Icariin-Curcumol promotes docetaxel sensitivity in prostate cancer through modulation of the PI3K-Akt signaling pathway and the Warburg effect.

BACKGROUND: Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. METHODS: Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. RESULTS: Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. CONCLUSION: Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.

Guilu-Erxian-Glue alleviates Tripterygium wilfordii polyglycoside-induced oligoasthenospermia in rats by resisting ferroptosis via the Keap1/Nrf2/GPX4 signaling pathway.

CONTEXT: Guilu-Erxian-Glue (GLEXG) is a traditional Chinese formula used to improve male reproductive dysfunction. OBJECTIVE: To investigate the ferroptosis resistance of GLEXG in the improvement of semen quality in the oligoasthenospermia (OAS) rat model. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were administered Tripterygium wilfordii polyglycoside, a compound extracted from Tripterygium wilfordii Hook F. (Celastraceae), at a dose of 40 mg/kg/day, to establish an OAS model. Fifty-four SD rats were randomly divided into six groups: sham, model, low-dose GLEXG (GLEXGL, 0.25 g/kg/day), moderate-dose GLEXG (GLEXGM, 0.50 g/kg/day), high-dose GLEXG (GLEXGH, 1.00 g/kg/day) and vitamin E (0.01 g/kg/day) group. The semen quality, structure and function of sperm mitochondria, histopathology, levels of oxidative stress and iron, and mRNA levels and protein expression in the Keap1/Nrf2/GPX4 pathway, were analyzed. RESULTS: Compared with the model group, GLEXGH significantly improved sperm concentration (35.73 ± 15.42 vs. 17.40 ± 4.12, p < 0.05) and motility (58.59 ± 11.06 vs. 28.59 ± 9.42, p < 0.001), and mitigated testicular histopathology. Moreover, GLEXGH markedly reduced the ROS level (5684.28 ± 1345.47 vs. 15500.44 ± 2307.39, p < 0.001) and increased the GPX4 level (48.53 ± 10.78 vs. 23.14 ± 11.04, p < 0.01), decreased the ferrous iron level (36.31 ± 3.66 vs. 48.64 ± 7.74, p < 0.05), and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway. DISCUSSION AND CONCLUSIONS: Ferroptosis resistance from GLEXG might be driven by activation of the Keap1/Nrf2/GPX4 pathway. Targeting ferroptosis is a novel approach for OAS therapy.

[Xiongcan Yishen Formula up-regulates the clock gene expressions in the testis tissue of the rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Formula (XYF) on the expressions of the clock genes in the testis tissue of the rats with late-onset hypogonadism (LOH). METHODS: Forty-eight 8-week-old male SD rats were randomly divided into 6 groups, normal control, model control, testosterone propionate (TP), and low-, medium- and high-dose XYF. The LOH model was made in the later 5 groups of rats by intraperitoneal injection of D-galactose at 480 mg/kg/d for 56 successive days, while the normal controls were injected with the same volume of normal saline. After modeling, the rats in the low-, medium- and high-dose XYF groups were treated intragastrically with XYF at 10.4, 20.8 and 41.6 g/kg/d, bid, respectively, those in the normal and model control groups with the same volume of distilled water, and those in the TP group intramuscularly with TP at 5.21 mg/kg/d, qd alt, all for 28 days. After treatment, the supernatant was obtained for measurement of the serum T level by ELISA, and the testis tissue collected for determination of the mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 by RT-qPCR and Western blot. RESULTS: Compared with the normal controls, the rats in the LOH model control group showed significantly decreased serum T and mRNA and protein expressions of BMAL1, NR1D1, PER2, CRY1, StAR and CYP11A1 (P < 0.05). In comparison with the findings in the model controls, the T level was remarkably increased in the TP and XYF groups (P < 0.05), the expressions of StAR mRNA and CYP11A1 mRNA and protein markedly up-regulated in the high-dose XYF group (P < 0.05), and so was the expression of the StAR protein in the XYF and TP groups (P < 0.05), those of BMAL1 and NR1D1 proteins and PER2 mRNA and protein in the high-dose XYF group (P < 0.05), those of BMAL1 mRNA and CRY1 protein in the medium- and high-dose XYF groups (P < 0.05), that of NR1D1 mRNA in the XYF and TP groups (P < 0.05), and that of CRY1 mRNA in the medium- and high-dose XYF and TP groups (P < 0.05). CONCLUSION: Xiongcan Yishen Formula could up-regulate the expressions of the clock genes in the testis tissue of the LOH rats and increase the serum T level as well, which may underlie the mechanisms of Xiongcan Yishen Formula acting on LOH.

