Bioaccumulation of arsenic in fish (Labeo rohita) in presence of periphyton: ameliorative effect on oxidative stress, physiological condition, immune response and risk assessment.

The present study explores the use of periphyton to ameliorate toxic properties of arsenic (As) to Labeo rohita and also assesses the human food safety aspects. Fish were introduced to arsenite [As(III)] contaminated water (0.3 and 3 mg/L) along with periphyton. Biochemical, physiological and immunological parameters, including gene expression, were assessed after 30 days of exposure. Periphyton incorporation significantly improved (p < 0.05) the adverse effects of As on respiration, NH3 excretion and brain AChE activity by reducing oxidative stress and As bioaccumulation. The presence of periphyton in As(III) exposed fish (3 mg/L) increased the immune response (Immunoglobulin M and Complement C3) in the serum and the regulation of the respective immune genes in the anterior kidney was found to be similar to the control. A speciation study using LC-ICP-MS confirmed the high accumulation of As by periphyton (5.0-31.9 µg/g) as arsenate [As (V)], resulting in a lower amount of As in fish muscle. The calculated human health risk indices, Target Hazard Quotient (THQ) and Target Cancer risk (TCR) indicate that fish grown in periphyton-treated water may lower the human health risks associated with As. The study signifies the importance of periphyton-based aquaculture systems in As contaminated regions for safe fish production with enhanced yield.

Copy number variation and elevated genetic diversity at immune trait loci in Atlantic and Pacific herring.

BACKGROUND: Genome-wide comparisons of populations are widely used to explore the patterns of nucleotide diversity and sequence divergence to provide knowledge on how natural selection and genetic drift affect the genome. In this study we have compared whole-genome sequencing data from Atlantic and Pacific herring, two sister species that diverged about 2 million years ago, to explore the pattern of genetic differentiation between the two species. RESULTS: The genome comparison of the two species revealed high genome-wide differentiation but with islands of remarkably low genetic differentiation, as measured by an FST analysis. However, the low FST observed in these islands is not caused by low interspecies sequence divergence (dxy) but rather by exceptionally high estimated intraspecies nucleotide diversity (π). These regions of low differentiation and elevated nucleotide diversity, termed high-diversity regions in this study, are not enriched for repeats but are highly enriched for immune-related genes. This enrichment includes genes from both the adaptive immune system, such as immunoglobulin, T-cell receptor and major histocompatibility complex genes, as well as a substantial number of genes with a role in the innate immune system, e.g. novel immune-type receptor, tripartite motif and tumor necrosis factor receptor genes. Analysis of long-read based assemblies from two Atlantic herring individuals revealed extensive copy number variation in these genomic regions, indicating that the elevated intraspecies nucleotide diversities were partially due to the cross-mapping of short reads. CONCLUSIONS: This study demonstrates that copy number variation is a characteristic feature of immune trait loci in herring. Another important implication is that these loci are blind spots in classical genome-wide screens for genetic differentiation using short-read data, not only in herring, likely also in other species harboring qualitatively similar variation at immune trait loci. These loci stood out in this study because of the relatively high genome-wide baseline for FST values between Atlantic and Pacific herring.

Immune Gene Networks from Lung Cancer Patients Treated with Immune Checkpoint Inhibitors.

The association between immune checkpoint inhibitors (ICIs) and immune gene networks in squamous lung cancer (LUSC) and lung adenocarcinoma (LUAD) was studied. Immune gene networks were constructed using RNA-seq data from the gene expression omnibus (GEO) database. Datasets with more than 10 samples of normal control and tumor tissues were selected; of these, GSE87340, GSE120622, and GSE111907 were suitable for analysis. Gene set enrichment for pathway analysis was performed. For immune gene network construction, 998 unique immune genes were selected from 21 pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene function annotation was performed based on the KEGG, Gene Ontology, and Reactome databases. Tumor tissues showed decreased coagulation, hematopoiesis, and innate immune pathways, whereas complement- and coagulation-related genes were prominent in the tumor immune gene network. The average numbers of neighbors, clustering coefficients, network diameters, path lengths, densities, and heterogeneities were highest for normal tissue, followed by LUAD and LUSC. Decreased coagulation genes, which were prominent in tumor immune networks, imply functional attenuation. LUAD was deviated from normal tissue, based on network parameters. Tumor tissues showed decreased immune function, and the deviation of LUSC from normal tissue might explain LUSC's better therapeutic response to ICI treatment.

