Massive field-of-view sub-cellular traction force videography enabled by Single-Pixel Optical Tracers (SPOT).

We report a massive field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13 mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction force into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave.

Novel adjuvants in allergen-specific immunotherapy: where do we stand?

Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.

Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

OBJECTIVES: Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD). METHODS: The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. RESULTS: Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD. CONCLUSIONS: This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5 years.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

Predicting the Influences of Depression and Sexual Stigma on Motivation to Get Vaccinated against COVID-19 in Lesbian, Gay, and Bisexual Young Adults: A 4-Year Follow-Up Study.

Vaccination is a crucial preventive measure against COVID-19. However, limited research has focused on identifying the factors predicting motivation to get vaccinated against COVID-19 (MoVAC-19) among lesbian, gay, and bisexual (LGB) individuals. This study examined the predictive effects of depression and sexual stigma (i.e., perceived sexual stigma from family members, perceived sexual orientation microaggression, and internalized sexual stigma) before the COVID-19 pandemic on MoVAC-19 among LGB individuals 4 years later during the COVID-19 pandemic in Taiwan. Baseline data related to depression and sexual stigma were collected in 2018 and 2019. Depression was assessed using the 20-item Mandarin Chinese version of the Center for Epidemiologic Studies Depression Scale. Perceived sexual stigma from family members was assessed using the Homosexuality-Related Stigma Scale. Internalized sexual stigma was assessed using the Measure of Internalized Sexual Stigma for Lesbians and Gay Men. Perceived sexual orientation microaggression was assessed using the Sexual Orientation Microaggression Inventory. Participant MoVAC-19 during the pandemic was assessed using the nine-item Motors of COVID-19 Vaccination Acceptance Scale. The associations of depression and sexual stigma at baseline with MoVAC-19 at follow-up were examined through multivariate linear regression analysis. Internalized sexual stigma was negatively associated with MoVAC-19, whereas perceived sexual orientation microaggression was positively associated with MoVAC-19. Depression and perceived sexual stigma from family members were not significantly associated with MoVAC-19. Although male sex and older age were positively associated with increased MoVAC-19, sex and age did not moderate the relationship between sexual stigma and motivation to get vaccinated. Among LGB individuals, sexual stigma experiences should be considered when developing intervention strategies aimed at enhancing MoVAC-19.

Massively Concurrent Sub-Cellular Traction Force Videography enabled by Single-Pixel Optical Tracers (SPOTs).

We report a large field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13mm 2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction stress into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave. One-Sentence Summary: An optical platform for fast, concurrent measurements of cell mechanics at 83 frames per second, over a large area of 13mm 2 .

Circadian typologies and insomnia in individuals with internet gaming disorder comorbid with attention deficit/hyperactivity disorder.

The alteration in circadian typology and insomnia were prevalent among both Individuals with IGD and those with attention deficit hyperactivity disorder (ADHD), the most comorbid psychiatric disorder of IGD. This study aimed to evaluate the relationships between circadian typologies, insomnia, and internet gaming disorder (IGD) and how ADHD affects this relationship. We recruited three groups of 69 young adults: an IGD group, a control group comprising age- and sex-matched nongamers, and a group of gamers without IGD through diagnostic interviews. The participants with IGD exhibited lower composite scale of morningness (CSM) scores and thus a higher eveningness preference In addition, the score of Pittsburgh insomnia rating scale-20-item version (PIRS_20) was significantly higher among those with IGD. The participants with IGD and ADHD exhibited lower CSM scores but higher PRIS_20 scores than the participants with IGD but without ADHD. The present findings indicate that participants with IGD exhibited a tendency of eveningness preference and experienced more severe insomnia. ADHD exacerbated the eveningness preference and insomnia of individuals with IGD. Close attention should be paid to sleep problems in individuals with IGD, particularly to those with ADHD.

Van der Waals Heterostructure Mid-Infrared Emitters with Electrically Controllable Polarization States and Spectral Characteristics.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations. Our devices are composed of two back-to-back p-n junctions formed by stacking anisotropic light-emitting materials, black phosphorus and black arsenic-phosphorus with MoS2. By controlling the crystallographic orientations and engineering the band profile of heterostructures, the emissions of two junctions exhibit distinct spectral ranges and polarization directions; more importantly, these two electroluminescence (EL) units can be independently activated, depending on the polarity of the applied bias. Furthermore, we show that when operating our emitter under the polarity-switched pulse mode, the time-averaged EL exhibits the characteristics of broad spectral coverage, encompassing the entire first mid-IR atmospheric window (λ: 3-5 µm), and electrically tunable spectral shapes.

