Herpotrichone A Exerts Neuroprotective Effects by Relieving Ferroptosis.

Inhibition of oxidative stress and ferroptosis is currently considered to be a promising therapeutic approach for neurodegenerative diseases. Herpotrichones, a class of compounds derived from insect symbionts, have shown potential for neuroprotective activity with low toxicity. However, the specific mechanisms through which herpotrichones exert their neuroprotective effects remain to be fully elucidated. In this study, the natural [4 + 2] adducts herpotrichone A (He-A) and its new analogues were isolated from the isopod-associated fungus Herpotrichia sp. SF09 and exhibited significantly protective effects in H2O2-, 6-OHDA-, and RSL3-stimulated PC12 cells and LPS-stimulated BV-2 cells. Moreover, He-A was able to relieve ferroptotic cell death in RSL3-stimulated PC12 cells and 6-OHDA-induced zebrafish larvae. Interestingly, He-A can activate antioxidant elements and modulate the SLC7A11 pathway without capturing oxidic free radical and chelating iron. These findings highlight He-A as a novel hit that protects against ferroptosis-like neuronal damage in the treatment of neurodegenerative diseases.

[Response of radial growth of different timberline species to climate change in Yading Nature Reserve, Sichuan, China]. / å››å·äºšä¸è‡ªç„¶ä¿æŠ¤åŒºä¸åŒæž—çº¿æ ‘ç§å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

The radial growth of trees in alpine timberline is particularly sensitive to climate change. We sampled and disposed tree-ring cores of three coniferous tree species including Juniperus saltuaria, Abies forrestii, and Larix potaninii at alpine timberline in Yading Nature Reserve. The standard tree-ring chronology was used to explore the response of radial growth of different timberline species to climate change. The results showed that radial growth of L. potaninii increased after 2000, while that of A. forrestii declined after 2002, and J. saltuaria showed a significant decreasing growth trend in the past 10 years. Such results indicated divergent growth responses to climate factors among the three tree species at alpine timberline. The radial growth of J. saltuaria was sensitive to temperature, and was positively correlated with the minimum temperature from previous October to current August, the mean tempera-ture from previous November to current April and from current July to October, but was negatively associated with the relative humidity from current July to October. The radial growth of A. forrestii showed negative correlation with mean temperature and the maximum temperature from May to June in the current year, while it exhibited positive association with the relative humidity and the Palmer drought severity index from May to June in the current year. L. potaninii radial growth was positively associated with mean temperature and the maximum temperature of November-December in the previous year, the maximum temperature of current March and mean temperature of current August. The temporal stability of climate-growth relationship varied among different timberline species. The positive correlation between radial growth of A. forrestii and J. saltuaria and temperature gradually decreased, while the posi-tive relationship of L. potaninii radial growth and temperature gradually increased. Under the background of climate warming, rapid rise in surface air temperatures may promote the radial growth of L. potaninii, while inhibit that of J. saltuaria and A. forrestii, which may change the position of regional timberline.

[Response of radial growth of Pinus wallichiana to climate change in Mount Qomolangma, Tibet, China]. / è¥¿è—ç å³°åœ°åŒºä¹”æ¾å¾„å‘ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

Global warming would significantly impact tree growth in the Tibetan Plateau. However, the specific effects of climate change on the radial growth of Pinus wallichiana in Mount Qomolangma are still uncertain. To investigate the responses of radial growth of P. wallichiana to climate change, we analyzed tree-ring samples in Mount Qomolangma. We removed the age-related growth trends and established three chronologies by using the modified negative exponential curve, basal area index, and regional curve standardization, and conducted Pearson correlation and moving correlation analyses to examine the association between radial growth of P. wallichiana and climatic factors. The results showed that this region had experienced a significant upward trend in temperature and that the Palmer drought severity index (PDSI) indicated a decreasing trend since 1980s, while the relative humi-dity changed from a significant upward to a downward trend around 2004, implying the climate shifted toward warmer and drier. Results of Pearson correlation analysis indicated a significant and positive relationship between the radial growth of P. wallichiana and the minimum temperature of April-June and July-September, and precipitation of January-April in the current year. The radial growth of P. wallichiana was significantly and negatively associated with the relative humidity of June, July, and August in the current year. As temperature rose after 1983, the relationship between radial growth of P. wallichiana and the minimum temperature in July and September of the current year increased from a non-significant association to a significant and positive association, while the relationship between radial growth of P. wallichiana and relative humidity in August and precipitation in September of the current year changed from non-significant correlation to a significant and negative correlation. Results of the moving correlation analysis suggested that the radial growth of P. wallichiana showed a significant and stable correlation with the July-September minimum temperature of the current year. Under the background of climate warming, the rapid increases of temperature would accelerate the radial growth of P. wallichiana in Mount Qomolangma.

