G protein subunit Gγ13-mediated signaling pathway is critical to the inflammation resolution and functional recovery of severely injured lungs.

Tuft cells are a group of rare epithelial cells that can detect pathogenic microbes and parasites. Many of these cells express signaling proteins initially found in taste buds. It is, however, not well understood how these taste signaling proteins contribute to the response to the invading pathogens or to the recovery of injured tissues. In this study, we conditionally nullified the signaling G protein subunit Gγ13 and found that the number of ectopic tuft cells in the injured lung was reduced following the infection of the influenza virus H1N1. Furthermore, the infected mutant mice exhibited significantly larger areas of lung injury, increased macrophage infiltration, severer pulmonary epithelial leakage, augmented pyroptosis and cell death, greater bodyweight loss, slower recovery, worsened fibrosis and increased fatality. Our data demonstrate that the Gγ13-mediated signal transduction pathway is critical to tuft cells-mediated inflammation resolution and functional repair of the damaged lungs.To our best knowledge, it is the first report indicating subtype-specific contributions of tuft cells to the resolution and recovery.

Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite.

Tumors employ various strategies to evade immune surveillance. Central nervous system (CNS) has multiple features to restrain immune response. Whether tumors and CNS share similar programs of immunosuppression is elusive. Here, we analyze multi-omics data of tumors from HER2+ breast cancer patients receiving trastuzumab and anti-PD-L1 antibody and find that CNS-enriched N-acetyltransferase 8-like (NAT8L) and its metabolite N-acetylaspartate (NAA) are overexpressed in resistant tumors. In CNS, NAA is released during brain inflammation. NAT8L attenuates brain inflammation and impairs anti-tumor immunity by inhibiting cytotoxicity of natural killer (NK) cells and CD8+ T cells via NAA. NAA disrupts the formation of immunological synapse by promoting PCAF-induced acetylation of lamin A-K542, which inhibits the integration between lamin A and SUN2 and impairs polarization of lytic granules. We uncover that tumor cells mimic the anti-inflammatory mechanism of CNS to evade anti-tumor immunity and NAT8L is a potential target to enhance efficacy of anti-cancer agents.

Potential of metallurgical iron-containing solid waste-based catalysts as activator of persulfate for organic pollutants degradation.

The production of solid wastes in the metallurgical industry has significant implications for land resources and environmental pollution. To address this issue, it is crucial to explore the potential of recycling these solid wastes to reduce land occupation while protecting the environment and promoting resource utilization. Steel slag, red mud, copper slag and steel picking waste liquor are examples of solid wastes generated during the metallurgical process that possess high iron content and Fe species, making them excellent catalysts for persulfate-based advanced oxidation processes (PS-AOPs). This review elucidates the catalytic mechanisms and pathways of Fe2+ and Fe0 in the activation PS. Additionally, it underscores the potential of metallurgical iron-containing solid waste (MISW) as a catalyst for PS activation, offering a viable strategy for its high-value utilization. Lastly, the article provides an outlook towards future challenges and prospects for MISW in PS activation for the degradation of organic pollutants.

Effect of microwave (MW)-subcritical extraction on oil recovery, oxidative stability, and lipid types from Katsuwonus pelamis livers.

Katsuwonus pelamis is a tuna species mostly sold for canned fillets, its livers were lack of utilization. This study thus investigated an oil production method combining microwave (MW) pretreatment and subcritical dimethyl ether (SDME) in aim to reach improved efficiency and oil quality. The heating characteristics from different MW powers (400, 600, and 800 W) were evaluated, and SEM showed MW having hydrolysis effect on matrix lipoprotein, the fortified recovery rate was also found. Under the MW-SDME condition with 600 W power, 1:5 solid-to-liquid ratio, and 100 min, the recovery reached 93.21% in maximal (SDME ∼50%). To further improve quality, MW powers was noticed affecting lipid types, fatty acid composition, and oxidative stability of produced oils. 1286 lipid types (mostly glyceride and phospholipid-type) were identified, while higher MW lowered the emulsifying phospholipids prompting phase separation. Several oxidation indexes consistently increased with the rising MW power, GC-MS suggested 400 W for higher DHA.

