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Ginsenosides, active compounds derived from Panax ginseng, exhibit promising potential in enhancing physical performance. This study investigates the impact of UG0712 (UG), a novel ginsenoside compound, on endurance capacity, body weight, organ weights, blood parameters, and specific transcriptomic changes in liver and muscle tissues using a C57BL/6N mouse model. The mice received UGs orally at three doses: UG50 (50 mg/kg), UG100 (100 mg/kg), and UG200 (200 mg/kg) for a specified duration. Endurance capacity, physiological parameters, and transcriptome signatures in liver and muscle tissues were assessed. UG administration significantly improved time to exhaustion, with UG50 and UG200 showing substantial enhancements. Body and organ weights exhibited no notable differences, suggesting a lack of adverse effects. Biochemical markers, except for decreased creatine kinase levels in the UG100 group, showed no significant variations. Transcriptome analysis revealed limited group separation and dose-dependent patterns. The UG100 group displayed significant enrichment in lipid metabolism and muscle-related terms. Identified dose-dependent improvements in endurance capacity highlight UGs' potential as supplements. The absence of adverse effects on body and organ weights, along with positive effects on biochemical markers, supports their safety. Despite limited dose-dependent patterns in transcriptomic analyses, the UG100 group showcased significant enrichment in pathways related to muscle and lipid metabolism. These findings offer valuable insights for athletes and aging individuals seeking to enhance physical performance, warranting further exploration into UG effects' on molecular mechanisms.

A series of experiments have elucidated the primary defects in group-III nitride epilayers, identifying vacancy clusters due to cation migration at interfaces to mitigate strained lattice. While the occurrence of these defects is well-documented, the underlying electronic mechanisms driving vacancy agglomeration in nitrides and their alloys remain poorly understood. In this study, we uncovered a previously unreported ground state of two metal vacancies driven by the migration of kinetically unstable nitrogen atoms using an ab initio approach. Our findings reveal that the mixed covalent-ionic bond character of nitrides is a crucial factor in determining the stability of vacancy clusters. Notably, the relatively strong ionic character of AlN facilitates the formation of exceptionally stable vacancy clusters with a pyramidal nitrogen complex. In contrast, GaN, despite having similar covalent bonding strength, exhibits less stable vacancy clusters due to its weaker ionic character. Moreover, in InN, we observe the formation of molecular-like azide anion that creates a trimer metallic-like bond between indium dangling bonds, accompanied by vigorous indium migration. In the process, we newly identified the formation of a Schottky-Frenkel composite defect. We believe that these novel insights into the bond character and stability of vacancy clusters in nitrides provide a new understanding that could drive the design and optimization of nitride-based materials and electronic devices.

Enabling reversible control over the topological invariants, transitioning them from nontrivial to trivial states, has fundamental implications for quantum information processing and spintronics. It offers a promising avenue for establishing an efficient on/off switch mechanism for robust and dissipationless spin-currents. While mechanical strain has traditionally been advantageous for such manipulation of topological invariants, it often comes with the drawback of in-plane fractures, rendering it unsuitable for high-speed, time-dependent operations. This study employs ultrafast optical and THz spectroscopy to explore topological phase transitions induced by light-driven strain in Bi 2 Se 3 . Bi 2 Se 3 requires substantial strain for Z 2 switching. Our observations provide experimental evidence of ultrafast switching behavior, demonstrating a transition from a topological insulator with spin-momentum-locked surfaces to hybridized states and normal insulating phases under ambient conditions. Notably, applying light-induced strong out-of-plane strain effectively suppresses surface-bulk coupling, facilitating the differentiation of surface and bulk conductance even at room temperature─significantly surpassing the Debye temperature. We expect various time-dependent sequences of transient hybridization and manipulation of topological invariant through photoexcitation intensity adjustments. The sudden surface and bulk transport alterations near the transition point enable coherent conductance modulation at hypersound frequencies. Our findings on the potential of light-triggered ultrafast switching of topological invariants hold promise for high-speed topological switching and its related applications.

