Functions of methyltransferase-like 3 in breast cancer: pathogenesis, drug resistance, and therapeutic target.

Breast cancer (BC) is a highly prevalent malignancy worldwide, with complex pathogenesis and treatment challenges. Research reveals that methyltransferase-like 3 (METTL3) is widely involved in the pathogenesis of several tumors through methylation of its target RNAs, and its role and mechanisms in BC are also extensively studied. In this review, we aim to provide a comprehensive interpretation of available studies and elucidate the relationship between METTL3 and BC. This review suggests that high levels of METTL3 are associated with the pathogenesis, poor prognosis, and drug resistance of BC, suggesting METTL3 as a potential diagnostic or prognostic biomarker and therapeutic target. Collectively, this review provides a comprehensive understanding of how METTL3 functions through RNA methylation, which provides a valuable reference for future fundamental studies and clinical applications.

Hydrogen alleviates hypoxic-ischaemic brain damage in neonatal rats by inhibiting injury of brain pericytes.

Hypoxia-ischaemia (HI) can induce the death of cerebrovascular constituent cells through oxidative stress. Hydrogen is a powerful antioxidant which can activate the antioxidant system. A hypoxia-ischaemia brain damage (HIBD) model was established in 7-day-old SD rats. Rats were treated with different doses of hydrogen-rich water (HRW), and brain pericyte oxidative stress damage, cerebrovascular function and brain tissue damage were assessed. Meanwhile, in vitro-cultured pericytes were subjected to oxygen-glucose deprivation and treated with different concentrations of HRW. Oxidative injury was measured and the molecular mechanism of how HRW alleviated oxidative injury of pericytes was also examined. The results showed that HRW significantly attenuated HI-induced oxidative stress in the brain pericytes of neonatal rats, partly through the Nrf2-HO-1 pathway, further improving cerebrovascular function and reducing brain injury and dysfunction. Furthermore, HRW is superior to a single-cell death inhibitor for apoptosis, ferroptosis, parthanatos, necroptosis and autophagy and can better inhibit HI-induced pericyte death. The liver and kidney functions of rats were not affected by present used HRW dose. This study elucidates the role and mechanism of hydrogen in treating HIBD from the perspective of pericytes, providing new theoretical evidence and mechanistic references for the clinical application of hydrogen in neonatal HIE.

Relative bioavailability of selenium in rice using a rat model and its application to human health risk assessment.

Deficiencies of selenium (Se), a necessary microelement for humans, can be remedied by appropriately supplying Se-enriched rice. However, overconsumption of Se-enriched rice poses a potential risk. To accurately assess Se human health risks associated with Se-enriched rice consumption, we developed a rat in vivo model to systematically explore the relative bioavailability of Se (Se-RBA) from Se-enriched rice from a wide geographic range. Se concentrations were in the range of 0.06 ± 0.05 to 0.15 ± 0.15 mg kg-1, averaging 0.12 ± 0.11 mg kg-1, in 196 rice samples from 21 Chinese provinces, and selenomethionine (SeMet) was the dominant Se fraction (58.0-96.5%). The Se-RBA of Se-enriched rice calculated from urine ranged from 34.86% to 102.29%, averaging 62.27% (n = 12), and was positively correlated with the proportion of SeMet in rice (p < 0.05, R2 = 0.51). Furthermore, the Se intake calculated based on the Se-RBA indicated that the Se intake of consumers of Se-enriched rice was far less than the tolerable upper intake level. Thus, the limits established by law assume overestimates of the actual nutritional value of the Se content in Se-enriched rice, and it is important to consider Se bioavailability. The current study offers suggestions for future research and provides methods to reduce the uncertainty in estimating the health risks associated with Se intake from rice.

Influence of Polyoxometalate Protecting Ligands on Catalytic Aerobic Oxidation at the Surfaces of Gold Nanoparticles in Water.

Metal oxide cluster-anion (polyoxometalate, or POM) protecting ligands, [α-PW11O39]7- (1), modify the rates at which 14 nm gold nanoparticles (Au NPs) catalyze an important model reaction, the aerobic (O2) oxidation of CO to CO2 in water. At 20 °C and pH 6.2, the following stoichiometry was observed: CO + O2 + H2O = CO2 + H2O2. After control experiments verified that the H2O2 product was sufficiently stable and did not react with 1 under turnover conditions, quantitative analysis of H2O2 was used to monitor the rates of CO oxidation, which increased linearly with the percent coverage of the Au NPs by 1 (0-64% coverage, with the latter value corresponding to 211 ± 19 surface-bound molecules of 1). X-ray photoelectron spectroscopy of Au NPs protected by a series of POM ligands (K+ salts): 1, the Wells-Dawson ion [α-P2W18O62]6- (2) and the monodefect Keggin anion [α-SiW11O39]8- (3) revealed that binding energies of electrons in the Au 4f7/2 and 4f5/2 atomic orbitals decreased as a linear function of the POM charge and percent coverage of Au NPs, providing a direct correlation between the electronic effects of the POMs bound to the surfaces of the Au NPs and the rates of CO oxidation by O2. Additional data show that this effect is not limited to POMs but occurs, albeit to a lesser extent, when common anions capable of binding to Au-NP surfaces, such as citrate or phosphate, are present.

