Edwardsiellosis, caused by Edwardsiella piscicida infection in eels (Anguilla japonica), is a major problem for Korean eel farms, so there is an urgent need to develop a vaccine. For both practical and cost reasons, it is preferable to develop an oral vaccine, administration of which is significantly more efficient than injection vaccines. To avoid destruction by gastric enzymes and ensure safe delivery to the intestines, it is essential to apply a coating technology to oral vaccine antigens. To develop an oral vaccine against Edwardsiellosis, liposomes were used as an antigen coating, and the efficacy was evaluated by comparing eels’ mortality rates following oral or injection vaccination and expeirmental infection with E. piscicida. Eels that received the highest concentration oral vaccines (20 mg/fish dosage) experienced only a 6% mortality rate; those that got intraperitoneal injection vaccines had 10% mortality. In addition, the control group mortality rate (46%) was 4.18 times higher than that of the most successful oral vaccine group, confirming the efficacy of the oral vaccine. Antibody agglutination in serum extracted after oral vaccine administration confirmed the efficacy of the oral vaccine: eels that received intraperitoneal (I.P.) injection vaccines had the highest antibody agglutinationvalues (28.25 ± 0.43), but the 20 mg/fish oral vaccine group also showed high antibody agglutination (25.125 ± 1.05). These results conclusively demonstrate that the oral vaccine containing liposome-coated inactivated E. piscicida can generate an immune response sufficient to prevent Edwardsiellosis in eels.

In recent years, antioxidant activity prediction has become increasingly vital for evaluating the quality and health-promoting potential of wine brandy and sweet wine. This task is challenging due to complex and highly correlated fluorescence spectra, where overlapping peaks and baseline variations hinder precise modelling. However, traditional models struggle to capture nonlinear spectral dependencies, leading to limited prediction accuracy. Hence, this research proposes a Synchronous Fluorescence Spectroscopy Separable Convolution and Coordinate Attention Network (SFS-SepCANet) for antioxidant activity prediction. The proposed model integrates Separable 1D Convolutional layers for efficient spectral feature extraction, Min-Max Pooling to retain both high- and low-intensity fluorescence information, and a Coordinate Attention (CA) mechanism to enhance wavelengthlevel feature representation. The learned features are flattened and passed through a fully connected layer to produce accurate antioxidant activity predictions. The proposed SFS-SepCA-Net model is evaluated using SFS datasets of wine brandy and sweet wine, where preprocessing includes normalization to improve spectral stability. Experimental evaluation demonstrates that the proposed SFS-SepCA-Net achieves a high coefficient of determination $\mathbf{R}^{\mathbf{2}} \boldsymbol{=} \mathbf{0. 9 7}$ and superior predictive performance compared to PLS, UPLS, and other baseline models, providing a green, interpretable, and computationally efficient framework for antioxidant activity prediction.

Liposomal delivery systems are utilized to enhance the bioavailability of nutrients. In this randomized, double-blind, two-period crossover clinical trial, healthy Korean adults (n = 20) were enrolled to assess the absorption of liposomal multinutrients compared to composition-matched non-liposomal comparators. Two distinct liposomal multinutrient formulations (LMN-1 and LMN-2) were compared with two corresponding non-liposomal multinutrient products (NLMN-1 and NLMN-2). Pharmacokinetic (PK) parameters—including C_max, T_max, and incremental area under the curve (iAUC)—were analyzed for vitamin B3, vitamin C, zinc, and iron. Vitamin C and zinc concentrations were significantly higher from 1 to 8 h and 0–6 h, respectively, while iron concentrations were elevated at most time points for the liposomal group. No clinically significant adverse events were observed during the study period. These findings indicate that liposomal multinutrients improve nutrient absorption and demonstrate good tolerability in humans. The results support the application of liposomal formulations in functional foods as a strategy to enhance nutrient delivery.

Quantile-quantile plots of the genome-wide interaction scans for red meat and processed meat.

