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Creating realistic materials is essential in the construction of immersive virtual environments. While existing techniques for material capture and conditional generation rely on flash-lit photos, they often produce artifacts when the illumination mismatches the training data. In this study, we introduce DiffMat, a novel diffusion model that integrates the CLIP image encoder and a multi-layer, cross-attention denoising backbone to generate latent materials from images under various illuminations. Using a pre-trained StyleGAN-based material generator, our method converts these latent materials into high-resolution SVBRDF textures, a process that enables a seamless fit into the standard physically based rendering pipeline, reducing the requirements for vast computational resources and expansive datasets. DiffMat surpasses existing generative methods in terms of material quality and variety, and shows adaptability to a broader spectrum of lighting conditions in reference images.

Atherosclerosis poses a significant threat to human health, impacting overall well-being and imposing substantial financial burdens. Current treatment strategies mainly focus on managing low-density lipids (LDL) and optimizing liver functions. However, it’s crucial to recognize that Atherosclerosis involves more than just lipid accumulation; it entails a complex interplay of immune responses. Research highlights the pivotal role of lipid-laden macrophages in the formation of atherosclerotic plaques. These macrophages attract lymphocytes like CD4 and CD8 to the inflamed site, potentially intensifying the inflammatory response. γδ T lymphocytes, with their diverse functions in innate and adaptive immune responses, pathogen defense, antigen presentation, and inflammation regulation, have been implicated in the early stages of Atherosclerosis. However, our understanding of the roles of γδ T cells in Atherosclerosis remains limited. This mini-review aims to shed light on the characteristics and functions of γδ T cells in Atherosclerosis. By gaining insights into the roles of γδ T cells, we may uncover a promising strategy to mitigate plaque buildup and dampen the inflammatory response, thereby opening new avenues for effectively managing this condition.

Lactic acid bacteria (LAB) possess the ability to argument T cell activity through functional modification of antigen presenting cells (APCs), such as dendritic cells (DCs) and macrophages. Nevertheless, the precise mechanism underlying LAB-induced enhancement of antigen presentation in APCs remains incompletely understood. To address this question, we investigated the detailed mechanism underlying the enhancement of major histocompatibility complex (MHC) class I-restricted antigen presentation in DCs using a probiotic strain known as Lactococcus lactis subsp. Cremoris C60. We found that Heat-killed-C60 (HK-C60) facilitated the processing and presentation of ovalbumin (OVA) peptide antigen OVA257-264 (SIINFEKL) via H-2Kb in bone marrow-derived dendritic cells (BMDCs), leading to increased generation of effector CD8+ T cells both in vitro and in vivo. We also revealed that HK-C60 stimulation augmented the activity of 20S immunoproteasome (20SI) in BMDCs, thereby enhancing the MHC class I-restricted antigen presentation machinery. Furthermore, we assessed the impact of HK-C60 on CD8+ T cell activation in an OVA-expressing B16-F10 murine melanoma model. Oral administration of HK-C60 significantly attenuated tumor growth compared to control treatment. Enhanced Ag processing and presentation machineries in DCs from both Peyer’s Patches (PPs) and lymph nodes (LNs) resulted in an increased tumor antigen specific CD8+ T cells. These findings shed new light on the role of LAB in MHC class-I restricted antigen presentation and activation of CD8+ T cells through functional modification of DCs.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection.

IntroductionA group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed.MethodsWe identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC).ResultsThrough these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores.ConclusionOur study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. This is due to increased lipid metabolism by macrophages which contributes to plaque resolution. However, the importance of ACE in peripheral blood monocytes, which are the primary precursors of lesional-infiltrating macrophages, is still unknown in atherosclerosis. Here, we show that the ACE-mediated metabolic phenotype is already triggered in peripheral blood circulating monocytes and that this functional modification is directly transferred to differentiated macrophages in ACE10/10 mice. We found that Ly-6Clo monocytes were increased in atherosclerotic ACE10/10 mice. The monocytes isolated from atherosclerotic ACE10/10 mice showed enhanced lipid metabolism, elevated mitochondrial activity, and increased adenosine triphosphate (ATP) levels which implies that ACE overexpression is already altered in atherosclerosis. Furthermore, we observed increased oxygen consumption (VO2), respiratory exchange ratio (RER), and spontaneous physical activity in ACE10/10 mice compared to WT mice in atherosclerotic conditions, indicating enhanced systemic energy consumption. Thus, ACE overexpression in myeloid lineage cells modifies the metabolic function of peripheral blood circulating monocytes which differentiate to macrophages and protect against atherosclerotic lesion progression due to better lipid metabolism.