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC.

BACKGROUND: Long noncoding RNAs (lncRNAs) are implicated in the tumor immunology of hepatocellular carcinoma (HCC). METHODS: HCC mRNA and lncRNA expression profiles were used to extract immune-related genes with the ImmPort database, and immune-related lncRNAs with the ImmLnc algorithm. The MOVICS package was used to cluster immune-related mRNA, immune-related lncRNA, gene mutation and methylation data on HCC from the TCGA. GEO and ICGC datasets were used to validate the model. Data from single-cell sequencing was used to determine the expression of genes from the model in various immune cell types. RESULTS: With this model, the area under the curve (AUC) for 1-, 3- and 5-year survival of HCC patients was 0.862, 0.869 and 0.912, respectively. Single-cell sequencing showed EREG was significantly expressed in a variety of immune cell types. Knockdown of the EREG target gene resulted in significant anti-apoptosis, pro-proliferation and pro-migration effects in HepG2 and HUH7 cells. Moreover, serum and liver tissue EREG levels in HCC patients were significantly higher than those of healthy control patients. CONCLUSION: We built a prognostic model with good accuracy for predicting HCC patient survival. EREG is a potential immunotherapeutic target and a promising prognostic biomarker.

Construction and evaluation of immune-related diagnostic model in patients with heart failure caused by idiopathic dilated cardiomyopathy.

OBJECTIVE: The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy. METHOD: GSE5406 and GSE57338 were downloaded from the GEO website ( https://www.ncbi.nlm.nih.gov/geo/ ). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein-protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338. RESULTS: Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes. CONCLUSION: Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.

Research progress of aphid immunity system: Potential effective target for green pest management.

Due to the absence of acquired immunity, insects primarily rely on their innate immune system to resist pathogenic microorganisms and parasitoids in natural habitats. This innate immune system can be classified into cellular immunity and humoral immunity. Cellular immunity is mediated by hemocytes, which perform phagocytosis, aggregation, and encapsulation to fight against invaders, whereas the humoral immunity primarily activates the immune signaling pathways and induces the generation of immune effectors. Existing studies have revealed that the hemipteran aphids lack some crucial immune genes compared to other insect species, indicating the different immune mechanisms in aphids. The current review summarizes the adverse impacts of pathogenic microorganisms and parasitoids on aphids, introduces the cellular and humoral immune systems in insects, and analyzes the differences between aphids and other insect species. Furthermore, our review also discussed the existing prospects and challenges in aphid immunity research, and proposed the potential application of immune genes in green pest management.

Identification and validation of an individualized metabolic prognostic signature for predicting the biochemical recurrence of prostate cancer based on the immune microenvironment.

BACKGROUND: Prostate cancer (PCa) is the most prevalent genitourinary malignancy in men, with a significant proportion of patients developing biochemical recurrence (BCR) after treatment. The immune microenvironment and metabolic alterations have crucial implications for the tumorigenesis and progression of PCa. Therefore, identifying metabolic genes associated with the immune microenvironment holds promise for predicting BCR and improving PCa prognosis. METHODS: In this study, ssGSEA and hierarchical clustering analysis were first conducted to evaluate and group PCa samples, followed by the use of the ESTIMATE and CIBERSORT algorithms to characterize the immunophenotypes and tumor microenvironment. The differential metabolic genes (MTGs) between groups were utilized to develop a prognostic-related signature. The predictive performance of the signature was assessed by principal component analysis (PCA), receiver operating characteristic (ROC) curve analysis, survival analysis, and the TIDE algorithm. A miRNA-MTGs regulatory network and predictive nomogram were constructed. Moreover, the expression of prognostic MTGs in PCa was detected by RT‒qPCR. RESULTS: PCa samples from the TCGA cohort were separated into two groups: the immune-low group and immune-high group. Forty-eight differentially expressed MTGs between the groups were identified, including 37 up-regulated and 11 down-regulated MTGs. Subsequently, CEL, CYP3A4, and PDE6G were identified as the genes most strongly associated with the BCR of PCa patients and these genes were utilized to establish the MTGs-based prognostic signatures. PCA, ROC curves analysis, Kaplan-Meier survival analysis, and the nomogram all showed the good predictive ability of the signature regardless of clinical variables. Furthermore, the MTGs-based signature was indicated as a potential predictive biomarker for immunotherapy response. Nine miRNAs involved in the regulation of prognostic MTGs were determined. In addition to the CEL gene, the PDE6G and CYP3A4 genes were expressed at higher levels in PCa samples. CONCLUSIONS: The MTGs-based signature represents a novel approach with promising potential for predicting BCR in PCa patients.