Feasibility of delta radiomics-based pCR prediction for rectal cancer patients treated with magnetic resonance-guided adaptive radiotherapy.

Magnetic resonance-guided adaptive radiotherapy (MRgART) represents the latest frontier in precision radiotherapy. It is distinguished from other modalities by the possibility of acquiring high-contrast soft tissue images, combined with the ability to recalculate and re-optimize the plan on the daily anatomy. The extensive database of available images offers ample scope for using disciplines such as radiomics to try to correlate features and outcomes. This study aimed to correlate the change of radiomics feature along the treatment to pathological complete response (pCR) for locally advanced rectal cancer (LARC) patients. Twenty-eight LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT) with a short course (25 Gy, 5 Gy × 5f) MRgART at 1.5 Tesla MR-Linac were enrolled. The T2-weighted images acquired at each fraction, corresponding target delineation, pCR result of the surgical specimen, and clinical variables were collected. Seven families of features [First Order, Shape, Gray-level Co-occurrence Matrix (GLCM), Gray-level Dependence Matrix (GLDM), Gray-level Run Length Matrix (GLRLM), Gray-level Size Zone Matrix (GLSZM), and Neighborhood Gray Tone Difference Matrix (NGTDM)] were extracted, and delta features were calculated from the ratio of features of each successive fraction to those of the first fraction. Mann-Whitney U test and LASSO were utilized to reduce the dimension of features and select those features that are most significant to pCR. At last, the radiomics signatures were established by linear regression with the final set of features and their coefficients. A total of 581 radiomics features were extracted, and 2,324 delta features were calculated for each patient. Nineteen features and delta features, and one clinical variable (cN) were significant (p< 0.05) to pCR; seven predictive features were further selected and included in the linear regression to construct the radiomics signature significantly discriminating pCR and non-pCR groups (p< 0.05). Delta features based on MRI images acquired during a short course MRgART could potentially be used to predict treatment response in LARC patients undergoing nCRT.

Comparison of the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints on intestinal sensitivity and autonomic nervous system function in rats with diarrhea-predominant irritable bowel syndrome. / "æ ‡æœ¬é ç©´"è‰¾ç¸ä¸Žé’ˆåˆºå¯¹è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾å¤§é¼ è‚ é“æ•æ„Ÿæ€§å’Œè‡ªä¸»ç¥žç»åŠŸèƒ½å½±å“çš„æ¯”è¾ƒ.

OBJECTIVES: To compare the effects of moxibustion and acupuncture of combined "Biao-Ben" acupoints (Biao indicates pathogenic factors of disease, Ben refers to body constitution) on a rat model of irritable bowel syndrome with diarrhea (IBS-D). METHODS: Forty female SD rats were randomly divided into 4 groups：normal group, model group, moxibustion group, and acupuncture group, with 10 rats in each group. The IBS-D rat model was established by administering acute-chronic stress combined with folium sennae gavage for 28 days. Rats in the moxibustion group received moxibustion at bilateral "Zusanli"(ST36), "Guanyuan"(CV4), and "Neiguan"(PC6), while those in the acupuncture group received acupuncture at the same acupoints, both for 15 min every time, once a day. The treatments were administered for 21 days. The loose stool rate was observed. Colonic pain threshold and colonic distension threshold were measured by a self-made balloon catheter. Total distance traveled and grid crossing numbers were observed by open field test. Heart rate variability(HRV) time domain indexes SDANN and PNN50 were acguired by using electrophysiological recorder. Histopathological changes in the colon tissue were observed after HE staining. Contents of interleukin-6(IL-6), IL-8, and tumor necrosis factor-alpha(TNF-α) in serum were detected by ELISA. RESULTS: Compared with the normal group, rats in the model group showed increased loose stool rate(P<0.05), decreased pain threshold and distension threshold(P<0.05), reduced total distance traveled and grid crossing numbers in the open field test(P<0.05), decreased HRV time domain indexes SDANN and PNN50(P<0.01, P<0.05), and elevated levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the model group, the moxibustion group and acupuncture group showed decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50 (P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). Compared with the acupuncture group, the moxibustion group showed further decreased loose stool rate(P<0.05), increased total distance traveled and grid crossing numbers in the open field test(P<0.05), increased pain threshold and distension threshold(P<0.05), increased SDANN and PNN50(P<0.05), and decreased levels of serum IL-6, IL-8, and TNF-α contents(P<0.05). No significant pathological changes were observed in the colon tissue of rats in each group. CONCLUSIONS: Moxibustion of combined "Biao-Ben" acupoints is more effective in regulating HRV and serum IL-6, IL-8, and TNF-α contents in the IBS-D rat model. Based on the combined "Biao-Ben" acupoints method, moxibustion has better therapeutic effects on IBS-D than acupuncture.

