Tyrosine catabolism enhances genotoxic chemotherapy by suppressing translesion DNA synthesis in epithelial ovarian cancer.

Amino acid metabolism has been actively investigated as a potential target for antitumor therapy, but how it may alter the response to genotoxic chemotherapy remains largely unknown. Here, we report that the depletion of fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the final step of tyrosine catabolism, reduced chemosensitivity in epithelial ovarian cancer (EOC). The expression level of FAH correlated significantly with chemotherapy efficacy in patients with EOC. Mechanistically, under genotoxic chemotherapy, FAH is oxidized at Met308 and translocates to the nucleus, where FAH-mediated tyrosine catabolism predominantly supplies fumarate. FAH-produced fumarate binds directly to REV1, resulting in the suppression of translesion DNA synthesis (TLS) and improved chemosensitivity. Furthermore, in vivo tyrosine supplementation improves sensitivity to genotoxic chemotherapeutics and reduces the occurrence of therapy resistance. Our findings reveal a unique role for tyrosine-derived fumarate in the regulation of TLS and may be exploited to improve genotoxic chemotherapy through dietary tyrosine supplementation.

Calcium-intercalated birnessite MnO2 anchored on carbon nanotubes as high-performance cathodes for aqueous zinc-ion batteries.

Aqueous Zn-ion batteries (ZIBs) show great potential in energy storage systems because of their high theoretical capacities, high safety, low cost, and environmental friendliness. The lack of suitable cathode materials for sustaining the Zn2+ intercalation/deintercalation severely restricts their further application. Herein, calcium-intercalated birnessite MnO2 anchored on carbon nanotubes (CNTs) was designed as a cathode for ZIBs. The cathode material can be facilely produced by a simple one-pot reaction process. The external calcium-intercalated MnO2 with large layer spacing affords a fast ionic migration rate and the internal CNTs serving as a structural framework endow the electrode with better electrical conductivity. Benefiting from the larger interlayer spacing and the enhanced electrical conductivity, the CNT-CaMO cathode shows a high specific capacity of 351.8 mA h g-1 at 200 mA g-1 and a long cycle life over 6000 cycles. Besides, the H+ and Zn2+ co-intercalation storage mechanism was confirmed by ex situ XRD, SEM, and XPS analyses. This work opens up a new way to develop aqueous ZIB cathode materials with a high reversible capacity and long cycle life.

Discovery of a New Family of Polyoxometalate-Based Hybrids with Improved Catalytic Performances for Selective Sulfoxidation: The Synergy between Classic Heptamolybdate Anions and Complex Cations.

A series of functional cation-regulated isopolymolybdate-based organic-inorganic hybrid compounds, Na2H2[Mo4O12(C8H17O5N)2]·10H2O (1), Na2[M(Bis-tris)(H2O)]2[Mo7O24]·10H2O [M = Cu, 2; Ni, 3; Co, 4; Zn, 5; Bis-tris = 2,2-Bis(hydroxymethyl)-2,2',2″-nitrilotriethanol], and (NH4)2[M(Bis-tris)(H2O)]2[Mo7O24]·6H2O (M = Zn, 6; Cu, 7), were synthesized and characterized toward advanced molecular catalyst design. Compound 1 is a covalently bonded adduct, and its self-assembly process can be probed by electrospray ionization mass spectrometry (ESI-MS). Compounds 2-7 are polyoxometalate (POM)-based hybrids containing classic heptamolybdate anions and complex cations with Bis-tris ligands. All of these compounds showed remarkable catalytic effects for selective sulfide oxidation. To the best of our knowledge, compound 5 presents the best catalytic activity so far among the reported hybrid materials with common easily synthesized small-molecule POM clusters and also exhibits outstanding reliability. The conclusion of the catalytic effect is drawn from the results that Zn-based compounds have better catalytic effects than other transition-metal-containing compounds and the compound constructed by Na+ has higher catalytic activity than that constructed by NH4+. The mechanism studies show that the improvements of the catalytic performance are caused by the synergy between classic heptamolybdate anions and complex cations. ESI-MS data and UV-vis spectra revealed that the POM anions can form intermediate peroxomolybdenum units during catalytic reaction. Further, the combination of the substrate thioanisole with complex cations was characterized by NMR experiments and UV-vis spectra. Thus, a new synergistic mechanism of anions and cations is proposed in which the activated thioanisole is used as a nucleophile to attack the peroxomolybdenum bonds, and this provides a new strategy in the design of reliable POM-based catalysts.