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19 pages, 2086 KiB  
Review
Ionizing Radiation Crosslinked Chitosan-Based Hydrogels for Environmental Remediation
by Muhammad Asim Raza
Gels 2025, 11(7), 492; https://doi.org/10.3390/gels11070492 - 25 Jun 2025
Viewed by 458
Abstract
Since water contamination has become a serious concern, more effective environmental remediation methods are required. Chitosan (CHT)-based adsorbents have demonstrated high efficacy in removing pollutants due to their unique chemical and structural properties. However, their utilization remains limited by low environmental stability and [...] Read more.
Since water contamination has become a serious concern, more effective environmental remediation methods are required. Chitosan (CHT)-based adsorbents have demonstrated high efficacy in removing pollutants due to their unique chemical and structural properties. However, their utilization remains limited by low environmental stability and the absence of effective adsorption sites. The functional moieties of CHT can be altered to improve its performance via graft modification and crosslinking. Compared to conventional hydrogel synthesis techniques, ionizing radiation-induced fabrication, using gamma or electron-beam irradiation, offers a promising platform for innovation across diverse fields. The prime focus of this review is on ionizing radiation developed CHT-based hydrogels to remove toxic heavy metals, dyes, organic contaminants, radionuclides, and humic substances. The fabrication strategy, adsorption mechanism, and factors affecting the adsorption capacity of CHT-based hydrogels are presented. This review aims to underscore the transformative potential of ionizing radiation-induced CHT hydrogels in environmental remediation by examining current research trends and identifying future prospects. Full article
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12 pages, 3795 KiB  
Article
Microstructural Investigation of Stress-Induced Degradation of Gamma and Gamma Prime Phases on the Surface of the Aerofoil of Nickel-Based Single Crystal Superalloy Turbine Blades
by KeeHyun Park, Jonathan Davies and Paul Withey
Crystals 2025, 15(6), 553; https://doi.org/10.3390/cryst15060553 - 10 Jun 2025
Viewed by 802
Abstract
Nickel-based single-crystal superalloy turbine blades are typically manufactured via investment casting followed by a well-established heat treatment process, resulting in a uniform microstructure composed of thin γ channels and cubic-shaped γ’. However, the region near the corner of the aerofoil/platform of the blade [...] Read more.
Nickel-based single-crystal superalloy turbine blades are typically manufactured via investment casting followed by a well-established heat treatment process, resulting in a uniform microstructure composed of thin γ channels and cubic-shaped γ’. However, the region near the corner of the aerofoil/platform of the blade exhibits a distinct contrast compared to the surrounding area. High-resolution scanning electron microscopy (SEM) reveals significant degradation of the γ and γ’ phases in the dark contrast region. In this area, the γ’ phase no longer maintains its characteristic cubic morphology and appears partially dissolved or even melted. Although the regularity of the γ/γ’ microstructure is disrupted, the region is still composed of irregular-shaped γ and γ’ phases. Based on these microstructural observations, a possible formation mechanism of the abnormal microstructure is discussed. Although the blades are not exposed to conventional creep conditions during casting and heat treatment, residual stress accumulated during casting may be relieved at elevated temperatures during the heat treatment process. The synergistic effect of stress, temperature, and time may contribute to the formation of the observed abnormal microstructure. Full article
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19 pages, 827 KiB  
Review
Omicron Variant Could Be an Antigenic Shift of SARS-CoV-2
by Anju Kaushal
COVID 2025, 5(5), 73; https://doi.org/10.3390/covid5050073 - 14 May 2025
Viewed by 1023
Abstract
In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and [...] Read more.