Diagnostic biomarker for type 2 diabetic peripheral neuropathy via comprehensive bioinformatics analysis.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN. METHODS: In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches. KEGGG and GO functional enrichments were performed. Hub genes and their correlation with infiltrating immune cells were analyzed. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to quantify hub gene expression. RESULTS: In total, 144 DEGs between DPN and the control were identified. Functional enrichment revealed that the DEGs were mainly enriched in immune-related pathways like the Fc epsilon receptor Ig signaling pathway. By protein-protein interaction (PPI) network analysis, FCER1G, SYK, ITGA4, F13A1, MS4A2, and PTK2B were screened as hub genes with higher expression in DPN patients, among which half were immune genes (FCER1G, PTK2B, and SYK). RT-qPCR demonstrated that mRNA expression of FCER1G, PTK2B, and SYK was significantly increased in patients with DPN compared with both diabetic nonperipheral neuropathy (DNN) and normal subjects. The area under the receiver operating characteristic (ROC) curve of FCER1G, PTK2B, and SYK was 0.84, 0.81, and 0.73, respectively, suggesting their great advantages as diagnostic biomarkers to predict the progression of neuropathy in T2DM. Further analysis indicated that the expression of FCER1G, PTK2B, and SYK was negatively correlated with the cell proportion of significantly altered resting natural killer cells, T follicular helper cells, and activated mast cells, but positively correlated with monocytes. CONCLUSIONS: Our findings demonstrated FCER1G, PTK2B, and SYK are potential diagnostic biomarkers and therapeutic targets for DPN, which provides new insight into DPN pathogenesis and therapies.

Development and validation of an immune-related gene prognostic index for lung adenocarcinoma.

Background: Lung cancer is the most common malignant tumor in the world, and its prognosis is still not optimistic. The aim of this study was to establish an immune-related gene (IRG) prognostic index (IRGPI) for lung adenocarcinoma (LUAD) based on IRGs, and to explore the prognosis, molecular and immune features, and response to immune checkpoint inhibitor (ICI) therapy in IRGPI-classified different subgroups of LUAD. Methods: Based on the LUAD transcriptome RNA-sequencing data in TCGA database, the differentially expressed genes (DEGs) were selected. Subsequently, DEGs were intersected with IRGs to obtain differentially expressed immune-related genes (DEIRGs). Weighted gene co-expression network analysis (WGCNA) identified hub genes in DEIRGs. Finally, univariate and multivariate Cox regression analyses were used to build an IRGPI model. Subsequently, TCGA patients were divided into high- and low-risk groups, and the survival of patients in different groups was further analyzed. Besides, we validated the molecular and immune characteristics, relationship with immune checkpoints, angiogenesis-related genes, and immune subtypes distribution in different subgroups. Meanwhile, we further validated the response to ICI therapy in different subgroups. Results: The IRGPI was constructed based on 13 DEIRGs. Compared with the low-risk group, overall survival (OS) was lower in the high-risk group, and the high-risk score was independently associated with poorer OS. Besides, the high-risk score was associated with cell cycle pathway, high mutation rate of TP53 and KRAS, high infiltration of M0 macrophages, and immunosuppressive state, and these patients had poorer prognosis but the TIDE score of the high-risk group was lower than that of the other group, which means that the high-risk group could benefit more from ICI treatment. In contrast, the low-risk score was related to low mutation rate of TP53 and KRAS, high infiltration of plasma cells, and immunoactive state, and these patients had better prognosis but the low-risk group less benefit from ICI treatment based on the results of TIDE score. Conclusions: IRGPI is a prospective biomarker based on IRGs that can distinguish high- and low-risk groups to predict patient prognosis, help characterize the tumor immune microenvironment, and evaluate the benefit of ICI therapy in LUAD.