Developmental Trends in the Application and Measurement of the Bidirectional Reflection Distribution Function.

The bidirectional reflection distribution function (BRDF) is among the most effective means to study the phenomenon of light-object interaction. It can precisely describe the characteristics of spatial reflection of the target surface, and has been applied to aerial remote sensing, imaging technology, materials analysis, and computer rendering technology. This study provides a comprehensive review of the development of devices to measure the BRDF. We gathered research in the area by using the Web of Science Core Collection, and show that work on the BDRF has been ongoing in the last 30 years. We also describe some typical measurement devices for the BRDF proposed in the literature. Finally, we summarise outstanding problems related to BRDF measurement and propose directions of future research in the area.

[Potential mechanisms of Jiarong Tablets in the treatment of late-onset hypogonadism in men: An exploration based on network pharmacology].

OBJECTIVE: To study the therapeutic targets and related signaling pathways of Jiarong Tablets (JRT) in the treatment of late-onset hypogonadism (LOH) in males by network pharmacology, and further analyze its potential action mechanism. METHODS: Using the Chinese Medicine System Pharmacology Analysis Platform (TCMSP), we obtained the active ingredients and therapeutic targets of JRT, disease targets of LOH through the GeneCards and OMIM databases, and drug-disease common targets, followed by drawing a Vennny's diagram of the common targets. We constructed a protein-protein interaction (PPI) network of the common targets using STRING and an intersection network of JRT active ingredients-LOH-targets with Cytoscape 3.7.2, performed GO bio-functional and KEGG enrichment analyses of the common targets using the R-Language software, and identified the potential signaling pathways of JRT acting on LOH. RESULTS: Totally, we obtained 80 bioactive ingredients from JRT and 64 common targets of LOH, with IL-6, INS, AKT1, JUN and MAPK8 as the core targets in the order of the frequency occurrences. GO and KEGG analyses showed that these targets mainly involved the MAPK, HIF-1, Ras and ErbB signaling pathways. CONCLUSION: JRT acts on LOH with multiple targets, through multiple routes and at multiple levels, which is related to the expression of testosterone synthetase, oxidative stress and apoptosis of Leydig cells.

[Establishment and evaluation of a rat model of late-on-set hypogonadism using D-galactose].

OBJECTIVE: To explore the feasibility and duration of establishing a model of late-on-set hypogonadism (LOH) in rats using D-galactose (D-gal) and the optimal concentration of D-gal in modeling. METHODS: Thirty-five 8-week-old male SD rats were randomly divided into seven groups of an equal number to receive intraperitoneal injection of normal saline (normal control) or D-gal at 480 mg/kg/d (high-dose), 240 mg/kg/d (medium-dose) and 120 mg/kg/d (low-dose) for 6 or 8 weeks respectively. Another five 18-month-old SD rats were taken as positive controls. After modeling, the animals were subjected to tail suspension test and mating test, weighed, and then sacrificed for examination of the levels of fasting blood glucose (FBG) and serum testosterone (T), testis index and semen parameters, determination of the expressions of the BMAL1 and NR1D1 proteins in the testis tissue by Western blot, and observation of the pathological and ultrastructural changes in the testis tissue under the light microscope and transmission electron microscope. RESULTS: Compared with the normal controls, the serum T level was significantly decreased in the 6-week medium-dose D-gal (6WMD), 6-week high-dose D-gal (6WHD), 8WMD, 8WHD and positive control groups (P < 0.05), and so were sperm concentration and the percentage of progressively motile sperm (PMS) in the 8WHD and positive control groups (P < 0.05), and the numbers of captures and ejaculations in all the model rats and positive controls (P < 0.05), while the body weight was markedly increased in the 8-week low-dose D-gal (8WLD), 8WMD and 8WHD groups (P < 0.05), and so were the tail suspension time in the 6WHD, 8WHD, 8WMD, 8WLD and positive control groups (P < 0.05) and the FBG level in all the model rats and positive controls (P < 0.05). The expression of the BMAL1 protein was significantly decreased in the 6WHD, 8WLD, 8WMD, 8WHD and positive control groups (P < 0.05), and so was that of NR1D1 in the 8WMD, 8WHD and positive control groups (P < 0.05). Compared with the positive controls, no statistically significant differences were observed in the serum T level in the 6WHD and 8WHD groups (P > 0.05), the testis index in the 8WMD and 8WHD groups (P > 0.05), sperm concentration, percentage of FMS, time of tail suspension and numbers of captures and ejaculations in the 8WHD group (P > 0.05), the level of FBG in the 6WMD, 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), the expression of BMAL1 in the 6WHD, 8WLD, 8WMD and 8WHD groups (P > 0.05), and that of NR1D1 in the 6WLD, 8WMD and 8WHD groups (P > 0.05). Pathological and ultrastructural changes in the testis tissue were observed in all the model rats and positive controls, most significantly in the 8WHD and positive control groups. CONCLUSION: It is feasible to establish an LOH model in male SD rats by intraperitoneal injection of D-gal, most recommendably at the centration of 480 mg/kg/d for 8 weeks.