In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and Delta. The requisition of prime boosting was essential within 3–6 months to improve the Nab response that had been not lasted for longer. Omicron subvariant BA.1.1 was less transmissible, but with an extra nine mutations in next variant BA.2 made it more transmissible. This remarkable heterogeneity was reported in ORF1ab or TRS sites, ORF7a, and 10 regions in the genomic sequences of Omicron BA.2 and its evolving subvariants BA.4.6, BF.7, BQ.2, BF. 7, BA.2.75.2, and BA.5 (BQ.1 and BQ.1.1). The mutational stability of subvariants XBB, XBB 1, XBB 1.5, and XBB 1.6 conferred a similar affinity towards ACE-2. This phenomenon has been reported in breakthrough infections and after booster vaccinations producing hybrid immunity. The reduced pathogenic nature of Omicron has implicated its adaptation either through immunocompromised individuals or other animal hosts. The binding capacity of RBD and ACE-2, including the proteolytic priming via TMPRSS2, reveals its (in-vitro) transmissibility behavior. RBD mutations signify transmissibility, S1/S2 enhances virulence, while S2 infers the effective immunogenic response. Initial mutations D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H, and G496S were found to increase the Ab escape. Some mutations such as, R346K, L452R, and F486Vwere seen delivering immune pressure. HR2 region (S2) displayed mutations R436S, K444T, F486S, and D1199N with altered spike positions. Later on, the booster dose or breakthrough infections contributed to elevating the immune profile. Several other mutations in BA.1.1-N460K, R346T, K444T, and BA.2.75.2-F486S have also conferred the neutralization resistance. The least studied T-cell response in SARS-CoV-2 affects HLA- TCR interactions, thus, it plays a role in limiting the virus clearance. Antigenic cartographic analysis has also shown Omicron’s drift from its predecessor variants. The rapidly evolving SARS-CoV-2 variants and subvariants have driven the population-based immunity escape in fully immunized individuals within short period. This could be an indication that Omicron is heading towards endemicity and may evolve in future with subvariants could lead to outbreaks, which requires regular surveillance. Full article
(This article belongs to the Section Human or Animal Coronaviruses)
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14 pages, 2998 KiB  
Article
In Vitro Immunomodulatory Effects of Equine Adipose Tissue-Derived Mesenchymal Stem Cells Primed with a Cannabidiol-Rich Extract
by Lorena Battistin, Luís Felipe Arantes Moya, Lucas Vinícius de Oliveira Ferreira, Aline Márcia Marques Braz, Márcio de Carvalho, Marjorie de Assis Golim and Rogério Martins Amorim
Int. J. Mol. Sci. 2025, 26(9), 4208; https://doi.org/10.3390/ijms26094208 - 29 Apr 2025
Viewed by 512
Abstract
Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may [...] Read more.
Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2–P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis. These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies. Full article
(This article belongs to the Special Issue Biomedical Applications of Mesenchymal Stem Cells)
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14 pages, 3636 KiB  
Article
Regulation of Colonic Inflammation and Macrophage Homeostasis of IFN-γ-Primed Canine AMSCs in Experimental Colitis in Mice
by Chan-Hee Jo, Sang-Yun Lee, Young-Bum Son, Won-Jae Lee, Yong-Ho Choe, Hyeon-Jeong Lee, Seong-Ju Oh, Tae-Seok Kim, Chae-Yeon Hong, Sung-Lim Lee and Gyu-Jin Rho
Animals 2024, 14(22), 3283; https://doi.org/10.3390/ani14223283 - 14 Nov 2024
Viewed by 1636
Abstract
Mesenchymal stem cells (MSCs) have shown potential in treating immune-mediated diseases due to their immunomodulatory properties, which can be enhanced by priming with inflammatory cytokines like interferon-gamma (IFN-γ). This study evaluates the therapeutic effects of IFN-γ-primed canine adipose tissue-derived MSCs (AMSCs) in a [...] Read more.
