IDO1 promotes CSFV replication by mediating tryptophan metabolism to inhibit NF-κB signaling.

Tryptophan metabolism plays a crucial role in facilitating various cellular processes essential for maintaining normal cellular function. Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the conversion of tryptophan (Trp) into kynurenine (Kyn), thereby initiating the degradation of Trp. The resulting Kyn metabolites have been implicated in the modulation of immune responses. Currently, the role of IDO1-mediated tryptophan metabolism in the process of viral infection remains relatively unknown. In this study, we discovered that classical swine fever virus (CSFV) infection of PK-15 cells can induce the expression of IDO1, thereby promoting tryptophan metabolism. IDO1 can negatively regulate the NF-κB signaling by mediating tryptophan metabolism, thereby facilitating CSFV replication. We found that silencing the IDO1 gene enhances the expression of IFN-α, IFN-ß, and IL-6 by activating the NF-κB signaling pathway. Furthermore, our observations indicate that both silencing the IDO1 gene and administering exogenous tryptophan can inhibit CSFV replication by counteracting the cellular autophagy induced by Rapamycin. This study reveals a novel mechanism of IDO1-mediated tryptophan metabolism in CSFV infection, providing new insights and a theoretical basis for the treatment and control of CSFV.IMPORTANCEIt is well known that due to the widespread use of vaccines, the prevalence of classical swine fever (CSF) is shifting towards atypical and invisible infections. CSF can disrupt host metabolism, leading to persistent immune suppression in the host and causing significant harm when co-infected with other diseases. Changes in the host's metabolic profiles, such as increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, can also influence virus replication. Mammals utilize various pathways to modulate immune responses through amino acid utilization, including increased catabolic metabolism of amino acids and the production of immunoregulatory metabolites and their derivatives, thereby limiting viral replication. Therefore, this study proposes that targeting the modulation of tryptophan metabolism may represent an effective approach to control the progression of CSF.

Precise Tuning of the D-Band Center of Dual-Atomic Enzymes for Catalytic Therapy.

Single-atom nanozyme-based catalytic therapy is of great interest in the field of tumor catalytic therapy; however, their development suffers from the low affinity of nanozymes to the substrates (H2O2 or O2), leading to deficient catalytic activity in the tumor microenvironment. Herein, we report a new strategy for precisely tuning the d-band center of dual-atomic sites to enhance the affinity of metal atomic sites and substrates on a class of edge-rich N-doped porous carbon dual-atomic sites Fe-Mn (Fe1Mn1-NCe) for greatly boosting multiple-enzyme-like catalytic activities. The as-made Fe1Mn1-NCe achieved a much higher catalytic efficiency (Kcat/Km = 4.01 × 105 S-1·M-1) than Fe1-NCe (Kcat/Km = 2.41 × 104 S-1·M-1) with an outstanding stability of over 90% activity retention after 1 year, which is the best among the reported dual-atom nanozymes. Theoretical calculations reveal that the synergetic effect of Mn upshifts the d-band center of Fe from -1.113 to -0.564 eV and enhances the adsorption capacity for the substrate, thus accelerating the dissociation of H2O2 and weakening the O-O bond on O2. We further demonstrated that the superior enzyme-like catalytic activity of Fe1Mn1-NCe combined with photothermal therapy could effectively inhibit tumor growth in vivo, with an inhibition rate of up to 95.74%, which is the highest value among the dual-atom artificial enzyme therapies reported so far.

Spherical Nucleic Acid-Mediated Spatial Matching-Guided Nonenzymatic DNA Circuits for the Prediction and Prevention of Malignant Tumor Invasion.