Creatine is an indispensable organic compound utilized in physiological environments; however, its role in immunity is still poorly understood. Here, we show that creatine supplementation enhances anti-tumor immunity through the functional upregulation of macrophages by increasing adenosine triphosphate (ATP) production. Creatine supplementation significantly suppressed B16-F10-originated tumor growth in mice compared with the control treatment. Under these conditions, intratumor macrophages polarized towards the M1 phenotype rather than the M2 phenotype, and there was an increase in tumor antigen-specific CD8+ T cells in the mice. The cytokine production and antigen-presenting activity in the macrophages were enhanced by creatine supplementation, resulting in a substantial increase in tumor antigen-specific CD8+ T cells. ATP upregulation was achieved through the cytosolic phosphocreatine (PCr) system via extracellular creatine uptake, rather than through glycolysis and mitochondrial oxidative phosphorylation in the macrophages. Blockade of the creatine transporter (CrT) failed to upregulate ATP and enhance the immunological activity of macrophages in creatine supplementation, which also impaired CD8+ T cell activity. Consequently, CrT blockade failed to suppress tumor growth in the creatine-supplemented mice. Thus, creatine is an important nutrient that promotes macrophage function by increasing ATP levels, ultimately contributing to enhanced anti-tumor immunity orchestrated by CD8+ T cells.

Abstract Background We evaluated the relationship between the weight-bearing line (WBL) ratio and anatomical femorotibial angle (FTA) by simulated open wedge high tibial osteotomy (OWHTO). This study evaluated the correlation between the ‘‘Fujisawa point’’ and FTA, and identified factors which caused deviations between the two measurement methods. We hypothesized that the Fujisawa point corresponded with 170° of the FTA. Methods Preoperative antero-posterior full-length lower limb radiographs of 82 patients were obtained for the OWHTO to place the WBL ratio at a target of 62.5% of the width of the tibial plateau (Fujisawa point). The coronal alignment was measured pre- and post-planning. The patients were divided into two groups by the post-planning FTA: a correspondence group (168.5°≦FTA≦171.5°) and a non-correspondence group (FTA

ACE2 and TMPRSS2 are crucial for SARS-CoV-2 entry into the cell. Although ACE2 facilitates viral entry, its loss leads to promoting the devastating clinical symptoms of COVID-19 disease. Thus, enhanced ACE2/TMPRSS2 expression is likely to increase predisposition of target cells to SARS-CoV-2 infection. However, little evidence existed about the biological kinetics of these two enzymes and whether dexamethasone treatment modulates their expression. Here, we show that the expression of ACE2 at the protein and mRNA levels was significantly higher in the lung and heart tissues of neonatal compared to adult mice. However, the expression of TMPRSS2 was developmentally regulated. Our results may introduce a novel concept for the reduced susceptibility of the young to SARS-CoV-2 infection. Moreover, ACE2 expression but not TMPRSS2 was upregulated in adult female lungs compared to their male counterparts. Interestingly, the ACE2 and TMPRSS2 expressions were upregulated by dexamethasone treatment in the lung and heart tissues in both neonatal and adult mice. Furthermore, our findings provide a novel mechanism for the observed differential therapeutic effects of dexamethasone in COVID-19 patients. As such, dexamethasone exhibits different therapeutic effects depending on the disease stage. This was supported by increased ACE2/TMPRSS2 expression and subsequently enhanced infection of normal human bronchial epithelial cells (NHBE) and Vero E6 cells with SARS-CoV-2 once pre-treated with dexamethasone. Therefore, our results suggest that individuals who take dexamethasone for other clinical conditions may become more prone to SARS-CoV-2 infection.

Immunological aging is a critical event that causes serious functional impairment in the innate immune system. However, the identification markers and parameters are still poorly understood in immunological aging of myeloid lineage cells. Here, we show that a downregulation of lymphocyte antigen 6 complex locus G6D (Ly-6G) observed in aged mouse neutrophils could serve as a novel marker for the prediction of age-associated functional impairment in the neutrophils. Ly-6G expression was significantly downregulated in the bone marrow (BM) neutrophils of aged mice compared to young mice confirmed by flow cytometry analysis. In vitro experiments using BM-isolated neutrophils showed significant downregulations in their activities, such as phagocytosis, reactive oxygen species (ROS) production, interleukin (IL)-1β production, neutrophil extracellular trap (NET) formation, and migration as well as bacterial clearance, in the aged mouse neutrophils compared to those of young mice counterparts. Interestingly, the magnitudes of functional parameters were strongly correlated with the Ly-6G expression in the neutrophils. Thus, our results suggest that downregulation of Ly-6G reflects the age-associated functional attenuation of the neutrophils.