[Establishment and evaluation of an AAPH-induced oxidative stress model in mouse Leydig cells in vitro].

OBJECTIVE: To establish a model of oxidative stress (OS) injury in mouse Leydig cells using α-α'-azodiisobutyramidine hydrochloride (AAPH) and evaluate the physiological function. METHODS: In Experiment 1, we treated mouse TM3 Leydig cells with AAPH at 0, 1, 5, 10, 50 and 100 mmol/L for 4, 8 and 24 h respectively and measured the activity of the cells using MTS, their aging by ß-galactoside staining, mitochondrial membrane potential by JC-1 fluorescence and mitochondrial DNA copy number by qPCR. In Experiment 2, we treated the TM3 cells selected in Experiment 1 according to the AAPH concentration range (≤10 mmol/L) with AAPH at 0, 0.1, 0.5, 1, 2, 4, 6, 8 and 10 mmol/L for 24, 48 and 72 h respectively, detected the activity and aging of the cells and the ROS positive rate, and determined the optimal concentration and time of AAPH in inducing OS injury in the TM3 cells. RESULTS: Experiment 1 showed that the survival rate of the TM3 cells was ≥50% in the 4-h 50 mmol/L, 8-h 10 mmol/L and 24-h 5 mmol/L AAPH groups, the initial concentration of AAPH was ≤10 mmol/L, with the action time of ≥24 h. Experiment 2 manifested that in the 24-h 6 mmol/L AAPH group, the survival rate of the TM3 cells was ≥70%, with an ROS positive rate of 56.88%, normal mitochondrial membrane potential, increased number of mtDNA copies, but no senescence. CONCLUSIONS: Treatment with AAPH at the concentration of 6 mmol/L for 24 hours is suitable for induction of OS injury in the TM3 cells.

[Improving effect of Jiarong Tablets on the morphological structure and function of the testis in rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effect of Jiarong Tablets (JRT) on the testicular morphology and function of rats with late-onset hypogonadism (LOH). METHODS: LOH models were established in 8 eighteen-month-old male SD rats, treated intragastrically with distilled water (the model control group, n = 4) or JRT at 0.375 g/kg/d, qd (the JRT group, n = 4), and another 5 two-month-old normal male SD rats were also given distilled water by gavage (normal control group), all for 28 days. Then all the rats were weighed and sacrificed for measurement of the serum T level and pathological and electron microscopic examination of the testis tissue. RESULTS: Compared with the normal controls, the LOH models showed significantly decreased testis coefficient (P < 0.05) and serum T level (ï¼»3.40 ± 0.06ï¼½ vs ï¼»5.88 ± 0.46ï¼½ ng /ml, P < 0.05). No statistically significant differences were observed in the model control and JRT groups in the body weight and testis coefficient (P > 0.05), but the serum T level (ï¼»4.50 ± 0.78ï¼½ ng/ml) was remarkably decreased in the latter (P < 0.05). In comparison with the model controls, the rats treated with JRT exhibited increases in the sperm count in the seminiferous tubules and the amount of testicular interstitial cells. Electron microscopy revealed a markedly increased number of mitochondria in the JRT-treated animals, with some mitochondrial sheaths and cristae but no obvious mitochondrial edema. CONCLUSIONS: Jiarong Tablets can elevate the serum T level and improve the testicular morphology and ultrastructure of LOH rats.