Mesenchymal stem cells (MSCs) have shown potential in treating immune-mediated diseases due to their immunomodulatory properties, which can be enhanced by priming with inflammatory cytokines like interferon-gamma (IFN-γ). This study evaluates the therapeutic effects of IFN-γ-primed canine adipose tissue-derived MSCs (AMSCs) in a mouse model of inflammatory bowel disease (IBD). Canine AMSCs were primed with 50 ng/mL recombinant canine IFN-γ for 48 h, and the effects were compared to those seen in naïve (unprimed) AMSCs. IBD was induced in mice using dextran sodium sulfate (DSS), and AMSCs were injected intraperitoneally on days 1 and 3. The mice treated with IFN-γ-primed AMSCs showed improved clinical outcomes, including a reduced disease activity index (DAI), less body weight loss, and longer colon length compared to the mice treated with naïve AMSCs. A histological analysis revealed less damage to the intestinal structures and reduced inflammatory cell infiltration. IFN-γ priming led to a shift in the immune cell balance in the gut, decreasing pro-inflammatory macrophages (Ly6Chi) and increasing anti-inflammatory macrophages (Ly6Clo/MHC-IIhi). This was associated with the reduced expression of inflammatory cytokine genes (Il-1β, Il-6, and Il-18) and increased expression of the intestinal stem cell marker Lgr5. These findings suggest that IFN-γ-primed AMSCs offer enhanced therapeutic potential for treating CE in veterinary medicine. Full article
(This article belongs to the Section Veterinary Clinical Studies)
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17 pages, 892 KiB  
Article
Bivariate Pareto–Feller Distribution Based on Appell Hypergeometric Function
by Christian Caamaño-Carrillo, Moreno Bevilacqua, Michael Zamudio-Monserratt and Javier E. Contreras-Reyes
Axioms 2024, 13(10), 701; https://doi.org/10.3390/axioms13100701 - 9 Oct 2024
Cited by 1 | Viewed by 1153
Abstract
The Pareto–Feller distribution has been widely used across various disciplines to model “heavy-tailed” phenomena, where extreme events such as high incomes or large losses are of interest. In this paper, we present a new bivariate distribution based on the Appell hypergeometric function with [...] Read more.
The Pareto–Feller distribution has been widely used across various disciplines to model “heavy-tailed” phenomena, where extreme events such as high incomes or large losses are of interest. In this paper, we present a new bivariate distribution based on the Appell hypergeometric function with marginal Pareto–Feller distributions obtained from two independent gamma random variables. The proposed distribution has the beta prime marginal distributions as special case, which were obtained using a Kibble-type bivariate gamma distribution, and the stochastic representation was obtained by the quotient of a scale mixture of two gamma random variables. This result can be viewed as a generalization of the standard bivariate beta I (or inverted bivariate beta distribution). Moreover, the obtained bivariate density is based on two confluent hypergeometric functions. Then, we derive the probability distribution function, the cumulative distribution function, the moment-generating function, the characteristic function, the approximated differential entropy, and the approximated mutual information index. Based on numerical examples, the exact and approximated expressions are shown. Full article
(This article belongs to the Special Issue Advances in Statistical Simulation and Computing)
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23 pages, 4233 KiB  
Article
Characterization of the Immune-Modulating Properties of Different β-Glucans on Myeloid Dendritic Cells
by Hannah Rainer, Alexandra Goretzki, Yen-Ju Lin, Hannah Ruth Schiller, Maren Krause, Sascha Döring, Daniel Strecker, Ann-Christine Junker, Sonja Wolfheimer, Masako Toda, Stephan Scheurer and Stefan Schülke
Int. J. Mol. Sci. 2024, 25(18), 9914; https://doi.org/10.3390/ijms25189914 - 13 Sep 2024
Cited by 4 | Viewed by 2149
Abstract
In allergen-specific immunotherapy, adjuvants are explored for modulating allergen-specific Th2 immune responses to re-establish clinical tolerance. One promising class of adjuvants are β-glucans, which are naturally derived sugar structures and components of dietary fibers that activate C-type lectin (CLR)-, “Toll”-like receptors (TLRs), and [...] Read more.