A flagellin-conjugate protein induces dual NLRC4- and NLRP3-inflammasome activation which modulates inflammatory cytokine secretion from macrophages.

Background: A recombinant fusion protein combining the adjuvant and TLR5-ligand flagellin with the major birch pollen allergen Bet v 1 (rFlaA:Betv1) has been suggested to prevent the manifestation of birch allergy. Noteworthy, rFlaA:Betv1 induced both pro- and anti-inflammatory responses which were differentially regulated. However, the mechanism by which flagellin fusion proteins modulate allergen-specific immune responses, especially the mechanisms underlying IL-1ß secretion and their contribution to the overall immune responses remains elusive. Objective: To investigate the mechanisms underlying the production of IL-1ß from rFlaA:Betv1 stimulated macrophages. Methods: Macrophages were derived from mouse peritoneal-, human buffy-coat-, and PMA-differentiated THP-1 (wild type or lacking either ASC, NLRP3, or NLRC4) cells. Macrophages were stimulated with non-modified rFlaA:Betv1, mutant variants lacking either the flagellin DC0 domain or a sequence motif formerly described to mediate TLR5-activation, and respective controls in the presence or absence of inhibitors interfering with MAPK- and NFκB-signaling. Cytokine secretion was analyzed by ELISA and intracellular signaling by Western Blot. To study the contribution of IL-1ß to the overall immune responses, IL1R-deficient mouse peritoneal macrophages were used. Results: rFlaA:Betv1 consistently activated all types of investigated macrophages, inducing higher IL-1ß secretion compared with the equimolar mixture of both proteins. rFlaA:Betv1-induced activation of THP-1 macrophages was shown to be independent of either the TLR5-activating sequence motif or the flagellin DC0 domain but depended on both NLRP3- and NLRC4-inflammasomes. In addition, NFκB and SAP/JNK MAP kinases regulated rFlaA:Betv1-induced inflammasome activation and cytokine secretion by modulating pro-Caspase-1- and pro-IL-1ß-expression in THP-1 macrophages. Finally, lack of IL-1ß positive feedback via the IL1R strongly diminished the rFlaA:Betv1-induced secretion of IL-1ß, IL-6, and TNF-α from peritoneal macrophages. Conclusion: The mechanisms contributing to rFlaA:Betv1-induced IL-1ß secretion from macrophages were shown to be complex, involving both NLRC4- and NLRP3-inflammsomes, as well as NFκB- and SAP/JNK MAP kinase-signaling. Better understanding the mechanisms regulating the activation of immune cells by novel therapeutic candidates like the rFlaA:Betv1 fusion protein will allow us to further improve and develop new treatment strategies when using flagellin as an adjuvant.

Stimulation of naïve B cells with a fusion protein consisting of FlaA and Bet v 1 induces regulatory B cells ex vivo.

BACKGROUND: The experimental fusion protein rFlaA:Betv1 was shown to efficiently suppress allergen-specific sensitization in mice. However, the detailed mechanism of rFlaA:Betv1-mediated immune modulation is not fully understood. In this study, we investigated the effect of rFlaA:Betv1 on naïve murine B cells. METHODS: Immune modulating capacity of rFlaA:Betv1 was screened in IL-10 reporter mice. B cells were isolated from spleens of naïve C57Bl/6, TLR5-/- , or MyD88-/- mice, stimulated with rFlaA:Betv1 and controls, and monitored for the expression of the regulatory B cell markers CD1d, CD24, CD38, and surface IgM by flow cytometry. Secreted cytokines, antibodies, and reactivity of the induced antibodies were investigated by ELISA and intracellular flow cytometry. Suppressive capacity of rFlaA:Betv1-stimulated B cells was tested in mDC:CD4+ T cell:B cell triple cultures. RESULTS: Upon in vivo application of rFlaA:Betv1 into IL-10-GFP reporter mice, CD19+ B cells were shown to produce anti-inflammatory IL-10, suggesting B cells to contribute to the immune-modulatory properties of rFlaA:Betv1. rFlaA:Betv1-induced IL-10 secretion was confirmed in human B cells isolated from buffy coats. In vitro stimulation of naïve murine B cells with rFlaA:Betv1 resulted in an mTOR- and MyD88-dependent production of IL-10 and rFlaA:Betv1 induced Bet v 1-reactive IgG production, which was not observed for IgA. rFlaA:Betv1-stimulated B cells formed a CD19+ CD24+ CD1d+ IgM+ CD38+ Breg subpopulation capable of suppressing Bet v 1-induced TH2 cytokine secretion in vitro. CONCLUSION: rFlaA:Betv1 can act as a thymus-independent B cell antigen, stimulating the mTOR- and MyD88-dependent differentiation of B cells displaying a regulatory phenotype, IL-10 secretion, antigen-binding antibody production, and a suppressive capacity in vitro.

