NRF3 activates mTORC1 arginine-dependently for cancer cell viability.

Cancer cells coordinate the mTORC1 signals and the related metabolic pathways to robustly and rapidly grow in response to nutrient conditions. Although a CNC-family transcription factor NRF3 promotes cancer development, the biological relevance between NRF3 function and mTORC1 signals in cancer cells remains unknown. Hence, we showed that NRF3 contributes to cancer cell viability through mTORC1 activation in response to amino acids, particularly arginine. NRF3 induced SLC38A9 and RagC expression for the arginine-dependent mTORC1 recruitment onto lysosomes, and it also enhanced RAB5-mediated bulk macropinocytosis and SLC7A1-mediated selective transport for arginine loading into lysosomes. Besides, the inhibition of the NRF3-mTORC1 axis impaired mitochondrial function, leading to cancer cell apoptosis. Consistently, the aberrant upregulation of the axis caused tumor growth and poor prognosis. In conclusion, this study sheds light on the unique function of NRF3 in arginine-dependent mTORC1 activation and the pathophysiological aspects of the NRF3-mTORC1 axis in cancer development.

The CNC-family transcription factor Nrf3 coordinates the melanogenesis cascade through macropinocytosis and autophagy regulation.

Melanin is a pigment produced from the amino acid L-tyrosine in melanosomes. The CNC-family transcription factor Nrf3 is expressed in the basal layer of the epidermis, where melanocytes reside, but its melanogenic function is unclear. Here, we show that Nrf3 regulates macropinocytosis and autophagy to coordinate melanogenesis cascade. In response to an exogenous inducer of melanin production, forskolin, Nrf3 upregulates the core melanogenic gene circuit, which includes Mitf, Tyr, Tyrp1, Pmel, and Oca2. Furthermore, Nrf3 induces the gene expression of Cln3, an autophagosome-related factor, for melanin precursor uptake by macropinocytosis. Ulk2 and Gabarapl2 are also identified as Nrf3-target autophagosome-related genes for melanosome formation. In parallel, Nrf3 prompts autolysosomal melanosome degradation for melanocyte survival. An endogenous melanogenic inducer αMSH also activates Nrf3-mediated melanin production, whereas it is suppressed by an HIV-1 protease inhibitor, nelfinavir. These findings indicate the significant role of Nrf3 in the melanogenesis and the anti-melanogenic potential of nelfinavir.

Precise Purity Analysis of High-Purity Lanthanum Oxide by Gravimetric Analysis Assisted With Trace Elemental Analysis by Inductively Coupled Plasma Mass Spectrometry.

Gravimetric analysis was used to determine the purity of high-purity La2O3 by stepwise conversions of the weighing forms. In this study, lanthanum in the sample was converted to La oxalate, La2O3, and La2(SO4)3 to evaluate the stoichiometry of the weighing forms for accurate gravimetric determination. The losses of La in the filtrate, the washing solution of the precipitate, and the mechanical loss of La during filtration were measured using inductively coupled plasma optical emission spectrometry. The weighing forms were evaluated by comparing the observed mass ratio with the theoretical value at each conversion step. The final converted La2(SO4)3 was consistent with the theoretical composition based on the observed mass ratio of La2(SO4)3/La2O3. Additionally, impurities in the high-purity La2O3 were determined by inductively coupled plasma tandem mass spectrometry. The purity of the original La2O3 sample was precisely determined to be 99.977 % ± 0.057% (mass fraction as La2O3; the value following "±" indicates the expanded uncertainty with a coverage factor k = 2.18) by a combination of the gravimetric analysis using the precipitation from the homogeneous solution method and verification of the weighing forms for La compound.

Evaluation of flame retardancy and flexural property on prepared plastic disks containing known concentrations of flame retardants through simulated weathering tests.

The standardized acrylonitrile-butadiene-styrene (ABS) or polycarbonate (PC) resin disk with added flame retardants (FRs) has a potential to be a suitable tool for predictions of both aging of the plastic materials and release rate of a flame retardants exposed under different outdoor and indoor conditions. The experiments examined the dynamics and kinetics of the release of dechlorane plus, tetrabromobisphenol A, triphenyl phosphate and antimony trioxide as FRs from a standardized plastic disk before and after exposure to artificial sunlight. Assessments were carried out independently to measure changes in the content of flame retardants and monitor the flame retardancy and flexural properties after exposure (60 W/m2) over a period of 200 h and 500 h, which are reasonable to predict a short-time tendency and to receive any advice for a safe re-use. The releases of three organic flame retardants and four elements (Cl, Br, P and Sb) from weathered ABS and PC disks were very limited, except for surface delamination and resin microparticles. Triphenyl phosphate was stable without hydrolysis, while the degradation of tetrabromobisphenol A was observed (approximately 20% decrease for ABS disk and approximately 50% decrease for PC disk). During the study, no significant differences in the flame retardancy and flexural properties of the disks could be detected. In practice, the results obtained from disks of acrylonitrile-butadiene-styrene or polycarbonate resin with selected flame retardants used in specific conditions may provide technical expertise regarding weathering processes.

Determination of ultra-trace sulfur in high-purity metals by isotope dilution inductively coupled plasma sector field mass spectrometry combined with chemical separation procedure.

