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Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), shows superior lung cancer treatment efficacy. However, osimertinib-induced severe hypersensitivity, including Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), is frequently observed in Asian populations and hinders cancer treatment.

Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. DHOase is divided into two types (I and II). Type II DHOase generally contains a binuclear metal center in its active site. Recently, the crystal structure of DHOase domain in human CAD protein (huDHOase) has revealed three metal ions in the protein’s active site. However, whether type II DHOase can have the critical third metal ion, as observed in huDHOase, remains unknown. In the present study, the putative third metal binding site in type II enzymes, such as the prokaryotic Salmonella enterica serovar Typhimurium LT2 DHOase (StDHOase) and the eukaryotic Saccharomyces cerevisiae DHOase (ScDHOase), was created and identified. StDHOase T198E and ScDHOase T208E mutants had higher activities compared with their wild-type enzymes. The need for a higher DHOase stability and activity may drive creation of the third metal ion binding site in huDHOase, which can be achieved by mutating a highly conserved position T in type II dihydroorotases to E, similar to that in huDHOase.

Nowadays in a household PV generation system, it is generally connecting PV modules in series and then output to the power-conditioner. However, when PV modules are mismatched, it will lead to a wrong maximum power point tracking (MPPT) to all modules and a power decreasing of the whole system. Aiming at this problem, this paper presents the idea which improves the MPPT without changing the conventional power-conditioner, by adding a boost type DC-DC converter behind each module. Simulations of PSIM and experiments are taken to prove this theory. The result shows that, by this idea, the generated power of the conventional PV generation system can be greatly increased under the condition of mismatch.

PriB is a primosomal protein required for re-initiation of replication in bacteria. We characterized and compared the DNA-binding properties of PriB from Salmonella entericaserovar Typhimurium LT2 (StPriB) and Escherichia coli(EcPriB). Only one residue of EcPriB, V6, was different in StPriB (replaced by A6). Previous structural information revealed that this residue is located on the putative dimer-dimer interface of PriB and is not involved in single-stranded DNA (ssDNA) binding. The cooperative binding mechanism of StPriB to DNA is, however, very different from that of EcPriB. Unlike EcPriB, which forms a single complex with ssDNAs of various lengths, StPriB forms two or more distinct complexes. Based on these results, as well as information on structure, binding modes for forming a stable complex of PriB with ssDNA of 25 nucleotides (nt), (EcPriB)25, and (StPriB)25are proposed.

A pulse oximeter is a noninvasive instrument used in clinical medicine to monitor arterial oxygen saturation. Fingertip-type pulse oximeters are popular, but their inconvenience for long-term monitoring in daily life means that other types of wearable pulse oximeters, such as a ring-type reflection pulse oximeter, needs to be developed. However, designing a ring-type pulse oximeter for measuring the oxygen saturation is difficult due to the complex tissue architecture of the finger base. This study used human tissue simulations to evaluate the practicability of a ring-type reflection pulse oximeter design. Moreover, given that the collection of diffusely reflected light can be enhanced by using a parabolic reflector, the efficacy of a ring-type reflection pulse oximeter with a parabolic reflector was also evaluated.

DnaB helicases are motor proteins essential for DNA replication, repair, and recombination and may be a promising target for developing new drugs for antibiotic-resistant bacteria. Previously, we established that flavonols significantly decreased the binding ability of Klebsiella pneumoniae DnaB helicase (KpDnaB) to dNTP. Here, we further investigated the effect of flavonols on the inhibition of the ssDNA binding, ATPase activity, and dsDNA-unwinding activity of KpDnaB. The ssDNA-stimulated ATPase activity of KpDnaB was decreased to 59%, 75%, 65%, and 57%, in the presence of myricetin, quercetin, kaempferol, and galangin, respectively. The ssDNA-binding activity of KpDnaB was only slightly decreased by flavonols. We used a continuous fluorescence assay, based on fluorescence resonance energy transfer (FRET), for real-time monitoring of KpDnaB helicase activity in the absence and presence of flavonols. Using this assay, the flavonol-mediated inhibition of the dsDNA-unwinding activity of KpDnaB was observed. Modeled structures of bound and unbound DNA showed flavonols binding to KpDnaB with distinct poses. In addition, these structural models indicated that L214 is a key residue in binding any flavonol. On the basis of these results, we proposed mechanisms for flavonol inhibition of DNA helicase. The resulting information may be useful in designing compounds that target K. pneumoniae and other bacterial DnaB helicases.