In allergen-specific immunotherapy, adjuvants are explored for modulating allergen-specific Th2 immune responses to re-establish clinical tolerance. One promising class of adjuvants are β-glucans, which are naturally derived sugar structures and components of dietary fibers that activate C-type lectin (CLR)-, “Toll”-like receptors (TLRs), and complement receptors (CRs). We characterized the immune-modulating properties of six commercially available β-glucans, using immunological (receptor activation, cytokine secretion, and T cell modulating potential) as well as metabolic parameters (metabolic state) in mouse bone marrow-derived myeloid dendritic cells (mDCs). All tested β-glucans activated the CLR Dectin-1a, whereas TLR2 was predominantly activated by Zymosan. Further, the tested β-glucans differentially induced mDC-derived cytokine secretion and activation of mDC metabolism. Subsequent analyses focusing on Zymosan, Zymosan depleted, β-1,3 glucan, and β-1,3 1,6 glucan revealed robust mDC activation with the upregulation of the cluster of differentiation 40 (CD40), CD80, CD86, and MHCII to different extents. β-glucan-induced cytokine secretion was shown to be, in part, dependent on the activation of the intracellular Dectin-1 adapter molecule Syk. In co-cultures of mDCs with Th2-biased CD4+ T cells isolated from birch allergen Bet v 1 plus aluminum hydroxide (Alum)-sensitized mice, these four β-glucans suppressed allergen-induced IL-5 secretion, while only Zymosan and β-1,3 glucan significantly suppressed allergen-induced interferon gamma (IFNγ) secretion, suggesting the tested β-glucans to have distinct effects on mDC T cell priming capacity. Our experiments indicate that β-glucans have distinct immune-modulating properties, making them interesting adjuvants for future allergy treatment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Allergy and Asthma: 3rd Edition)
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17 pages, 4472 KiB  
Article
The Human Neonatal Skin Fibroblast, an Available Cell Source for Tissue Production and Transplantation, Exhibits Low Risk of Immunogenicity In Vitro
by Brice Magne, Karel Ferland, Étienne Savard, Martin A. Barbier, Amélie Morissette, Danielle Larouche, Chanel Beaudoin-Cloutier and Lucie Germain
Int. J. Mol. Sci. 2024, 25(13), 6965; https://doi.org/10.3390/ijms25136965 - 26 Jun 2024
Viewed by 2168
Abstract
The immunogenicity of allogeneic skin fibroblasts in transplantation has been controversial. Whether this controversy comes from a natural heterogeneity among fibroblast subsets or species-specific differences between human and mouse remains to be addressed. In this study, we sought to investigate whether fibroblasts derived [...] Read more.
The immunogenicity of allogeneic skin fibroblasts in transplantation has been controversial. Whether this controversy comes from a natural heterogeneity among fibroblast subsets or species-specific differences between human and mouse remains to be addressed. In this study, we sought to investigate whether fibroblasts derived from either adult or neonatal human skin tissues could induce different immune responses toward phagocytosis and T cell activation using in vitro co-culture models. Our results indicate that both phagocytosis and T cell proliferation are reduced in the presence of neonatal skin fibroblasts compared to adult skin fibroblasts. We also show that neonatal skin fibroblasts secrete paracrine factors that are responsible for reduced T cell proliferation. In addition, we show that neonatal skin fibroblasts express less class II human leukocyte antigen (HLA) molecules than adult skin fibroblasts after interferon gamma priming, which might also contribute to reduced T cell proliferation. In conclusion, this study supports the use of allogeneic neonatal skin fibroblasts as a readily available cell source for tissue production and transplantation to treat patients with severe injuries. Full article
(This article belongs to the Section Biochemistry)
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18 pages, 1566 KiB  
Article
Effects of Seed Priming with Gamma Radiation on Growth, Photosynthetic Functionality, and Essential Oil and Phytochemical Contents of Savory Plants
by Vahideh Mohammadi, Mahboobeh Zare Mehrjerdi, Anshu Rastogi, Nazim S. Gruda and Sasan Aliniaeifard
Horticulturae 2024, 10(7), 677; https://doi.org/10.3390/horticulturae10070677 - 26 Jun 2024
Cited by 5 | Viewed by 3021
Abstract
Gamma radiation has been suggested to have post-effects on emerging plants when applied to the seeds. In the present study, we aimed to induce alterations in photosynthetic functionality and subsequent modifications in secondary metabolites of summer savory following seed priming with gamma radiation. [...] Read more.
