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Objective: Prostate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/ß-catenin pathway. Methods: In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP's anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP's impact on prostate cancer, validating the expression of Wnt/ß-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes. Results: In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP's active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/ß-catenin pathway. Conclusion: XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP's active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the ß-catenin/HIF-1α-mediated glycolysis.
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Prokaryotes are effective biosorbents for the recovery of uranium and other heavy metals. However, the potential mechanism of uranium bioaccumulation by filamentous strain (actinobacteria) remains unclear. This study demonstrates the potential for and mechanism of uranium bioaccumulation by living (L-SS) and inactivated (I-SS) Streptomyces sp. HX-1 isolated from uranium mine waste streams. Uranium accumulation experiments showed that L-SS and I-SS had efficient uranium adsorption potentials, with removal rates of 92.93 and 97.42%, respectively. Kinetic and equilibrium data indicated that the bioaccumulation process was consistent with the pseudo-second-order kinetic, Langmuir, and Sips isotherm models. FTIR indicated that the main functional groups of L-SS and I-SS binding uranium were uranyl, carboxyl, and phosphate groups. Moreover, the results of XRD, XPS, SEM-EDS, and TEM-EDS analyses revealed for the first time that L-SS has biomineralization and bioreduction capacity against uranium. L-SS mineralize U(VI) into NH4UO2PO4 and [Formula: see text] through the metabolic activity of biological enzymes (phosphatases). In summary, Streptomyces sp. HX-1 is a novel and efficient uranium-fixing biosorbent for the treatment of uranium-contaminated wastewater.
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Biodegradación Ambiental , Streptomyces , Uranio , Aguas Residuales , Uranio/metabolismo , Streptomyces/metabolismo , Aguas Residuales/química , Adsorción , Minería , Contaminantes Radiactivos del Agua/metabolismo , CinéticaRESUMEN
Silicon nanowire is a potential candidate to be used as polarization-sensitive material, but the relative mechanism of polarization response must be carried out. Herein, a sub-micron metal-single silicon nanowire-metal photodetector exhibits polarization-sensitive characteristics with an anisotropic photocurrent ratio of 1.59 at 780â nm, an excellent responsivity of 24.58â mA/W, and a high detectivity of 8.88 × 109 Jones at 980â nm. The underlying principle of optical anisotropy in silicon nanowire is attributed to resonance enhancement verified by polarizing light microscopy and simulation. Furthermore, Stokes parameter measurements and imaging are all demonstrated by detecting the characteristics of linearly polarized light and imaging the polarizer array, respectively. Given the maturity of silicon processing, the sub-micron linearly polarized light detection proposed in this study lays the groundwork for achieving highly integrated, simplified processes, and cost-effective on-chip polarization-sensitive optical chips in the future.