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy.

Chemoradiotherapy, as a well-established paradigm to treat various cancers, still calls for novel strategies. Recently, gold nanoparticles (AuNPs) have been shown to play an important role as a radiosensitizer in cancer radiotherapy. The aim of this study was to evaluate the combination of polyethylene glycol (PEG) modified AuNPs and doxorubicin (DOX) to improve cancer chemoradiotherapy, in which the AuNPs was the radiosensitizer and the DOX was the model chemotherapeutic. A Pluronic® F127-based thermosensitive hydrogel (Au-DOX-Gel) loading AuNPs and DOX was developed by "cold method" for intratumoral injection. The formulation was optimized at a F127 concentration of 22% for Au-DOX-Gel. The release profiles compared to a control group were assessed in vitro and in vivo. Au-DOX-Gel showed sustained release of AuNPs and DOX. The cell viability and surviving fraction of mouse melanoma (B16) and Human hepatocellular liver carcinoma (HepG2) cells were significantly inhibited by the combination treatment of DOX and AuNPs under radiation. Tumor sizes of mice were significantly decreased by Au-DOX-Gel compared to controls. Interestingly, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki-67 staining results showed that tumor cell growth and proliferation were inhibited by AuNPs combined with DOX under radiation, suggesting that the radiosensitization activity and combination effects might be caused by inhibition of tumor cell growth and proliferation. Furthermore, the results of skin safety tests, histological observation of organs, and the body weight changes indicated in vivo safety of Au-DOX-Gel. In conclusion, the Au-DOX-Gel developed in this study could represent a promising strategy for improved cancer chemoradiotherapy.

Phonon dynamics in γ-ray irradiated sapphire crystals studied by fs-CARS technique.

We have studied the ultrafast dynamics of coherent phonons in sapphire crystals irradiated with 60Co γ-rays for three different doses by femtosecond time-resolved coherent anti-Stokes Raman scattering (fs-CARS) technique at room temperature. The obtained fs-CARS signals exhibit well-defined quantum beats, which are ascribed to the interference of the 645 and 750 cm-1 phonon modes. The dephasing times of the two modes both decrease with increasing irradiation dose, which is due to the scattering of coherent phonons by the defects introduced by γ-ray irradiation.

Neutron irradiation and post annealing effect on sapphire by positron annihilation.

Sapphire single crystals grown by an improved Kyropoulos-like method are irradiated by fast neutron flux. The irradiated doses of neutron are 10(18) and 10(19)n/cm(2). The infrared transmission spectra of sapphire were studied before and after irradiation. The irradiated samples were annealed at 200, 400, 600, 800 and 1000 degrees C for 10min in ambient atmosphere. Positron annihilation studies have been carried out before and after neutron irradiation. The experimentally measured positron lifetime in the pristine specimen is 143ps. There were aluminum vacancies produced in sapphire crystals after neutron irradiation. The positron lifetime increased with the dose of neutron flux. A longer value tau(2) was found after annealing at 600 degrees C, which indicated vacancies were aggregated with each other. The second long-time component tau(2) has been found to increase with the annealing temperature. There was almost no change in peak position of the CDB spectra after neutron irradiation and isothermal annealing. The chemical environment of core in sapphire did not change greatly after neutron irradiation.

Instabilities in nanoporous media.

Rayleigh instabilities in thin polymer films confined within nanoporous alumina membranes were studied. Thin films of poly(methyl methacrylate) (PMMA) were prepared by filling cylindrical nanopores in an anodic aluminum oxide (AAO) membrane with a PMMA solution in chloroform followed by solvent evaporation. When the PMMA nanotubes were annealed above the glass transition temperature (Tg), undulations in the film thickness were observed that were induced by a Rayleigh instability. The amplitude of the undulations increased with time and eventually bridged across the cylindrical nanopore in the AAO membrane, resulting in the formation of polymer nanorods with periodic encapsulated holes. A similar behavior was observed when PMMA films were confined within carbon nanotubes (CNTs). The Rayleigh instabilities in these confined geometries offer a novel means of controlling and fabricating the polymer nanostructures. These compartmentalized nanorods may have potential applications as delivery devices.

Amphiphilic Janus micelles with polystyrene and poly(methacrylic acid) hemispheres.

We describe the synthesis and the solution properties of Janus micelles containing a polybutadiene (PB) core and a compartmentalized corona consisting of a poly(methacrylic acid) (PMAA) and a polystyrene (PS) hemisphere. The Janus micelles were obtained via cross-linking the middle block of a microphase-separated PS-block-PB-block-PMMA triblock copolymer in the bulk state, followed by alkaline hydrolysis of the poly(methyl methacrylate) (PMMA) ester groups. Results of fluorescence correlation spectroscopy, field flow fractionation, light scattering, cryogenic transmission electron microscopy, scanning electron microscopy, and scanning force microscopy indicate that above a critical aggregation concentration of about 0.03 g/L spherical supermicelles are formed from about 30 PS-PMAA micelles in aqueous solution in the presence of NaCl. These supermicelles have radii of 40-60 nm, significantly increasing on ionization (pH >6). In addition, very large spherical objects are observed with radii of 100-250 nm.