Detection of intracellular miRNAs, especially sensitive imaging of in vivo miRNAs, is vital to the precise prediction and timely prevention of tumorgenesis but remains a technical challenge in terms of nuclease resistance and signal amplification. Here, we demonstrate a gold nanoparticle-based spherical nucleic acid-mediated spatial matching-guided nonenzymatic DNA circuit (SSDC) for efficient screening of intracellular miRNAs and, in turn, finding cancerous tissues in living organisms before the appearance of clinical symptoms. Due to the substantially enhanced nuclease resistance, the false positive signal is avoided even in a complex biological medium. Target miRNA can straighten out the hairpin DNA probe to be linear, allowing the probe to penetrate into the internal region of a core/shell DNA-functionalized signal nanoampfilier and initiate a strand displacement reaction, generating an amplified fluorescence signal. The detection limit is as low as 17 pM, and miRNA imaging is in good accordance with the gold standard polymerase chain reaction method. The ability to image intracellular miRNAs is substantially superior to that of conventional fluorescence in situ hybridization techniques, making in vivo SSDC-based imaging competent for the precise prediction of tumorigenesis. By intratumoral chemotherapy guided by SSDC-based imaging, tumorigenesis and progression are efficiently controlled before the onset of clinical symptoms.

Y-Shaped Backbone-Rigidified DNA Tiles for the Construction of Supersized Nondeformable Tetrahedrons for Precise Cancer Therapies.

While engineered DNA nanoframeworks have been extensively exploited for delivery of diagnostic and therapeutic regents, DNA tiling-based DNA frameworks amenable to applications in living systems lag much behind. In this contribution, by developing a Y-shaped backbone-based DNA tiling technique, we assemble Y-shaped backbone-rigidified supersized DNA tetrahedrons (RDT) with 100% efficiency for precisely targeted tumor therapy. RDT displays unparalleled rigidness and unmatched resistance to nuclease degradation so that it almost does not deform under the force exerted by the atomic force microscopy tip, and the residual amount is not less than 90% upon incubating in biological media for 24 h, displaying at least 11.6 times enhanced degradation resistance. Without any targeting ligand, RDT enters the cancer cell in a targeted manner, and internalization specificity is up to 15.8. Moreover, 77% of RDT objects remain intact within living cells for 14 h. The drug loading content of RDT is improved by 4-8 times, and RDT almost 100% eliminates the unintended drug leakage in a stimulated physiological medium. Once systemically administrated into HeLa tumor-bearing mouse models, doxorubicin-loaded RDTs preferentially accumulate in tumor sites and efficiently suppress tumor growth without detectable off-target toxicity. The Y-DNA tiling technique offers invaluable insights into the development of structural DNA nanotechnology for precise medicine.

Electrical Polarity Modulation in V-Doped Monolayer WS2 for Homogeneous CMOS Inverters.

As demand for higher integration density and smaller devices grows, silicon-based complementary metal-oxide-semiconductor (CMOS) devices will soon reach their ultimate limits. 2D transition metal dichalcogenides (TMDs) semiconductors, known for excellent electrical performance and stable atomic structure, are seen as promising materials for future integrated circuits. However, controlled and reliable doping of 2D TMDs, a key step for creating homogeneous CMOS logic components, remains a challenge. In this study, a continuous electrical polarity modulation of monolayer WS2 from intrinsic n-type to ambipolar, then to p-type, and ultimately to a quasi-metallic state is achieved simply by introducing controllable amounts of vanadium (V) atoms into the WS2 lattice as p-type dopants during chemical vapor deposition (CVD). The achievement of purely p-type field-effect transistors (FETs) is particularly noteworthy based on the 4.7 at% V-doped monolayer WS2, demonstrating a remarkable on/off current ratio of 105. Expanding on this triumph, the first initial prototype of ultrathin homogeneous CMOS inverters based on monolayer WS2 is being constructed. These outcomes validate the feasibility of constructing homogeneous CMOS devices through the atomic doping process of 2D materials, marking a significant milestone for the future development of integrated circuits.