Prediction of Tumor Microenvironment Characteristics and Treatment Response in Lung Squamous Cell Carcinoma by Pseudogene OR7E47P-related Immune Genes.

OBJECTIVE: Pseudogenes are initially regarded as nonfunctional genomic sequences, but some pseudogenes regulate tumor initiation and progression by interacting with other genes to modulate their transcriptional activities. Olfactory receptor family 7 subfamily E member 47 pseudogene (OR7E47P) is expressed broadly in lung tissues and has been identified as a positive regulator in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). This study aimed to elucidate the correlation between OR7E47P and tumor immunity in lung squamous cell carcinoma (LUSC). METHODS: Clinical and molecular information from The Cancer Genome Atlas (TCGA) LUSC cohort was used to identify OR7E47P-related immune genes (ORIGs) by weighted gene correlation network analysis (WGCNA). Based on the ORIGs, 2 OR7E47P clusters were identified using non-negative matrix factorization (NMF) clustering, and the stability of the clustering was tested by an extreme gradient boosting classifier (XGBoost). LASSO-Cox and stepwise regressions were applied to further select prognostic ORIGs and to construct a predictive model (ORPScore) for immunotherapy. The Botling cohorts and 8 immunotherapy cohorts (the Samstein, Braun, Jung, Gide, IMvigor210, Lauss, Van Allen, and Cho cohorts) were included as independent validation cohorts. RESULTS: OR7E47P expression was positively correlated with immune cell infiltration and enrichment of immune-related pathways in LUSC. A total of 57 ORIGs were identified to classify the patients into 2 OR7E47P clusters (Cluster 1 and Cluster 2) with distinct immune, mutation, and stromal programs. Compared to Cluster 1, Cluster 2 had more infiltration by immune and stromal cells, lower mutation rates of driver genes, and higher expression of immune-related proteins. The clustering performed well in the internal and 5 external validation cohorts. Based on the 7 ORIGs (HOPX, STX2, WFS, DUSP22, SLFN13, GGCT, and CCSER2), the ORPScore was constructed to predict the prognosis and the treatment response. In addition, the ORPScore was a better prognostic factor and correlated positively with the immunotherapeutic response in cancer patients. The area under the curve values ranged from 0.584 to 0.805 in the 6 independent immunotherapy cohorts. CONCLUSION: Our study suggests a significant correlation between OR7E47P and TME modulation in LUSC. ORIGs can be applied to molecularly stratify patients, and the ORPScore may serve as a biomarker for clinical decision-making regarding individualized prognostication and immunotherapy.

Establishment and verification of a prognostic risk score model based on immune genes for hepatocellular carcinoma in an Asian population.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with the highest incidence in East Asia, and hepatitis B virus (HBV) infection is the most common cause of HCC in Asian population. The immune system is closely related to the development of HCC and plays an important role in the treatment of this disease. In this study, we analyzed the data of HCC from The Cancer Genome Atlas (TCGA) database and constructed a risk-score prognostic model based on immune genes of an Asian HCC population, aiming to provide new perspectives for clinical treatment and management of HCC in Asian population. Methods: Data concerning clinical attributes and transcriptomic profiles of individuals in the Asian population diagnosed with HCC were retrieved from the TCGA database. Concurrently, immune-related genes were sourced from the Immport database for incorporation into our analysis. A total of 265 immune-related genes displaying differential expression were identified through wilcoxTest analysis in R. Further refinement using univariate and multivariate Cox regression analysis led to the identification of 15 genes that exhibited strong associations with prognosis. MICB/PSMD14/TRAF3/SP1/NDRG1/HDAC1/HRAS/NRAS/SEMA5B/GMFB/ACVR2B/BRD8/MMP12/KITLG/DCK, and a prognostic risk score model was constructed based on the above genes. Results: The findings demonstrated notable differences in survival rates between the low-risk and high-risk groups, as depicted by the Kaplan-Meier (K-M) survival curves (P<0.001). Furthermore, the model's predictive capability was evidenced by receiver operating characteristic (ROC) curves, with area under the curve (AUC) =0.901. Finally, the relationship of the model with each clinical trait and immune cells was assessed by correlation analysis. Conclusions: The prognostic risk score model constructed by immune genes based on the Asian HCC population has certain predictive capacity.

