Frequent methylation and oncogenic role of microRNA-34b/c in small-cell lung cancer

Small-cell lung cancer (SCLC) is an aggressive tumor with a dismal prognosis among primary lung cancers. MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human malignancy. The miR-34 family is comprised of tumor-suppressive miRNAs, and its reduced expression by methylation has been reported in various cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the alteration and tumor-suppressive impact of miR-34s in SCLC. The methylation of miR-34a and miR-34b/c was observed in 4 (36%) and 7 (64%) of 11 SCLC cell lines, respectively. Among the 27 SCLC clinical specimens, miR-34a and miR-34b/c were methylated in 4(15%) and 18 (67%), respectively. In contrast, 13 (28%) miR-34a methylated cases and 12 (26%) miR-34b/c methylated cases were found in 47 NSCLC primary tumors. The frequency of miR-34b/c methylation was significantly higher in SCLC than in NSCLC (p < 0.001). The expressions of miR-34s were reduced in methylated cell lines and tumors and restored after 5-aza-2'-deoxycytidine treatment, indicating that methylation was responsible for the reduced expression of miR-34s. Because the frequency of methylation was higher in miR-34b/c, we focused on miR-34b/c for a functional analysis. We examined the effect of miR-34b/c introduction on cell proliferation, migration and invasion. The transfection of miR-34b/c to two SCLC cell lines (H1048 and SBC5) resulted in the significant inhibition of cell growth, migration, and invasion, compared with control transfectants. Our results indicate that the aberrant methylation of miR-34b/c plays an important role in the pathogenesis of SCLC, implying that miR-34b/c may be a useful therapeutic target for SCLC

Microstructural transitions in resistive random access memory composed of molybdenum oxide with copper during switching cycles

The switching operation of a Cu/MoOx/TiN resistive random access memory (ReRAM) device was investigated using in situ transmission electron microscopy (TEM), where the TiN surface was slightly oxidized (ox-TiN). The relationship between the switching properties and the dynamics of the ReRAM microstructure was confirmed experimentally. The growth and/or shrinkage of the conductive filament (CF) can be classified into two set modes and two reset modes. These switching modes depend on the device's switching history, factors such as the amount of Cu inclusions in the MoOx layer and the CF geometry. High currents are needed to produce an observable change in the CF. However, sharp and stable switching behaviour can be achieved without requiring such a major change. The local region around the CF is thought to contribute to the ReRAM switching process

Vapor-Phase-Mediated Encapsulation of Guest Drug Molecules in the Hexagonal Columnar Form Structure of Polyethylene Glycol/γ-Cyclodextrin-Polypseudorotaxane

The drug/(PEG/γ-CD-PPRX) complex is a unique multicomponent supramolecular structure where the drug molecules are incorporated in the intermolecular spaces of the polypseudorotaxane (PPRX) prepared from polyethylene glycol (PEG) and γ-cyclodextrin (γ-CD). Herein, we report a sealed-heating preparation method to obtain an unanticipated polymorphic form of the drug/(PEG/γ-CD-PPRX) complex, which is the hexagonal-columnar (HC) form. The encapsulation efficiency of the six guest drugs was evaluated. The crystalline structural changes and the guest encapsulation monitored by powder X-ray diffraction revealed that a low sealed-heating temperature with a small amount of water was the optimal preparation condition for obtaining the HC form complex. The solution-state 1H nuclear magnetic resonance measurement demonstrated that stoichiometric complexation was dependent on the cross-sectional area of the guest drug molecule. However, stoichiometric complexation could not be achieved with all guest drugs, and the encapsulation efficiency was found to be governed by the guest drug properties, such as vapor pressure and molecular size. The findings of this study would contribute to understanding the complexation behavior of guest molecules in multicomponent supramolecular complexes and offer new insights into the fabrication of novel ordered supramolecular structures

