Identification of gp96 as a Novel Target for Treatment of Autoimmune Disease in Mice

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Chronic expression of heat shock protein gp96 on cell surfaces induces significant DC activations and systemic lupus erythematosus (SLE)-like phenotypes in mice. However, its potential as a therapeutic target against SLE remains to be evaluated. In this work, we conducted chemical approach to determine whether SLE-like phenotypes can be compromised by controlling surface translocation of gp96. From screening of chemical library, we identified a compound that binds and suppresses surface presentation of gp96 by facilitating its oligomerization and retrograde transport to endoplasmic reticulum. In vivo administration of this compound reduced maturation of DCs, populations of antigen presenting cells, and activated B and T cells. The chemical treatment also alleviated the SLE-associated symptoms such as glomerulonephritis, proteinuria, and accumulation of anti-nuclear and –DNA antibodies in the SLE model mice resulting from chronic surface exposure of gp96. These results suggest that surface translocation of gp96 can be chemically controlled and gp96 as a potential therapeutic target to treat autoimmune disease like SLE

Reversible Symptomatic Myocarditis Induced by All-Trans Retinoic Acid Administration during Induction Treatment of Acute Promyelocytic Leukemia: Rare Cardiac Manifestation as a Retinoic Acid Syndrome

Treatment by All-trans retinoic acid (ATRA) followed by anthracycline-AraC chemotherapy has improved the outcome of acute promyelocytic leukemia. ATRA is usually well tolerated, but a few major side effects can be observed. Retinoic acid syndrome (RAS) often occurs during the induction chemotherapy of acute promyelocytic leukemia. A pericardial effusion is a common cardiac manifestation but myocarditis has been rarely documented. Here we reports a very rare case of fully recovered myocarditis as a result of RAS related to ATRA administration during induction treatment of acute promyelocytic leukemia which documented by echocardiographic evidence

Guidelines for Tailored Chemical Functionalization of Graphene

Graphene oxide (GO) has been synthesized by the Hummers method with modification of experimental condition by different research groups, but there is no guideline to prepare tailored GO for targeted applications. In this research, we suggest a guideline for tailor-fittable functionalization of graphene on the basis of the scope of our previous report on the two-step oxidation of GO. We describe a detailed procedure for synthesis of GO, effects of degree of step I oxidation on characteristics of GO and comparing them with effects of degree of step II oxidation. Characteristic changes of GO occurring during step I oxidation and those occurring during step II oxidation are different in species of oxygen functional groups, interlayer spacing, thermal stability, size distribution, and yield of GO. On the basis of the results, three types of tailor-fitted GO for a fiber, transparent conducting film, and hydrogen storage material are synthesized by controlling the degree of step I and step II oxidation. Compared to the reference GO synthesized by conventional modified Hummers method, the tailor-fitted GO showed 33.5%, 117%, and 104% enhanced performance in strength of the fiber, figure of merits of transparent conducting film, and hydrogen storage, respectively. Our results show that the performance of GO based application is significantly influenced by the synthesis condition of GO, and optimized performance of the applications can be obtained by the tailor-fitted functionalization of GO. We anticipate that this study would be helpful for a variety of researches, both synthesis and application of GO

The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells

Abstract Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (NRF-2018R1A5A2025964) and the Seoul National University Hospital (SNUH) Research Fund (04–20200230). This study was also carried out with support from the R&D Program for Forest Science Technology (Project No. 2020195A00–2122-BA01) of the Korea Forest Service (Korea Forestry Promotion Institute) and Cooperative Research Program for the Agriculture Science and Technology Development (Project No. PJ01589402 and No. PJ016202022) Rural Development Administration, Republic of Korea

Effects of Simultaneous Cognitive Task on Gait Event Accuracy with Auditory Stimuli: Comparison between Young Adults in Their 20s and the Elderly in their 70s

