Limited vaccine availability and logistical barriers during the COVID-19 pandemic have hindered homologous boosting in resource-limited regions. Therefore, heterologous prime-boost regimens have gained attention as versatile and practical alternatives. We evaluated the immunogenicity and longevity of four vaccine regimens in adults from Mozambique and Madagascar: single-dose Ad26.COV2.S (Ad26.S), homologous BBIBP-CorV (BBIBP), and two heterologous combinations (BBIBP-Ad26.S and Ad26.S-BBIBP, in prime-boost order). Using systems serology, we characterized Fc-mediated antibody responses against SARS-CoV-2 wild-type and Omicron BA.1. Among all regimens, Ad26.S-BBIBP elicited broad and sustained humoral immunity for up to 6 months, with enhanced IgG levels, Fcγ receptor binding, and Fc-mediated effector functions. These responses declined more slowly than with single-Ad26.S. Compared to the other regimens, antibody-dependent natural killer cell activation (ADNKA) emerged as a distinct characteristic of durable cross-variant immunity in Ad26.S-BBIBP recipients. These findings highlight that the Ad26.S-BBIBP regimen is immunologically advantageous, with Fc-mediated effector functions, particularly ADNKA, representing an important characteristic of its relatively durable and cross-strain protection even as neutralizing antibody titers decline.

During the 2015/16 Zika virus (ZIKV) epidemic, ZIKV associated neurological diseases were reported in adults, including microcephaly, Guillain-Barre syndrome, myelitis, meningoencephalitis, and fatal encephalitis. However, the mechanisms underlying the neuropathogenesis of ZIKV infection are not yet fully understood. In this study, we used an adult ZIKV-infection mouse model ( Ifnar1 −/−) to investigate the mechanisms underlying neuroinflammation and neuropathogenesis. ZIKV infection induced the expression of proinflammatory cytokines, including IL-1β, IL-6, IFN-γ, and TNF-α, in the brains of Ifnar1 −/− mice. RNA-seq analysis of the infected mouse brain also revealed that genes involved in innate immune responses and cytokine-mediated signaling pathways were significantly upregulated at 6 days post infection. Furthermore, ZIKV infection induced macrophage infiltration and activation, and augmented IL-1β expression, whereas microgliosis was not observed in the brain. Using human monocyte THP-1 cells, we confirmed that ZIKV infection promotes inflammatory cell death and increases IL-1β secretion. In addition, the expression of complement component C3, which is associated with neurodegenerative diseases and known to be upregulated by proinflammatory cytokines, was induced by ZIKV infection through the IL-1β-mediated pathway. An increase in C5a produced by complement activation in the brains of ZIKV-infected mice was also confirmed. Taken together, our results suggest that ZIKV infection of the brain in this animal model augments IL-1β expression in infiltrating macrophages and elicits IL-1β-mediated inflammation, which can lead to the destructive consequences of neuroinflammation.Importance Zika virus (ZIKV) associated neurological impairments are an important global health problem. Our results suggest that ZIKV infection of the mouse brain can induce IL-1β-mediated inflammation and complement activation, contributing to the development of neurological disorders. Thus, our findings reveal a mechanism by which ZIKV induces neuroinflammation in the mouse brain. Although we used adult type I IFN receptor IFNAR knockout ( Ifnar1 −/−) mice owing to the limited mouse model of ZIKV pathogenesis, our conclusion could contribute to understanding ZIKV associated neurological diseases to develop treatment strategies based on these findings for the patients with ZIKV infection.

Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes various neurological symptoms in coronavirus disease 2019 (COVID-19) patients. The most dominant immune cells in the brain are microglia. Yet, the relationship between neurological manifestations, neuroinflammation, and host immune response of microglia to SARS-CoV-2 has not been well characterized. Here, we report that SARS-CoV-2 can directly infect human microglia, eliciting M1-like pro-inflammatory responses, followed by cytopathic effects. Specifically, SARS-CoV-2 infected human microglial clone 3 (HMC3), leading to inflammatory activation and cell death. RNA-seq analysis also revealed that ER stress and immune responses were induced in the early and apoptotic processes in the late phase of viral infection. SARS-CoV-2-infected HMC3 showed the M1 phenotype and produced pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumour necrosis factor α (TNF-α), but not the anti-inflammatory cytokine IL-10. After this pro-inflammatory activation, SARS-CoV-2 infection promoted both intrinsic and extrinsic death receptor-mediated apoptosis in HMC3. Using K18-hACE2 transgenic mice, murine microglia were also infected by intranasal inoculation of SARS-CoV-2. This infection induced the acute production of pro-inflammatory microglial IL-6 and TNF-α and provoked a chronic loss of microglia. Our findings suggest that microglia are potential mediators of SARS-CoV-2-induced neurological problems and, consequently, can be targets of therapeutic strategies against neurological diseases in COVID-19 patients.IMPORTANCE Recent studies reported neurological manifestations and complications in COVID-19 patients, which are associated with neuroinflammation. As microglia are the dominant immune cells in brains, it needs to be elucidate the relationship between neuroinflammation and host immune response of microglia to SARS-CoV-2. Here, we suggest that SARS-CoV-2 can directly infect human microglia with cytopathic effect (CPE) using human microglial clone 3 (HMC3). The infected microglia were promoted to pro-inflammatory activation following apoptotic cell death. This pro-inflammatory activation was accompanied by the high production of pro-inflammatory cytokines, and led to neurotoxic-M1 phenotype polarization. In vivo , murine microglia were infected and produced pro-inflammatory cytokines and provoked a chronic loss using K18-hACE2 mice. Thus, our data present that SARS-CoV-2-infected microglia are potential mediators of neurological problems in COVID-19 patients. In addition, HMC3 cells are susceptible to SARS-CoV-2 and exhibit the CPE, which can be further used to investigate cellular and molecular mechanisms of neuroinflammation reported in COVID-19 patients.