ABSTRACT SARS-CoV-2 variants exhibit different viral transmissibility and disease severity. However, their impact on erythropoiesis has not been investigated. Here, we show SARS-CoV-2 variants differentially affect erythropoiesis. This is illustrated by the abundance of CD71+ erythroid cells (CECs) in the blood circulation of COVID-19 patients infected with the original Wuhan strain followed by the Delta and Omicron variants. We observed the CD45+CECs are the dominant subpopulation of CECs expressing the receptor, ACE2, and coreceptor, TMPRSS2, and thus, can be targeted by SARS-CoV-2. Also, we found CECs exhibit immunosuppressive properties, specifically CD45+CECs are the dominant immunosuppressive cells and via reactive oxygen species (ROS) and arginase I expression can impair CD8+ T cell functions. In agreement, we observed CECs suppress CD8+ T cell effector (e.g., Granzyme B expression and degranulation capacity [CD107]), which was partially but significantly reversed with l-arginine supplementation. In light of the enriched frequency of CECs, in particular, CD45+CECs in patients infected with the original (Wuhan) strain, we believe this strain has a more prominent impact on hematopoiesis compared with the Delta and Omicron variants. Therefore, our study provides an important insight into the differential impact of SARS-CoV-2 variants on erythropoiesis in COVID-19 patients. IMPORTANCE Silent hypoxia has been the hallmark of SARS-CoV-2 infection. Red blood cells (RBCs) work as gas cargo delivering oxygen to different tissues. However, their immature counterparts reside in the bone marrow and normally absent in the blood circulation. We show SARS-CoV-2 infection is associated with the emergence of immature RBCs so called CD71+ erythroid cells (CECs) in the blood. In particular, we found these cells were more prevalent in the blood of those infected with the SARS-CoV-2 original strain (Wuhan) followed by the Delta and Omicron variants. This suggests SARS-CoV-2 directly or indirectly impacts RBC production. In agreement, we observed immature RBCs express the receptor (ACE2) and coreceptor (TMPRSS2) for SARS-CoV-2. CECs suppress T cells functions (e.g., Granzyme B and degranulation capacity) in vitro. Therefore, our study provides a novel insight into the differential impact of SARS-CoV-2 variants on erythropoiesis and subsequently the hypoxia commonly observed in COVID-19 patients.

Abstract Angiotensin-converting enzyme (ACE), a dicarboxypeptidase, plays a major role in the regulation of blood pressure by cleaving angiotensin I into angiotensin II (Ang II), a potent vasoconstrictor. Because of its wide substrate specificity and tissue distribution, ACE affects many diverse biological processes. In inflammatory diseases, including granuloma, atherosclerosis, chronic kidney disease and bacterial infection, ACE expression gets upregulated in immune cells, especially in myeloid cells. With increasing evidences connecting ACE functions to the pathogenesis of these acquired diseases, it is suggested that ACE plays a vital role in immune functions. Recent studies with mouse models of bacterial infection and tumor suggest that ACE plays an important role in the immune responses of myeloid cells. Inhibition of ACE suppresses neutrophil immune response to bacterial infection. In contrast, ACE overexpression in myeloid cells strongly induced bacterial and tumor resistance in mice. A detailed biochemical understanding of how ACE activates myeloid cells and which ACE peptide(s) (substrate or product) mediate these effects could lead to the development of novel therapies for boosting immunity against a variety of stimuli, including bacterial infection and tumor.