Rare and common coding variants in lipid metabolism-related genes and their association with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. METHODS: A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing. Associations between common variants and CAD were evaluated by Fisher's exact test. A gene-based association test of rare variants was performed by the sequence kernel association test-optimal (SKAT-O test). RESULTS: We found 51 rare variants and 17 common variants in this study. One common missense variant, LIPC rs6083, was significantly associated with CAD after Bonferroni correction (OR = 0.47, 95% CI = 0.29-0.76, p = 1.9 × 10- 3). Thirty-three nonsynonymous rare variants were identified, including two novel variants located in the ANGPTL4 (p.Gly47Glu) and SCARB1 (p.Leu233Phe) genes. We did not find a significant association between rare variants and CAD via gene-based analysis via the SKAT-O test. CONCLUSIONS: Targeted sequencing is a powerful tool for identifying rare and common variants in CAD. The common missense variant LIPC rs6083 confers protection against CAD. The clinical relevance of rare variants in CAD aetiology needs to be investigated in larger sample sizes in the future.

Local resection via partial lamellar sclerouvectomy for ciliary body tumors - a case series.

BACKGROUND: Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. METHODS: Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. RESULTS: Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00-10.00) and the mean tumor thickness was 3.50 mm (range: 2.00-5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. CONCLUSIONS: Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

The Relationship Between Men's Sociosexuality, Drinking Intake, and Blackouts.

Background: Sociosexuality-attitudes, behaviors, and desires related to casual sex-partly predicts drinking behavior in both men and women because drinking is thought to facilitate interactions that lead to casual sex. It follows that sociosexuality would predict drinking intake (e.g., quantity consumed)-but perhaps not drinking consequences (e.g., blacking out)-on the premise that drinking large quantities with high frequency (but not to such high degrees/levels of intoxication that negative consequences occur) would facilitate casual sex. Objectives: This set of studies evaluated whether baseline measures of sociosexuality predict drinking intake (i.e., frequency, quantity, and binge drinking) but not experiencing blacking out at follow-up in two samples (Study 1, N = 172; Study 2, N = 1,038) of college-aged men. Results: As predicted, men's sociosexuality prospectively predicted drinking frequency, quantity, and binge drinking. Contrary to our predictions, men's sociosexuality also predicted blacking out. Conclusions: College men's drinking interventions should be tailored to high-risk groups and consider individual differences like sociosexuality.

Adaptive Event-Triggered Consensus of Multi-Agent Systems in Sense of Asymptotic Convergence.

In this paper, the asymptotic consensus control of multi-agent systems with general linear agent dynamics is investigated. A neighbor-based adaptive event-triggering strategy with a dynamic triggering threshold is proposed, which leads to a fully distributed control of the multi-agent system, depending only on the states of the neighboring agents at triggering moments. By using the Lyapunov method, we prove that the states of the agents converge asymptotically. In addition, the proposed event-triggering strategy is proven to exclude Zeno behavior. The numerical simulation results illustrate that the agent states achieve consensus in sense of asymptotic convergence. Furthermore, the proposed strategy is shown to be scalable in case of variable agent numbers.

Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.

Au-Seeded CsPbI3 Nanowire Optoelectronics via Exothermic Nucleation.

Converting vapor precursors to solid nanostructures via a liquid noble-metal seed is a common vapor deposition principle. However, such a noble-metal-seeded process is excluded from the crystalline halide perovskite synthesis, mainly hindered by the growth mechanism shortness. Herein, powered by a spontaneous exothermic nucleation process (ΔH < 0), the Au-seeded CsPbI3 nanowires (NWs) growth is realized based on a vapor-liquid-solid (VLS) growth mode. It is energetically favored that the Au seeds are reacted with a Pb vapor precursor to form molten Au-Pb droplets at temperatures down to 212 °C, further triggering the low-temperature VLS growth of CsPbI3 NWs. More importantly, this Au-seeded process reduces in-bandgap trap states and consequently avoids Shockley-Read-Hall recombination, contributing to outstanding photodetector performances. Our work extends the powerful Au-seeded VLS growth mode to the emerging halide perovskites, which will facilitate their nanostructures with tailored material properties.