Effect of Grain Size on Nanometric Cutting of Polycrystalline Silicon via Molecular Dynamics Simulation.

The grain size effect is an important factor in determining the material removal behavior of polycrystalline silicon (p-Si). In the present study, to improve the understanding of nanoscale machining of p-Si, we performed molecular dynamics simulation of nanometric cutting on a p-Si workpiece and discussed the grain size effect on material removal behavior and subsurface damage formation. The simulation results indicate that when cutting on the polycrystal workpiece, the material removal process becomes unstable compared with single crystals. Higher removal efficiency, less elastic recovery and higher frictional coefficient are observed as the average grain size decreases. In the subsurface workpiece, when the grain size decreases, slip along grain boundaries merges as a nonnegligible process of the plastic deformation and suppresses the elastic deformation ahead of the cutting tool. It is also revealed that when cutting on a polycrystal workpiece with smaller grains, the average stress decreases while the workpiece temperature increases due to the impediment of heat transfer by grain boundaries. These results could provide a fundamental understanding in the material deformation mechanism of p-Si during nanoscale machining.

Design and development of pH-responsive levofloxacin-loaded metal-organic framework for the promising treatment of pediatric abdominal wound repair.

With over 9 million fatalities per year expected by 2030, infectious diseases will remain a significant burden on the world economy and cause high mortality rates. An excellent method to increase the bioactivity of levofloxacin (LEV) in pediatric abdominal wound repair is the finding of a stimuli-based drug delivery system (DDS). We designed and developed an LEV incorporated with zeolite imidazole framework-8 (ZIF-8) as a promising nanocarrier for wound healing applications. The spectral analysis and morphological analysis confirm the formation of our newly fabricated composites. Mouse embryonic fibroblast NIH3T3 cells, the cytotoxicity, cytocompatibility, and cell proliferation characteristics of LEV@ZIF-8 were evaluated in vitro. LEV@ZIF-8 composite considerably improved the biocompatibility against NIH3T3 cells after 72-h of exposure, according to in vitro experiments. Under acidic circumstances, the pH-responsive drug release studies exhibit superior LEV release, and in physiological circumstances, there is no unintended drug release. The LEV@ZIF-8 composite-treated cells demonstrate the most remarkable cell growth and migration method in a very short time, according to the results of the wound scratch experiment. The composite exposure concentration depended on inhibition against various microorganisms in the antibacterial activity testing. According to the study, LEV@ZIF-8 are appropriate and effective DDS for stimuli-based pediatric abdominal wound repair.

Controllable Fabrication of Hydrophilic Surface Micro/Nanostructures of CFRP by Femtosecond Laser.

Carbon fiber reinforced polymer (CFRP), a highly engineered lightweight material with superior properties, is widely used in industrial fields, such as aerospace, automobile, and railway transportation, as well as medical implants and supercapacitor. This work presents an effective surface treatment method for the controllable fabrication of hydrophilic surface micro/nanostructures of CFRP through femtosecond laser processing. Selective removal of the epoxy resin and leaving the carbon fibers exposed are achieved when CFRP is weakly ablated by a femtosecond laser. The diameters and structures of the carbon fibers can be controlled by adjusting the laser processing parameters. Three-dimensional surface micro/nanostructures are processed when CFRP is strongly ablated by a femtosecond laser. Meanwhile, the transformation of the sp2 orbitals to sp3 orbitals of graphitic carbons of carbon fibers is induced by a femtosecond laser. Moreover, the investigation of surface roughness and wettability of femtosecond laser-processed CFRP indicates increased roughness and excellent hydrophilicity (a contact angle of 28.1°). This work reveals the effect of femtosecond laser processing on the regulation of the physicochemical properties of CFRP, which can be applicable to surface treatment and performance control of other fiber-resin composites. The excellent hydrophilicity will be conducive to the combination of CFRP with other materials or to reducing the friction resistance of CFRP used in medical implants.

