Introduction: A histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort.Methods: We performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica's system).Results: Of 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica's system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death). Conclusions:We reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment.

Ionospheric Pedersen and Hall conductances play significant roles in electromagnetic coupling between the planetary ionosphere and magnetosphere. Several observations and models have suggested the existence of meteoric ions with interplanetary origins in the lower part of Jupiter’s ionosphere; however, no models have considered the contributions of meteoric ions to ionospheric conductance. This study is designed to evaluate the contribution of meteoric ions to ionospheric conductance by developing an ionospheric model combining a meteoroid ablation model and a photochemical model. We find that the largest contribution to Pedersen and Hall conductivities occurs in the meteoric ion layer at altitudes of 350–600 km due to the large concentration of meteoric ions resulting from their long lifetimes of more than 100 Jovian days. Pedersen and Hall conductances are enhanced by factors of 3 and 10, respectively, in the middle‐ and low‐latitude and auroral regions when meteoric ions are included. The distribution of Pedersen and Hall conductances becomes axisymmetric in the middle‐ and low‐latitude regions. Enhanced axisymmetric ionospheric conductance should impact magnetospheric plasma convection. The contribution of meteoric ions to the ionospheric conductance is expected to be important only on Jupiter in our solar system because of Jupiter’s intense magnetic and gravitational fields.

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Chemotherapeutic nucleoside analogs, such as Ara-C, 5-Fluorouracil (5-FU) and Trifluridine (FTD), are frequently incorporated into DNA by the replicative DNA polymerases. However, it remains unclear how this incorporation kills cycling cells. There are two possibilities: Nucleoside analog triphosphates inhibit the replicative DNA polymerases, and/or nucleotide analogs mis-incorporated into genomic DNA interfere with the next round of DNA synthesis as replicative DNA polymerases recognize them as template DNA lesions, arresting synthesis. To address the first possibility, we selectively disrupted the proofreading exonuclease activity of DNA polymerase ε (Polε), the leading-strand replicative polymerase in avian DT40 and human TK6 cell lines. To address the second, we disrupted RAD18, a gene involved in translesion DNA synthesis, a mechanism that relieves stalled replication. Strikingly, POLE1exo−/− cells, but not RAD18−/− cells, were hypersensitive to Ara-C, while RAD18−/− cells were hypersensitive to FTD. gH2AX focus formation following a pulse of Ara-C was immediate and did not progress into the next round of replication, while gH2AX focus formation following a pulse of 5-FU and FTD was delayed to the next round of replication. Biochemical studies indicate that human proofreading-deficient Polε-exo− holoenzyme incorporates Ara-CTP, but subsequently extend from this base several times less efficiently than from intact nucleotides. Together our results suggest that Ara-C acts by blocking extension of the nascent DNA strand and is counteracted by the proofreading activity of Polε, while 5-FU and FTD are efficiently incorporated but act as replication fork blocks in the subsequent S phase, which is counteracted by translesion synthesis.

[CpCo(dithiolene)] complex with a boronate group, which is formulated as [CpCo{S2C2(Ph)(Bpin)}] (1, Bpin = 4,4,5,5-tetramethyl-1,3,2-dioxaboronate), was prepared from the one-pot reaction of [CpCo(CO)2], elemental sulfur, and boronated alkyne. 1 underwent Pd-catalyzed Suzuki–Miyaura cross-coupling reactions with 3-bromopyridine or 9-bromoanthracene.