Gamma radiation has been suggested to have post-effects on emerging plants when applied to the seeds. In the present study, we aimed to induce alterations in photosynthetic functionality and subsequent modifications in secondary metabolites of summer savory following seed priming with gamma radiation. Savory seeds were treated with 0, 50, 100, 200, and 300 Gy gamma radiation in a completely randomized design with ten replications for morphological and photosynthetic parameters and three for phytochemical assessments. The results showed that gamma radiation on seeds adversely affected photosynthetic performance, especially at the highest doses. It negatively influenced the growth, while increasing the shoot branching, the number of nodes, and the diameter of the stem. Gamma radiation on seeds generally reduced pigmentation in savory leaves, such as chlorophylls, carotenoids, and anthocyanins. However, soluble sugar, starch, total phenolics, and total flavonoid contents were elevated in the leaves of plants that emerged from gamma-primed seeds. Gamma radiation priming reduced essential oil’s percentage and yield. Carvacrol and limonene components of essential oil were diminished, whereas linalool and thymol were increased. In conclusion, due to its inherent stress-inducing effects, and despite some positive effects on phytochemicals, seed priming with gamma radiation adversely influenced growth, photosynthesis, and quantity and quality of savory essential oils. Further research is still needed to target the use of gamma radiations before harvesting the seeds or determine the cytogenetic characteristics of irradiated plants. Full article
(This article belongs to the Special Issue Medicinal Herbs: Latest Advances and Prospects)
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38 pages, 2653 KiB  
Review
Therapeutic Efficacy of Interferon-Gamma and Hypoxia-Primed Mesenchymal Stromal Cells and Their Extracellular Vesicles: Underlying Mechanisms and Potentials in Clinical Translation
by Yu Ling Tan, Maimonah Eissa Al-Masawa, Sue Ping Eng, Mohamad Nasir Shafiee, Jia Xian Law and Min Hwei Ng
Biomedicines 2024, 12(6), 1369; https://doi.org/10.3390/biomedicines12061369 - 20 Jun 2024
Cited by 8 | Viewed by 3694
Abstract
Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, along with immunomodulatory properties and trophic factor secretion. Extracellular vesicles (EVs) from MSCs offer similar therapeutic effects. However, MSCs are heterogeneous and lead [...] Read more.
Multipotent mesenchymal stromal cells (MSCs) hold promises for cell therapy and tissue engineering due to their self-renewal and differentiation abilities, along with immunomodulatory properties and trophic factor secretion. Extracellular vesicles (EVs) from MSCs offer similar therapeutic effects. However, MSCs are heterogeneous and lead to variable outcomes. In vitro priming enhances MSC performance, improving immunomodulation, angiogenesis, proliferation, and tissue regeneration. Various stimuli, such as cytokines, growth factors, and oxygen tension, can prime MSCs. Two classical priming methods, interferon-gamma (IFN-γ) and hypoxia, enhance MSC immunomodulation, although standardized protocols are lacking. This review discusses priming protocols, highlighting the most commonly used concentrations and durations, along with mechanisms and in vivo therapeutics effects of primed MSCs and their EVs. The feasibility of up-scaling their production was also discussed. The review concluded that priming with IFN-γ or hypoxia (alone or in combination with other factors) boosted the immunomodulation capability of MSCs and their EVs, primarily via the JAK/STAT and PI3K/AKT and Leptin/JAK/STAT and TGF-β/Smad signalling pathways, respectively. Incorporating priming in MSC and EV production enables translation into cell-based or cell-free therapies for various disorders. Full article
(This article belongs to the Section Gene and Cell Therapy)
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17 pages, 4899 KiB  
Article
Seed Priming with Poly-Gamma-Glutamic Acid (γ-PGA) Improves Rice Germination Performance under Drought Conditions
by Conrado Dueñas, Cinzia Calvio, Inez Hortense Slamet-Loedin, Untung Susanto and Anca Macovei
Agriculture 2024, 14(6), 926; https://doi.org/10.3390/agriculture14060926 - 12 Jun 2024
Cited by 3 | Viewed by 2161
Abstract
Drought poses a significant threat to global food security, particularly impacting rice cultivation during the germination stage. In this study, a soil-based system that utilizes soil moisture content was used to simulate optimal and stress conditions to assess the effect of the specific [...] Read more.