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Objective: Screening out potential herbal medicines and herbal ingredients for the treatment of gastric cancer based on transcriptomic analysis of immune infiltration and ferroptosis. Methods: Gene expression profiles of gastric tumour tissues and normal tissue samples were obtained from the GEO database and the samples were analysed for immune cell infiltration condition and differential expressed genes of ferroptosis. Key genes were screened by protein-protein interaction (PPI) and enrichment analysis, and molecular docking was used to predict and preliminary validate potential herbal and traditional Chinese medicine components for gastric cancer based on the key genes. Finally, RT-QPCR was used to validate the prediction results. Results: Immune cell infiltration analysis revealed high levels of infiltration of activated CD4 memory T cells, monocytes, M0 macrophages in gastric tumor tissues, while plasma cells and resting mast cells had higher levels of infiltration in the paraneoplastic tissues. Differential gene expression analysis identified 1,012 upregulated genes and 880 downregulated genes, of which 84 immune related differentially expressed genes such as CTSB, PGF and PLAU and 10 ferroptosis-related differentially expressed genes such as HSF1, NOX4 and NF2 were highly expressed in gastric cancer tissues. The results of enrichment analysis showed that they mainly involve 343 biological processes such as extracellular matrix organization and extracellular structural organization; 37 cellular components such as complexes of collagen trimer and basement membrane; 35 molecular functions such as signal receptor activator activity and receptor ligand activity; 19 regulatory pathways such as cytokine-cytokine receptor interactions and retinol metabolism. Finally, two key genes, TLR4 and KRAS, were selected and 12 herbal medicines such as Radix Salviae liguliobae, Rhizoma Coptidis, Rhizoma Polygoni cuspidati and 27 herbal ingredients such as resveratrol, salvianolic acid b were predicted on the basis of key genes. Molecular docking results showed that KRAS binds tightly to coumarin and magnolol, while TLR4 can bind tightly to resveratrol, curcumin, salvianolic acid b, shikonin. Subsequently, the effect of resveratrol and magnolol was experimentally verified. Conclusion: Herbal medicines such as S. liguliobae, Rhizoma Coptidis, Rhizoma P. cuspidati and herbal ingredients such as resveratrol, curcumin, salvianolic acid b may provide research directions and alternative therapeutic approaches for immunomodulation of TME and ferroptosis of tumour cells in gastric cancer.
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Subwavelength grating structure has excellent filtering characteristics, and its traditional design method needs a lot of computational costs. This work proposed a design method of two-dimensional subwavelength grating filter based on a series feedback neural network, which can realize forward simulation and backward design. It was programed in Python to study the filtering characteristics of two-dimensional subwavelength grating in the range of 0.4-0.7 µm. The shape, height, period, duty cycle, and waveguide layer height of two-dimensional subwavelength grating were taken into consideration. The dataset, containing 46,080 groups of data, was generated through numerical simulation of rigorous coupled-wave analysis (RCWA). The optimal network was five layers, 128 × 512 × 512 × 128 × 61 nodes, and 64 batch size. The loss function of the series feedback neural network is as low as 0.024. Meanwhile, it solves the problem of non-convergence of the network reverse design due to the non-uniqueness of data. The series feedback neural network can give the geometrical structure parameters of two-dimensional subwavelength grating within 1.12 s, and the correlation between the design results and the theoretical spectrum is greater than 0.65, which belongs to a strong correlation. This study provides a new method for the design of two-dimensional subwavelength grating, which is quicker and more accurate compared with the traditional method.
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Aprendizaje Profundo , Retroalimentación , Diseño de Equipo , Simulación por Computador , Redes Neurales de la ComputaciónRESUMEN
In this paper, the Fe3+ doped rutile phase TiO2 nanotubes arrays (NTAs) were prepared in a low temperature water-assistant crystallization method. It is noteworthy that the Fe3+ doping hardly hinders either the crystallization of rutile TiO2 NTAs or the highly-ordered nanotubular morphologies. Moreover, Fe3+ did not form other compound impurities, which indicated that Fe3+ substitute Ti4+ into the lattice of TiO2. With the introduction of Fe3+, the light absorption range of TiO2 NTAs extends from the ultraviolet band to the visible light range. Photocatalytic testing results indicate that Fe3+ doped TiO2 NTAs can effectively improve the degradation rate of methyl orange aqueous solution in visible light, and the TiO2 NTAs with 0.2 mol/L Fe3+ doping exhibits the highest photocatalytic degradation efficiency.