A highly sensitive amperometric galactose biosensor was developed by encapsulating galactose oxidase within the graphene-doped sol-gel titania-Nafion composite film on platinized glassy carbon electrode. Due to the combined electrocatalytic activity of graphene and Pt NPs on the electrode towards hydrogen peroxide as well as the mesoporous nature of the titania-Nafion composite, the present galactose biosensor exhibited relatively fast response time under 2 s, high sensitivity of 40.6 mAM(-1)cm(-2), and wide dynamic range over three orders of magnitude with a detection limit of 3.78x10(-6) M (S/N=3). In addition, the biocompatible composite in the biosensor secures excellent long-term stability.

COVID-19, caused by a novel coronavirus, SARS-CoV-2, poses a serious global threat.It was first reported in 2019 in China and has now dramatically spread across the world.It is crucial to develop therapeutics to mitigate severe disease and viral spread.The receptor-binding domains (RBDs) in the spike protein of SARS-CoV and MERS-CoV have shown anti-viral activity in previous reports suggesting that this domain has high potential for development as therapeutics.To evaluate the potential antiviral activity of recombinant SARS-CoV-2 RBD proteins, we determined the RBD residues of SARS-CoV-2 using a homology search with RBD of SARS-CoV.For efficient expression and purification, the signal peptide of spike protein was identified and used to generate constructs expressing recombinant RBD proteins.Highly purified RBD protein fused with the Fc domain of human IgG showed potent anti-viral efficacy, which was better than that of a protein fused with a histidine tag.Intranasally pre-administrated RBD protein also inhibited the attachment of SARS-COV-2 to mouse lungs.These findings indicate that RBD protein could be used for the prevention and treatment of SARS-CoV-2 infection.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.

The catalytic upgrading pyrolysis of pine sawdust was performed at 500 °C with various metal oxides to improve the quality of the bio-oil. The aim of this study was to investigate the potential of the metal oxides instead of traditional zeolites for catalytic upgrading pyrolysis with the analysis of Gas Chromatograph/Mass Spectrometer. In this study, the used catalysts were Calcium-oxide, Magnesium oxide, Titanium dioxide, and Zeolite (Si/Al = 80). The influence of catalysts on products yields and compositions were investigated. Most metal oxides can enhance the bio-gas with the bio-oil yields decreased. The metal oxides led to a decrease of Acids, Aldehydes, Ketones and an increase of Furfural, Cresols, Catechols in Furans and Phenolics. Among the catalysts, the MgO catalysts was the most effective to convert the high molecular into lights ones (6.65% Cresols) with yield of 20.48% for Furfural. The deoxygenation reaction in bio-oil was suggested to convert oxygenated compounds into the low molecular weight of the materials (6.39% Guaiacols). Thus, the used metal oxides can improve the quality of bio-oil by decreasing undesirable compounds as well as increasing the desirable compounds with low oxygen contents via deoxygenation reaction.

The Th2 locus control region (LCR) has been shown to be important in efficient and coordinated cytokine gene regulation during Th2 cell differentiation. However, the molecular mechanism for this is poorly understood. To study the molecular mechanism of the Th2 LCR, we searched for proteins binding to it. We discovered that transcription factor YY1 bound to the LCR and the entire Th2 cytokine locus in a Th2-specific manner. Retroviral overexpression of YY1 induced Th2 cytokine expression. CD4-specific knockdown of YY1 in mice caused marked reduction in Th2 cytokine expression, repressed chromatin remodeling, decreased intrachromosomal interactions, and resistance in an animal model of asthma. YY1 physically associated with GATA-binding protein-3 (GATA3) and is required for GATA3 binding to the locus. YY1 bound to the regulatory elements in the locus before GATA3 binding. Thus, YY1 cooperates with GATA3 and is required for regulation of the Th2 cytokine locus and Th2 cell differentiation.

