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Single-stranded DNA-binding proteins (SSBs) play a crucial role in DNA metabolism by binding and stabilizing single-stranded DNA (ssDNA) intermediates. Through their multifaceted roles in DNA replication, recombination, repair, replication restart, and other cellular processes, SSB emerges as a central player in maintaining genomic integrity. These attributes collectively position SSBs as essential guardians of genomic integrity, establishing interactions with an array of distinct proteins. Unlike Escherichia coli, which contains only one type of SSB, some bacteria have two paralogous SSBs, referred to as SsbA and SsbB. In this study, we identified Staphylococcus aureus SsbA (SaSsbA) as a fresh addition to the roster of the anticancer drug 5-fluorouracil (5-FU) binding proteins, thereby expanding the ambit of the 5-FU interactome to encompass this DNA replication protein. To investigate the binding mode, we solved the complexed crystal structure with 5-FU at 2.3 Å (PDB ID 7YM1). The structure of glycerol-bound SaSsbA was also determined at 1.8 Å (PDB ID 8GW5). The interaction between 5-FU and SaSsbA was found to involve R18, P21, V52, F54, Q78, R80, E94, and V96. Based on the collective results from mutational and structural analyses, it became evident that SaSsbA's mode of binding with 5-FU diverges from that of SaSsbB. This complexed structure also holds the potential to furnish valuable comprehension regarding how 5-FU might bind to and impede analogous proteins in humans, particularly within cancer-related signaling pathways. Leveraging the information furnished by the glycerol and 5-FU binding sites, the complexed structures of SaSsbA bring to the forefront the potential viability of several interactive residues as potential targets for therapeutic interventions aimed at curtailing SaSsbA activity. Acknowledging the capacity of microbiota to influence the host's response to 5-FU, there emerges a pressing need for further research to revisit the roles that bacterial and human SSBs play in the realm of anticancer therapy. [ABSTRACT FROM AUTHOR]

Allantoinase (ALLase; EC 3.5.2.5) possesses a binuclear metal center in which two metal ions are bridged by a posttranslationally carbamylated lysine. ALLase acts as a key enzyme for the biogenesis and degradation of ureides by catalyzing the conversion of allantoin into allantoate. Biochemically, ALLase belongs to the cyclic amidohydrolase family, which also includes dihydropyrimidinase, dihydroorotase, hydantoinase (HYDase), and imidase. Previously, the crystal structure of ALLase from Escherichia coli K-12 (EcALLase-K12) was reported; however, the two active site loops crucial for substrate binding were not determined. This situation would limit further docking and protein engineering experiments. Here, we solved the crystal structure of E. coli BL21 ALLase (EcALLase-BL21) at a resolution of 2.07 Å (PDB ID 8HFD) to obtain more information for structural analyses. The structure has a classic TIM barrel fold. As compared with the previous work, the two missed active site loops in EcALLase-K12 were clearly determined in our structure of EcALLase-BL21. EcALLase-BL21 shared active site similarity with HYDase, an important biocatalyst for industrial production of semisynthetic penicillin and cephalosporins. Based on this structural comparison, we discussed the functional role of the two active site loops in EcALLase-BL21 to better understand the substrate/inhibitor binding mechanism for further biotechnological and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Dihydroorotase (DHOase) is the third enzyme in the pathway used for the biosynthesis of pyrimidine nucleotides. In mammals, DHOase is active in a trifunctional enzyme, CAD, which also carries out the activities of carbamoyl phosphate synthetase and aspartate transcarbamoylase. Prior to this study, it was unknown whether the FDA-approved clinical drug 5-fluorouracil (5-FU), which is used as an anticancer therapy, could bind to the DHOase domain of human CAD (huDHOase). Here, we identified huDHOase as a new 5-FU binding protein, thereby extending the 5-FU interactome to this human enzyme. In order to investigate where 5-FU binds to huDHOase, we solved the complexed crystal structure at 1.97 Å (PDB ID 8GVZ). The structure of huDHOase complexed with malate was also determined for the sake of comparison (PDB ID 8GW0). These two nonsubstrate ligands were bound at the active site of huDHOase. It was previously established that the substrate N-carbamoyl-L-aspartate is either bound to or moves away from the active site, but it is the loop that is extended towards (loop-in mode) or moved away (loop-out mode) from the active site. DHOase also binds to nonsubstrate ligands via the loop-out mode. In contrast to the Escherichia coli DHOase model, our complexed structures revealed that huDHOase binds to either 5-FU or malate via the loop-in mode. We further characterized the binding of 5-FU to huDHOase using site-directed mutagenesis and the fluorescence quenching method. Considering the loop-in mode, the dynamic loop in huDHOase should be a suitable drug-targeting site for further designing inhibitors and clinical chemotherapies to suppress pyrimidine biosynthesis in cancer cell lines. [ABSTRACT FROM AUTHOR]