Background & Aims: Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment., Methods: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis., Results: The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance., Conclusions: Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection., Impact and Implications: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: Recently, anti-programmed cell death-1/anti-programmed cell death ligand-1 (anti-PD1/L1) immunotherapy has been demonstrated for its efficacy when combined with cytotoxic chemotherapy in randomized phase 3 trials for advanced biliary tract cancer (BTC). However, no biomarker predictive of benefit has been established for anti-PD1/L1 in BTC. Here, we evaluated tumor-infiltrating lymphocytes (TIL) using artificial intelligence-powered immune phenotype (AI-IP) analysis in advanced BTC treated with anti-PD1., Experimental Design: Pretreatment hematoxylin and eosin (H&E)-stained whole-slide images from 339 patients with advanced BTC who received anti-PD1 as second-line treatment or beyond, were employed for AI-IP analysis and correlative analysis between AI-IP and efficacy outcomes with anti-PD1. Next, data and images of the BTC cohort from The Cancer Genome Atlas (TCGA) were additionally analyzed to evaluate the transcriptomic and mutational characteristics of various AI-IP in BTC., Results: Overall, AI-IP were classified as inflamed [high intratumoral TIL (iTIL)] in 40 patients (11.8%), immune-excluded (low iTIL and high stromal TIL) in 167 patients (49.3%), and immune-desert (low TIL overall) in 132 patients (38.9%). The inflamed IP group showed a substantially higher overall response rate compared with the noninflamed IP groups (27.5% vs. 7.7%, P < 0.001). Median overall survival and progression-free survival were significantly longer in the inflamed IP group than in the noninflamed IP group (OS, 12.6 vs. 5.1 months; P = 0.002; PFS, 4.5 vs. 1.9 months; P < 0.001). In the TCGA cohort analysis, the inflamed IP showed increased cytolytic activity scores and IFNγ signature compared with the noninflamed IP., Conclusions: AI-IP based on spatial TIL analysis was effective in predicting the efficacy outcomes in patients with BTC treated with anti-PD1 therapy. Further validation is necessary in the context of anti-PD1/L1 plus gemcitabine-cisplatin., (©2024 American Association for Cancer Research.)

Purpose: Optimal treatment for stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT)., Materials and Methods: In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1)., Results: Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified., Conclusion: Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

Vegetables and fruits, high in starch and sugars, are promising substrates for bioethanol production, but can also yield valuable nootropic compounds, such as α-glycerylphosphorylcholine (α-GPC). This compound is a known cognitive enhancer that works by increasing the release of acetylcholine, a neurotransmitter essential for learning and memory. In this study, select root and tuber crops, as well as fruits, were subjected to Saccharomyces cerevisiae fermentation to observe the co-production of ethanol and α-GPC. The ethanol yields from these substrates were comparable to those from wheat (var. AC Andrew), ranging from 30.44 g/L (beet) to 70.04 g/L (lotus root). Aside from ethanol, α-GPC was also produced, with purple top turnip yielding 0.91 g/L, the second highest concentration after wheat (used as a reference), which produced 1.25 g/L. Although α-GPC yields in the tested substrates were lower than those from cereal grains (e.g., wheat and barley), a noteworthy observation was the production of methanol in many of these substrates. Methanol was detected in all feedstocks except wheat, with concentrations ranging from 0.10 g/L (cassava) to 1.69 g/L (purple top turnip). A linear regression analysis revealed a strong correlation between methanol and α-GPC content (R 2 = 0.876; slope = 0.52), suggesting a potential link in their biosynthetic pathways. These feedstocks not only proved effective as substrates for bioethanol production, but also showed potential for generating value-added compounds such as α-GPC. This dual-purpose potential presents new market opportunities for producers by leveraging both biofuel and nootropic compound production. Furthermore, the observed relationship between methanol and α-GPC production warrants further investigation to elucidate the metabolic pathways involved.

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8 + T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8 + T cells. We detect multimer + CD8 + T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer + CD8 + T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer + CD8 + T cells-particularly the CD49a + subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM + CD8 + T cells confirms the enhanced effector function of the CD49a + subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a + CD8 + memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection., (© 2024. The Author(s).)

Purpose: To overcome the limited efficacy of immune checkpoint blockade, there is a need to find novel cancer immunotherapeutic strategies for the optimal treatment of cancer. The novel anti-4-1BB×PDL1 bispecific antibody-ABL503 (also known as TJ-L14B)-was designed to simultaneously target PDL1 and 4-1BB and demonstrated strong antitumor T-cell responses without considerable toxicity. In this study, we investigated the mechanisms by which the combination of ABL503 and anti-PD1 blockade affected the reinvigoration of exhausted tumor-infiltrating CD8+ T cells (CD8+ TIL) and antitumor efficacy., Experimental Design: Single-cell suspensions of hepatocellular carcinoma and ovarian cancer tissues from treatment-naïve patients were used for immunophenotyping of CD8+ TILs and in vitro functional assays. Humanized hPD1/hPDL1/h4-1BB triple-knock-in mice were used to evaluate the effects of ABL503 and anti-PD1 blockade in vivo., Results: We observed that ABL503 successfully restored the functions of 4-1BB+ exhausted CD8+ TILs, which were enriched for tumor-specific T cells but unresponsive to anti-PD1 blockade. Importantly, compared with anti-PD1 blockade alone, the combination of ABL503 and anti-PD1 blockade further enhanced the functional restoration of human CD8+ TILs in vitro. Consistently, the combination of ABL503 with anti-PD1 in vivo significantly alleviated tumor growth and induced enhanced infiltration and activation of CD8+ TILs., Conclusions: ABL503, a PDL1 and 4-1BB dual-targeting bispecific antibody, elicits pronounced additive tumor growth inhibition, with increased infiltration and functionality of exhausted CD8+ T cells, which in turn enhances the anticancer effects of anti-PD1 blockade. These promising findings suggest that ABL503 (TJ-L14B) in combination with PD1 inhibitors will likely further enhance therapeutic benefit in clinical trials. See related commentary by Molero-Glez et al., p. 3971., (©2024 American Association for Cancer Research.)