[Xiongcan Yishen Prescription upregulates the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency].

OBJECTIVE: To investigate the effect of Xiongcan Yishen Prescription (XYP) on the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency (LDKD). METHODS: The model of ED-LDKD was established in 30 eight-week-old SPF-class male SD rats by injecting hydrocortisone intramuscularly and binding the limbs for 14 days, and another 10 rats were taken as blank controls. Then, the model rats were randomized into six groups of equal number and treated intragastrically with distilled water (model control), tadalafil tablets at 0.52 mg/kg/d (tadalafil control), Shugan Yiyang Capsules 0.3125 g/kg/d (SYC control), and XYP at 10.4 g/kg/d (low-dose XYP), 20.8 g/kg/d (medium-dose XYP) and 41.6 g/kg/d (high-dose XYP), bid, for 28 successive days, respectively. Before and after modeling and after 28-day treatment, the animals were subjected to tail suspension and mating tests. The next day after medication, the penile tissues of the rats were harvested for determining the expression levels of eNOS and cGMP proteins by immunohistochemical analysis of the mean optical density. RESULTS: Compared with the model controls, the rats of the high-, medium- and low-dose XYP and SYC control groups all showed significant decreases in the tail suspension time (ï¼»3.17 ± 0.11ï¼½ vs ï¼»2.58 ± 0.25ï¼½, ï¼»2.52 ± 0.31ï¼½, ï¼»2.51 ± 0.3ï¼½ and ï¼»2.57 ± 0.29ï¼½ min, P < 0.05) and mount latency (ML) (ï¼»9.23 ± 0.11ï¼½ vs ï¼»1.21 ± 0.12ï¼½, ï¼»2.17 ± 0.16ï¼½, ï¼»2.26 ± 0.13ï¼½, ï¼»1.23 ± 0.15ï¼½ and ï¼»2.48 ± 0.18ï¼½ min, P < 0.05) but increases in mount frequency (MF) (ï¼»0.48 ± 0.18ï¼½ vs ï¼»3.29 ± 0.11ï¼½, ï¼»3.18 ± 0.11ï¼½, ï¼»3.05 ± 0.05ï¼½, ï¼»3.23 ± 0.12ï¼½ and ï¼»3.2 ± 0.28ï¼½ times, P < 0.05) and intromission frequency (IF) (ï¼»0.8 ± 0.84ï¼½ vs ï¼»11.8 ± 0.84ï¼½, ï¼»11.2 ± 1.48ï¼½, ï¼»9.4 ± 1.14ï¼½, ï¼»11.4 ± 1.14ï¼½ and ï¼»10 ± 1.22ï¼½ times, P < 0.05). The eNOS and cGMP proteins were mainly expressed in the nucleus and cytoplasm of the arterial and venous endothelial cells and sinusoidal endothelial cells of the cavernous, as brownish yellow particles in a scattered and focal pattern. Both the expressions of eNOS and cGMP in the penile tissue were remarkably upregulated in the high-, medium- and low-dose XYP and SYC control groups as compared with those in the model control (P < 0.05) but exhibited no statistically significant difference between the tadalafil and model control groups (P > 0.05). CONCLUSIONS: Xiongcan Yishen Prescription can relieve the depression symptoms, increase the mount frequency, activate the NO/cGMP pathway, and upregulate the expressions of eNOS and cGMP in the penile tissue of ED rats with liver depression and kidney deficiency.

[Xiongcanyishen Prescription increases mitochondrial autophagy of Leydig cells in LOH rats via PINK1 and Parkin pathways].

