No causal association between the volume of strenuous exercise and coronary atherosclerosis: a two-sample Mendelian randomization study.

Objective: Several observational studies have shown that high-volume and high-intensity exercise training increases the prevalence and severity of coronary atherosclerosis, but the causal effect still remains uncertain. This study aims to explore the causal relationship between the volume of strenuous exercise (SE) and coronary atherosclerosis (CA) using the Mendelian randomization (MR) method. Method: The exposure factors were two basic parameters of the volume of strenuous exercise (duration and frequency of strenuous exercise), the outcome factor was coronary atherosclerosis, and the relevant genetic loci were extracted from the summary data of the genome-wide association study (GWAS) as the instrumental variables, and MR analyses were performed using the inverse variance weighting (IVW) method, the weighted median method, and the MR-egger method. Sensitivity analyses were performed using heterogeneity analysis, pleiotropy analysis, and the "leave-one-out" method. The original results were tested using other coronary atherosclerosis data sets. Result: IVW results showed no causal association between duration of strenuous exercise (DOSE) [OR = 0.9937, 95% CI (0.9847, 1.0028), P = 0.1757] and frequency of strenuous exercise (FOSE) in the last 4 weeks [OR = 0.9930, 95% CI (0.9808, 1.0054), P = 0.2660] and coronary atherosclerosis. All of the above results were validated with other coronary atherosclerosis data sets. Conclusion: The present study supports that the causal association of duration and frequency of SE with CA was not found, and provides valuable insights into the choice of scientific and correct volume of SE to cardiac rehabilitation (CR).

Identification of host proteins interacting with the E protein of porcine epidemic diarrhea virus.

Introduction: Porcine epidemic diarrhea (PED) is an acute, highly contagious, and high-mortality enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV). PEDV is globally endemic and causes substantial economic losses in the swine industry. The PEDV E protein is the smallest structural protein with high expression levels that interacts with the M protein and participates in virus assembly. However, how the host proteins interact with E proteins in PEDV replication remains unknown. Methods: We identified host proteins that interact with the PEDV E protein using a combination of PEDV E protein-labeled antibody co-immunoprecipitation and tandem liquid-chromatography mass-spectroscopy (LC-MS/MS). Results: Bioinformatical analysis showed that in eukaryotes, ribosome biogenesis, RNA transport, and amino acid biosynthesis represent the three main pathways that are associated with the E protein. The interaction between the E protein and isocitrate dehydrogenase [NAD] ß-subunit (NAD-IDH-ß), DNA-directed RNA polymerase II subunit RPB9, and mRNA-associated protein MRNP 41 was validated using co-immunoprecipitation and confocal assays. NAD-IDH-ß overexpression significantly inhibited viral replication. Discussion: The antiviral effect of NAD-IDH-ß suggesting that the E protein may regulate host metabolism by interacting with NAD-IDH-ß, thereby reducing the available energy for viral replication. Elucidating the interaction between the PEDV E protein and host proteins may clarify its role in viral replication. These results provide a theoretical basis for the study of PEDV infection mechanism and antiviral targets.

Quercetin inhibition of porcine intestinal alpha coronavirus in vitro and in vivo.

BACKGROUND: Porcine acute diarrhea syndrome coronavirus (SADS-CoV) is one of the novel pathogens responsible for piglet diarrhea, contributing to substantial economic losses in the farming sector. The broad host range of SADS-CoV raises concerns regarding its potential for cross-species transmission. Currently, there are no effective means of preventing or treating SADS-CoV infection, underscoring the urgent need for identifying efficient antiviral drugs. This study focuses on evaluating quercetin as an antiviral agent against SADS-CoV. RESULTS: In vitro experiments showed that quercetin inhibited SADS-CoV proliferation in a concentration-dependent manner, targeting the adsorption and replication stages of the viral life cycle. Furthermore, quercetin disrupts the regulation of the P53 gene by the virus and inhibits host cell cycle progression induced by SADS-CoV infection. In vivo experiments revealed that quercetin effectively alleviated the clinical symptoms and intestinal pathological damage caused by SADS-CoV-infected piglets, leading to reduced expression levels of inflammatory factors such as TLR3, IL-6, IL-8, and TNF-α. CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.