Realizing of ZSM-5 microspheres with enhanced catalytic properties prepared from iron ore tailings via solid-phase conversion method.

The comprehensive utilization of iron ore tailings (IOTs) not only resolved environmental problems but also brought huge economic benefits. In this study, the synthetic route presented herein provides a novel method for the synthesis of ZSM-5 microspheres from IOTs. The effects of Si/Al molar ratios and the pH of the precursor solution on the formation of zeolite was evaluated by various analytical methods. The catalytic performance of the catalyst prepared by the solid-phase conversion method (denoted as MP-ZSM-5) was evaluated by methanol-to-propylene (MTP) reaction. Compared with the zeolite catalyst that synthesized via the conventional hydrothermal method (denoted as HM-ZSM-5), MP-ZSM-5 not only prolongs catalytic lifetime from 18.7 to 36.0 h but also has higher selectivity for propylene by MP-ZSM-5 (43.7%) than that for HM-ZSM-5 (38.6%). In addition, Kissinger-Akahira-Sunose (KAS) model is applied to the TG result to study the template removal process kinetics. The average activation energy values required for the removal of CTAB and TPABr are 201.11 ± 13.42 and 326.88 ± 16.91 kJ∙mol-1, respectively. Furthermore, this result is well coupled with the model-free kinetic algorithms to determine the conversion and isoconversion of the TPABr and CTAB decomposition in ZSM-5, which serves as important guidelines for the industrial production process.

Genome-Directed Discovery of Bicyclic Cinnamoyl-Containing Nonribosomal Peptides with Anticoronaviral Activity from Streptomyces griseus.

Two novel cinnamoyl-containing nonribosomal peptides (CCNPs) grisgenomycin A and B were identified in Streptomyces griseus NBRC 13350 (CGMCC 4.5718) and ATCC 12475, through genome mining using conserved adjacent LuxR family regulators as probes and activators. Notably, grisgenomycins represent a new group of bicyclic decapeptides featuring an unprecedented C-C bond between the tryptophan carbocycle and the cinnamoyl group. A plausible biosynthetic pathway for grisgenomycins was deduced by a bioinformatics analysis. Grisgenomycins exhibited activity against human coronaviruses at the micromolar level.

Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid ß-Oxidation.

Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long-term prognosis in these patients. The CD96+ cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell-intrinsic CD96 enhances the chemotherapeutic response in a patient-derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid ß-oxidation via the CD155-CD96-Src-Stat3-Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell-intrinsic CD96 and an attractive target in improving the chemotherapeutic response.

Macrophage mitochondrial fission improves cancer cell phagocytosis induced by therapeutic antibodies and is impaired by glutamine competition.

