From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs.

BACKGROUND: Cisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated for pharmacological activity, and the approved complexes have been applied as drugs. OBJECTIVES: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes. METHODS: A search was conducted in the literature databases, and the obtained information was summarized and analyzed. RESULTS: Myelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes, such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin. From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects, the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence microscopy, are important for the investigation of the conformational changes in the binding of platinum complexes and DNA. CONCLUSION: In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes.

Changes in oral pathology teaching methods during the COVID-19 pandemic and the impact on student performance (oral pathology teaching changes during the COVID-19 pandemic).

Abstract Background/purpose: Coronavirus disease 2019 (COVID-19) has influenced the dental education in Osaka Dental University. The purpose of this study was to summarize the impact of COVID-19 on student performance and the current more appropriate teaching methods by comparing the changes in various oral pathology exam results before and after COVID-19. Materials and methods: The experimental and control groups consisted of second year students in the department of dentistry at our university for the years 2019 (136 people) and 2020 (125 people). The impact of different teaching methods on student performance was compared by calculating the mean scores and percentage of failures on various exams and whether or not class credits were earned between the two years. A t test was used to determine statistical significance. Results: The mean scores on the mini-tests were lower in 2020 than in 2019, while the average score of the intermediate exam and the number of students receiving class credits were higher. The mean scores on the practical and unit exams were not statistically significant between the years, but the failure rate on both exams was higher in 2019 than in 2020. Conclusion: COVID-19 had impacts on student performance. A comparison of the mean scores on the exams revealed that the use of microscopy, oral questions, and online animations contributed to improved performance on different exams. Therefore, to promote students' understanding and retention of memorized knowledge of oral pathology, the use of microscopes will be resumed whenever possible, as well as continuation with oral questions and online animations.

Auxin-Induced WUSCHEL-RELATED HOMEOBOX13 Mediates Asymmetric Activity of Callus Formation upon Cutting.

Plants have the regenerative ability to reconnect cut organs, which is physiologically important to survive severe tissue damage. The ability to reconnect organs is utilized as grafting to combine two different individuals. Callus formation at the graft junction facilitates organ attachment and vascular reconnection. While it is well documented that local wounding signals provoke callus formation, how callus formation is differentially regulated at each cut end remains elusive. Here, we report that callus formation activity is asymmetrical between the top and bottom cut ends and is regulated by differential auxin accumulation. Gene expression analyses revealed that cellular auxin response is preferentially upregulated in the top part of the graft. Disruption of polar auxin transport inhibited callus formation from the top, while external application of auxin was sufficient to induce callus formation from the bottom, suggesting that asymmetric auxin accumulation is responsible for active callus formation from the top end. We further found that the expression of a key regulator of callus formation, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), is induced by auxin. The ectopic callus formation from the bottom end, which is triggered by locally supplemented auxin, requires WOX13 function, demonstrating that WOX13 plays a pivotal role in auxin-dependent callus formation. The asymmetric WOX13 expression is observed both in grafted petioles and incised inflorescence stems, underscoring the generality of our findings. We propose that efficient organ reconnection is achieved by a combination of local wounding stimuli and disrupted long-distance signaling.

Synthesis and Properties of a Decacyclene Monoimide and a Naphthalimide Derivative as Three-Dimensional Acceptor-Donor-Acceptor Systems.

A method involving the Diels-Alder (DA) cycloaddition of diacenaphtheno[1,2-b;1',2'-d]thiophenes (DATs) with N-alkylacenaphthylene-5,6-dicarboximides (AIs) was developed to synthesize decacyclene monoimides (DCMIs). The reactions generate the corresponding 1:2 adducts (BAIAs) as major products together with 1:1 adducts (the DCMIs). The molecular structure of BAIAb (N-octyl derivative) was unambiguously assigned as the bis-adduct having an endo,endo spatial disposition of the two acenaphthylene-5,6-dicarboximide moieties by using X-ray crystallographic analysis. Relative to the absorption spectrum of decacyclene triimide (DCTIa, N-2-ethylhexyl derivative), that of the analogous N-2-ethylhexyl-substituted monoadduct, DCMIa, is bathochromically shifted despite the fact that it possesses a less delocalized π-electron system. DCMIa does not fluoresce in various organic solvents, whereas DCTIa emits yellow fluorescence in CH2 Cl2 with a low quantum yield (ΦSN ). Moreover, DCMIa in CDCl3 displays concentration-dependent 1 H NMR spectroscopy behavior, which suggests that it self-aggregates with an association constant (Ka ) of (193±50) m-1 at 20 °C. Despite the presence of four bulky tert-butyl groups in DCMIa, its Ka value for aggregate formation is comparable to that of DCTIa [(495±42) m-1 ], which does not contain tert-butyl substituents. Spectroscopic studies with the bis-adduct BAIAa (N-2-ethylhexyl derivative) show that it displays remarkable solvatofluorochromism corresponding to an emission maximum shift (ΔλEM ) of 100 nm. The results of density functional theory calculations on BAIAc (N-methyl derivative) demonstrate that a considerable spatial separation exists between the HOMO and LUMO coefficient distributions, which indicates that the ground-to-excited state transition of the novel three-dimensional acceptor-donor-acceptor BAIAa system should have intramolecular charge-transfer character.