It has been shown that acute and chronic alcohol administrations increase the production of reactive oxygen species, lower cellular antioxidant levels and enhance oxidative stress in many tissues. We recently reported that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) functions as an antioxidant enzyme by supplying NADPH to the cytosol. Upon exposure to ethanol, IDPc was susceptible to the loss of its enzyme activity in HepG2 cells. Transfection of HepG2 cells with an IDPc small interfering RNA noticeably downregulated IDPc and enhanced the cells' vulnerability to ethanol-induced cytotoxicity. Our results suggest that suppressing the expression of IDPc enhances ethanol-induced toxicity in HepG2 cells by further disruption of the cellular redox status.

SummaryGATA‐binding protein‐3 (GATA‐3) regulates the T helper type 2 (Th2) cytokine locus through induction of chromatin remodelling. However, the molecular mechanism for this is poorly understood. To understand this mechanism better, we screened GATA‐3 interacting proteins using affinity purification and mass spectrometry. We found that GATA‐3 bound to metastasis‐associated protein 2 (MTA‐2), a component of the NuRD chromatin remodelling complex. GATA‐3 and MTA‐2 in turn bound to several regulatory regions of the Th2 cytokine locus and the ifng promoter. Cell transfection assay showed that MTA‐2 acted as an antagonist with GATA‐3 in the expression of Th2 cytokines, but co‐operated with GATA‐3 in the repression of the ifng gene expression. These results suggest that GATA‐3 interacts with MTA‐2 to co‐ordinately regulate Th2 cytokine and ifng loci during T helper cell differentiation.

Highly efficient production of monoglycerides was achieved from lipase-catalyzcd oil hydrolysis by the continuous addition of CaCl2 to remove the fatty acids produced. A fusion protein produced by connecting a cellulose-binding domain of Trichoderma hazianum cellulase to Bacillus stearothermophilus L1 lipase was used as a model 1,3-regiospecific lipase. The reaction was performed at pH 10 and 50 degrees C, and the relationship between continuous removal of fatty acids and the production of monoglyceride was investigated by microscopic and HPLC analysis of oil emulsions and the reaction products. Without the addition of Ca2+ the reaction was inhibited by fatty acids, with the decrease in reaction rate being proportional to the concentration of fatty acids. When CaCl2 was continuously added in a 1:2 molar ratio with the released fatty acids, the reaction progressed unimpeded due to the formation of Ca-soaps. Both the yield and the fraction of monoglyceride in the reaction product increased due to the continuous removal of fatty acids.

Myeloperoxidase catalyzes the formation of hypochlorous acid (HOCI) via reaction of H 2 O 2 with CI − ions. Although HOCI plays a major role in the human immune system by killing bacteria and other invading pathogens, excessive generation of this oxidant causes damage to tissues. Exposure of HeLa cells to HOCI decreased viability, inactivated antioxidant enzymes, damaged mitochondria, and modulated cellular redox status. HOCI also induced significant increases in cellular oxidative damage reflected by lipid peroxidation, protein oxidation, and DNA damage. HOCI-mediated oxidative damage to HeLa cells may perturb the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant state.

Myeoloperoxidase catalyses the formation of hypochlorous acid (HOCl) via reaction of H2O2 with Cl− ion. Although HOCl is known to play a major role in the human immune system by killing bacteria and other invading pathogens, excessive generation of this oxidant is known to cause damage to tissue. Recently, it was demonstrated that the control of mitochondrial redox balance and oxidative damage is one of the primary functions of mitochondrial NADP+-dependent isocitrate dehydrogenase (IDPm) to supply NADPH for antioxidant systems. This study investigated whether the IDPm would be a vulnerable target of HOCl as a purified enzyme and in intact cells. Loss of enzyme activity was observed and the inactivation of IDPm was reversed by thiols. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly enhanced HOCl-induced oxidative damage to cells. The HOCl-mediated damage to IDPm may result in the perturbation of the cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

The relationship between the kinetics of the lipase-catalyzed oil hydrolysis and the surface area distribution of oil droplets was investigated using ethyl decanoate and gum Arabic (GA) as a model oil and an emulsifier, respectively. Along an ethyl decanoate concentration gradient between 2 and 8 mM, the initial hydrolysis rate increased at 0.25% (w/v) GA but did not change at 1.0% (w/v) GA. At 0.25% GA, the surface area of droplets was narrowly distributed regardless of the ethyl decanoate concentration. However, at 1.0% GA and with ethyl decanoate concentrations higher than 2 mM, the fraction of relatively large droplets with a surface area larger than approximately 200 μm2, suddenly increased. The microscopy of ethyl decanoate emulsion during the hydrolysis reaction indicates that the large oil droplets were not hydrolyzed. At 20 mM ethyl decanoate where the hydrolysis rate remained the same between 0.25% and 1.0% GA, the surface area of droplets was narrowly distributed at 0.25% and 1.0% GA. Therefore, the constant hydrolysis rate observed in the emulsion of ethyl decanoate between 2 and 8 mM containing GA at 1.0%, is believed to be caused by the relatively large oil droplets with the interface quality differing from that of the small oil droplets.