Rapid prototyping of functional acoustic devices using laser manufacturing.

Acoustic patterning of micro-particles has many important biomedical applications. However, fabrication of such microdevices is costly and labor-intensive. Among conventional fabrication methods, photo-lithography provides high resolution but is expensive and time consuming, and not ideal for rapid prototyping and testing for academic applications. In this work, we demonstrate a highly efficient method for rapid prototyping of acoustic patterning devices using laser manufacturing. With this method we can fabricate a newly designed functional acoustic device in 4 hours. The acoustic devices fabricated using this method can achieve sub-wavelength, complex and non-periodic patterning of microparticles and biological objects with a spatial resolution of 60 µm across a large active manipulation area of 10 × 10 mm2.

Role of Glycolysis and Fatty Acid Synthesis in the Activation and T Cell-Modulating Potential of Dendritic Cells Stimulated with a TLR5-Ligand Allergen Fusion Protein.

Trained immune responses, based on metabolic and epigenetic changes in innate immune cells, are de facto innate immune memory and, therefore, are of great interest in vaccine development. In previous studies, the recombinant fusion protein rFlaA:Betv1, combining the adjuvant and toll-like receptor (TLR)5-ligand flagellin (FlaA) and the major birch pollen allergen Bet v 1 into a single molecule, significantly suppressed allergic sensitization in vivo while also changing the metabolism of myeloid dendritic cells (mDCs). Within this study, the immune-metabolic effects of rFlaA:Betv1 during mDC activation were elucidated. In line with results for other well-characterized TLR-ligands, rFlaA:Betv1 increased glycolysis while suppressing oxidative phosphorylation to different extents, making rFlaA:Betv1 a suitable model to study the immune-metabolic effects of TLR-adjuvanted vaccines. In vitro pretreatment of mDCs with cerulenin (inhibitor of fatty acid biosynthesis) led to a decrease in both rFlaA:Betv1-induced anti-inflammatory cytokine Interleukin (IL) 10 and T helper cell type (TH) 1-related cytokine IL-12p70, while the pro-inflammatory cytokine IL 1ß was unaffected. Interestingly, pretreatment with the glutaminase inhibitor BPTES resulted in an increase in IL-1ß, but decreased IL-12p70 secretion while leaving IL-10 unchanged. Inhibition of the glycolytic enzyme hexokinase-2 by 2-deoxyglucose led to a decrease in all investigated cytokines (IL-10, IL-12p70, and IL-1ß). Inhibitors of mitochondrial respiration had no effect on rFlaA:Betv1-induced IL-10 level, but either enhanced the secretion of IL-1ß (oligomycin) or decreased IL-12p70 (antimycin A). In extracellular flux measurements, mDCs showed a strongly enhanced glycolysis after rFlaA:Betv1 stimulation, which was slightly increased after respiratory shutdown using antimycin A. rFlaA:Betv1-stimulated mDCs secreted directly antimicrobial substances in a mTOR- and fatty acid metabolism-dependent manner. In co-cultures of rFlaA:Betv1-stimulated mDCs with CD4+ T cells, the suppression of Bet v 1-specific TH2 responses was shown to depend on fatty acid synthesis. The effector function of rFlaA:Betv1-activated mDCs mainly relies on glycolysis, with fatty acid synthesis also significantly contributing to rFlaA:Betv1-mediated cytokine secretion, the production of antimicrobial molecules, and the modulation of T cell responses.

Modulation of dendritic cell metabolism by an MPLA-adjuvanted allergen product for specific immunotherapy.