Optical coherence tomography angiography for the differentiation of diabetic nephropathy from non-diabetic renal disease.

BACKGROUND: To provide a new non-invasive method for the differentiation of diabetic nephropathy (DN) from non-diabetic renal disease (NDRD) by assessing retinal microstructure using optical coherence tomography angiography (OCTA). METHODS: OCTA parameters were recorded and their relationship with DN was analysed. A differential diagnosis regression model for DN was established, and the diagnostic efficiency was evaluated. RESULTS: Based on the pathological results of renal biopsy, 31 DN patients and 35 NDRD patients were included. Multivariate logistic regression analysis showed that DN was independently associated with the following parameters: 15.3 mm-1 ≤ vessel density (VD) full < 17.369 mm-1 (odds ratio [OR]=8.523; 95% confidence interval [CI]=1.387-52.352; P = 0.021), VD full < 15.3 mm-1 (OR=8.202; 95% CI=1.110-60.623; P = 0.039), DM duration > 60 months (OR=7.588; 95% CI=1.569-36.692; P = 0.012), and estimated glomerular filtration rate < 60 mL/min/1.73 m2 (OR=24.484; 95% CI=4.308-139.142; P < 0.001). The area under the receiver operating characteristic curve was 0.911, indicating a high diagnostic efficiency. CONCLUSIONS: VD full < 17.369 mm-1, DM duration > 60 months, and eGFR < 60 mL/min/1.73 m2 may indicate the presence of DN. OCTA may be an effective non-invasive method for identifying DN and NDRD.

Evaluating the effect of body mass index and 25-hydroxy-vitamin D level on basal cell carcinoma using Mendelian randomization.

Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[- 0.22, - 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.

Human placental mesenchymal stromal cells modulate IFN-γ and IL-10 secretion by CD4+T cells via CD73, and alleviate intestinal damage in mice with graft-versus-host disease.

BACKGROUND: Intestinal inflammatory damage is an important factor in the development of graft-versus-host disease (GVHD). IFN-γ and IL-10 play key roles in gastrointestinal inflammation, and human placental mesenchymal stromal cells (hPMSCs) can alleviate inflammatory damage during GVHD. CD73 is highly expressed by hPMSCs. We aimed to study whether hPMSCs could alleviate intestinal damage in GVHD mice by modulating IFN-γ and IL-10 in CD4+T cells by CD73. METHODS: A GVHD mouse model was induced using 8-week-old C57BL/6J and BALB/c mice, which were treated with regular hPMSCs (hPMSCs) or hPMSCs expressing low level of CD73 (shCD73). Then, the levels of IFN-γ and IL-10 in CD4+T cells were determined using flow cytometry. Transmission electron microscopy, western blotting, and morphological staining were employed to observe the intestinal damage. RESULTS: hPMSCs ameliorated pathological damage and inhibited the reduction of the tight junction molecules occludin and ZO-1. They also downregulated IFN-γ and upregulated IL-10 secretion in CD4+T cells via CD73. Moreover, IL-10 mitigated the inhibitory effects of IFN-γ on the expression of occludin in both Caco-2 and NCM460 cells in vitro, but did not affect ZO-1. In addition, hPMSCs upregulated the level of AMPK phosphorylation in CD4+T cells by CD73, which is positively associated with the proportion of CD4+IFN-γ+IL-10+T, and CD4+IFN-γ-IL-10+T cells. CONCLUSIONS: Our findings suggested that hPMSCs may balance the levels of IFN-γ and IL-10 in CD4+T cells by promoting the phosphorylation of AMPK via CD73, which alleviates the loss of occludin and ZO-1 in intestinal epithelial cells and, in turn, reduces inflammatory injury in GVHD mice.

Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome.

Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.

The Novel Role of Zfp296 in Mammalian Embryonic Genome Activation as an H3K9me3 Modulator.

