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Summary: 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.

Summary: 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.

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.

The Kamioka mine, located in Gifu Prefecture in Japan, is famous for the large water Cherenkov detector system, the Super-Kamiokande. The Kamioka skarn-type Pb–Zn deposits are formed in crystalline limestone and are replaced by skarn minerals within the Hida metamorphic rocks. The Kamioka deposits mainly consist of the Tochibora, Maruyama, and Mozumi deposits. The present study focuses on the ore-forming hydrothermal fluid activity in the Kamioka deposits and the peripheral exploration area based on the carbon and oxygen isotope ratios of calcite and rare earth element (REE) analyses. The carbon and oxygen isotope ratios of crystalline limestone (as the host rock) are not homogeneous, and depending on the degree of hydrothermal activity, they decreased to various degrees because of the reaction with the ore fluids. Thus, the carbon and oxygen isotope ratios of crystalline limestone can be used as an indicator of the influence of the hydrothermal fluids for the ore mineralization. The REE contents in the ores of igneous origin are one order of magnitude higher than the limestone origin. Further, depending on the formation temperatures, calcites precipitated during ore mineralization have a stable carbon isotope ratio and a widely varying oxygen isotope ratios. The Kamioka district fracture system is likely a major control factor on ore mineralization from hydrothermal activity. In addition, the skarnization-related ore-forming fluids are mostly meteoric in origin, confirming the conclusions from previous studies.