Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.

Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development.

The Absence of IL-12Rß2 Expression on Recipient Nonhematopoietic Cells Diminishes Acute Graft-versus-Host Disease in the Gastrointestinal Tract.

The gastrointestinal (GI) tract is a frequent target organ in acute graft-versus-host disease (aGVHD), which can determine the morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells recognize allogeneic Ags presented by host APCs, proliferate, and differentiate into Th1 and Th17 cells that drive GVHD pathogenesis. IL-12 has been shown to play an important role in amplifying the allogeneic response in preclinical and clinical studies. This study demonstrates that IL-12Rß2 expression on recipient nonhematopoietic cells is required for optimal development of aGVHD in murine models of allo-HCT. aGVHD attenuation by genetic depletion of IL-12R signaling is associated with reduced MHC class II expression by intestinal epithelial cells and maintenance of intestinal integrity. We verified IL-12Rß2 expression on activated T cells and in the GI tract. This study, to our knowledge, reveals a novel function of IL-12Rß2 in GVHD pathogenesis and suggests that selectively targeting IL-12Rß2 on host nonhematopoietic cells may preserve the GI tract after allo-HCT.

Murine Coronavirus Disease 2019 Lethality Is Characterized by Lymphoid Depletion Associated with Suppressed Antigen-Presenting Cell Functionality.

The disease severity of coronavirus disease 2019 (COVID-19) varies considerably from asymptomatic to serious, with fatal complications associated with dysregulation of innate and adaptive immunity. Lymphoid depletion in lymphoid tissues and lymphocytopenia have both been associated with poor disease outcomes in patients with COVID-19, but the mechanisms involved remain elusive. In this study, human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were used to investigate the characteristics and determinants of lethality associated with the lymphoid depletion observed in SARS-CoV-2 infection. The lethality of Wuhan SARS-CoV-2 infection in K18-hACE2 mice was characterized by severe lymphoid depletion and apoptosis in lymphoid tissues related to fatal neuroinvasion. The lymphoid depletion was associated with a decreased number of antigen-presenting cells (APCs) and their suppressed functionality below basal levels. Lymphoid depletion with reduced APC function was a specific feature observed in SARS-CoV-2 infection but not in influenza A infection and had the greatest prognostic value for disease severity in murine COVID-19. Comparison of transgenic mouse models resistant and susceptible to SARS-CoV-2 infection revealed that suppressed APC function could be determined by the hACE2 expression pattern and interferon-related signaling. Thus, we demonstrated that lymphoid depletion associated with suppressed APC function characterizes the lethality of COVID-19 mouse models. Our data also suggest a potential therapeutic approach to prevent the severe progression of COVID-19 by enhancing APC functionality.

Near eye display based on multiplexed retinal projections for robust compensation of eye pupil variance.

Among various specifications of near eye display (NED) devices, a compact formfactor is essential for comfortable user experience but also the hardest one to accomplish due to the slowest progresses. A pinhole/pinlight array based light-field (LF) technique is considered as one of the candidates to achieve that goal without thicker and heavier refractive optics. Despite those promising advantages, however, there are critical issues, such as dark spots and contrast distortion, which degrade the image quality because of the vulnerability of the LF retinal image when the observer's eye pupil size changes. Regardless of previous attempts to overcome those artifacts, it was impossible to resolve both issues due to their trade-off relation. In this paper, in order to resolve them simultaneously, we propose a concept of multiplexed retinal projections to integrate the LF retinal image through rotating transitions of refined and modulated elemental images for robust compensation of eye pupil variance with improved conservation of contrast distribution. Experimental demonstrations and quantitative analysis are also provided to verify the principle.

Associations Between Phthalate, Eosinophil, and Aeroallergen Sensitization in Schoolchildren.

