genes (DEGs) were obtained, including 2110 up-regulated and 1949 down-regulated DEGs in P vs TM+P. COG and KOG analysis indicated that DEGs were mainly enriched in signal transduction mechanisms. We then focused on the pesticide detoxification pathway and screened out cytochrome P450 CYP736A12 as a putative gene for functional analysis. We suppressed the expression of CYP736A12 in tomato plants by virus-induced gene silencing and analyzed tissue-specific phoxim residues, oxidative stress markers, glutathione pool, GST activity and related gene expression. Silencing CYP736A12 significantly increased phoxim residue and induced oxidative stress in tomato plants, by attenuating the TM-induced increased activity of antioxidant and detoxification enzymes, redox homeostasis and transcripts of detoxification genes including CYP724B2, GSH1, GSH2, GR, GPX, GST1, GST2, GST3, and ABC. The study revealed a critical mechanism by which TM promotes the metabolism of phoxim in tomato roots, which can be useful for further understanding the Trichoderma-induced xenobiotic detoxification and improving food safety.

Flavonoid synthesis is crucial for Trichoderma asperellum-induced systemic resistance to root-knot nematodes in tomato plants.

Trichoderma spp. can enhance plant resistance against a wide range of biotic stressors. However, the fundamental mechanisms by which Trichoderma enhances plant resistance against Meloidogyne incognita, known as root-knot nematodes (RKNs), are still unclear. Here, we identified a strain of Trichoderma asperellum (T141) that could effectively suppress RKN infestation in tomato (Solanum lycopersicum L.). Nematode infestation led to an increase in the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) in roots but pre-inoculation with T141 significantly decreased oxidative stress. The reduction in ROS and MDA was accompanied by an increase in the activity of antioxidant enzymes and the accumulation of flavonoids and phenols. Moreover, split root test-based analysis showed that T141 inoculation in local roots before RKN inoculation increased the concentration of phytohormone jasmonate (JA) and the transcripts of JA synthesis and signaling-related genes in distant roots. UPLC-MS/MS-based metabolomics analysis identified 1051 differentially accumulated metabolites (DAMs) across 4 pairwise comparisons in root division test, including 81 flavonoids. Notably, 180 DAMs were found in comparison between RKN and T141-RKN, whereas KEGG annotation and enrichment analysis showed that the secondary metabolic pathways, especially the flavonoid biosynthesis, played a key role in the T141-induced systemic resistance to RKNs. The role of up-regulated flavonoids in RKN mortality was further verified by in vitro experiments with the exogenous treatment of kaempferol, hesperidin and rutin on J2-stage RKNs. Our results revealed a critical mechanism by which T141 induced resistance of tomato plants against the RKNs by systemically promoting secondary metabolism in distant roots.