Comparative Analysis of the Biochemical Composition, Amino Acid, and Fatty Acid Contents of Diploid, Triploid, and Tetraploid Crassostrea gigas.

Tetraploid oysters are artificially produced oysters that do not exist in nature. The successful breeding of 100% triploid oysters resolved the difficulties of traditional drug-induced triploids, such as the presence of drug residues and a low triploid induction rate. However, little is known concerning the biochemical composition and nutrient contents of such tetraploids. Therefore, we investigated compositional differences among diploid, triploid, and tetraploid Crassostrea gigas as well as between males and females of diploids and tetraploids. The findings indicated that glycogen, EPA, ∑PUFA, and omega-3 contents were significantly higher in triploid oysters than in diploids or tetraploids; tetraploid oysters had a significantly higher protein content, C14:0, essential amino acid, and flavor-presenting amino acid contents than diploids or triploids. For both diploid and tetraploids, females had significantly higher levels of glutamate, methionine, and phenylalanine than males but lower levels of glycine and alanine. In addition, female oysters had significantly more EPA, DHA, omega-3, and total fatty acids, a result that may be due to the fact that gonadal development in male oysters requires more energy to sustain growth, consumes greater amounts of nutrients, and accumulates more proteins. With these results, important information is provided on the production of C. gigas, as well as on the basis and backing for the genetic breeding of oysters.

Psychosocial Characteristics by Pain Presence and Limitations Among Older Adults.

PURPOSE: To compare psychosocial outcomes of older adults according to pain experience. METHOD: Using cross-sectional 2021 data from the National Health and Aging Trends Study, we examined psychosocial characteristics in older adults (N = 3,376) divided into three groups: no pain, pain without activity limitations, and activity-limiting pain. RESULTS: In multiple regression models, older adults with activity-limiting pain compared to those without pain had significantly higher depression, anxiety, and fear of falling, as well as reduced positive affect, self-realization, self-efficacy, resilience, and social participation. Older adults with non-activity-limiting pain had significantly higher social participation than those without pain, but no differences in self-realization, self-efficacy, or resilience. CONCLUSION: Pain is strongly associated with all psychosocial outcomes, especially in older adults with activity-limiting pain. Future research should examine the impact of self-realization, self-efficacy, resilience, and social participation on activity limitations. [Journal of Gerontological Nursing, 50(7), 27-34.].

Mesenchymal stem cells can prevent or promote the progression of colon cancer based on their timing of administration.

BACKGROUND: Mesenchymal stem cell (MSC) therapy has been shown to have some therapeutic effects in rodent models and patients with IBD; however, its role in colon tumor models is controversial. In this study, the potential role and mechanisms of bone marrow-derived MSCs (BM-MSCs) in colitis-associated colon cancer (CAC) were investigated. METHODS: The CAC mouse model was established with azoxymethane (AOM) and dextran sulfate sodium (DSS). The mice were administered an intraperitoneal injection of MSCs once weekly for different periods. The progression of CAC and the cytokine expression in tissues was assessed. Immunofluorescence staining was used to detect MSCs localization. Levels of immune cells in the spleen and lamina propria of the colon were detected using flow cytometry. A co-culture of MSCs and naïve T cells was performed to determine the effect of MSCs on naïve T cell differentiation. RESULTS: Early administration of MSCs inhibited the occurrence of CAC, while late administration promoted the progression of CAC. The inhibitory effect of early injection in mice was characterized by the expression of inflammatory cytokines in colon tissue was decreased, and induction of T regulatory cells (Tregs) infiltration via TGF-ß. The promotive effect of late injection was characterized by a shift of T helper (Th) 1/Th2 immune balance toward a Th2 phenotype through IL-4 secretion. IL-12 can reverse this shift to Th2 accumulation in mice. CONCLUSION: MSCs can curb the progression of colon cancer by inducing Treg accumulation via TGF-ß at the early stage of inflammatory transformation but promote the progression of colon cancer by inducing a shift in Th1/Th2 immune balance to Th2 through IL-4 secretion at the late stage. And the immune balance of Th1/Th2 influenced by MSCs could be reversed by IL-12.

Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM.

BACKGROUND: Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. RESULTS: The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. CONCLUSIONS: The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.

Trends in the incidence of cirrhosis in global from 1990 to 2019: A joinpoint and age-period-cohort analysis.

Cirrhosis remains a major public health concern globally; the burden of cirrhosis should be further clarified worldwide and helped us to understand the current situation of cirrhosis. In the present study, we estimate DALYs and mortality rates attributable to several major cirrhosis risk factors and use joinpoint and age-period-cohort methods to determine the trends of cirrhosis incidence and deaths in the global population in the 1990-2019 period. Globally, from 1990 to 2019, the incidence of cirrhosis, deaths due to cirrhosis, and cirrhosis DALY cases increased from 1274 (103 , 95% uncertainty interval [UI]: 1027.2-1548.5) to 2051.6 (103 , 95% UI: 1661.4-2478.1), 1013 (103 , 95% UI: 948.9-1073.9) to 1472 (103 , 95% UI: 1374.6-1578.7), and 34727.7 (103 , 95% UI: 32383.0-37132.8) to 46189.4 (103 , 95% UI: 43027.1-49551.3), respectively. Hepatitis virus was the most important cirrhosis mortality risk factor. Globally, hepatitis virus infection (HBV+HCV) accounted for more than 45% of the incidence of cirrhosis cases and about 50% of cirrhosis deaths. Importantly, from 1990 to 2019, the proportion of cirrhosis incidence due to HBV decreased from 24.3% to 19.8%, whereas that due to alcohol use increased from 18.7% to 21.3%. Additionally, the proportion of NAFLD-induced cirrhosis incidence increased from 5.5% to 6.6% over the same period. Our findings on the global disease burden of cirrhosis provide a valuable resource for developing targeted prevention strategies.

PIK3CA somatic mutations as potential biomarker for immunotherapy in elder or TP53 mutated gastric cancer patients.

Immune checkpoint inhibitors (ICIs) improve overall survival in patients with advanced gastric cancer (GC). However, the molecular characterization of GC in ICIs responders is unclear. A total of 288 advanced GC patients were included in this study. Next-generation sequencing analysis was performed on tumor tissue and paired blood to screen for somatic mutants in 639 tumor-associated genes. We demonstrated that ARID1A, HER2/3/4, KMT2C/2D, LRP1B, PIK3CA, SPTA1, and TP53 mutations were significantly correlated with high tumor mutation burden (TMB) score, as well as HER2 amplification. For HER2 and PIK3CA mutations types, this relationship was statistically significant with age and TP53 mutation status, which was also found in the CDH1 gene. These results were confirmed by sequencing 873 GC cases in the cBioPortal database. PIK3CA mutations appear to be associated with longer survival in elderly population and TP53 mutant subtypes. For the first time, we found that GC patients ≥60 years old or with TP53 mutated type and PIK3CA mutations were associated with higher TMB and better ICI response. Building upon the age and TP53 mutation status, this study suggested a novel stratification approach to GC patients and explored the correlations between genetic somatic mutations and TMB score.

FUT2 inhibits the EMT and metastasis of colorectal cancer by increasing LRP1 fucosylation.