BACKGROUND: Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals and may cause immunological disorders in children. Therefore, according to the region, we investigated urinary phthalates and BPA levels and the relationship between urinary phthalate, aeroallergen sensitization, and eosinophil count during the coronavirus disease 2019 pandemic. METHODS: In total, 203 schoolchildren (134 residential and 69 industrial) aged 7-10 years were enrolled between July 2021 and July 2022. The BPA, metabolites of four high-molecular-weight phthalates (Σ4HMWP) and three low-molecular-weight phthalates (Σ3LMWP), were measured in the urine samples. Total eosinophil count and transepidermal water loss (TEWL) were also measured along with the skin prick test. RESULTS: The two groups had no differences in terms of BPA. The industrial group had significantly more plastic container usage, and there was a difference in the Σ3LMWP (P < 0.001) between the two groups but no difference in the Σ4HMWP (P = 0.234). The quartiles of urinary Σ4HMWP and Σ3LMWP (P < were not associated with the total eosinophil count, vitamin D level, or TEWL. After adjusting for cofactors, the quartiles of urinary Σ4HMWP and Σ3LMWP were significantly associated with total eosinophil count (P < 0.001) but not with aeroallergen sensitization or vitamin D. CONCLUSION: Exposure to phthalates was significantly associated with eosinophil count but not with aeroallergen sensitization or vitamin D. Therefore, reducing the use of plastic containers may effectively prevent exposure to phthalates and reduce Th2 cell-mediated inflammation in children.

Non-hogel-based computer generated hologram with occlusion processing between the foreground light field and background hologram.

A novel technique is proposed to process the occlusion of a background hologram when synthesizing a front scene hologram from its light field. Unlike conventional techniques which process the occlusion in the light field domain after converting the background hologram to its light field, the proposed technique directly processes the occlusion between different domains, i.e., the background hologram and foreground light field. The key idea is to consider the background hologram as a carrier wave illuminating the front scene when synthesizing the front scene hologram from its light field. The proposed technique is not only computationally efficient as it does not require conversion between the light field and hologram domains but also accurate because all angular information of the background hologram and foreground light field is naturally considered in the occlusion processing. The proposed technique was verified by numerical synthesis and reconstruction.

Flicker-free dual-volume augmented reality display using a pixelated interwoven integral floating technique with a geometric phase lens.

A geometric phase (GP) integral floating display can provide multifocal three-dimensional (3D) augmented reality (AR) images with enhanced depth expression by switching the focal modes of the GP lens via polarization control. However, using temporal multiplexing to switch between the focal modes of GP optics causes flickering as each 3D AR image is fully presented in different frames and their temporal luminance profile becomes easily recognizable, particularly as the number of available focal modes increases. Here, we propose a novel integral floating technique to generate pixelated interwoven 3D AR images; a half of each image is spatially mixed with another and presented in both focal modes simultaneously to resolve the flickering issue. The principle was verified via experimental demonstration and optically measured data.

Insights from the Applications of Single-Cell Transcriptomic Analysis in Germ Cell Development and Reproductive Medicine.

Mechanistic understanding of germ cell formation at a genome-scale level can aid in developing novel therapeutic strategies for infertility. Germ cell formation is a complex process that is regulated by various mechanisms, including epigenetic regulation, germ cell-specific gene transcription, and meiosis. Gonads contain a limited number of germ cells at various stages of differentiation. Hence, genome-scale analysis of germ cells at the single-cell level is challenging. Conventional genome-scale approaches cannot delineate the landscape of genomic, transcriptomic, and epigenomic diversity or heterogeneity in the differentiating germ cells of gonads. Recent advances in single-cell genomic techniques along with single-cell isolation methods, such as microfluidics and fluorescence-activated cell sorting, have helped elucidate the mechanisms underlying germ cell development and reproductive disorders in humans. In this review, the history of single-cell transcriptomic analysis and their technical advantages over the conventional methods have been discussed. Additionally, recent applications of single-cell transcriptomic analysis for analyzing germ cells have been summarized.

The Oral Administration of Sanguisorba officinalis Extract Improves Physical Performance through LDHA Modulation.

Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.

Compensation of color breaking in bi-focal depth-switchable integral floating augmented reality display with a geometrical phase lens.

A bi-focal integral floating system using a geometrical phase (GP) lens can provide switchable integrated spaces with enhanced three-dimensional (3D) augmented reality (AR) depth expression. However, due to the chromatic aberration properties of the GP lens implemented for the switchable depth-floating 3D images, the floated 3D AR images with the red/green/blue (R/G/B) colors are formed at different depth locations with different magnification effects, which causes color breaking. In this paper, we propose a novel technique to resolve the color breaking problem by integrating the R/G/B elemental images with compensated depths and sizes along with experiments to demonstrate the improved results. When we evaluated the color differences of the floated 3D AR images based on CIEDE2000, the experimental results of the depth-switchable integral floating 3D AR images showed that the color accuracies were greatly improved after applying a pre-compensation scheme to the R/G/B sub-images in both concave and convex lens operation modes of the bi-focal switching GP floating lens.