Larval diet and temperature alter mosquito immunity and development: using body size and developmental traits to track carry-over effects on longevity.

BACKGROUND: Estimating arbovirus transmission potential requires a mechanistic understanding of how environmental factors influence the expression of adult mosquito traits. While preimaginal exposure to environmental factors can have profound effects on adult traits, tracking and predicting these effects remains challenging. METHODS: Using Aedes albopictus and a structural equation modeling approach, we explored how larval nutrition and temperature jointly affect development rate and success, female body size, and whether these metrics capture carry-over effects on adult female longevity. Additionally, we investigated how larval diet and temperature affect the baseline expression of 10 immune genes. RESULTS: We found that larval development success was primarily determined by diet, while temperature and diet both affected development rate and female body size. Under a low larval diet, pupal wet weight and wing length both declined with increasing temperature. In contrast, responses of the two morphometric measures to rearing temperature diverged when females were provided higher larval nutrition, with pupal wet weight increasing and wing length decreasing at higher temperatures. Our analyses also revealed opposing relationships between adult female lifespan and the two morphometric measures, with wing length having a positive association with longevity and pupal weight a negative association. Larval diet indirectly affected adult longevity, and the time to pupation was negatively correlated with longevity. The expression of eight immune genes from the toll, JAK-STAT and Imd pathways was enhanced in mosquitoes with higher nutrition. CONCLUSIONS: Our results highlight deficiencies from using a single body size measure to capture carry-over effects on adult traits. Further studies of larval development rate under varying environmental conditions and its potential for tracking carry-over effects on vectorial capacity are warranted.

Erratum: Analysis of the regulatory mechanisms of prognostic immune factors in thyroid cancer.

[This corrects the article DOI: 10.3389/fonc.2022.1059591.].

Oral administration of terpenoids and phenol fraction of Padina gymnospora stimulates the nonspecific immune response and expression of immune genes, and protects the common carp (Cyprinus carpio) from experimental Aeromonas hydrophila infection.

Common carp (Cyprinus carpio), a valuable aquaculture species susceptible to various infections, requires effective immune enhancement strategies. This study investigates the immunomodulatory effects of orally administered terpenoids and phenol fraction (TPF) from Padina gymnospora in C. carpio, focusing on stimulation of nonspecific immune response, immune gene expression, and protection against experimental infection. P. gymnospora is a brown seaweed species known for its bioactive compounds and medicinal properties. TPF was extracted using the Harborne fractionation method, and the presence of terpenoids and phenol compounds was confirmed by qualitative analysis and high-performance thin layer chromatography (HPTLC). TPF was administered orally in different doses to carp. Nonspecific immune responses were evaluated by measuring cellular ROS, RNI, and peroxidase production. The expression of immune genes (lysozyme and interleukin-1ß) was assessed by reverse transcriptase PCR. Furthermore, the protective efficacy of TPF was determined by infecting carp with a virulent pathogen, Aeromonas hydrophila, and monitoring mortality rates and disease symptoms. The results demonstrate that oral TPF administration significantly enhances nonspecific immune responses, with increased ROS, RNI, and peroxidase production, indicating improved immune function. Expression levels of lysozyme and interleukin-1ß were upregulated, suggesting immune system activation. Moreover, TPF exhibited significant protection against experimental infection, with lower mortality rates compared to the control group. These findings highlight TPF's potential as an effective immunostimulatory agent, enhancing immune responses and providing infection protection in carp. In conclusion, oral TPF administration stimulates nonspecific immune responses, modulates immune gene expression, and confers protection against experimental infection in carp, displaying its potential for enhancing immune responses and disease resistance in aquaculture species, and contributing to sustainable fish health management.