Background: Recently, bacterial components were shown to enhance immune responses by shifting immune cell metabolism towards glycolysis and lactic acid production, also known as the Warburg Effect. Currently, the effect of allergen products for immunotherapy (AIT) and commercial vaccines on immune cell metabolism is mostly unknown. Objective: To investigate the effect of AIT products (adjuvanted with either MPLA or Alum) on myeloid dendritic cell (mDC) metabolism and activation. Methods: Bone marrow-derived mDCs were stimulated with five allergoid-based AIT products (one adjuvanted with MPLA, four adjuvanted with Alum) and two MPLA-adjuvanted vaccines and analyzed for their metabolic activation, expression of cell surface markers, and cytokine secretion by ELISA. mDCs were pre-incubated with either immunological or metabolic inhibitors or cultured in glucose- or glutamine-free culture media and subsequently stimulated with the MPLA-containing AIT product (AIT product 1). mDCs were co-cultured with allergen-specific CD4+ T cells to investigate the contribution of metabolic pathways to the T cell priming capacity of mDCs stimulated with AIT product 1. Results: Both the MPLA-containing AIT product 1 and commercial vaccines, but not the Alum-adjuvanted AIT products, activated Warburg metabolism and TNF-α secretion in mDCs. Further experiments focused on AIT product 1. Metabolic analysis showed that AIT product 1 increased glycolytic activity while also inducing the secretion of IL-1ß, IL-10, IL-12, and TNF-α. Both rapamycin (mTOR-inhibitor) and SP600125 (SAP/JNK MAPK-inhibitor) dose-dependently suppressed the AIT product 1-induced Warburg Effect, glucose consumption, IL-10-, and TNF-α secretion. Moreover, both glucose- and glutamine deficiency suppressed secretion of all investigated cytokines (IL-1ß, IL-10, and TNF-α). Glucose metabolism in mDCs was also critical for the (Th1-biased) T cell priming capacity of AIT product 1-stimulated mDCs, as inhibition of mTOR signaling abrogated their ability to induce Th1-responses. Conclusion: The AIT product and commercial vaccines containing the adjuvant MPLA were shown to modulate the induction of immune responses by changing the metabolic state of mDCs. Better understanding the mechanisms underlying the interactions between cell metabolism and immune responses will allow us to further improve vaccine development and AIT.

Cardiomyocytes disrupt pyrimidine biosynthesis in nonmyocytes to regulate heart repair.

Various populations of cells are recruited to the heart after cardiac injury, but little is known about whether cardiomyocytes directly regulate heart repair. Using a murine model of ischemic cardiac injury, we demonstrate that cardiomyocytes play a pivotal role in heart repair by regulating nucleotide metabolism and fates of nonmyocytes. Cardiac injury induced the expression of the ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which hydrolyzes extracellular ATP to form AMP. In response to AMP, cardiomyocytes released adenine and specific ribonucleosides that disrupted pyrimidine biosynthesis at the orotidine monophosphate (OMP) synthesis step and induced genotoxic stress and p53-mediated cell death of cycling nonmyocytes. As nonmyocytes are critical for heart repair, we showed that rescue of pyrimidine biosynthesis by administration of uridine or by genetic targeting of the ENPP1/AMP pathway enhanced repair after cardiac injury. We identified ENPP1 inhibitors using small molecule screening and showed that systemic administration of an ENPP1 inhibitor after heart injury rescued pyrimidine biosynthesis in nonmyocyte cells and augmented cardiac repair and postinfarct heart function. These observations demonstrate that the cardiac muscle cell regulates pyrimidine metabolism in nonmuscle cells by releasing adenine and specific nucleosides after heart injury and provide insight into how intercellular regulation of pyrimidine biosynthesis can be targeted and monitored for augmenting tissue repair.

The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells.

Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins.

Immune Metabolism of IL-4-Activated B Cells and Th2 Cells in the Context of Allergic Diseases.

Over the last decades, the frequency of allergic disorders has steadily increased. Immunologically, allergies are caused by abnormal immune responses directed against otherwise harmless antigens derived from our environment. Two of the main cell types driving allergic sensitization and inflammation are IgE-producing plasma cells and Th2 cells. The acute activation of T and B cells, their differentiation into effector cells, as well as the formation of immunological memory are paralleled by distinct changes in cellular metabolism. Understanding the functional consequences of these metabolic changes is the focus of a new research field termed "immune metabolism". Currently, the contribution of metabolic changes in T and B cells to either the development or maintenance of allergies is not completely understood. Therefore, this mini review will introduce the fundamentals of energy metabolism, its connection to immune metabolism, and subsequently focus on the metabolic phenotypes of IL-4-activated B cells and Th2 cells.

High-Efficiency Ultrathin Si-Based Solar Cells by Cascading Dilute-Nitride GaNAsP.

