SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production.

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.

Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for immune checkpoint inhibitors in biliary tract cancer.

PURPOSE: Anti-PD-1/L1 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-PD-1/L1 in BTC. Here, we evaluated tumor-infiltrating lymphocytes (TILs) using artificial intelligence-powered immune phenotype (AI-IP) analysis in advanced BTC treated with anti-PD-1. PATIENTS AND METHODS: Pre-treatment H&E-stained whole-slide images from 339 advanced BTC patients who received anti-PD-1 as second-line treatment or beyond, were utilized for AI-IP analysis and correlative analysis between AI-IP and efficacy outcomes with anti-PD-1. Next, data and images of BTC cohort from The Cancer Genome Atlas (TCGA) were additionally analyzed to evaluate the transcriptomic and mutational characteristics of various AI-IPs in BTC. RESULTS: Overall, AI-IPs were classified as inflamed (high intratumoral TIL [iTIL]) in 40 patients (11.8%), immune-excluded (low iTIL and high stromal TIL) in 167 (49.3%), and immune-deserted (low TIL overall) in 132 (38.9%). The inflamed IP group showed a significantly higher overall response rate compared to the non-inflamed 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 non-inflamed IP group (OS: 12.6 vs. 5.1 months, P=0.002; PFS: 4.5 vs. 1.9 months, P<0.001). In the analysis using TCGA cohort, the inflamed IP showed increased cytolytic activity scores and an interferon-gamma signature compared to the non-inflamed IP. CONCLUSIONS: AI-powered IP based on spatial TIL analysis was effective in predicting the efficacy outcomes in patients with BTC treated with anti-PD-1.

Mitochondrial DNA mosaicism in normal human somatic cells.

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.

Unique immune characteristics and differential anti-PD-1-mediated reinvigoration potential of CD8+ TILs based on BRCA1/2 mutation status in epithelial ovarian cancers.

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 (BRCA1/2mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with BRCA1/2 non-mutated (BRCA1/2wt) patients. Furthermore, CD8+ TILs within BRCA1/2mt tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8+ TILs was significantly greater in BRCA1/2wt tumors compared with BRCA1/2mt tumors. Additionally, within the BRCA1/2wt group, the frequency of PD-1highCD8+ 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 BRCA1/2wt EOC patients.

Oven-Roasting Effects the Fatty Acid Composition, Antioxidant Properties, and Oxidative Stability of Pomegranate (Punica granatum L.) Seed Oil.

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.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

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.

Hypoglycemic and hypolipidemic effects of unsaponifiable matter from okra seed in diabetic rats.

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.

Anti-4-1BB×PDL1 Bispecific Antibody Reinvigorates Tumor-Specific Exhausted CD8+ T Cells and Enhances the Efficacy of Anti-PD1 Blockade.

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.

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non-Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial.

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 two 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%), 9 (26%), and 4 (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 five-year DFS rate of 29%. The OS rate was 86% at two years and 76% at five years. Patients with tumor recurrence within six 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.

Comparative study on volatile compounds and taste components of various citrus cultivars using electronic sensors, GC-MS, and GC-olfactometry.

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, ß-myrcene, limonene, γ-terpinene, nonanal, and D-carvone, respectively.

Mycoproteins and their health-promoting properties: Fusarium species and beyond.

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.

Ruxolitinib Improves Immune-Dysregulation Features but not Epigenetic Abnormality in a Patient with STAT1 GOF.

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.

Investigation of volatile profiles and odor-active compounds in Osmanthus fragrans var. aurantiacus separated by different polarities using GC/MS, GC-olfactometry and electronic-nose system.

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.

The inhalation effect of Osmanthus fragrans var. Aurantiacus on physiological parameters in chronically stressed rats.

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.

Physicochemical and chemosensory properties of pomegranate (Punica granatum L.) seeds under various oven-roasting conditions.

This study investigated the effects of oven-roasting temperature (160, 180, and 200 â„ƒ) 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 â„ƒ and, 5-10 min at 180 â„ƒ. 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.

IL-15 in T-Cell Responses and Immunopathogenesis.

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.

Chemosensory of hemp seed oil extracted with hemp seed(Cannabis sativa L.) roasted under various conditions using electronic sensors and GC-MS/Olfactometry.

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_9 min, 140 °C_12 min, 160 °C_12 min, 180 °C_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 ℃_12 min and 180 ℃_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.

Chemometric approach for an application of Atlantic salmons (Oncorhynchus keta) by-product for potential food sources.

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.