Somatic cells accumulate genomic alterations with age; however, our understanding of mitochondrial DNA (mtDNA) mosaicism remains limited. Here we investigated the genomes of 2,096 clones derived from three cell types across 31 donors, identifying 6,451 mtDNA variants with heteroplasmy levels of ≳0.3%. While the majority of these variants were unique to individual clones, suggesting stochastic acquisition with age, 409 variants (6%) were shared across multiple embryonic lineages, indicating their origin from heteroplasmy in fertilized eggs. The mutational spectrum exhibited replication-strand bias, implicating mtDNA replication as a major mutational process. We evaluated the mtDNA mutation rate (5.0 × 10 -8 per base pair) and a turnover frequency of 10-20 per year, which are fundamental components shaping the landscape of mtDNA mosaicism over a lifetime. The expansion of mtDNA-truncating mutations toward homoplasmy was substantially suppressed. Our findings provide comprehensive insights into the origins, dynamics and functional consequences of mtDNA mosaicism in human somatic cells., (© 2024. The Author(s).)

This study investigated the effects of oven-roasting temperature (160, 180, and 200 ℃) and time (5, 10, 15, and 20 min) on pomegranate seeds. Physicochemical properties, such as color (L*, a*, and b* values), browning index (BI), total phenolic and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity, and chemosensory properties, including taste and volatile compounds, were analyzed. The L* and a* values, and level of sourness, umami, sweetness, and terpenes decreased, whereas the b* value, BI, and level of saltiness, bitterness, furan derivatives, pyrazines, and sulfur-containing compounds, increased with roasting time. The findings of this study showed that the positive roasting conditions for pomegranate seeds were 10-20 min at 160 ℃ and, 5-10 min at 180 ℃. This study is expected to be used as a primary reference for selecting the optimal oven-roasting conditions in which positive effects appear and for developing products utilizing pomegranate seeds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations status and differential PD-1 expression levels., Methods: Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to BRCA1/2 status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without BRCA1/2 mutations. In vitro functional assays were conducted to evaluate the reinvigorating ability of CD8 + TILs on anti-PD-1 treatment., Results: We found that EOC patients with BRCA1/2 mutations ( BRCA1/2 mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with BRCA1/2 non-mutated ( BRCA1/2 wt) patients. Furthermore, CD8 + TILs within BRCA1/2 mt tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2 wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8 + TILs was significantly greater in BRCA1/2 wt tumors compared with BRCA1/2 mt tumors. Additionally, within the BRCA1/2 wt group, the frequency of PD-1 high CD8 + TILs was positively correlated with the reinvigoration capacity of CD8 + TILs after anti-PD-1 treatment., Conclusion: Our results highlight unique immune features of CD8 + TILs in EOC and a differential response to anti-PD-1 treatment, contingent on BRCA1/2 mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected BRCA1/2 wt EOC patients., Competing Interests: Competing interests: JYL reports grants and personal fees from AstraZeneca, Beigene, Bergenbio, Clovis Oncology, Immunogen, Janssen, Merck, MSD, Novartis, Roche, Seagen, Synthon, and Takeda. All other authors have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we investigated the effect of roasting conditions and time on the physicochemical properties of pomegranate seed oil. We analyzed the fatty acid, total phenolic, flavonoid, tocopherol, and phytosterol contents of pomegranate seed oil extracted under four conditions: raw, heated at 160°C for 15 min, heated at 160°C for 20 min, and heated at 180°C for 10 min, which included three that were well-established to enhance nutritional and flavor properties. Furthermore, the oxidative stability was evaluated based on the acid value, peroxide value, and induction period. Roasting significantly decreased the contents of punicic acid, polyunsaturated fatty acids, tocopherol, and phytosterol and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity ( P <0.05) of the oil. Conversely, saturated fatty acids, monounsaturated fatty acids, acid value, peroxide value, total phenolic and flavonoid contents, and induction period were significantly increased ( P <0.05). Our results suggest that the roasting conditions were nutritionally and oxidatively stable, thereby enhancing the roasting process and providing a database for essential roasting treatments for pomegranate seed oil., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2024 by The Korean Society of Food Science and Nutrition.)