Single and joint toxic effects of waterborne exposure to copper and cadmium on Coregonus ussuriensis Berg.

Heavy metal contamination severely affects the aquatic environment and organisms. Copper (Cu) and cadmium (Cd) are two of the most common heavy metal contaminants that impair the survival, development, and reproduction of aquatic organisms. With the growth of agriculture and industry, there is a possibility of heavy metal pollution in Coregonus ussuriensis Berg's water source. However, there are no published studies on the toxicity to C. ussuriensis. Acute toxicity experiments in C. ussuriensis revealed the 96-h median lethal concentrations of copper and cadmium to be 0.492 mg·L-1 (95% confidence interval: 0.452-0.529) and 1.548 mg·L-1 (95% confidence interval: 1.434-1.657), respectively, and safe concentrations of 4.92 µg·L-1 and 15.48 µg·L-1, respectively. C. ussuriensis was then treated for 96 h with Cu (20% of 96 h LC50), Cd (20% of 96 h LC50), and a combination of Cu and Cd (20% of Cu 96 h LC50 + 20% of Cd 96 h LC50). The histological damage caused by the three different exposure modes to the liver and gills of C. ussuriensis was verified using hematoxylin and eosin staining. All three exposure modes caused different degrees of vacuolization, nuclear consolidation, and necrosis in the liver tissue of C. ussuriensis and edema, hyperplasia, laminar fusion, and epithelial elevation in the gill tissue compared with the reference group. The severity of the damage increased with increasing exposure time. Anti-oxidant activity in the gill and liver tissues were measured using enzyme activity assay kits to reflect oxidative stress induced by copper and cadmium exposure alone and in combination. The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH) were substantially higher than those in the reference groups. However, the activities of the enzymes decreased with increasing exposure time. Malondialdehyde (MDA) activity significantly increased during exposure in relation to that in the reference group. Analysis of immune gene expression in C. ussuriensis gill and liver tissues was executed using real-time inverse transcript polymerase chain response (RT-PCR). The expression levels of the pro-inflammatory cytokines interleukin one beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were positively correlated with exposure time and were significantly upregulated with increasing exposure time. Metallothionein (MT) gene expression levels were significantly upregulated in the short term after exposure compared to the reference group but decreased with increasing exposure time. Our results indicate that exposure to aqueous copper and cadmium solutions, either alone or in combination, causes histopathological damage, oxidative stress, and immunotoxicity in C. ussuriensis gill and liver tissue. This study investigated the toxic effects of copper and cadmium on C. ussuriensis to facilitate the monitoring of heavy metals in water sources for healthy aquaculture.

Effects of Scallop Visceral Mass and Mantle as Dietary Supplements on the Growth, Immune Response and Intestinal Microflora of Juvenile Sea Cucumber Apostichopus japonicus.

Scallop visceral mass and mantle are aquatic byproducts and waste, but they have high contents of protein. In this study, scallop visceral mass and mantle were used as supplements in the diet of juvenile sea cucumber (A. japonicus) and their effects on the growth, fatty acid and amino acid compositions, the non-specific immune responses and the intestinal microflora of A. japonicus were investigated through a 40 d feeding experiment. The results showed that dietary supplementation of scallop visceral mass significantly accelerated the specific growth rate (SGR) of juvenile A. japonicus by 3 times within 20 days, and also raised the contents of ω-3 fatty acids including EPA and DHA and the ω-3/ω-6 ratio of the sea cucumber tissue, which is favorable to the health and commercial value of the sea cucumber. Furthermore, it was found that the supplementation of scallop visceral mass and mantle stimulated the expression of immune-related genes and enhanced the immune defense in A. japonicus. Scallop visceral mass and mantle supplementation also increased the microbial diversity and the abundance of beneficial microbes including Bifidobacteriaceae, Streptomycetaceae, Clostridiaceae and Rhizobiales in the gut of A. japonicus. This study reveals the beneficial effects of dietary supplementation of scallop visceral mass and mantle on the growth of juvenile A. japonicus, which might be a promising way to reutilize this scallop waste and raise its economic value.