Design of 45° periscopic visual field expansion device for peripheral field loss.

Patients with visual field loss have difficulty in mobility due to collision with pedestrians/obstacles from the blind side. In order to retrieve the lost visual field, prisms which deflect the field from the blind to the seeing side, have been widely used. However, the deflection power of current clinical Fresnel prisms is limited to ~30° and only provides a 5° eye scanning range to the blind side. This is not sufficient to avoid collision and results in increasing demands for a device with a higher power. In this paper, we propose a novel design and optimization of a higher power prism-like device (cascaded structure of mirror pairs filled with high refractive index) and verify enhanced expansion of up to 45° in optical ray tracing and photorealistic simulations.

Luteolin inhibits recruitment of monocytes and migration of Lewis lung carcinoma cells by suppressing chemokine (C-C motif) ligand 2 expression in tumor-associated macrophage.

Tumor-associated macrophages (TAMs) play pivotal roles in the progression of cancer. In order to investigate a novel candidate that inhibits the tumor-supporting M2-like phenotype of TAMs, a murine macrophage cell line RAW 264.7 cells were treated with interleukin (IL)-4. Luteolin inhibited phosphorylation of signal transducer and activator of transcription 6 (STAT6), a main downstream signal of IL-4, and reduced the expression of the M2-associated genes. In addition, Luminex multiplex analysis for secreted cytokines revealed that IL-4-enhanced secretion of chemokine (C-C motif) ligand 2 (CCL2) was reduced by luteolin treatment. IL-4-stimulated migration of monocyte, THP-1 cells, was inhibited by luteolin treatment and recovered by recombinant CCL2 supplement. Moreover, luteolin decreased migration of Lewis lung carcinoma cells in a CCL2-dependent manner. Given the important role of the TAM phenotype in the tumor microenvironment, inhibitory effect of luteolin on the monocyte recruitment and cancer migration via suppression of the TAM-secreted CCL2 may suggest a novel therapeutic approach to treat malignant tumors.

Abiotic stress of ambient cold temperature regulates the host receptivity to pathogens by cell surfaced sialic acids.

Ambient cold temperature, as an abiotic stress, regulates the survival, stability, transmission, and infection of pathogens. However, the effect of cold temperature on the host receptivity to the pathogens has not been fully studied. In this study, the expression of terminal α-2,3- and α-2,6-sialic acids were increased in murine lung tissues, especially bronchial epithelium, by exposure to cold condition. The expression of several sialyltransferases were also increased by exposure to cold temperature. Furthermore, in human bronchial epithelial BEAS-2B cells, the expressions of α-2,3- and α-2,6-sialic acids, and mRNA levels of sialyltransferases were increased in the low temperature condition at 33 °C. On the other hand, the treatment of Lith-Gly, a sialyltransferase inhibitor, blocked the cold-induced expression of sialic acids on surface of BEAS-2B cells. The binding of influenza H1N1 hemagglutinin (HA) toward BEAS-2B cells cultured at low temperature condition was increased, compared to 37 °C. In contrast, the cold-increased HA binding was blocked by treatment of lithocholicglycine and sialyl-N-acetyl-D-lactosamines harboring α-2,3- and α-2,6-sialyl motive. These results suggest that the host receptivity to virus at cold temperature results from the expressions of α-2,3- and α-2,6-sialic acids through the regulation of sialyltransferase expression.

Enhancement of the perceived image quality of a 2D/3D convertible directional-backlight unit system using a double-slit barrier array and an active diffuser.

In this paper, a method to construct a directional-backlight unit system to separate the left-eye image and the right-eye image by adopting a double-slit barrier array is proposed to enhance the perceived quality of the realized 3D image. Additionally, the two-dimensional/three-dimensional convertible function is also realized by adopting an active diffuser to the spatial interlacing directional-backlight system.

Resolution-enhanced integral imaging in focal mode with a time-multiplexed electrical mask array.