This study was to identify taste and volatile characteristics in broccoli florets under various storage conditions (room and cold temperatures). Electronic tongue (E-tongue) analysis revealed that the differences were not represented obviously according to the storage temperatures. The sourness sensor (SRS) was the highest in the 2nd week, and the saltiness sensor (STS) was the highest in the 1st week. The umami (UMS) and bitterness sensors (BRS) were the highest in the 3rd week, and the sweetness sensor (SWS) was the highest in the initial sample. Clusters were discriminated according to storage periods, regardless of storage temperature. Electronic nose (E-nose) analysis detected a total of 41 and 35 volatiles during the room and cold temperature storages, respectively. Clusters were discriminated according to storage types. These findings provide valuable data for broccoli flavor quality by different storage types., Competing Interests: Conflict of interestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background/objectives: Okra seed is a rich source of various nutritional and bioactive constituents, but its mechanism of action is still unclear. The aim of this study was to evaluated the effects on glucose uptake and serum lipid profiles of unsaponifiable matter (USM) from okra seed in adipocytes and diabetic animal models., Materials/methods: USM was prepared from okra seed powder by saponification. The contents of phytosterols and vitamin E in USM were measured. 3T3-L1 preadipocytes were cultured for 6 days with different concentrations of USM (0-200 μg/mL). The diabetic rats were administered with or without USM for 5 wk., Results: In the USM, the contents of phytosterols and vitamin E were 394.13 mg/g USM and 31.16 mg/g USM, respectively. USM showed no cytotoxicity and led to an approximately 1.4-fold increase in glucose uptake in 3T3-L1 adipocytes. The treatment of USM also increased the expressions of peroxisome proliferator-activated receptor-γ and glucose transporter-4 in a dose-dependent manner in adipocytes. The body weight change was not significantly different in all diabetic rats. However, blood glucose and the weights of liver and adipose tissues were significantly reduced compared to those in the control diabetic rats. Treatment with USM decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the control group. The USM group also showed significantly decreased atherogenic indices and cardiac risk factors., Conclusion: These results suggest that USM from okra seed improves the hypoglycemic and hypolipidemic effects in diabetic rats, and provides valuable information for improving the functional properties of okra seed., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Filamentous fungal mycoproteins have gained increasing attention as sustainable alternatives to animal and plant-based proteins. This comprehensive review summarizes the nutritional characteristics, toxicological aspects, and health-promoting effects of mycoproteins, focusing on those derived from filamentous fungi, notably Fusarium venenatum. Mycoproteins are characterized by their high protein content, and they have a superior essential amino acid profile compared to soybeans indicating excellent protein quality and benefits for human nutrition. Additionally, mycoproteins offer enhanced digestibility, further highlighting their suitability as a protein source. Furthermore, mycoproteins are rich in dietary fibers, which have been associated with health benefits, including protection against metabolic diseases. Moreover, their fatty acids profile, with significant proportions of polyunsaturated fatty acids and absence of cholesterol, distinguishes them from animal-derived proteins. In conclusion, the future of mycoproteins as a health-promoting protein alternative and the development of functional foods relies on several key aspects. These include improving the acceptance of mycoproteins, conducting further research into their mechanisms of action, addressing consumer preferences and perceptions, and ensuring safety and regulatory compliance. To fully unlock the potential of mycoproteins and meet the evolving needs of a health-conscious society, continuous interdisciplinary research, collaboration among stakeholders, and proactive engagement with consumers will be vital., (© 2024 Institute of Food Technologists®.)

Purpose: Patients with STAT1 gain-of-function (GOF) mutations often exhibit autoimmune features. The JAK1/2 inhibitor ruxolitinib can be administered to alleviate autoimmune symptoms; however, it is unclear how immune cells are molecularly changed by ruxolitinib treatment. Then, we aimed to investigate the trnscriptional and epigenetic status of immune cells before and after ruxolitinib treatment in a patient with STAT1 GOF., Methods: A patient with a heterozygous STAT1 GOF variant (p.Ala267Val), exhibiting autoimmune features, was treated with ruxolitinib, and peripheral blood mononuclear cells (PBMCs) were longitudinally collected. PBMCs were transcriptionally analyzed by single-cell cellular indexing of the transcriptomes and epitopes by sequencing (CITE-seq), and epigenetically analyzed by assay of transposase-accessible chromatin sequencing (ATAC-seq)., Results: CITE-seq analysis revealed that before treatment, the patient's PBMCs exhibited aberrantly activated inflammatory features, especially IFN-related features. In particular, monocytes showed high expression levels of a subset of IFN-stimulated genes (ISGs). Ruxolitinib treatment substantially downregulated aberrantly overexpressed ISGs, and improved autoimmune features. However, epigenetic analysis demonstrated that genetic regions of ISGs-e.g., STAT1, IRF1, MX1, and OAS1-were highly accessible even after ruxolitinib treatment. When ruxolitinib was temporarily discontinued, the patient's autoimmune features were aggravated, which is in line with sustained epigenetic abnormality., Conclusions: In a patient with STAT1 GOF, ruxolitinib treatment improved autoimmune features and downregulated aberrantly overexpressed ISGs, but did not correct epigenetic abnormality of ISGs., (© 2024. The Author(s).)