Trade-offs between immunity and competitive ability in fighting ant males.

BACKGROUND: Fighting disease while fighting rivals exposes males to constraints and trade-offs during male-male competition. We here tested how both the stage and intensity of infection with the fungal pathogen Metarhizium robertsii interfere with fighting success in Cardiocondyla obscurior ant males. Males of this species have evolved long lifespans during which they can gain many matings with the young queens of the colony, if successful in male-male competition. Since male fights occur inside the colony, the outcome of male-male competition can further be biased by interference of the colony's worker force. RESULTS: We found that severe, but not yet mild, infection strongly impaired male fighting success. In late-stage infection, this could be attributed to worker aggression directed towards the infected rather than the healthy male and an already very high male morbidity even in the absence of fighting. Shortly after pathogen exposure, however, male mortality was particularly increased during combat. Since these males mounted a strong immune response, their reduced fighting success suggests a trade-off between immune investment and competitive ability already early in the infection. Even if the males themselves showed no difference in the number of attacks they raised against their healthy rivals across infection stages and levels, severely infected males were thus losing in male-male competition from an early stage of infection on. CONCLUSIONS: Males of the ant C. obscurior have a well-developed immune system that raises a strong immune response very fast after fungal exposure. This allows them to cope with mild pathogen exposures without compromising their success in male-male competition, and hence to gain multiple mating opportunities with the emerging virgin queens of the colony. Under severe infection, however, they are weak fighters and rarely survive a combat already at early infection when raising an immune response, as well as at progressed infection, when they are morbid and preferentially targeted by worker aggression. Workers thereby remove males that pose a future disease threat by biasing male-male competition. Our study thus reveals a novel social immunity mechanism how social insect workers protect the colony against disease risk.

The transcriptome response of astronaut leukocytes to long missions aboard the International Space Station reveals immune modulation.

Introduction: Spaceflight leads to the deconditioning of multiple body systems including the immune system. We sought to characterize the molecular response involved by capturing changes in leukocyte transcriptomes from astronauts transitioning to and from long-duration spaceflight. Methods: Fourteen male and female astronauts with ~6-month- long missions aboard the International Space Station (ISS) had 10 blood samples collected throughout the three phases of the study: one pre-flight (PF), four in-flight (IF) while onboard the ISS, and five upon return to Earth (R). We measured gene expression through RNA sequencing of leukocytes and applied generalized linear modeling to assess differential expression across all 10 time points followed by the analysis of selected time points and functional enrichment of changing genes to identify shifts in biological processes. Results: Our temporal analysis identified 276 differentially expressed transcripts grouped into two clusters (C) showing opposite profiles of expression with transitions to and from spaceflight: (C1) decrease-then-increase and (C2) increase-then-decrease. Both clusters converged toward average expression between ~2 and ~6 months in space. Further analysis of spaceflight transitions identified the decrease-then-increase pattern with most changes: 112 downregulated genes between PF and early spaceflight and 135 upregulated genes between late IF and R. Interestingly, 100 genes were both downregulated when reaching space and upregulated when landing on Earth. Functional enrichment at the transition to space related to immune suppression increased cell housekeeping functions and reduced cell proliferation. In contrast, egress to Earth is related to immune reactivation. Conclusion: The leukocytes' transcriptome changes describe rapid adaptations in response to entering space followed by opposite changes upon returning to Earth. These results shed light on immune modulation in space and highlight the major adaptive changes in cellular activity engaged to adapt to extreme environments.

Identification of a novel immune-related transcriptional regulatory network in sarcopenia.