The analytical method of ultra-trace sulfur (S) in high-purity metal by isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS) combined with chemical separation procedure was developed in the present study. In order to determine the ultra-trace S in high-purity metal, a chemical separation with alumina column was carried out before ICP-MS measurement. This method enabled to prevent the polyatomic ion interference arising from the metal matrix and the signal suppression derived from the space charge effect in ICP-MS. In order to achieve high sensitive analysis, an ICP-sector field mass spectrometer (ICP-SFMS) was used. The isolation of polyatomic ion interference with respect to S was also carried out in medium-resolution mode. In addition, measurement conditions including detector dead time, which affects the precision and accuracy of the isotope dilution method, and washout conditions that were employed to reduce memory effects were optimized. The developed method was validated by the determination of S in a high-purity iron reference material (JSS-001-4). The analytical result obtained by the developed method (1.86 mg kg-1 ±â€¯0.12 mg kg-1 (k = 2)) was in good agreement with the certified value (1.90 mg kg-1 ±â€¯0.42 mg kg-1). The method was also applied to the determination of S in high-purity zinc, revealing a content of 0.08 mg kg-1 ±â€¯0.08 mg kg-1 (k = 2). Since the developed method enabled the determination of ultra-trace S at µg kg-1 level in the high-purity zinc, it is expected to be useful for high sensitive and accurate determination of ultra-trace S in high-purity metals.

Self-aggregation of synthetic zinc methyl 20-substituted 3-hydroxymethyl-pyropheophorbides as models of bacteriochlorophyll-c.

Zinc 3-hydroxymethyl-131-oxo-chlorins bearing a variety of primary alkyl groups at the 20-position were prepared as models of bacteriochlorophyll-c by chemical modification of naturally occurring chlorophyll-a. The synthetic chlorophyll-a derivatives self-aggregated in an aqueous Triton X-100 solution to afford large oligomers whose Soret and Qy bands were red-shifted and broadened, compared with the bands of their monomers in tetrahydrofuran. The oligomeric bands are similar to those of bacteriochlorophyll-c self-aggregates in chlorosomes, the main light-harvesting antennae of photosynthetic green bacteria. The 20-alkylation led to bathochromic shifts of the visible Soret maxima in J-type self-aggregates of the synthetic models, while elongation of the 20-alkyl group decreased the chlorosomal Qy maxima due to an increase in steric hindrance. Considering the light-harvesting and energy-transferring processes in a chlorosome, the 20-methylation in bacteriochlorophyll-c would be more suitable for efficient culturing of green bacteria than the 20-ethylation and propylation as well as the 20-unsubstitution in bacteriochlorophyll-d.

Determination of Ultra-trace Metal Impurities in High-purity Cadmium Using Inductively Coupled Plasma Mass Spectrometry after Matrix Separation with Anion Exchange Resin.

The analytical method for ultra-trace metal impurities at µg kg-1 level in high-purity Cd was examined by inductively coupled plasma mass spectrometry (ICP-MS) combined with matrix separation by Bio-Rad AG MP-1M anion exchange resin. After the separation of Cd, the metal impurities such as Li, In, Cr, Mn, Fe, Co, Ni, Cu, Ga, Sr, Ba and Pb were measured by an ICP-quadrupole mass spectrometer (ICP-QMS) and ICP-sector field mass spectrometer (ICP-SFMS). From the comparison of measured results, it was evaluated that the analytical sensitivity by ICP-SFMS was 10 times higher than ICP-QMS. In addition, ICP-SFMS could obtain determined values of Li and Fe that could not be determined by ICP-QMS. These results suggest the ICP-SFMS combined with matrix separation by anion exchange resin could be utilized for the determination of ultra-trace metal impurities in high-purity materials for the assessment of the purity of the materials.

Development of plastic disks containing flame retardants for elucidating changes in their concentrations due to simulated weathering and the application of these disks to weathering tests.

Flame retardants (FRs) are useful because they can prevent combustion and delay the spread of fire after the ignition on commercial products containing plastics. However, such commercial products could be a primary source of environmental contamination with FRs. Plastic disks containing FRs were prepared to elucidate changes in the concentrations of the FRs after weathering tests. Acrylonitrile-butadiene-styrene (ABS) and polycarbonate (PC) resin were separately kneaded with a combination of three organic FRs [Dechlorane plus (DP), tetrabromobisphenol A (TBBPA), and triphenyl phosphate (TPhP)] and one inorganic FR [antimony trioxide (Sb2O3)]. The concentrations of TBBPA/TPhP and DP/Sb2O3 in the final preparations were respectively 1000 and 500 mg/kg in compliance with the RoHS directive on organobromine FR. The concentrations of elements in the final preparations were 300 mg/kg for chlorine, 600 mg/kg for bromine, 100 mg/kg for phosphorus, and 400 mg/kg for antimony, respectively. The analytical concentrations (three FRs and four elements) were consistent with the expected concentrations (maximum difference -9.5% in the PC disks). The FRs and elements in the disks were sufficiently homogenous (maximum inhomogeneity 4.3% in the PC disks). The prepared disks were subjected to weathering tests; the concentrations of TBBPA in the disks decreased significantly (30 to 40%) whereas the concentrations of the elements did not change under the condition of this study. On the other hand, there were no drastic differences on relationships of FRs and elements such as DP/chlorine and TPhP/phosphorus.