This study evaluated the effects of inhaling Osmanthus fragrans var. aurantiacus (OFA) extracts in Sprague-Dawley (SD) rats experiencing chronic stress. Rats were exposed to restraint stress or circadian disruption and were inhaled either distilled water or OFA extracts. Electronic nose (E-nose) analysis identified 35 volatile aromatic compounds (VACs) in OFA extracts. Chronic stress led to a decrease in body weight initially, serotonin concentration, and the weights of the liver, kidneys, and fat pads. Additionally, circadian disruption increased melatonin levels and decreased cholesterol concentrations. Inhalation of OFA increased dietary intake during the early phase and restored the tissue weights that have changed by chronic stress. Furthermore, it led to an increase in melatonin levels and changes in cholesterol levels. Taken together, our results indicate that OFA inhalation improves physiological changes caused by chronic stress through regulating dietary intake, restoring tissue weights, and modulating hormone and cholesterol levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: Preclinical studies have shown that radiation therapy modulates antitumor immune responses. However, circulating T-cell responses after radiation therapy in patients with cancer have been poorly characterized. This study aims to explore the changes in circulating T cells after stereotactic body radiation therapy (SBRT)., Methods and Materials: Peripheral blood samples of 30 patients with breast cancer who underwent SBRT for bone metastasis were analyzed using multicolor flow cytometry. Phenotypes of PD-1 + CD8 + T cells and regulatory T (T REG ) cells were examined. Additionally, plasma protein levels were analyzed using a bead-based immunoassay., Results: Circulating PD-1 + CD8 + T cells, which are enriched for tumor-specific clonotypes, were activated at 1 week after SBRT. However, circulating T REG cells were also activated after SBRT; this pattern was also evident among effector Foxp3 hi CD45RA - T REG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of T REG cells was more prominent in patients who experienced greater activation of PD-1 + CD8 + T cells. Plasma level changes in TGF-β1, soluble CTLA-4, and soluble 4-1BB at 1 week after SBRT were associated with PD-1 + CD8 + T-cell responses. Activation of T REG cells at 1 week after SBRT was associated with worse progression-free survival. Clinical factors including molecular subtype were not associated with the T-cell responses., Conclusions: SBRT induced activation of both potentially tumor-specific CD8 + T cells and T REG cells, which were tightly associated with each other. These results may support the use of T REG cell-modulating strategies with SBRT to improve the antitumor immune response., (Copyright © 2023 Elsevier Inc. All rights reserved.)

IL-15 belongs to the common gamma chain cytokine family and has pleiotropic immunological functions. IL-15 is a homeostatic cytokine essential for the development and maintenance of NK cells and memory CD8 + T cells. In addition, IL-15 plays a critical role in the activation, effector functions, tissue residency, and senescence of CD8 + T cells. IL-15 also activates virtual memory T cells, mucosal-associated invariant T cells and γδ T cells. Recently, IL-15 has been highlighted as a major trigger of TCR-independent activation of T cells. This mechanism is involved in T cell-mediated immunopathogenesis in diverse diseases, including viral infections and chronic inflammatory diseases. Deeper understanding of IL-15-mediated T-cell responses and their underlying mechanisms could optimize therapeutic strategies to ameliorate host injury by T cell-mediated immunopathogenesis. This review highlights recent advancements in comprehending the role of IL-15 in relation to T cell responses and immunopathogenesis under various host conditions., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2024. The Korean Association of Immunologists.)