Thin-film solar cells are currently an important research subject. In this study, a lattice-matched GaNAsP/Si tandem cell was designed. We adopted the drift-diffusion model to analyze the power conversion efficiency (PCE) of the solar cell. To find the maximum solar cell PCE, the recombination terms and the interlayer between subcells was omitted. For an optimal tandem cell PCE, this study analyzed the mole fraction combinations of GaNAsP and the thickness combinations between the GaNAsP and the Si subcells of the tandem cell. Our results showed the superiority of the tandem cell over the Si cell. The 4.5 µm tandem cell had a 12.5% PCE, the same as that of the 10.7 µm Si cell. The 11.5 µm tandem cell had 20.2% PCE, while the 11.5 µm Si cell processed 12.7% PCE. We also analyzed the Si subcell thickness ratio of sub-12 µm tandem cells for maximum PCE. The tandem cell with a thickness between 40% to 70% of a Si cell would have a max PCE. The ratio depended on the tandem cell thickness. We conclude that the lattice-matched GaNAsP/Si tandem cell has potential for ultrathin thin Si-based solar cell applications.

The Flagellin:Allergen Fusion Protein rFlaA:Betv1 Induces a MyD88- and MAPK-Dependent Activation of Glucose Metabolism in Macrophages.

TLR5 ligand flagellin-containing fusion proteins are potential vaccine candidates for many diseases. A recombinant fusion protein of flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) modulates immune responses in vitro and in vivo. We studied the effects of rFlaA:Betv1 on bone marrow-derived macrophages (BMDMs). BMDMs differentiated from BALB/c, C57BL/6, TLR5-/-, or MyD88-/- mice were pre-treated with inhibitors, stimulated with rFlaA:Betv1 or respective controls, and analyzed for activation, cytokine secretion, metabolic state, RNA transcriptome, and modulation of allergen-specific Th2 responses. Stimulation of BMDMs with rFlaA:Betv1 resulted in MyD88-dependent production of IL-1ß, IL-6, TNF-α, IL-10, CD69 upregulation, and a pronounced shift towards glycolysis paralleled by activation of MAPK, NFκB, and mTOR signaling. Inhibition of either mTOR (rapamycin) or SAP/JNK-MAPK signaling (SP600125) resulted in dose-dependent metabolic suppression. In BMDM and T cell co-cultures, rFlaA:Betv1 stimulation suppressed rBet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. mRNA-Seq analyses showed HIF-1a, JAK, STAT, phagosome, NLR, NFκB, TNF, TLR, and chemokine signaling to participate in the interplay of cell activation, glycolysis, and immune response. rFlaA:Betv1 strongly activated BMDMs, resulting in MyD88-, MAPK-, and mTOR-dependent enhancement of glucose metabolism. Our results suggest macrophages are important target cells to consider during restauration of allergen tolerance during AIT.

Differences in Sources of Information, Risk Perception, and Cognitive Appraisals between People with Various Latent Classes of Motivation to Get Vaccinated against COVID-19 and Previous Seasonal Influenza Vaccination: Facebook Survey Study with Latent Profile Analysis in Taiwan.

The present study aimed (1) to identify distinct latent classes of motivation to get vaccinated against coronavirus disease 2019 (COVID-19) and previous seasonal influenza vaccination among people in Taiwan and (2) to examine the roles of sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 in these classes. We recruited 1047 participants through a Facebook advertisement. The participants' motivation to get vaccinated against COVID-19, previous seasonal influenza vaccination, sources of information about COVID-19 vaccination, risk perception of COVID-19, and cognitive appraisals of vaccination against COVID-19 were determined. We examined the participants' motivation for COVID-19 vaccination and previous seasonal influenza vaccination through latent profile analysis. Four latent classes of motivation were identified: participants with high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those with high motivation for COVID-19 vaccination but low seasonal influenza vaccination, those with low motivation for COVID-19 vaccination but high seasonal influenza vaccination, and those with low motivation for COVID-19 vaccination and low seasonal influenza vaccination. Compared with participants in the latent class of high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those in the other three latent classes had lower levels of positive appraisals of COVID-19 vaccination; participants in the latent class of low motivation for COVID-19 vaccination and low seasonal influenza vaccination had lower risk perception of COVID-19 and were also less likely to obtain information about COVID-19 vaccination from the internet, friends, and family members. The various motivations and behaviors for vaccination, sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 should be considered in intervention programs aiming to increase people's motivation to get vaccinated against COVID-19.