The inferior resolution of the three-dimensional (3D) image is one of the main problems to be resolved for realizing a commercial autosteresosopic 3D display device. In this paper, a time-multiplexing technique using electrically moving masks is proposed to enhance the resolution of the 3D image realized by integral imaging in a focal mode while preserving the viewing angle of it.

Effect of interlacing methods of stereoscopic displays on perceived image quality.

To provide two-eyed views with one device, stereoscopic 3D (S3D) displays interlace the two views either temporally or spatially: temporal interlacing (TI) alternates the two views in time with full resolution, while spatial interlacing (SI) presents the two views simultaneously but with half resolution for each eye. We investigate the effect of interlacing methods on image quality through a psychophysical experiment. We compared four experimental conditions: three S3D interlacing methods (TI, SI with raw sampling, and SI with vertical interpolation), and one nonconventional interlacing method (vertical interpolation). The stimuli were 10 natural stereo images presented at nine levels of pixel sizes (0.64, 0.78, 0.89, 1.00, 1.28, 1.55, 1.78, 2.00, and 2.56 arcmin). To test the effect of interlacing methods per se, we provided all the experimental conditions to the subjects using a single experimental setup: a mirror stereoscope. The results show that TI does not degrade the image quality for any pixel size. SI degrades the image quality when the pixel size is relatively large, but the effect of the two SI methods does not differ significantly. Comparison of SI methods against the vertical interpolation method implies that the primary cause of the degradation in image quality for SI methods is the visibility of the interlacing pattern rather than the loss of high-frequency information.

Tiled integral floating display without occlusion effect using an offset lens array and a perpendicular barrier.

Low resolution and narrow viewing angle are common problems for most of the existing autostereoscopic display systems. Although integral imaging is among the promising candidates for future autostereoscopic display, it is not yet free from the above bottlenecks. In this paper, a new technique to enhance the picture quality of a three-dimensional image using an offset lens array is proposed. The proposed system is suitable to realize a tiled integral floating display with high pixel density, while it also increases the viewing angle to match all of the optical devices in a single display unit. The proposed scheme was also verified with experimental results.

Transmission-type photonic crystal structures for color filters.

A transmission-type structure based on woodpile photonic crystal layers is proposed for use in color filters. Selective bandpass filters for red, green, and blue wavelength bands are constructed using optimally designed multilayered woodpile photonic crystals. The R/G/B color filtering for a wide range of incidence angles of light is demonstrated numerically, and the operation principle and design method are described.

ER stress: an emerging regulator in GVHD development.

Allogeneic hematopoietic cell transplantation (allo-HCT) is a promising therapeutic option for hematologic malignancies. However, the clinical benefits of allo-HCT are limited by the development of complications including graft-versus-host disease (GVHD). Conditioning regimens, such as chemotherapy and irradiation, which are administered to the patients prior to allo-HCT, can disrupt the endoplasmic reticulum (ER) homeostasis, and induce ER stress in the recipient's cells. The conditioning regimen activates antigen-presenting cells (APCs), which, in turn, activate donor cells, leading to ER stress in the transplanted cells. The unfolded protein response (UPR) is an evolutionarily conserved signaling pathway that manages ER stress in response to cellular stress. UPR has been identified as a significant regulatory player that influences the function of various immune cells, including T cells, B cells, macrophages, and dendritic cells (DCs), in various disease progressions. Therefore, targeting the UPR pathway has garnered significant attention as a promising approach for the treatment of numerous diseases, such as cancer, neurodegeneration, diabetes, and inflammatory diseases. In this review, we summarize the current literature regarding the contribution of ER stress response to the development of GVHD in both hematopoietic and non-hematopoietic cells. Additionally, we explore the potential therapeutic implications of targeting UPR to enhance the effectiveness of allo-HCT for patients with hematopoietic malignancies.

Tiling integral floating display system with optimized viewing window.

A tiling integral floating display system is proposed using the optimization of viewing window. The integral floating display, which is a combination of an integral imaging system and a floating lens, has many advantages, but it is hard to realize a large system due to the cost and difficulties in making the large floating device. In this paper, the stackable integral floating display is proposed by modifying the size of the viewing window to be the same as that of the display device, which can be a solution for the large scale autostereoscopic three-dimensional display system.