The changes in epigenetic modifications during early embryonic development significantly impact mammalian embryonic genome activation (EGA) and are species-conserved to some degree. Here, we reanalyzed the published RNA-Seq of human, mouse, and goat early embryos and found that Zfp296 (zinc finger protein 296) expression was higher at the EGA stage than at the oocyte stage in all three species (adjusted p-value < 0.05 |log2(foldchange)| ≥ 1). Subsequently, we found that Zfp296 was conserved across human, mouse, goat, sheep, pig, and bovine embryos. In addition, we identified that ZFP296 interacts with the epigenetic regulators KDM5B, SMARCA4, DNMT1, DNMT3B, HP1ß, and UHRF1. The Cys2-His2(C2H2) zinc finger domain TYPE2 TYPE3 domains of ZFP296 co-regulated the modification level of the trimethylation of lysine 9 on the histone H3 protein subunit (H3K9me3). According to ChIP-seq analysis, ZFP296 was also enriched in Trim28, Suv39h1, Setdb1, Kdm4a, and Ehmt2 in the mESC genome. Then, knockdown of the expression of Zfp296 at the late zygote of the mouse led to the early developmental arrest of the mouse embryos and failure resulting from a decrease in H3K9me3. Together, our results reveal that Zfp296 is an H3K9me3 modulator which is essential to the embryonic genome activation of mouse embryos.

Resveratrol Promotes Gluconeogenesis by Inhibiting SESN2-mTORC2-AKT Pathway in Calf Hepatocytes.

BACKGROUND: The glucose requirement of dairy cows is mainly met by increasing the rate of hepatic gluconeogenesis. However, due to negative energy balance, the liver of periparturient cows is under oxidative stress induced by lipid over-mobilization, and hepatic gluconeogenesis is reduced. Studies have demonstrated that resveratrol, which is widely known for its antioxidant properties, can alter hepatic gluconeogenesis. However, it is not clear whether resveratrol could regulate hepatic gluconeogenesis by its antioxidant properties. OBJECTIVES: This study aims to investigate the precise effect of resveratrol in hepatic gluconeogenesis, the role of resveratrol on hydrogen peroxide (H2O2)-induced oxidative stress in hepatocytes and the potential mechanism using primary hepatocytes. METHODS: Primary hepatocytes were isolated from 5 healthy Holstein calves (1 d old, 30 to 40 kg, fasted) and treated with different concentrations of resveratrol (0, 5, 10, 25, or 50 µM) combined with or without H2O2 (0, 100, or 200 µM) induction for 12 h. RESULTS: Resveratrol enhanced the expression of gluconeogenic genes of calf hepatocytes in a dose-dependent manner (P < 0.05). Conversely, H2O2 suppressed the expression of gluconeogenic genes and induced oxidative stress (P < 0.05), which was improved by resveratrol in calf hepatocytes (P < 0.001). Furthermore, the mechanistic target of rapamycin complex 2 (mTORC2)-AKT pathway was found to negatively regulate gluconeogenesis. An AKT inhibitor was used to assess the role of the mTORC2-AKT pathway in the effects of resveratrol. The results showed resveratrol promoted hepatic gluconeogenesis by inhibiting the mTORC2-AKT pathway. Moreover, sestrin 2 (SESN2) upregulated the activity of mTORC2. We further found that resveratrol decreased SESN2 levels (P < 0.001). CONCLUSIONS: This study indicated that resveratrol enhances the gluconeogenic capacity of calf hepatocytes by improving H2O2-induced oxidative stress and modulating the activity of the SESN2-mTORC2-AKT pathway, implying that resveratrol may be a promising target for ameliorating liver oxidative stress in transition cows.

IGFBP3 induced by the TGF-ß/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.

Dual or multi-targets therapy targeting epidermal growth factor receptor variant III (EGFRvIII) and other molecular may relax the constraint for glioblastoma (GBM), putting forward the urgent requirement of finding candidate molecules. Here, the insulin-like growth factor binding protein-3 (IGFBP3) was considered a candidate, whereas the mechanisms of IGFBP3 production remain unclear. We treated GBM cells with exogenous transforming growth factor ß (TGF-ß) to simulate the microenvironment. We found that TGF-ß and EGFRvIII transactivation induced the activation of transcription factor c-Jun, which specifically bound to the promoter region of IGFBP3 through Smad2/3 and ERK1/2 pathways and promoted the production and secretion of IGFBP3. IGFBP3 knockdown inhibited the activation of TGF-ß and EGFRvIII signals and the malignant behaviors triggered by them in vitro and in vivo. Collectively, our results indicated a positive feedback loop of p-EGFRvIII/IGFBP3 under administration of TGF-ß, blocking IGFBP3 may be an additional target in EGFRvIII-expressing GBM-selective therapeutic strategy.

Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling.

Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis and autophagy. However, it remains largely unclear whether butyrate can regulate cell ferroptosis, and the mechanism by which has not been studied. In this study, we found that RAS-selective lethal compound 3 (RSL3)- and erastin-induced cell ferroptosis were enhanced by sodium butyrate (NaB). With regard to the underlying mechanism, our results showed that NaB promoted ferroptosis by inducing lipid ROS production via downregulating the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Moreover, the FFAR2-AKT-NRF2 axis and FFAR2-mTORC1 axis accounts for the NaB-mediated downregulation of SLC7A11 and GPX4, respectively, in a cAMP-PKA-dependent manner. Functionally, we found that NaB can inhibit tumor growth and the inhibitory effect could be eliminated by administrating MHY1485 (mTORC1 activator) and Ferr-1 (ferroptosis inhibitor). Altogether, in vivo results suggest that NaB treatment is correlated to the mTOR-dependent ferroptosis and consequent tumor growth through xenografts and colitis-associated colorectal tumorigenesis, implicating the potential clinical applications of NaB for future colorectal cancer treatments. Based on all these findings, we have proposed a regulatory mechanism via which butyrate inhibits the mTOR pathway to control ferroptosis and consequent tumorigenesis.

Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.

The amino acid-stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase-mediated mTORC1 activation. Here, a highly conserved insulin-responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2-AKT1 is localized on lysosomes, and RagD-specific recruitment of mTORC2-AKT1 on lysosomes is identified as an essential step in insulin-AKT1-mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin-induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1-dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross-talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation.

Influences of environment, human activity, and climate on the invasion of Ageratina adenophora (Spreng.) in Southwest China.

With economic and social globalization, invasive alien species have significantly threatened local ecological security. Identifying the invasive mechanisms of invasive alien species can aid in preventing species invasions and protecting local ecological and economic security. As a globally invasive plant, Ageratina adenophora (Asteraceae) has spread to many parts of the world and had a seriously impacted the ecology and economy of its invaded areas. Using observational data and Landsat OLI images in an arid valley region in southwest China, this study examined how climate, human activity and environmental factors influence the invasion of A. adenophora and its underlying mechanism. Our results showed that the invasion abundance of A. adenophora was significantly affected by environmental factors (the relative importance was 87.2%), but was less influenced by human activity and climate factors (the relative importance was 2% and 10.8%, respectively). The A. adenophora abundance significantly decreased with aspect, community canopy density, shrub layer coverage, herb layer coverage, Simpson diversity index of shrub and herb layers, the shortest distance to residential areas and temperature seasonality, whereas it increased with soil moisture, temperature annual range, precipitation of wettest month and precipitation of driest month. We conclude that biotic competition is the most influential factor in the invasion of this plant in the arid valley regions. Our results are of great significance for invasion prevention and forest conservation and management in southwest China. Our work emphasized that optimizing the community structure, such as by increasing canopy and shrub coverage and species biodiversity, may help control and mitigate the A. adenophora invasion in southwest China.

Chicken infectious anemia virus (CIAV) VP1 antagonizes type I interferon (IFN-I) production by inhibiting TBK1 phosphorylation.

Chicken infectious anemia virus (CIAV) infection induces immunosuppression or subclinical immunosuppression in chickens. CIAV infection has been reported to repress type I interferon (IFN-I) expression, but the underlying mechanisms are not yet understood. Here we reported that VP1, the capsid protein of CIAV, the major immunogenic protein that triggers the production of neutralizing antibodies in chickens, inhibited type I interferon (IFN-I) expression induced by cGAS-STING signaling. We showed that VP1 inhibited TBK1 phosphorylation and down stream signal transduction, leading to the inhibition of IFN-I expression. Subsequently, we demonstrated that VP1 interacted with TBK1. Finally, we clarified that aa 120-150 in VP1 was essential for VP1 to interact with TBK1 and inhibit cGAS-STING signaling. These findings will help us further understand the pathogenesis of CIAV in chickens.

Pharmacological vitamin C inhibits mTOR signaling and tumor growth by degrading Rictor and inducing HMOX1 expression.

Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.