As first responder cells in host defense, neutrophils must be carefully regulated to prevent collateral tissue injury. However, the intracellular events that titrate the neutrophil’s response to inflammatory stimuli remain poorly understood. As a molecular switch, Ras activity is tightly regulated by Ras GTPase activating proteins (RasGAP) to maintain cellular active-inactive states. Here, we show that RASAL3, a RasGAP, is highly expressed in neutrophils and that its expression is upregulated by exogenous stimuli in neutrophils. RASAL3 deficiency triggers augmented neutrophil responses and enhanced immune activation in acute inflammatory conditions. Consequently, mice lacking RASAL3 (RASAL3-KO) demonstrate accelerated mortality in a septic shock model via induction of severe organ damage and hyperinflammatory response. The excessive neutrophilic hyperinflammation and increased mortality were recapitulated in a mouse model of sickle cell disease, which we found to have low neutrophil RASAL3 expression upon LPS activation. Thus, RASAL3 functions as a RasGAP that negatively regulates the cellular activity of neutrophils to modulate the inflammatory response. These results demonstrate that RASAL3 could serve as a therapeutic target to regulate excessive inflammation in sepsis and many inflammatory disease states.

This study proposed a new type of optical device with variable transmittance based on the incident angle direction. These devices consist of two liquid crystal devices (LCDs) with a half-wave plate between them. Hybrid aligned nematic (HAN)-type guest-host (GH) LCDs or GH-LCDs with antiparallel alignment of high pretilt angles were used. The use of a half-wave plate allowed for the control of the p- and s-waves. Using these devices, a wide range of transmittances were obtained because no polarizer was used. The newly proposed LCDs have a wide range of applications, including use on buildings, vehicles, and glasses.

Abstract We report on the IR sensitivity enhancement of back-illuminated CMOS Image Sensor (BI-CIS) with 2-dimensional diffractive inverted pyramid array structure (IPA) on crystalline silicon (c-Si) and deep trench isolation (DTI). FDTD simulations of semi-infinite thick c-Si having 2D IPAs on its surface whose pitches over 400 nm shows more than 30% improvement of light absorption at λ = 850 nm and the maximum enhancement of 43% with the 540 nm pitch at the wavelength is confirmed. A prototype BI-CIS sample with pixel size of 1.2 μm square containing 400 nm pitch IPAs shows 80% sensitivity enhancement at λ = 850 nm compared to the reference sample with flat surface. This is due to diffraction with the IPA and total reflection at the pixel boundary. The NIR images taken by the demo camera equip with a C-mount lens show 75% sensitivity enhancement in the λ = 700–1200 nm wavelength range with negligible spatial resolution degradation. Light trapping CIS pixel technology promises to improve NIR sensitivity and appears to be applicable to many different image sensor applications including security camera, personal authentication, and range finding Time-of-Flight camera with IR illuminations.

Toll-like receptor (TLR) signaling is an indispensable factor in immune cells activation. Many TLR ligands have been identified, and were characterized the immunological functions such as inflammatory cytokine production in immune cells. However, the anti-inflammatory response in TLR ligand-mediated manner is poorly understood. In this report, we show that bacterial lipoteichoic acid (LTA), which is a TLR2 ligand from gram-positive bacteria including Staphylococcus aureus (S. aureus), suppresses TLR-mediated inflammatory response in dendritic cells (DCs). The TLR ligand-induced Tumor Necrosis Factor-alpha (TNF-α) production was suppressed in the bone marrow derived dendritic cells (BMDCs) by co-treatment of LTA. The cellular activation, which was characterized as upregulations of CD80, CD86 and major histocompatibility complex II (MHC II) expression, was also suppressed in the TLR ligand stimulated BMDCs in the presence of LTA. While LTA itself didn’t induced both TNF-α production and upregulation of cell surface markers. The LTA mediated immunosuppressive function was abolished by TLR2 blocking in lipopolysaccharide (LPS)-stimulated BMDCs. Furthermore, LTA also showed the immunosuppressive function in the generation of IFN-γ+CD4+ T (Th1) cells by attenuation of antigen presenting activity in the BMDCs. In the imiquimod (IMQ)-induced acute skin inflammation, LTA suppressed the inflammation by downregulation of the activation in skin accumulated DCs. Thus, LTA is a TLR2 dependent immunological suppressor against inflammatory response induced by other TLR ligands in the DCs.