OBJECTIVE: To investigate the effects of PINK1 and Parkin pathways mediated by Xiongcanyishen Prescription (XP) on the mitochondrial autophagy of Leydig cells in male rats with late-onset hypogonadism (LOH). METHODS: Twenty 18-month-old male SD rats were randomly divided into an LOH model control, a low-dose XP, a medium-dose XP and a high-dose XP group, and another 5 two-month-old male SD rats were included as normal controls. The animals in the low-, medium- and high-dose XP groups were treated intragastrically with XP granules at 10.4, 20.8 and 41.6 g/kg, while the normal and LOH model controls with the same volume of distilled water, all for 28 successive days. Then the testis tissues of the rats were harvested for observation of the ultrastructure of the Leydig cells under the electron microscope, and the expressions of PINK1, Parkin and p62 proteins were detected by Western blot. RESULTS: The mitochondria in the Leydig cells of the normal controls were basically normal in morphology, with evident autophagy, those of the model controls showed less autophagy, and those in the XP intervention groups all exhibited autophagy. The expressions of PINK1 and Parkin proteins in the testis tissue were significantly lower and that of p62 markedly higher in the LOH model than in the normal controls (P < 0.05). Compared with the rats in the model control group, those treated with XP showed remarkable elevation in the expression of PINK1 in the low-, medium- and high-dose groups and that of Parkin in the medium- and high-dose groups (P < 0.05), but a significantly down-regulated expression of p62 in all the three XP groups (P < 0.05). CONCLUSIONS: Xiongcanyishen Prescription can enhance the decreased mitochondrial autophagy of Leydig cells in LOH rats, which may be related to its ability of up-regulating the expressions of PINK1 and Parkin and down-regulating that of p62 and its influence on the ultrastructure of Leydig cells.

[Xiongcan Yishen Prescription up-regulates the expressions of cholesterol transport proteins, steroidogenic enzymes and SF-1 in the Leydig cells of rats with late-onset hypogonadism].

OBJECTIVE: To investigate the effects of Xiongcan Yishen Prescription (XYP) on the expressions of cholesterol transport proteins, steroidogenic enzymes and steroidogenic factor-1 (SF-1) in the Leydig cells of the rats with late-onset hypogonadism (LOH). METHODS: Twenty-five 18-month-old male SD rats were randomly divided into five groups of equal number, LOH model control, testosterone propionate (TP) and low-, medium- and high-dose XYP, and another 5 two-month-old male SD rats included as normal controls. After modeling, the animals in the TP group were treated by intramuscular injection of TP at 5.21 mg/kg qd alt, those in the low-, medium- and high-dose XYP groups intragastrically with XYP at 10.4, 20.8 and 41.6 g/kg qd alt respectively, and those in the LOH model and normal control groups with saline, all for 28 successive days. Then, all the rats were sacrificed for determination of the expressions of the cholesterol transport proteins StAR and TSPO, steroidogenic enzymes CYP11A1, HSD3B7 and HSD17B4, and SF-1 in the Leydig cells by Western blot. RESULTS: The expressions of StAR, TSPO, CYP11A1, HSD3B7, HSD17B4 and SF-1 in the Leydig cells were significantly decreased in the LOH model controls compared with those in the normal controls (P< 0.05), but remarkably increased in the low-, medium- and high-dose XYP groups in comparison with those in the LOH model control group (P< 0.05). CONCLUSIONS: Xiongcan Yishen Prescription can up-regulate the expressions of the cholesterol transport proteins StAR and TSPO, steroidogenic enzymes CYP11A1, HSD3B7 and HSD17B4, and SF-1 in the rat Leydig cells, which might be one of the possible mechanisms of the prescription in the treatment of LOH.

Icariin­curcumol promotes ferroptosis in prostate cancer cells through Nrf2/HO­1 signaling.