This study analyzed the flavor of six types of hemp seed oil (HSO) extracted with roasted hemp seed (RHS) under various conditions (Raw, 140 °C&#95;9 min, 140 °C&#95;12 min, 160 °C&#95;12 min, 180 °C&#95;6 min). Electronic tongue (E-tongue), electronic nose (E-nose), GC-MS (gas chromatography-mass spectrometry), and GC-O (gas chromatography-olfactometry) were used for HSO flavor analysis. As a result of the E-tongue analysis, the sweetness tends to increase in most samples as roasting. A total of 89 and 77 volatile compounds were detected through E-nose and GC-MS, and the main volatile compounds were identified as Maillard reaction products. A total of 16 odor active compounds were detected in the GC-O analysis, and in the case of 160 ℃&#95;12 min and 180 ℃&#95;6 min, the scent of Roasted hemp seed oil was more dominant than other aroma profiles. The results of this study are basic data on the flavor characteristics of HSO., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: Recent studies using single-cell transcriptomic analysis have reported several distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic cancer tumor microenvironment. However, their molecular characteristics and biological significance have not been clearly elucidated due to intra- and inter-tumoral heterogeneity., Methods: We performed single-cell RNA sequencing using enriched non-immune cell populations from 17 pancreatic tumor tissues (16 pancreatic cancer and one high-grade dysplasia) and generated paired spatial transcriptomic data from seven patient samples., Results: We identified five distinct functional subclusters of pancreatic cancer cells and six distinct cancer-associated fibroblast subclusters. We deeply profiled their characteristics, and we found that these subclusters successfully deconvoluted most of the features suggested in bulk transcriptome analysis of pancreatic cancer. Among those subclusters, we identified a novel cancer cell subcluster, Ep&#95;VGLL1, showing intermediate characteristics between the extremities of basal-like and classical dichotomy, despite its prognostic value. Molecular features of Ep&#95;VGLL1 suggest its transitional properties between basal-like and classical subtypes, which is supported by spatial transcriptomic data., Conclusions: This integrative analysis not only provides a comprehensive landscape of pancreatic cancer and fibroblast population, but also suggests a novel insight to the dynamic states of pancreatic cancer cells and unveils potential therapeutic targets., (© 2024. The Author(s).)

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8 + T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ-producing CD8 + T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ-producing CD8 + T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike-specific CD8 + T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8 + T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8 + T cell responses that recognize epitopes within the spike of newly emerging subvariants.

Background: Major histocompatibility complex (MHC) class I chain-related protein (MIC) is a stress-induced ligand released from multiple myeloma (MM) cells during progression, and soluble MIC impairs natural killer group 2D (NKG2D) activating receptor-mediated recognition and function of natural killer (NK) cells. However, whether clearing soluble MIC with a monoclonal antibody (mAb) can restore NK cell activity of MM patients remains undetermined., Methods: We analyzed The Cancer Genome Atlas (TCGA) Multiple Myeloma Research Foundation (MMRF) CoMMpass data set to examine the prognostic significance of MIC expression in MM. We examined the level of soluble MIC in paired peripheral blood (PB) and bone marrow (BM) plasma of patients with MM at diagnosis by ELISA. We evaluated the correlation between the level of soluble MIC and immunophenotype of NK cells from MM patients by multicolor flow cytometry. We also generated MIC-overexpressing MM cell line and characterized the cytotoxic function of patient NK cells in the presence of soluble MIC, and examined the impact of clearing soluble MIC with a humanized mAb (huB10G5)., Results: We characterize the importance of MICA in MM by revealing the significantly better overall survival of patients with high MICA expression from TCGA MMRF CoMMpass data set. The level of soluble MICA is more highly elevated in MM than in precursor stages, and the concentration of soluble MICA is higher in BM plasma than in PB. The concentration of soluble MICA in BM was correlated with myeloma burden, while it was negatively correlated with the frequency of NKG2D + NK cells in diagnostic BM aspirates of MM patients. Soluble MICA downregulated NKG2D expression and decreased cytotoxicity of MM patient NK cells ex vivo , which were reversed by a humanized soluble MIC-clearing mAb (huB10G5) with enhanced degranulation of NK cells., Conclusions: Our findings indicate targeting soluble MIC with huB10G5 might be a viable therapeutic approach to promote NKG2D-dependent cellular immunotherapy outcome in MM., Competing Interests: Competing interests: JW is the inventor of the huB10G5 antibody with international patents and the remaining authors declare no potential conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study investigated the effects of roasting conditions on the physicochemical, taste, and volatile and odor-active compound (OAC) profiles of Coffea arabica L. At 150 ℃, roasting increased chlorogenic acid, total flavonoids, and caffeine concentrations. However, umami and sourness sensor decreased during the roasting process. At 210 ℃ roasting, total flavonoid and caffeine concentrations increased during the roasting process. Aldehydes, ketones, and sulfur-containing compounds dramatically increased during the roasting at 210 ℃ for 20 and 30 min in E-nose analysis. Pyrazines were mainly generated during the roasting at 210 ℃ for 20 and 30 min, and pyrazines showed the highest concentrations among all OACs in GC-olfactometry (GC-O) analysis. E-tongue data showed the separation of beans by roasting temperature. However, the E-nose and GC-O data showed the separation of beans by both roasting temperature and time via multivariate analysis. We identified similar results and patterns in the E-nose and GC-O analyses., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Various citrus fruits' flavor compounds were analyzed using an electronic sensor (E-sensor), and odor-active compounds were identified using gas chromatography-mass spectrometry-olfactometry (GC-MS-O). In the E-tongue analysis, the intensity of sweetness, saltiness, and bitterness was highest in Citrus unshiu , while sourness and umami were highest in C. setomi . A total of 43 volatile compounds were detected in the E-nose analysis, and the compound with the highest peak area was limonene, a type of terpenoid, which exhibited a prominent peak area in C. unshiu . Principal component analysis between flavor compounds and each sample explained a total variance of 83.15% and led to the classification of three clusters. By GC-MS-O, 32 volatile compounds were detected, with limonene being the most abundant, ranging from 20.28 to 56.21 mg/kg. The odor-active compounds were identified as (E)-2-hexenal, hexanal, α -pinene, β -myrcene, limonene, γ -terpinene, nonanal, and D-carvone, respectively., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