BACKGROUND: Fucosyltransferase 2(FUT2) and its induced α-1,2 fucosylation is associated with cancer metastasis. However, the role of FUT2 in colorectal cancer (CRC) metastasis remains unclear. METHODS: The expression levels and clinical analyses of FUT2 were assessed in CRC samples. Migration and invasion assays, EMT detection, nude mice peritoneal dissemination models and intestinal specific FUT2 knockout mice (FUT2△IEC mice) were used to investigate the effect of FUT2 on metastasis in colorectal cancer. Quantitative proteomics study of glycosylated protein, UEA enrichment, Co-immunoprecipitation identified the mediator of the invasive-inhibiting effects of FUT2. RESULTS: FUT2 is downregulated in CRC tissues and is positively correlated with the survival of CRC patients. FUT2 is an inhibitor of colorectal cancer metastasis which, when overexpressed, suppresses invasion and tumor dissemination in vitro and in vivo. FUT2 knock-out mice (FUT2△IEC mice) develop AMO and DSS-induced tumors and promote EMT in colorectal cancers. FUT2-induced α-1,2 fucosylation impacts the ability of low-density lipoprotein receptor-related protein 1(LRP1) to suppress colorectal cancer invasion. CONCLUSIONS: Our study demonstrated that FUT2 induces α-1,2 fucosylation and inhibits EMT and metastasis of colorectal cancer through LRP1 fucosylation, suggesting that FUT2 may serve as a therapeutic target for colorectal cancer. Video Abstract.

Gene network analyses of larvae under different egg-protecting behaviors provide novel insights into immune response mechanisms of Amphioctopus fangsiao.

Amphioctopus fangsiao was a representative economic species in cephalopods, which was vulnerable to marine bacteria. Vibrio anguillarum was a highly infectious pathogen that have recently been found to infect A. fangsiao and inhibit its growth and development. There were significant differences in the immune response mechanisms between egg-protected and egg-unprotected larvae. To explore larval immunity under different egg-protecting behaviors, we infected A. fangsiao larvae with V. anguillarum for 24 h and analyzed the transcriptome data about egg-protected and egg-unprotected larvae infected with 0, 4, 12, and 24 h using weighted gene co-expression networks (WGCNA) and protein-protein interaction (PPI) networks. Network analyses revealed a series of immune response processes after infection, and identified six key modules and multiple immune-related hub genes. Meanwhile, we found that ZNF family, such as ZNF32, ZNF160, ZNF271, ZNF479, and ZNF493 might play significant roles in A. fangsiao immune response processes. We first creatively combined WGCNA and PPI network analysis to deeply explore the immune response mechanisms of A. fangsiao larvae with different egg-protecting behaviors. Our results provided further insights into the immunity of V. anguillarum infected invertebrates, and laid the foundation for exploring the immune differences among cephalopods with different egg protecting behaviors.

Sequencing-based network analysis provides a core set of genes for understanding hemolymph immune response mechanisms against Poly I:C stimulation in Amphioctopus fangsiao.

Aquatic viruses can spread rapidly and widely in seawater for their high infective ability. Polyinosinic-polycytidylic acid (Poly I:C), a viral dsRNA analog, is an immunostimulant that has been proved to activate various immune responses of immune cells in invertebrate. Hemolymph is a critical site that host immune response in invertebrates, and its transcriptome information obtained from Amphioctopus fangsiao stimulated by Poly I:C is crucial for understanding the antiviral molecular mechanisms of this species. In this study, we analyzed gene expression data in A. fangsiao hemolymph tissue within 24 h under Poly I:C stimulation and found 1082 and 299 differentially expressed genes (DEGs) at 6 and 24 h, respectively. Union set (1,369) DEGs were selected for subsequent analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out for identifying DEGs related to immunity. Several significant immune-related terms and pathways, such as toll-like receptor signaling pathways term, inflammatory response term, TNF signaling pathway, and chemokine signaling pathway were identified. A protein-protein interaction (PPI) network was constructed for examining the relationships among immune-related genes. Finally, 12 hub genes, including EGFR, ACTG1, MAP2K1, and other nine hub genes, were identified based on the KEGG enrichment analysis and PPI network. The quantitative RT-PCR (qRT-PCR) was used to verify the expression profile of 12 hub genes. This research provides a reference for solving the problem of high mortality of A. fangsiao and other mollusks and provides a reference for the future production of some disease-resistant A. fangsiao.