Ferroptosis is a form of regulatory cell death that relies on iron and reactive oxygen species (ROS) to inhibit tumors. The present study aimed to investigate whether icariin-curcumol could be a novel ferroptosis inducer in tumor inhibition. Various concentrations of icariin-curcumol were used to stimulate prostate cell lines (RWPE-2, PC-3, VCAP and DU145). Small interfering negative control (si-NC) and si-nuclear factor erythroid 2-related factor 2 (Nrf2) were used to transfect DU145 cells. Cell viability was determined by using cell counting kit-8. Ferroptosis-related factor levels were analyzed using western blotting and reverse transcription-quantitative PCR. Enzyme-linked immunosorbent assays were used to assess the ferrous (Fe2+), glutathione and malondialdehyde (MDA) content. The ROS fluorescence intensity was assessed using flow cytometry. DU145 cells were most sensitive to icariin-curcumol concentration. The Fe2+ content, ROS fluorescence intensity and MDA level gradually increased, while solute carrier family 7 member 11 (SLC7A11) level, glutathione peroxidase 4 (GPX4) level, GSH content, Nrf2 and heme oxygenase-1 (HO-1) decreased with icariin-curcumol in a dose-dependent manner. After si-Nrf2 was transfected, the cell proliferation ability, SLC7A11 and GPX4 levels declined compared with the si-NC group. In contrast to the control group, the icariin + curcumol group showed reductions in Nrf2 and HO-1 levels, cell proliferation, SLC7A11 and GPX4 levels, with an increase in Fe2+ content and ROS fluorescence intensity. Overexpression of Nrf2 reversed the regulation observed in the icariin + curcumol group. Icariin-curcumol induced ferroptosis in PCa cells, mechanistically by inhibiting the Nrf2/HO-1 signaling pathway. Icariin-curcumol could be used as a new type of ferroptosis inducer to treat PCa effectively.

Recent developments in photocatalytic production of hydrogen peroxide.

Hydrogen peroxide (H2O2), an environmentally friendly strong oxidant and energy carrier, has attracted widespread attention in photocatalysis. Artificial photosynthesis of H2O2 using water and oxygen as raw materials, solar energy as an energy source, and semiconductor materials as catalysts is considered a promising technology. In the past few decades, encouraging progress has been made in the photocatalytic production of H2O2. Therefore, we summarize the research achievements in this field in recent years. This review first briefly introduces the reaction pathway, detection techniques and evaluation metrics. Then, the recent advances in photocatalysts are highlighted. Furthermore, the existing challenges and possible solutions in this field are presented. At last, we look forward to the future development direction of this field. This review provides valuable insights and guidance for efficient photocatalytic H2O2 production.

Enhancement of NiTiO3 piezocatalytic hydrogen evolution by doping with large radius elements.

Piezocatalysis is a direct method for converting mechanical vibration into chemical energy. Herein, NiTiO3 is used in the piezocatalytic hydrogen evolution field for the first time. The noncentral symmetry of NiTiO3 is enhanced by doping with large radius elements. It is demonstrated that when a metal element replaces the sites of nickel, it results in lattice distortion and a higher piezoelectric response. In particular, Cd-doped NiTiO3 exhibits the highest H2 generation rate (1.52 mmol g-1 h-1), which is 13 times that of original NiTiO3.

Icaritin-curcumol activates CD8+ T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer.

BACKGROUND: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa. METHODS: A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development. RESULTS: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3+CD8+IFN-γ, CD3+CD8+Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2. CONCLUSIONS: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.

Efficient photocatalytic hydrogen production over ZnIn2S4 by producing sulfur vacancies and coupling with nickel-based polyoxometalate.

A composite catalytic system using sulfur-vacancy-containing ZnIn2S4-Sv as a light-harvesting material and nickel-based polyoxometalate Na6K4[Ni4(H2O)2(PW9O34)2] (Ni4POM) as a co-catalyst was developed. The Ni4POM/ZnIn2S4-Sv composite gave a good hydrogen production rate of 337.5 µmol h-1, a value 11.8 times higher than that of ZnIn2S4-Sv. The direction of electron transfer, from ZnIn2S4-Sv to Ni4POM, was verified using surface photovoltage spectra.

Effects of icariin and curcumol on autophagy, ferroptosis, and lipid metabolism based on miR-7/m-TOR/SREBP1 pathway on prostate cancer.