Phagocytosis is required for the optimal efficacy of many approved and promising therapeutic antibodies for various malignancies. However, the factors that determine the response to therapies that rely on phagocytosis remain largely elusive. Here, we demonstrate that mitochondrial fission in macrophages induced by multiple antibodies is essential for phagocytosis of live tumor cells. Tumor cells resistant to phagocytosis inhibit mitochondrial fission of macrophages by overexpressing glutamine-fructose-6-phosphate transaminase 2 (GFPT2), which can be targeted to improve antibody efficacy. Mechanistically, increased cytosolic calcium by mitochondrial fission abrogates the phase transition of the Wiskott-Aldrich syndrome protein (WASP)-Wiskott-Aldrich syndrome interacting protein (WIP) complex and enables protein kinase C-θ (PKC-θ) to phosphorylate WIP during phagocytosis. GFPT2-mediated excessive use of glutamine by tumor cells impairs mitochondrial fission and prevents access of PKC-θ to compartmentalized WIP in macrophages. Our data suggest that mitochondrial dynamics dictate the phase transition of the phagocytic machinery and identify GFPT2 as a potential target to improve antibody therapy.

Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic Xylaria sp.

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A (1), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A (1) involving a rare trans-acting N-methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A (1) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC50 values of 2.5 and 9.5 µM, respectively.

Oral and gastric microbiome in relation to gastric intestinal metaplasia.

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case-control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case-control pairs and antral mucosal brushing samples from 55 case-control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic-net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29-1.50, P = .004-.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.66-0.76, P = .006-.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under-represented (ORs = 0.61-0.75, P = .024-.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under-represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.

A CD10-OGP Membrane Peptolytic Signaling Axis in Fibroblasts Regulates Lipid Metabolism of Cancer Stem Cells via SCD1.

Carcinoma-associated fibroblasts (CAFs) consist of heterogeneous subpopulations that play a critical role in the dynamics of the tumor microenvironment. The extracellular signals of CAFs have been attributed to the extracellular matrix, cytokines, cell surface checkpoints, and exosomes. In the present study, it is demonstrated that the CD10 transmembrane hydrolase expressed on a subset of CAFs supports tumor stemness and induces chemoresistance. Mechanistically, CD10 degenerates an antitumoral peptide termed osteogenic growth peptide (OGP). OGP restrains the expression of rate-limiting desaturase SCD1 and inhibits lipid desaturation, which is required for cancer stem cells (CSCs). Targeting CD10 significantly improves the efficacy of chemotherapy in vivo. Clinically, CD10-OGP signals are associated with the response to neoadjuvant chemotherapy in patients with breast cancer. The collective data suggest that a nexus between the niche and lipid metabolism in CSCs is a promising therapeutic target for breast cancer.

CCRL2 promotes antitumor T-cell immunity via amplifying TLR4-mediated immunostimulatory macrophage activation.

Macrophages are the key regulator of T-cell responses depending on their activation state. C-C motif chemokine receptor-like 2 (CCRL2), a nonsignaling atypical receptor originally cloned from LPS-activated macrophages, has recently been shown to regulate immune responses under several inflammatory conditions. However, whether CCRL2 influences macrophage function and regulates tumor immunity remains unknown. Here, we found that tumoral CCRL2 expression is a predictive indicator of robust antitumor T-cell responses in human cancers. CCRL2 is selectively expressed in tumor-associated macrophages (TAM) with immunostimulatory phenotype in humans and mice. Conditioned media from tumor cells could induce CCRL2 expression in macrophages primarily via TLR4, which is negated by immunosuppressive factors. Ccrl2-/- mice exhibit accelerated melanoma growth and impaired antitumor immunity characterized by significant reductions in immunostimulatory macrophages and T-cell responses in tumor. Depletion of CD8+ T cells or macrophages eliminates the difference in tumor growth between WT and Ccrl2-/- mice. Moreover, CCRL2 deficiency impairs immunogenic activation of macrophages, resulting in attenuated antitumor T-cell responses and aggravated tumor growth in a coinjection tumor model. Mechanically, CCRL2 interacts with TLR4 on the cell surface to retain membrane TLR4 expression and further enhance its downstream Myd88-NF-κB inflammatory signaling in macrophages. Similarly, Tlr4-/- mice exhibit reduced CCRL2 expression in TAM and accelerated melanoma growth. Collectively, our study reveals a functional role of CCRL2 in activating immunostimulatory macrophages, thereby potentiating antitumor T-cell response and tumor rejection, and suggests CCLR2 as a potential biomarker candidate and therapeutic target for cancer immunotherapy.