In this research, the results of the photocatalytic coagulation of humic acids (HAs) in aqueous solution were investigated, and the effect of the photocatalytic coagulation on the fouling of nanofiltration (NF) membrane was investigated. Nanoparticles of copper-doped titania were synthesized by a sol-gel method using titanium isopropoxide and cuperous chloride. The behavior of a thin-film composite NF membrane was investigated as a function of solution chemistry (ionic composition and strength and calcium and organic concentration). In the membrane fouling test, calcium bridges between the natural organic matter (NOM) and the membrane led to severe flux decline because of the development of densely compacted fouling layer on the membrane surface. The photocatalytic coagulation was applied to remove humic acids prior to membrane filtration. In the photocatalytic coagulation, the UV absorbance, chemical oxygen demand (COD), and cations decreased by 99%, 90%, and 10%, respectively, while anions and conductivity increased to 39% and 79%. The results emphasized that the photocatalytic coagulation could be an effective alternative solution for the elimination of the humic acids and for the prevention of the membrane fouling.

The Arabidopsis thaliana secretome was analyzed by the proteomic approach, which led to the identification of secreted proteins implicated in many aspects of cell biology. We then investigated the change in the Arabidopsis secretome in response to salicylic acid and identified several proteins involved in pathogen response. One of these, a secreted lipase with a GDSL-like motif designated GDSL LIPASE1 (GLIP1), was further characterized for its function in disease resistance. glip1 plants were markedly more susceptible to infection by the necrotrophic fungus Alternaria brassicicola compared with the parental wild-type plants. The recombinant GLIP1 protein possessed lipase and antimicrobial activities that directly disrupt fungal spore integrity. Furthermore, GLIP1 appeared to trigger systemic resistance signaling in plants when challenged with A. brassicicola, because pretreatment of the glip1 mutant with recombinant GLIP1 protein inhibited A. brassicicola-induced cell death in both peripheral and distal leaves. Moreover, glip1 showed altered expression of defense- and ethylene-related genes. GLIP1 transcription was increased by ethephon, the ethylene releaser, but not by salicylic acid or jasmonic acid. These results suggest that GLIP1, in association with ethylene signaling, may be a critical component in plant resistance to A. brassicicola.

The Arabidopsis thaliana secretome was analyzed by the proteomic approach, which led to the identification of secreted proteins implicated in many aspects of cell biology. We then investigated the change in the Arabidopsis secretome in response to salicylic acid and identified several proteins involved in pathogen response. One of these, a secreted lipase with a GDSL-like motif designated GDSL LIPASE1 (GLIP1), was further characterized for its function in disease resistance. glip1 plants were markedly more susceptible to infection by the necrotrophic fungus Alternaria brassicicola compared with the parental wild-type plants. The recombinant GLIP1 protein possessed lipase and antimicrobial activities that directly disrupt fungal spore integrity. Furthermore, GLIP1 appeared to trigger systemic resistance signaling in plants when challenged with A. brassicicola, because pretreatment of the glip1 mutant with recombinant GLIP1 protein inhibited A. brassicicola–induced cell death in both peripheral and distal leaves. Moreover, glip1 showed altered expression of defense- and ethylene-related genes. GLIP1 transcription was increased by ethephon, the ethylene releaser, but not by salicylic acid or jasmonic acid. These results suggest that GLIP1, in association with ethylene signaling, may be a critical component in plant resistance to A. brassicicola.

In this paper, we examined the characteristics of tactual motion while evaluating the hand of fabrics. So we made the experimental glove type measurement system with accelerator sensor. The acceleration of finger motion in evaluating the hand of fabric such as resilience, roughness, flexibility and softness was measured. Subjects who consisted of experts and non-experts wore this measurement system on their right hand and with their eyes closed, and evaluated a piece of non woven fabric. As the result, human had the phase of finger movement to evaluate the hand. And they had different characteristics of finger movement according to the purpose of hand evaluation. Especially, it was found that the linear finger movement was the important factor to improve the discrimination ability in evaluating the hand of fabric.

NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP+-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor γ were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.