#44 : Effects of Optimum (Optimization of Thyroid, Thrombophilia, Immunity, and Uterine Milieu) Treatment Strategy on Euploid Blastocyst Transfer in Advanced Aged Women with Recurrent Reproductive Failure

Background and Aims: Does the Optimization of Thyroid function, Thrombophilia, Immunity and Uterine Milieu (OPTIMUM) treatment strategy contribute to improving pregnancy outcomes after single euploid blastocyst transfer (SEBT) in patients with a history of repeated implantation failure (RIF) and/or recurrent pregnancy loss (RPL)? Method: Between January 2019 and May 2022, women aged ≥ 40 years with RIF after three or more embryo transfer using morphology good embryos and/or RPL after two or more clinical pregnancy losses underwent preimplantation genetic testing for aneuploidy (PGT-A) and RIF/RPL testing, including a hysteroscopy, endometrial biopsy for CD138 immunostaining and bacterial culture, and serum 25-hydroxyvitamin D3, interferon-γ-producing helper-T (Th1) cell, IL-4-producing helper-T (Th2) cell, thyroid-stimulating hormone, thyroid peroxidase antibody, and thrombophilia screening. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 160 consecutive women who underwent SEBT, we compared 127 and 33 women with and without the OPTIMUM treatment strategy, respectively. Results: RIF/RPL testing identified intrauterine abnormalities in 67 (52.8%), aberrant high Th1/Th2 cell ratios in 38 (29.9%), thyroid dysfunction in 19 (15.0%), and thrombophilia in 24 (18.9%). The clinical pregnancy and live birth rates in the OPTIMUM group was significantly higher than that in the control group (73.9% and 45.5%, respectively; p = 0.005 and 64.7% and 39.4%, respectively; p = 0.01) in women with RIF (Table 1). Whereas there was no significant difference of miscarriage rate in RPL women with and without OPTIMUM (5.5% and 13.3%, respectively; p = 0.58). Conclusion: In the women aged ≥40 years with RIF who underwent PGT-A, the OPTIMUM treatment strategy improved pregnancy outcomes after SEBT. In RPL, however, both PGT-A with and without OPTIMUM resulted in low miscarriage rates and no significant difference was recognized

#95 : Analysis of the Incidence of and Risk Factors for Chronic Endometritis Recurrence in Infertile Women

Background and Aims: Chronic endometritis (CE) is an inflammatory condition of the endometrium which is related to repeated implantation failure. Recovery from CE can increase opportunities for successful pregnancy; however, some of them remain incapable of conceiving or have a miscarriage and concern CE recurrence. The aim of this study is to identify the incidence rates of and risk factors for the recurrence of CE in infertile women. Method: The study population consisted of 1,897 infertile women from a hospital specializing in reproductive medicine who recovered from CE between December 2018 and August 2021. Among the 152 women (13.0%) who did not conceive or experienced pregnancy loss, 105 consecutive women who underwent repeat endometrial biopsy for CD138 immunostaining and endometrial bacterial culturing within 18 months from CE recovery were recruited. Thereafter, patients with and without CE recurrence were compared. Results: The total recurrence rate of CE was 29.5% (31 women). Multivariable logistic regression analysis to determine risk factors for CE recurrence revealed that hysteroscopic surgery (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02–0.56) and pregnancy loss (OR, 4.13; 95% CI, 1.31–13.05) were significantly associated with decreased and increased CE recurrence rates, respectively. Also, re-examination with CD138 immunostaining after 16–18 months (OR, 9.75; 95% CI, 1.47–64.64) was significantly associated with increased CE recurrence rates. Among 40 patients without a history of hysteroscopic surgery and pregnancy loss, the cumulative CE recurrence rates after 6, 12, and 18 months were 12.5%, 23.3%, and 30.0%, respectively (Graph 1). Conclusion: We recommend re-examination with endometrial CD138 immunostaining in patients with pregnancy loss or long-term infertility during fertility treatment. Hysteroscopic surgery without antibiotic therapy for CE associated with intrauterine abnormalities is also recommended