BACKGROUNDPemphigus, a rare autoimmune bullous disease mediated by antidesmoglein autoantibodies, can be controlled with systemic medication like rituximab and high-dose systemic corticosteroids combined with immunosuppressants. However, some patients continue to experience chronically recurrent blisters in a specific area and require long-term maintenance systemic therapy.METHODSSkin with chronic blisters was obtained from patients with pemphigus. Immunologic properties of the skin were analyzed by immunofluorescence staining, bulk and single-cell RNA and TCR sequencing, and a highly multiplex imaging technique known as CO-Detection by indEXing (CODEX). Functional analyses were performed by flow cytometry and bulk RNA-Seq using peripheral blood from healthy donors. Intralesional corticosteroid was injected into patient skin, and changes in chronically recurrent blisters were observed.RESULTSWe demonstrated the presence of skin tertiary lymphoid structures (TLSs) with desmoglein-specific B cells in chronic blisters from patients with pemphigus. In the skin TLSs, CD4+ T cells predominantly produced CXCL13. These clonally expanded CXCL13+CD4+ T cells exhibited features of activated Th1-like cells and downregulated genes associated with T cell receptor-mediated signaling. Tregs are in direct contact with CXCL13+CD4+ memory T cells and increased CXCL13 production of CD4+ T cells through IL-2 consumption and TGF-β stimulation. Finally, intralesional corticosteroid injection improved chronic blisters and reduced skin TLSs in patients with pemphigus.CONCLUSIONThrough this study we conclude that skin TLSs are associated with the persistence of chronically recurrent blisters in patients with pemphigus, and the microenvironmental network involving CXCL13+CD4+ T cells and Tregs within these structures plays an important role in CXCL13 production.TRIAL REGISTRATIONClinicalTrials.gov NCT04509570.FUNDINGThis work was supported by National Research Foundation of South Korea (NRF-2021R1C1C1007179) and Korea Drug Development Fund, which is funded by Ministry of Science and ICT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (grant RS-2022-00165917).

This research investigated volatiles and odor active compounds in Osmanthus fragrans var. aurantiacus . Heterocyclics were mainly extracted from hexane and dichloromethane extracts. Ketones were mainly detected from butanol fraction, and alcohols were mainly extracted from the ethanol fraction. GC-O analysis investigated the contents and intensities of three major odor active compounds increasing by ramping up polarity Multivariate analysis, which includes principal component analysis (PCA) and hierarchical cluster analysis (HCA), by E-nose data showed 45.83% (PC1) and 29.27 (PC2) variances, respectively, and segregated two clusters. Multivariate analysis by GC-O data showed 65.64% (PC1) and 24.17% (PC2) variances, respectively, and segregated the three clusters, cluster I by ethanol extract, cluster II by dichloromethane extract, and cluster III by hexane and butanol extracts. This study demonstrates that different polarity solvents can collect various volatiles and odor active compound groups. Our findings can support basic research data as a natural and functional food additive., Competing Interests: Competing interestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log 10 IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56 dim CD16 + NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells., Competing Interests: Conflict of Interest: Yun Bin Lee reports receiving research grants from Samjin Pharmaceuticals and Yuhan Pharmaceuticals. Yoon Jun Kim reports receiving research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals, and Handok Pharmaceuticals. Jung-Hwan Yoon reports receiving research grants from Bayer HealthCare Pharmaceuticals, Daewoong Pharmaceuticals, and Bukwang Pharmaceuticals. Jeong-Hoon Lee reports receiving research grants from Yuhan Pharmaceuticals, and lecture fee from GreenCross Cell, Daewoong Pharmaceuticals, and Gilead Korea. All other authors have declared that no conflict of interest exists., (Copyright © 2023. The Korean Association of Immunologists.)