Staphylococcus aureus (S. aureus) is a commensal bacterium in the human body; however, the bacterium frequently generates serious inflammation and infectious diseases. Some strains of S. aureus, such as methicillin-resistant Staphylococcus aureus (MRSA), are still a serious problem in public health facilities. Thus, an effective protection strategy is eagerly expected for the prevention and cure of MRSA infection. Here, we report that a specific fraction of an S. aureus lipoprotein (SA-LP) established a protective response against MRSA infection. The fractionated S. aureus lipoprotein SA-LP-F2, which is contained in 30−50 kDa of crude S. aureus lipoprotein (SA-LP-C), effectively activated dendritic cells (DCs) and the SA-LP-F2-pulsed DCs generated IFN-γ+CD4+ T (Th1) and IL-17A+CD4+ T (Th17) cells by in vitro antigen presentation. The SA-LP-F2 immunization upregulated the Th1 and Th17 populations so that MRSA colonization on the skin was suppressed during the challenge phase with MRSA. By following the effector T cell upregulation, the neutrophil function, which was a substantial effector cell against MRSA, was also enhanced in the SA-LP-F2-immunized mice. Finally, we found that the protective effect of SA-LP-F2 immunization was maintained for at least 90 days because the immunized mice continued to show a protective response during the MRSA challenge period. In the MRSA challenge, reactivated Th1 and Th17 populations were maintained in the SA-LP-F2-immunized mice as compared to naive mice. In addition, the neutrophil population was also upregulated in the mice. The memory CD4+ T cell (central memory T; TCM and effector memory T; TEM) population was established by SA-LP-F2 immunization and was maintained at higher levels than usual. Taken together, our findings may provide a breakthrough in the establishment of an immunization strategy against MRSA infection.

The sample condition is an important factor in urine proteomics with stability and accuracy. However, a general protocol of urine protein preparation in mass spectrometry analysis has not yet been established. Here, we proposed a workflow for optimized sample preparation based on methanol/chloroform (M/C) precipitation and in-solution trypsin digestion in LC-MS/MS-based urine proteomics. The urine proteins prepared by M/C precipitation showed around 80% of the protein recovery rate. The samples showed the largest number of identified proteins, which were over 1000 on average compared with other precipitation methods in LC-MS/MS-based urine proteomics. For further improvement of the workflow, the essences were arranged in protein dissolving and trypsin digestion step for the extraction of urine proteins. Addition of Ethylene diamine tetraacetic acid (EDTA) dramatically enhanced the dissolution of protein and promoted the trypsin activity in the digestion step because the treatment increased the number of identified proteins with less missed cleavage sites. Eventually, an optimized workflow was established by a well-organized strategy for daily use in the LC-MS/MS-based urine proteomics. The workflow will be of great help for several aims based on urine proteomics approaches, such as diagnosis and biomarker discovery.

Staphylococcus aureus (S. aureus) is a commensal bacteria on the human skin, which causes serious skin inflammation. Several immune cells, especially effector T cells (Teff), have been identified as key players in S. aureus-derived skin inflammation. However, the bacterial component that induces dramatic host immune responses on the skin has not been well characterized. Here, we report that S. aureus lipoprotein (SA-LP) was recognized by the host immune system as a strong antigen, so this response induced severe skin inflammation. SA-LP activated dendritic cells (DCs), and this activation led to Teff accumulation on the inflamed skin in the murine intradermal (ID) injection model. The skin-accumulated Teff pool was established by IFN-ɤ-producing CD4+ and CD8+T (Th1 and Tc1). SA-LP activated dermal DC (DDC) in a dominant manner, so that these DCs were presumed to possess the strong responsibility of SA-LP-specific Teff generation in the skin-draining lymph nodes (dLN). SA-LP activated DC transfer into the mice ear, which showed similar inflammation, accompanied with Th1 and Tc1 accumulation on the skin. Thus, we revealed that SA-LP has a strong potential ability to establish skin inflammation through the DC-Teff axis. This finding provides novel insights not only for therapy, but also for the prevention of S. aureus-derived skin inflammation.

Diabetic mellitus (DM) is a disease that affects glucose homeostasis and causes complications, such as diabetic nephropathy (DN). For early diagnosis of DN, microalbuminuria is currently one of the most frequently used biomarkers. However, more early diagnostic biomarkers are desired in addition to microalbuminuria. In this study, we performed comprehensive proteomics analysis of urine proteomes of diabetic mellitus patients without microalbuminuria and healthy volunteers to compare the protein profiles by mass spectrometry. With high confidence criteria, 942 proteins in healthy volunteer urine and 645 proteins in the DM patient urine were identified with label-free semi-quantitation, respectively. Gene ontology and pathway analysis were performed with the proteins, which were up- or down-regulated in the DM patient urine to elucidate significant changes in pathways. The discovery of a useful biomarker for early DN discovery is expected.