Drought poses a significant threat to global food security, particularly impacting rice cultivation during the germination stage. In this study, a soil-based system that utilizes soil moisture content was used to simulate optimal and stress conditions to assess the effect of the specific seed priming protocols on germination. Eleven rice varieties, representative of indica and japonica subspecies, grown in different ecosystems and having diverse nutrient contents, were treated with water or solutions of either poly-gamma-glutamic acid (γ-PGA) or denatured γ-PGA. Collected data regarding germinability and stress indices revealed different drought sensitivity between japonica and indica subspecies and genotype-specific responses to priming. Particularly, γ-PGA improved germination of highly susceptible indica varieties whereas water soaking was more effective for the moderately sensitive japonica varieties. Integrative analyses evidenced differences between biofortified and non-biofortified rice under γ-PGA treatment, suggesting a possible correlation between γ-PGA efficacy and Zn/Fe seed content. These findings underline that priming strategies should be tailored based on genotype and therefore this factor should be always taken under consideration for future works. The current study provides relevant information for optimizing seed priming techniques to sustain the development of drought-resilient crops as a sustainable strategy to address agricultural resilience and safeguard food security amidst environmental challenges. Full article
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23 pages, 881 KiB  
Review
Emerging Trends in Non-Protein Amino Acids as Potential Priming Agents: Implications for Stress Management Strategies and Unveiling Their Regulatory Functions
by Kincső Decsi, Mostafa Ahmed, Roquia Rizk, Donia Abdul-Hamid, Gergő Péter Kovács and Zoltán Tóth
Int. J. Mol. Sci. 2024, 25(11), 6203; https://doi.org/10.3390/ijms25116203 - 4 Jun 2024
Cited by 4 | Viewed by 2598
Abstract
Plants endure the repercussions of environmental stress. As the advancement of global climate change continues, it is increasingly crucial to protect against abiotic and biotic stress effects. Some naturally occurring plant compounds can be used effectively to protect the plants. By externally applying [...] Read more.
Plants endure the repercussions of environmental stress. As the advancement of global climate change continues, it is increasingly crucial to protect against abiotic and biotic stress effects. Some naturally occurring plant compounds can be used effectively to protect the plants. By externally applying priming compounds, plants can be prompted to trigger their defensive mechanisms, resulting in improved immune system effectiveness. This review article examines the possibilities of utilizing exogenous alpha-, beta-, and gamma-aminobutyric acid (AABA, BABA, and GABA), which are non-protein amino acids (NPAAs) that are produced naturally in plants during instances of stress. The article additionally presents a concise overview of the studies’ discoveries on this topic, assesses the particular fields in which they might be implemented, and proposes new avenues for future investigation. Full article
(This article belongs to the Section Molecular Plant Sciences)
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12 pages, 2330 KiB  
Article
The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine
by Yuri Fujioka, Hideto Ueki, Ruhan A, Akari Sasajima, Takumi Tomono, Masami Ukawa, Haruya Yagi, Shinji Sakuma, Koichi Kitagawa and Toshiro Shirakawa
Int. J. Mol. Sci. 2024, 25(11), 5997; https://doi.org/10.3390/ijms25115997 - 30 May 2024
Cited by 5 | Viewed by 2187
Abstract
Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell [...] Read more.
Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell line to improve antigen uptake and then determined the anti-tumor effect in tumor-bearing mice. DC2.4 cells were pulsed with the cell lysate of EL4, a murine lymphoma cell line, and VP-R8 to generate the DC2.4 vaccine. For the in vivo study, DC2.4 cells pulsed with EL4 lysate and VP-R8 were subcutaneously injected into the inguinal lymph node to investigate the anti-tumor effect against EL4 and EL4-specific T cell immune responses. VP-R8 significantly improved antigen uptake into DC2.4 compared to conventional keyhole limpet hemocyanin (p < 0.05). The expression of MHC class I, MHC class II, and CD86 in DC2.4 cells significantly increased after pulsing tumor lysates with VP-R8 compared to other treatments (p < 0.05). The intra-lymph node injection of DC2.4 pulsed with both VP-R8 and EL4 lysate significantly decreased tumor growth compared to DC2.4 pulsed with KLH and lysates (p < 0.05) and induced tumor-infiltrating CD8T cells. The DC2.4 vaccine also remarkably increased the population of IFN-gamma-producing T cells and CTL activity against EL4 cells. In conclusion, we demonstrated that VP-R8 markedly enhances the efficiency of dendritic cell-based vaccines in priming robust anti-tumor immunity, suggesting its potential as a beneficial additive for dendritic cell-based immunotherapy. Full article
(This article belongs to the Special Issue Dendritic Cell and Cancer Therapy 2.0)
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12 pages, 2482 KiB  
Article
Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming
by Jaewon Park, Sungjun Kim, Ashok Kumar Jangid, Hee Won Park and Kyobum Kim
Int. J. Mol. Sci. 2024, 25(3), 1556; https://doi.org/10.3390/ijms25031556 - 26 Jan 2024
Cited by 3 | Viewed by 1544
Abstract
Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol [...] Read more.
Current cytokine-based natural killer (NK) cell priming techniques have exhibited limitations such as the deactivation of biological signaling molecules and subsequent insufficient maturation of the cell population during mass cultivation processes. In this study, we developed an amphiphilic trigonal 1,2-distearoyl-sn-glycero-3-phosphorylethanolamine (DSPE) lipid-polyethylene glycol (PEG) material to assemble NK cell clusters via multiple hydrophobic lipid insertions into cellular membranes. Our lipid conjugate-mediated ex vivo NK cell priming sufficiently augmented the structural modulation of clusters, facilitated diffusional signal exchanges, and finally activated NK cell population with the clusters. Without any inhibition in diffusional signal exchanges and intrinsic proliferative efficacy of NK cells, effectively prime NK cell clusters produced increased interferon-gamma, especially in the early culture periods. In conclusion, the present study demonstrates that our novel lipid conjugates could serve as a promising alternative for future NK cell mass production. Full article
(This article belongs to the Special Issue Recent Advances in Nanoparticles in Molecular Biology)
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18 pages, 9528 KiB  
Article
Computational and Experimental Study on Failure Mechanism of a GTD-111 First-Stage Blade of an Industrial Gas Turbine
by Roberto Guillermo Bayro-Lazcano, Saúl Piedra-Gonzalez, Angel-Iván García-Moreno, Diego German Espinosa-Arbelaez and Jhon Alexander Villada-Villalobos
Metals 2023, 13(12), 1968; https://doi.org/10.3390/met13121968 - 1 Dec 2023
Cited by 1 | Viewed by 2068
Abstract
This paper investigates the root cause of a recurring failure observed in the first-stage blades of an industrial gas turbine. The failure involves the loss of the trailing edge tip of the blades. The study employs a combination of metallographic analysis and computational [...] Read more.
This paper investigates the root cause of a recurring failure observed in the first-stage blades of an industrial gas turbine. The failure involves the loss of the trailing edge tip of the blades. The study employs a combination of metallographic analysis and computational simulations utilizing the finite element method and computational fluid dynamics. The metallographic analysis reveals significant degradation in the GTD-111 nickel-based superalloy within the region where the failure occurs. This degradation is characterized by the coarsening and coalescence of the gamma prime phase, which can be attributed to localized overheating. Additionally, the computational study enables the calculation of the trajectory, pressure, and temperature profiles of the hot gases, as well as the distribution of temperatures within the blade. These findings demonstrate that the cooling airflow is influenced by the hot gas flow, particularly in the vicinity of the fault location, owing to the orientation of the cooling ducts, which results in overheating in this area. Ultimately, the temperatures derived from the microstructural analysis using the Ostwald-ripening theory align remarkably well with the results obtained from the simulation, validating the accuracy of the computational model. By combining metallographic analysis and computational simulations, this study provides crucial insights into the failure mechanism of the first-stage blades. Full article
(This article belongs to the Section Computation and Simulation on Metals)
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