Background: Despite the low measles antibody positivity rate among young healthcare workers (HCWs) who have previously received two doses of a measles-containing vaccine (MCV), whether an additional dose of MCV acts as a booster remains unknown. Thus, we aimed to evaluate the immune responses to a third dose of MCV in young HCWs., Methods: Hospital-wide measles seroprevalence was assessed using enzyme-linked immunosorbent assay (ELISA). The immunogenicity of a third dose of MCV was determined in young seronegative HCWs (born between 1986 and 1997) who had previously received a two-dose measles vaccination., Results: A total of 3033 (92.6%) HCWs had anti-measles immunoglobulin G. The lowest seropositivity rate was observed in HCWs aged 20-24 years (87.7%). In this group, HCWs who received a third dose of MCV had higher seropositivity than those who received a second dose (89.5% vs. 75.4%). A third dose of MCV was administered to 18 HCWs who did not have anti-measles IgG despite two doses. Neutralizing antibody titers increased significantly 4 weeks after the third vaccination. Although neutralizing antibody titers decreased 1 year post vaccination, 17 (94.4%) HCWs had medium (121-900 mIU/mL) or high (>900 mIU/mL) levels. Furthermore, the third dose of MCV increased the measles virus-specific T-cell effector function., Conclusions: The third dose of MCV induced a strong immune response against measles in young seronegative HCWs who had previously received a two-dose measles vaccination., Competing Interests: Declaration of Competing Interest We have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JL declared a shared affiliation with the author JHK to the handling editor at the time of review., (Copyright © 2023 Lee, Nam, Kim, Kim, Kim, Shin, Kim and Choi.)

Efficient detection methods must be developed for 1,4-dioxane due to its suspected status as a human carcinogen, which is highly mobile in food and environmental resources. In this regard, this experiment has been conducted to develop reliable and selective detection and measurement methods by using static headspace (SH) isolation, followed by gas chromatography-mass spectrometry (GC-MS). A new method was developed for determining the spiked 1,4-dioxane contents in a polyethylene glycol 600 (PEG 600). The optimal condition for SH-GC-MS was discussed. The representative ions of 1,4-dioxane and 1,4-dioxane-d8 in the SIM mode of MS are 88 and 96, respectively, and the peaks of the SIM mode were separated and confirmed. The linear range for the method covers 0.25 to 100 mg/L with a coefficient of determination (R 2 )  ≥  0.999. The method applicability was demonstrated by spike recovery across a variety of food additives (i.e., chlorine bitartrate, choline chloride, polysorbate 20 and 60, and PEG 1000). All spike recovery from the tested samples was in the range of 89.50-102.68% with a precision of 0.44-11.22%. These findings suggest a new analytical method for food safety inspection, and could be applicable for ensuring the safety of foods and environmental and public health on a broad scale.

This study identified the aroma profile of salmon by-product for high utilization of by-products, including hydrolysates of head, frame, and skin were treated with reducing sugars and thermal processing. Electronic nose (E-nose) and gas chromatography-mass spectrometry (GC-MS) coupled with gas chromatography-olfactometry (GC-O) were used to analyzed the aroma profile. A total of 140 and 90 volatile compounds were detected through E-nose and GC-MS respectively, and the main volatile compounds were aldehydes. A total of 23 odor active compounds were recognized using GC-O, and 3-methyl-butanal, heptanal, benzaldehyde, octanal, furfural, and methoxy-phenyl-oxime were identified as the aroma of salmon. Using multivariate analysis, the pattern between the pretreated samples and aroma profiles was confirmed, and there were clear separations among the samples. The results of this study provide the aroma profile of salmon by-products and are expected salmon by-products to be used as a potential food source., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Korean Society of Food Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization. However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccine-induced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARS-CoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4 + T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4 + T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein. The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

Virtual memory T (T VM ) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although T VM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a T VM cell-originated CD44 super-high(s-hi) CD49d lo CD8 + T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8 + T VM cells and can cause alopecia areata. Mechanistically, CD44 s-hi CD49d lo CD8 + T cells could be induced from conventional T VM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44 s-hi CD49d lo CD8 + T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which T VM cells can cause chronic inflammatory disease by innate-like cytotoxicity., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Pet owners think of their animals as part of their family, which further promotes the growth of the pet food market, encouraging pet owners to select nutritious, palatable, and high-quality foods for pets. Therefore, the evaluation of taste and volatile compounds in pet foods is essential to improve palatability. In this study, the sensory characteristics of taste and odor compounds in 10 commercially available dry dog foods were investigated using electronic tongue (E-tongue), electronic nose (E-nose), gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O). Dry dog foods were separated based on the sensory properties of taste and volatile compounds through the multivariate analysis of integrated results of the E-tongue and E-nose. A total of 67 odor active compounds were detected through GC-MS and GC-O, and octanal, nonanal, 2-pentyl furan, heptanal, and benzaldehyde were identified as key odor compounds which may have positive effects on food intake. The multivariate analysis was used to classify samples based on key odor compounds. Volatile compounds responsible for aroma properties of samples were evaluated using GC-O and multivariate analysis in this present study for the first time. These results are expected to provide fundamental data for sensory evaluation in producing new dog foods with improved palatability.