The abnormal lattice expansion of commercial polypropylene (PP)/polyethylene (PE)/polypropylene (PP) separator in lithium-ion battery under different charging current densities was observed by in-situ X-ray diffraction. Significant lattice changes of both PP and PE were found during the low current density charging. The capacity fading and the resistance value of the cell measured at 0.025 C (5th retention, 92%) is unexpectedly larger than that at 1.0 C (5th retention, 97.3%) from the electrochemical impedance spectroscopic data. High-resolution scanning electron microscopy is employed to witness the pore changes of the trilayered membrane. Density functional theory calculations were used to investigate the mechanism responsible for the irregular results. The calculations revealed that the insertion of Li-ion and EC molecule into PP or PE are thermodynamically favourable process which might explain the anomalous significant lattice expansion during the low current density charging. Therefore, designing a new separator material with a more compact crystalline structure or surface modification to reduce the Li insertion during the battery operation is desirable. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we fabricated and analyzed resistance switching characteristics for resistance random access memory (RRAM) in a Pt/In2O3/SiO2/TiN structure. By applying opposing electric fields to perform a soft breakdown of the In2O3/SiO2 insulating bi-layer, different switching behaviors are exhibited. When positive forming voltage was applied to the TiN electrode to soft breakdown the device, the resistance switching behavior was dominated by the bipolar mode. However, the negative voltage forming process exhibited both unipolar switching characteristics in addition to a bipolar switch mode. In order to analyze the composition of the conduction path and resistance switching mechanism, resistance value trends versus temperature was extracted and showed that the conduction paths of bipolar and unipolar modes are dominated by oxygen vacancies and metallic filament, respectively. Hence, metallic filament was considered to be formed by the migration of indium ions because the unipolar characteristic was only present during negative bias forming condition. [Copyright &y& Elsevier]

Abstract: High-performance polycrystalline silicon thin-film transistors (TFTs) using an excimer laser crystallization of the prepatterned channel layer on the bottom-gate (BG) structure were fabricated to exhibit a field-effect mobility as high as 339cm2/Vs and an on/off current ratio of 9.5×107 with respect to 102cm2/Vs and 1.5×107 for the conventional top-gate (TG) TFTs, respectively. Such a superior performance is attributed to the cross-shaped grain boundary structure formed in the channel region owing to the two-dimensional location control of grain boundaries. Moreover, the prepatterned BG TFTs show better device-to-device uniformity than the conventional TG ones due to the manipulated grain boundaries. This technology is thus promising for the future applications of system-on-panel and three-dimension integrated circuits. [Copyright &y& Elsevier]

Abstract: An extended-gate field-effect transistor (EGFET) of coaxial-structured ZnO/silicon nanowires as pH sensor was demonstrated in this paper. The oriented 1-μm-long silicon nanowires with the diameter of about 50nm were vertically synthesized by the electroless metal deposition method at room temperature and were sequentially capped with the ZnO films using atomic layer deposition at 50°C. The transfer characteristics (IDS–V REF ) of such ZnO/silicon nanowire EGFET sensor exhibited the sensitivity and linearity of 46.25mV/pH and 0.9902, respectively for the different pH solutions (pH 1–pH 13). In contrast to the ZnO thin-film ones, the ZnO/silicon nanowire EGFET sensor achieved much better sensitivity and superior linearity. It was attributed to a high surface-to-volume ratio of the nanowire structures, reflecting a larger effective sensing area. The output voltage and time characteristics were also measured to indicate good reliability and durability for the ZnO/silicon nanowires sensor. Furthermore, the hysteresis was 9.74mV after the solution was changed as pH 7→pH 3→pH 7→pH 11→pH 7. [Copyright &y& Elsevier]