BACKGROUND: Sarcopenia is highly prevalent in elderly individuals and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and the immune microenvironment play a vital role in skeletal muscle atrophy. METHODS: RNA-seq data of 40 muscle samples were downloaded from the GEO database. Then, differentially expressed genes (DEGs), TFs(DETFs), pathways(DEPs), and the expression of immune gene sets were identified with limma, edgeR, GO, KEGG, ORA, GSVA, and ssGSEA. Furthermore, the results above were integrated into coexpression analysis by Pearson correlation analysis (PCA). Significant coexpression patterns were used to construct the immune-related transcriptional regulatory network by Cytoscape and potential medicine targeting the network was screened by Connectivity Map. Finally, the regulatory mechanisms and RNA expression of DEGs and DETFs were identified by multiple online databases and RT‒qPCR. RESULTS: We screened 808 DEGs (log2 fold change (FC) > 1 or < - 1, p < 0.05), 4 DETFs (log2FC > 0.7 or < - 0.7, p < 0.05), 304 DEPs (enrichment scores (ES) > 1 or < - 1, p < 0.05), and 1208 differentially expressed immune genes sets (DEIGSs) (p < 0.01). Based on the results of PCA (correlation coefficient (CC) > 0.4 or < - 0.4, p < 0.01), we then structured an immune-related network with 4 DETFs, 9 final DEGs, 11 final DEPs, and 6 final DEIGSs. Combining the results of online databases and in vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC ≤ 0.444, p ≤ 0.004) was a potential transcriptional regulation axis, and B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of trichostatin A (enrichment = -0.365, specificity = 0.4257, p < 0.0001) might be a potential medicine for sarcopenia based on the PubChem database and the result of the literature review. CONCLUSIONS: We first identified immune-related transcriptional regulatory network with high-throughput RNA-seq data in sarcopenia. We hypothesized that PAX5-SERPIAN5-PI3K/Akt axis is a potential mechanism in sarcopenia and that B cells may play a vital role in this signal transduction. In addition, trichostatin A might be a potential medicine for sarcopenia.

Effects of the pyrE deletion mutant from Bacillus thuringiensis on gut microbiota and immune response of Spodoptera exigua.

The gut microbiota is essential for the growth and development of insects, and the intestinal immune system plays a critical role in regulating the homeostasis of intestinal microorganisms and their interactions with pathogenic bacteria. Infection with Bacillus thuringiensis (Bt) can disrupt the gut microbiota of insects, but the regulatory factors governing the interaction between Bt and gut bacteria are not well understood. Uracil secreted by exogenous pathogenic bacteria can activate DUOX-mediated reactive oxygen species (ROS) production, which helps maintain intestinal microbial homeostasis and immune balance. To elucidate the regulatory genes involved in the interaction between Bt and gut microbiota, we investigate the effects of uracil derived from Bt on gut microbiota, and host immunity using a uracil deficient Bt strain (Bt GS57△pyrE) obtained by homologous recombination. We analyze the biological characteristics of the uracil deficient strain and found that the deletion of uracil in Bt GS57 strain changed the diversity of gut bacteria in Spodoptera exigua, as investigated using Illumina HiSeq sequencing. Furthermore, qRT-PCR analysis showed that compared with Bt GS57 (control), the expression of the SeDuox gene and the level of ROS were significantly decreased after feeding with Bt GS57△pyrE. Adding uracil to Bt GS57△pyrE restored the expression level of DUOX and ROS to a higher level. Additionally, we observed that PGRP-SA, attacin, defensin and ceropin genes were significant different in the midgut of S. exigua infected by Bt GS57 and Bt GS57△pyrE, with a trend of increasing first and then decreasing. These results suggest that uracil regulates and activates the DUOX-ROS system, affects the expression of antimicrobial peptide genes, and disturb intestinal microbial homeostasis. We preliminarily speculate that uracil is a key factor in the interaction between Bt and gut microbiota, and these findings provide a theoretical basis for clarifying the interaction between Bt, host, and intestinal microorganisms, as well as for gaining new insights into the insecticidal mechanism of B. thuringiensis in insects.