A Maize ZmAT6 Gene Confers Aluminum Tolerance via Reactive Oxygen Species Scavenging.

Aluminum (Al) toxicity is the primary limiting factor that affects crop yields in acid soil. However, the genes that contribute to the Al tolerance process in maize are still poorly understood. Previous studies have predicted that ZmAT6 is a novel protein which could be upregulated under Al stress condition. Here, we found that ZmAT6 is expressed in many tissues and organs and can be dramatically induced by Al in both the roots and shoots but particularly in the shoots. The overexpression of ZmAT6 in maize and Arabidopsis plants increased their root growth and reduced the accumulation of Al, suggesting the contribution of ZmAT6 to Al tolerance. Moreover, the ZmAT6 transgenic maize plants had lower contents of malondialdehyde and reactive oxygen species (ROS), but much higher proline content and even lower Evans blue absorption in the roots compared with the wild type. Furthermore, the activity of several enzymes of the antioxidant system, such as peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), increased in ZmAT6 transgenic maize plants, particularly SOD. Consistently, the expression of ZmSOD in transgenic maize was predominant upregulated by Al stress. Taken together, these findings revealed that ZmAT6 could at least partially confer enhanced tolerance to Al toxicity by scavenging ROS in maize.

Higher healthy lifestyle scores are associated with greater bone mineral density in middle-aged and elderly Chinese adults.

This study examined the association between healthy lifestyle score (HLS), which contained 7 items (smoking, BMI, physical activity, diet, alcohol, sleep and anxiety) and BMD. Results showed HLS was positively associated with BMD at all studied sites, suggesting that healthier lifestyle patterns might be beneficial to bone health. PURPOSE: Previous studies have reported favourable associations of individual healthy lifestyle factors with bone mineral density (BMD), but limited evidence showed the relationship of a combined healthy lifestyle score (HLS) with BMD. This study examined the association between the HLS and BMD. METHODS: This community-based cross-sectional study included 3051 participants aged 40-75 years. The HLS contained 7 items (smoking, BMI, physical activity, diet quality, alcohol intake, sleep and anxiety). BMD values of whole body (WB), lumbar spine 1-4 (L1-4), total hip (TH) and femur neck (FN) were measured using dual-energy X-ray absorptiometry. RESULTS: After adjusting for potential covariates, HLS was positively associated with BMD at all studied sites (P-trend < 0.01). The mean BMDs were 2.69% (WB), 5.62% (L1-4), 6.13% (TH) and 5.71% (FN) higher in participants with HLS of 6-7 points than in those with HLS of 0-2 points. The per 1 of 7 unit increase in the HLS was associated with increases of 7.63 (WB)-13.4 (TH) mg/cm2 BMD levels at all sites. These favourable associations tended to be more pronounced in men than in women. Among the 7 items, physical activity contributed most to the favourable associations, followed by BMI, non-smoking and diet; the other three items played little roles. Sensitivity analyses showed that the significant associations remained after excluding any one of the 7 components or excluding fracture subjects at all sites. CONCLUSION: Higher HLS was associated with greater BMD in middle-aged and elderly Chinese, suggesting that healthier lifestyle patterns might be beneficial to bone health.

Complement Signals Determine Opposite Effects of B Cells in Chemotherapy-Induced Immunity.

Understanding molecular mechanisms that dictate B cell diversity is important for targeting B cells as anti-cancer treatment. Through the single-cell dissection of B cell heterogeneity in longitudinal samples of patients with breast cancer before and after neoadjuvant chemotherapy, we revealed that an ICOSL+ B cell subset emerges after chemotherapy. Using three immunocompetent mouse models, we recapitulated the subset switch of human tumor-infiltrating B cells during chemotherapy. By employing B-cell-specific deletion mice, we showed that ICOSL in B cells boosts anti-tumor immunity by enhancing the effector to regulatory T cell ratio. The signature of ICOSL+ B cells is imprinted by complement-CR2 signaling, which is triggered by immunogenic cell death. Moreover, we identified that CD55, a complement inhibitory protein, determines the opposite roles of B cells in chemotherapy. Collectively, we demonstrated a critical role of the B cell subset switch in chemotherapy response, which has implications in designing novel anti-cancer therapies. VIDEO ABSTRACT.