This study aimed to investigate the effects and underlying molecular mechanisms of icariin (ICA) and curcumol on autophagy, ferroptosis, and lipid metabolism in prostate cancer (PCa), in vitro and in vivo. Normal prostate epithelial cells RWPE-1 and PCa cell lines DU145 and PC-3 were treated with ICA and curcumol. Ferrostatin-1 (Fer-1) or 3-MA was added to treat DU145 and PC-3 cells. In addition, we knocked down miR-7. The mechanism of ICA and curcumol in PCa cells after the knockdown of miR-7 was verified by in vitro nude mice tumorigenesis experiments. ICA and curcumol had no significant effect on the viability of RWPE-1 cells, but there was a significant difference between DU145 and PC-3 cells. After treatment with ICA and curcumol, the proliferation of PCa cells was inhibited, apoptosis, reactive oxygen species (ROS) levels, and miR-7 expression were increased. The combined treatment of ICA and curcumol had a more significant effect. ICA and curcumol treatment induced autophagy and ferroptosis in PCa cells, and si-miR-7 reversed the effects of ICA and curcumol on autophagy and ferroptosis. MiR-7 targeted mTOR and regulated the expression of the mTOR/SREBP1 pathway in PCa cells. ICA and curcumol may affect the lipid metabolism of PCa cells by affecting SREBP1. In addition, the effects and mechanisms of ICA and curcumol on autophagy, ferroptosis, and lipid metabolism in PCa cells were verified in vivo. ICA and curcumol synergistically regulated the miR-7/mTOR/SREBP1 pathway to induce autophagy and ferroptosis in PCa cells and affected lipid metabolism.

Zeolite-encaged mononuclear copper centers catalyze CO2 selective hydrogenation to methanol.

The selective hydrogenation of CO2 to methanol by renewable hydrogen source represents an attractive route for CO2 recycling and is carbon neutral. Stable catalysts with high activity and methanol selectivity are being vigorously pursued, and current debates on the active site and reaction pathway need to be clarified. Here, we report a design of faujasite-encaged mononuclear Cu centers, namely Cu@FAU, for this challenging reaction. Stable methanol space-time-yield (STY) of 12.8 mmol gcat-1 h-1 and methanol selectivity of 89.5% are simultaneously achieved at a relatively low reaction temperature of 513 K, making Cu@FAU a potential methanol synthesis catalyst from CO2 hydrogenation. With zeolite-encaged mononuclear Cu centers as the destined active sites, the unique reaction pathway of stepwise CO2 hydrogenation over Cu@FAU is illustrated. This work provides a clear example of catalytic reaction with explicit structure-activity relationship and highlights the power of zeolite catalysis in complex chemical transformations.

Mononuclear ruthenium (II) complex covalently anchored on melem and g-C3N4 as efficient heterogeneous catalysts for chemical water oxidation.

Ru-melem and Ru-C3N4 were synthesized by a simple and facile strategy to construct a novel covalently anchoring by introducing easily synthesized amide bond as a bridge connecting the Ru-terpy and melem or g-C3N4, respectively. The covalent anchoring of Ru complex on melem or C3N4 not only makes these materials exhibit water oxidation activity under CeIV-driven (CeIV = Ce(NH4)2(NO3)6) reaction condition, but also makes the obtained heterogeneous catalysts show higher catalytic activity than the corresponding homogeneous catalysts, which reveals that the covalent anchoring strategy of Ru complex is beneficial to improve the catalytic activity of homogeneous Ru catalysts. The synthetic method of hybrid catalysts offers an insightful strategy for enhancing water oxidation activity of molecular catalysts.

Efficient water splitting over a hybrid photocatalyst with (002) active facets and heterostructure.

A series of P-CdS@P-MWOx (M = Ni, Mn, Co, Zn, Fe, Cu) hybrid photocatalysts was constructed using different transition metal polyoxometalates [SiW11M(H2O)O39]n- as precursors via a pyrolysis-phosphidation strategy. Under visible light irradiation (λ = 420 nm), P-CdS@P-NiWOx shows a good H2 evolution rate of 418.4 µmol g-1 h-1 and an AQE of 29.9% at 420 nm without adding a sacrificial reagent, which is a nearly 140-fold enhancement over CdS. This study provides a feasible strategy for designing efficient photocatalysts with highly active facets and heterostructure.