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Ga2O3 thin films were fabricated by the electron-beam evaporation technique at a varying oxygen partial pressure from 0 to 2.0 × 10-2 Pa. The effect of oxygen partial pressure on the crystalline structure and optical properties of the Ga2O3 films was analyzed using sophisticated techniques including X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, spectroscopic ellipsometry, ultraviolet-visible spectroscopy and a laser-induced damage test system. The correlation between the oxygen partial pressure and the film's properties in optics and materials were investigated. XRD and Raman revealed that all films were amorphous in spite of applying a varying oxygen partial pressure. With the change of oxygen partial pressure, XPS data indicated that the content of oxygen in the Ga2O3 films could be broadly modulable. As a result, a changeable refractive index of the Ga2O3 film is realizable and a variable blue-shift of absorption edges in transmittance spectra of the films is achievable. Moreover, the damage threshold value varied from 0.41 to 7.51 J/cm2 according to the rise of oxygen partial pressure. These results demonstrated that the optical properties of Ga2O3 film can be broadly tunable by controlling the oxygen content in the film.
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As one of the drinking water quality parameters, natural radioactivity parameters are recommended to prevent a potential health threat to the public. In this study, the gross-α and gross-ß activity concentrations in 15 different brands of commercial bottled mineral water consumed in China were analyzed to evaluate the quality and corresponding health impact on the population. The activity concentrations of gross-α and gross-ß in different samples varied from 4.4 to 130.6 and 17.3-320.3 mBq L-1, respectively. The values of the annual effective dose equivalent rate (AED) for infants, children and adults ranged from 1.3 to 21.6, 2.9-52.5 and 5.5-97.8 µSv y-1, respectively. The average excess lifetime cancer risk caused by the consumption of bottled mineral water samples was estimated as 6.0 × 10-5. These results show that all the measured gross-α and gross-ß are found to be obviously less than the guidance level by WHO and the domestic standard. The values of AED are below the World Health Organization (WHO) recommended limit of 0.1 mSv y-1. Combined with the lifetime cancer risk assessment, it is concluded that there is no significant risk for consumption of the observed brands of bottled mineral water and it can be consumed safely.
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Agua Potable , Aguas Minerales , Monitoreo de Radiación , Radiactividad , Contaminantes Radiactivos del Agua , Adulto , Niño , China , Humanos , Lactante , Dosis de RadiaciónRESUMEN
BACKGROUND: Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs. METHODS: The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in the hydroxy group were reviewed in vivo and in vitro including the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol. RESULTS: The differences in stereoselective pharmacokinetics could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo. CONCLUSION: In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide the basis for the drug R&D and the safety of drugs in clinical therapy.
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Ácidos Mandélicos/farmacocinética , Nitrilos/farmacocinética , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , Pirimidinas/farmacocinética , Alcohol Deshidrogenasa/metabolismo , Animales , Humanos , Hígado/enzimología , Ácidos Mandélicos/química , Estructura Molecular , Nitrilos/química , Pirimidinas/química , Especificidad de la Especie , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
ABSTRACT: Many studies have evaluated the antimicrobial activity of natural products against various microorganisms, but to our knowledge there have been no studies of the possible use of natural products for their antimicrobial activity against Enterobacter hormaechei. In this study, we investigated vanillic acid (VA) for its antimicrobial activities and its modes of action against carbapenem-resistant E. hormaechei (CREH). The MIC of VA against CREH was determined by the agar diffusion method. The antibacterial action of VA against CREH was elucidated by measuring variations in intracellular ATP concentration, intracellular pH, membrane potential, and cell morphology. Moreover, the efficacy of VA against biofilm formation and VA damage to CREH cells embedded in biofilms were further explored. Our results show that VA was effective against CREH with a MIC of 0.8 mg/mL. VA could rupture the cell membrane integrity of CREH, as measured by a decrease of intracellular ATP, pH, and membrane potential, along with distinctive alternations in cell morphology. In addition, VA exerted a remarkable inhibitory effect on the biofilm formation of CREH and also killed CREH cells within biofilms. These findings show that VA has a potent antibacterial and antibiofilm activity against CREH and, hence, has the potential to be used clinically as a novel candidate agent to treat CREH infections and in the food industry as a food preservative and surface disinfectant.