Locus Zoom plots for the two polymorphisms reported in the genome-wide gene-interaction main results.

BACKGROUND:Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. METHODS:A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. FINDINGS:The 3-DF joint test revealed two significant loci with p-value <5 × 10-8. Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10-3) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10-7). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10-8) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029). INTERPRETATION:We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. FUNDING:National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.

BACKGROUND:Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS:Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS:There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS:Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

AbstractBackground: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene–environment (GxE) interaction analysis to identify genetic variants that may modify these associations. Methods: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan. Results: Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21–1.41; processed meat OR = 1.40; 95% CI = 1.20–1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29–1.46), 1.20 (95% CI = 1.12–1.27), and 1.07 (95% CI = 0.95–1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11–1.24), 1.35 (95% CI = 1.26–1.44), and 1.46 (95% CI = 1.26–1.69) for CC, CT, and TT, respectively. Conclusions: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer. Impact: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.

Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit rs72833769), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit rs350047), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.

BACKGROUND:Menopausal hormone therapy (MHT), a common treatment to relieve symptoms of menopause, is associated with a lower risk of colorectal cancer (CRC). To inform CRC risk prediction and MHT risk-benefit assessment, we aimed to evaluate the joint association of a polygenic risk score (PRS) for CRC and MHT on CRC risk. METHODS:We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent. A PRS based on 141 CRC-associated genetic variants was modeled as a categorical variable in quartiles. Multiplicative interaction between PRS and MHT use was evaluated using logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). 30-year cumulative risks of CRC for 50-year-old women according to MHT use and PRS were calculated. RESULTS:The reduction in odds ratios by MHT use was larger in women within the highest quartile of PRS compared to that in women within the lowest quartile of PRS (p-value = 2.7 × 10-8). At the highest quartile of PRS, the 30-year CRC risk was statistically significantly lower for women taking any MHT than for women not taking any MHT, 3.7% (3.3%-4.0%) vs 6.1% (5.7%-6.5%) (difference 2.4%, P-value = 1.83 × 10-14); these differences were also statistically significant but smaller in magnitude in the lowest PRS quartile, 1.6% (1.4%-1.8%) vs 2.2% (1.9%-2.4%) (difference 0.6%, P-value = 1.01 × 10-3), indicating 4 times greater reduction in absolute risk associated with any MHT use in the highest compared to the lowest quartile of genetic CRC risk. CONCLUSIONS:MHT use has a greater impact on the reduction of CRC risk for women at higher genetic risk. These findings have implications for the development of risk prediction models for CRC and potentially for the consideration of genetic information in the risk-benefit assessment of MHT use.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.

Supplementary Figure 1. Stomach cancer incidence rates by subsite, time period, race/ethnicity and sex in California (1988-2012) and in South Korea and in Japan (2003-2008). Supplementary Figure 2. Stomach cancer incidence rate by stage, time period, race/ethnicity and sex in California, 1988-2012. A: Localized stage, men; B: Regional stage, men; C: Distant stage, men; D: Unknown/Unspecified stage, men; E: Localized stage, women; F: Regional stage, women; G: Distant stage, women; H: Unknown/Unspecified stage, women.

Summary of G × BMI analyses using 1DF, two-step, and 3DF analyses.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

BACKGROUND:Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. OBJECTIVES:Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS:We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS:Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS:Variation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Supplementary Table 1. Ageâ€adjusted (world population) incidence rates of stomach cancer in California by race/ethnic groups, 1988â€2012. Supplementary Table 2. Ageâ€adjusted (world population) incidence rates of stomach cancer in California by race/ethnic groups and subsite 1988â€2012. Supplementary Table 3. Ageâ€adjusted (world population) incidence rates of stomach cancer in California by race/ethnic groups and stage, 1988â€2012. Supplementary Table 4. Ageâ€adjusted incidence rates of stomach cancer in California by race/ethnic groups and histology, 1988â€2012.

Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.