The purpose of this study was to compare the difference in the accuracy of gait events between young and older adults during metronomic walking by auditory cueing. Additionally, age-specific changes in the gait event accuracy according to additional simultaneous cognitive tasks were examined. The time interval (or temporal error) between the auditory cue (i.e., metronome) and the heel contact was used as the accuracy of the gait event. Fifteen young group (YG, 24.7 ± 0.8 years) and 14 elderly (EG, 78.4 ± 5.5 years) people participated in the experiment. The temporal errors under two gait conditions (MET: walking with metronome; MET + BC: walking with metronome while counting backward) were compared for each group. The results revealed that all the temporal errors of EG were significantly greater than those of YG. While the addition of simultaneous cognitive tasks resulted in a significant increase in temporal error in both age groups, the coefficient of variation (CV) of the temporal error significantly increased only in the EG group. In other words, although heel contact accuracy with auditory stimuli was affected by the simultaneous cognitive task in both groups, it was demonstrated that the variability of the error in the young adults remained constant. Therefore, the time error measurement used in this study has the potential to be used as a tool to judge the gait instability of the elderly compared with young adults

Effects of Simultaneous Cognitive Task on Gait Event Accuracy with Auditory Stimuli: Comparison between Young Adults in Their 20s and the Elderly in their 70s

The purpose of this study was to compare the difference in the accuracy of gait events between young and older adults during metronomic walking by auditory cueing. Additionally, age-specific changes in the gait event accuracy according to additional simultaneous cognitive tasks were examined. The time interval (or temporal error) between the auditory cue (i.e., metronome) and the heel contact was used as the accuracy of the gait event. Fifteen young group (YG, 24.7 ± 0.8 years) and 14 elderly (EG, 78.4 ± 5.5 years) people participated in the experiment. The temporal errors under two gait conditions (MET: walking with metronome; MET + BC: walking with metronome while counting backward) were compared for each group. The results revealed that all the temporal errors of EG were significantly greater than those of YG. While the addition of simultaneous cognitive tasks resulted in a significant increase in temporal error in both age groups, the coefficient of variation (CV) of the temporal error significantly increased only in the EG group. In other words, although heel contact accuracy with auditory stimuli was affected by the simultaneous cognitive task in both groups, it was demonstrated that the variability of the error in the young adults remained constant. Therefore, the time error measurement used in this study has the potential to be used as a tool to judge the gait instability of the elderly compared with young adults

Slow-wave metamaterial open panels for efficient reduction of low-frequency sound transmission

Sound transmission reduction is typically governed by the mass law, requiring thicker panels to handle lower frequencies. When open holes must be inserted in panels for heat transfer, ventilation, or other purposes, the efficient reduction of sound transmission through holey panels becomes difficult, especially in the low-frequency ranges. Here, we propose slow-wave metamaterial open panels that can dramatically lower the working frequencies of sound transmission loss. Global resonances originating from slow waves realized by multiply inserted, elaborately designed subwavelength rigid partitions between two thin holey plates contribute to sound transmission reductions at lower frequencies. Owing to the dispersive characteristics of the present metamaterial panels, local resonances that trap sound in the partitions also occur at higher frequencies, exhibiting negative effective bulk moduli and zero effective velocities. As a result, low-frequency broadened sound transmission reduction is realized efficiently in the present metamaterial panels. The theoretical model of the proposed metamaterial open panels is derived using an effective medium approach and verified by numerical and experimental investigations

RCS Estimation of Singly Curved Dielectric Shell Structure with PMCHWT Method and Experimental Verification

In this paper, a numerical algorithm for the electromagnetic scattering analysis of singly curved dielectric structures, which can be applied to a canopy of fighter aircraft, is presented with experimental verification. At first, the Poggio–Miller–Chang–Harrington–Wu–Tsai (PMCHWT) method is used as a MoM-based solution for the electromagnetic scattering of a dielectric material. Its formulation was generated with the EFIE formulation in a multi-region condition. The PMCHWT algorithm is implemented with C++ code, and the accuracy is verified by calculating the bistatic RCS of some canonical structures with conductive or dielectric materials. RCS measurement under quasi-anechoic condition is presented with its procedure and calibration method. The monostatic RCS results of a specially modeled singly curved dielectric structures are obtained analytically with the PMCHWT, as well as experimentally, revealing excellent agreement