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Biopelículas/efectos de los fármacos , Carbapenémicos , Enterobacter/fisiología , Ácido Vanílico , Antibacterianos , Enterobacter/efectos de los fármacos , Conservantes de Alimentos/farmacología , Pruebas de Sensibilidad Microbiana , Ácido Vanílico/farmacologíaRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request ofthe corresponding author and the editor-in-chief. The authors have notified the journal that Fig. 3E and 3F in this article was a duplicate image of Fig. 3C of the article published by Weidong Qian, Miao Liu, Yuting Fu, Ting Wang, Jianing Zhang, Min Yang, Zhaohuan Sun, Xiang Li, and Yongdong Li in Foodborne Pathogens and Disease 129 (2020) 528-534 https://www.liebertpub.com/doi/10.1089/fpd.2019.2751 and requested for retraction. The authors have subsequently admitted that Figs. 3A, 3D and 4B in this article were duplicated from Figs. 3A, 5A and 7B of the article published by Weidong Qian, Yuting Fu, Miao Liu, Ting Wang, Jianing Zhang, Min Yang, Zhaohuan Sun, Xiang Li and Yongdong Li in Antibiotics 8 (2019) 220 https://www.mdpi.com/2079-6382/8/4/220, which has been retracted https://www.mdpi.com/2079-6382/9/6/322. The authors have claimed that there were errors in the preparation of figures for three papers which had been submitted to multiple journals from August to October 2019. The authors have provided replacement images for Figs. 3 and 4 of this article, but these data did not resolve the concerns that call into question the reliability of the study findings. In light of these issues, the journal has decided to retract the article. The authors assert the findings, that ursolic acid exerted antibacterial activity against carbapenem-resistant Enterobacter cloacae, are nevertheless reliable.
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Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Enterobacter cloacae/efectos de los fármacos , Triterpenos/farmacología , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana , Enterobacter cloacae/fisiología , Infecciones por Enterobacteriaceae/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Ácido UrsólicoRESUMEN
The [001]-oriented Pr3+ doped Pb(Mg1/3Nb2/3)O3-0.30PbTiO3 (Pr-PMN-PT) thin films with a composition near the morphotropic phase boundary (MPB) were synthesized by a solâ»gel method. The crystal structure was characterized using X-ray diffraction. It was found that a single perovskite phase was achieved in Pr-PMN-PT thin films annealed at 650 °C for 3 min. The dielectric constant (εr) value was 2400 in 2.5% Pr-PMN-PT thin films at room temperature, 110% higher than that of pure PMN-PT samples. Through 2.5% Pr3+ doping, remanent polarization (Pr) and coercive field (Ec) values increased from 11.5 µC/cm² and 35 kV/cm to 17.3 µC/cm² and 63.5 kV/cm, respectively, in PMN-PT thin films. The leakage current densities of pure and 2.5% Pr-PMN-PT thin films were on the order of 1.24 × 10-4 A/cm² and 5.8 × 10-5 A/cm², respectively, at 100 kV/cm. A high pyroelectric coefficient (py) with a value of 167 µC/m²K was obtained in 2.5% Pr-PMN-PT thin films on Si substrate, which makes this material suitable for application in infrared detectors.
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To generate an industrial strain of Hansenula polymorpha capable of yielding greater levels of glutathione (GSH), wild strain H. polymorpha DL-1 cells were mutated using a nitrogen ion beam, a novel mutagen. At an energy level of 20 keV and dose of 2.13 × 10(16) ions/cm(2), H. polymorpha strain 28 (HP28) with a high-yield of GSH was screened. HP28 intracellular GSH levels reached 337.16 mg/L by ion beam implantation, 1.56 times greater than that of the wild type strain when the fermentation time was shortened from 48 hr to 42 hr, greatly improving efficiency and reducing the cost of industrial-scale production. The enhanced efficiency of HP28 is promising for GSH production from lignocellulosic materials. Therefore, the ion beam implantation would be a cost-effective alternative to the conventional mutation method for engineering yeast and improving its utility.