Amentoflavone suppresses cell proliferation and induces cell death through triggering autophagy-dependent ferroptosis in human glioma.

AIMS: Glioma is the most common type of malignant tumor of the nervous system, and aggressiveness and recurrence are major obstacles for treatment. This study is designed to explore the effects of amentoflavone (AF) on glioma, and to investigate the underlying mechanism of the anti-cancer activities of AF. METHODS: Cell morphology was recorded under microscopy. Cell viability and cell death ratio were determined by CCK-8 assay and lactate dehydrogenase (LDH) release assay, respectively. Cell cycle progression was assessed by flow cytometry. The levels of iron, MDA (malondialdehyde), lipid ROS, and GSH (reduced glutathione) were assessed by ELISA kit. The cycle-related proteins, ferroptosis-related protein, autophagy-related protein, and the phosphorylation of AMPK, mTOR and p70S6K were analyzed by western blotting. The autophagic flux was observed by transfecting cells with mRFP-GFP-LC3 plasmids. The xenograft murine models were established to analyze the effects of amentoflavone in vivo. The immunohistochemistry assay was performed to analyze the expression of LC3B, Beclin1, ATG5, ATG7, and ferritin heavy chain (FTH). RESULTS: Our results showed that AF treatment led to reduction in cell viability and cell death. In addition, AF was found to block cell cycle progression in a dose-dependent manner in vitro. Following treatment with AF, the intracellular levels of iron, MDA, and lipid OS were increased, and the levels of GSH and the mitochondrial membrane potential were reduced. In addition, our results showed that AF promoted the autophagic by regulating autophagy-relevant proteins. Our results also showed that the autophagy-induction by AF was associated with regulation of AMPK/mTOR signaling. Mechanistically, the inhibition effects of AF on glioma cell were reversed by DFO, ferreostatin-1 as well as upregulation of FTH. Meanwhile, the FTH levels were increased by compound C and knockdown of ATG7. Moreover, both autophagy inhibitor Baf A1 and knockdown of ATG7 were able to compromising AF-induce ferroptosis and cell death. In vivo, the tumor growth was suppressed by AF in a dose-dependent manner. The level of MDA in the tumor tissue was increased while the level of GSH in tumor tissue was decreased by AF in a dose-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. Conclusion These results demonstrate that AF triggered ferroptosis in autophagy-dependent manner. Our results suggest that AF has the potential to be considered as a novel treatment agent in glioma.

Urinary equol is associated with bioavailable testosterone but not total testosterone in women.

Little is known about the association between equol and bioavailable testosterone (BT) in adults. In this study, we examined the associations of urinary equol concentrations with serum concentrations of total, bioavailable and free testosterone (FT), dehydroepiandrosterone sulfide (DHEAS), free androgen index (FAI) and sex hormone-binding globulin (SHBG). This cross-sectional study included 1,904 women with a mean age of 59.7 years. Urinary equol concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The serum androgenic indices and SHBG were also determined. Overall, urinary equol tended to be inversely associated with bioactive forms of androgenic indices (BT, FT or FAI) but not with total testosterone (TT) or DHEAS. Urinary equol was also positively associated with SHBG. In multi-covariate-adjusted analyses stratified by menopausal status, graded and inverse associations between urinary equol and bioactive forms of androgenic indices (BT, FT and FAI) were observed in postmenopausal women (all p-trends < 0.05), but not in premenopausal women. A significant positive association between urinary equol and SHBG was observed only in postmenopausal women. No significant associations were observed between urinary equol and TT or DHEAS in either group. A path analysis indicated that these associations of equol with androgens in postmenopausal women might be mediated by SHBG. In conclusion, urinary equol exhibited graded and inverse associations with BT or FT, but not TT in women. However, further longitudinal studies of human patients are needed to confirm these results and overcome the limitations of cross-sectional studies.