Nucleoside-diphosphate kinase of uropathogenic Escherichia coli inhibits caspase-1-dependent pyroptosis facilitating urinary tract infection.

Uropathogenic Escherichia coli (UPEC) is the most common causative agent of urinary tract infection (UTI). UPEC invades bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol, and establishes biofilm-like intracellular bacterial communities (IBCs). Nucleoside-diphosphate kinase (NDK) is secreted by pathogenic bacteria to enhance virulence. However, whether NDK is involved in UPEC pathogenesis remains unclear. Here, we find that the lack of ndk impairs the colonization of UPEC CFT073 in mouse bladders and kidneys owing to the impaired ability of UPEC to form IBCs. Furthermore, we demonstrate that NDK inhibits caspase-1-dependent pyroptosis by consuming extracellular ATP, preventing superficial BEC exfoliation, and promoting IBC formation. UPEC utilizes the reactive oxygen species (ROS) sensor OxyR to indirectly activate the regulator integration host factor, which then directly activates ndk expression in response to intracellular ROS. Here, we reveal a signaling transduction pathway that UPEC employs to inhibit superficial BEC exfoliation, thus facilitating acute UTI.

Deoxycholic acid inhibits ASFV replication by inhibiting MAPK signaling pathway.

African swine fever (ASF) is an acute, febrile, highly contagious infection of pigs caused by the African swine fever virus (ASFV). The purpose of this study is to understand the molecular mechanism of ASFV infection and evaluate the effect of DCA on MAPK pathway, so as to provide scientific basis for the development of new antiviral drugs. The transcriptome analysis found that ASFV infection up-regulated the IL-17 and MAPK signaling pathways to facilitate viral replication. Metabolome analysis showed that DCA levels were up-regulated after ASFV infection, and that exogenous DCA could inhibit activation of the MAPK pathway by ASFV infection and thus inhibit viral replication. Dual-luciferase reporter assays were used to screen the genes of ASFV and revealed that I73R could significantly up-regulate the transcription level of AP-1 transcription factor in the MAPK pathway. Confocal microscopy demonstrated that I73R could promote AP-1 entry into the nucleus, and that DCA could inhibit the I73R-mediated nuclear entry of AP-1, inhibiting MAPK pathway, and I73R interacts with AP-1. These results indicated that DCA can inhibit ASFV-mediated activation of the MAPK pathway, thus inhibiting ASFV replication. This study provides a theoretical basis for research on ASF pathogenesis and for antiviral drug development.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis.

The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Zinc-doped bioactive glass-functionalized polyetheretherketone to enhance the biological response in bone regeneration.

Polyether ether ketone (PEEK) is gaining recognition as a highly promising polymer for orthopedic implants, attributed to its exceptional biocompatibility, ease of processing, and radiation resistance. However, its long-term in vivo application faces challenges, primarily due to suboptimal osseointegration from postimplantation inflammation and immune reactions. Consequently, biofunctionalization of PEEK implant surfaces emerges as a strategic approach to enhance osseointegration and increase the overall success rates of these implants. In our research, we engineered a multifaceted PEEK implant through the in situ integration of chitosan-coated zinc-doped bioactive glass nanoparticles (Zn-BGNs). This novel fabrication imbues the implant with immunomodulatory capabilities while bolstering its osseointegration potential. The biofunctionalized PEEK composite elicited several advantageous responses; it facilitated M2 macrophage polarization, curtailed the production of inflammatory mediators, and augmented the osteogenic differentiation of bone marrow mesenchymal stem cells. The experimental findings underscore the vital and intricate role of biofunctionalized PEEK implants in preserving normal bone immunity and metabolism. This study posits that utilizing chitosan-BGNs represents a direct and effective method for creating multifunctional implants. These implants are designed to facilitate biomineralization and immunomodulation, making them especially apt for orthopedic applications.

Porcine alveolar macrophages host proteins interacting with African swine fever virus p72.

Introduction: African swine fever virus (ASFV) is a highly contagious virus that spreads rapidly and has a mortality rate of up to 100% in domestic pigs, leading to significant economic losses in the pig industry. The major capsid protein p72 of ASFV plays a critical role in viral invasion and immune evasion. Methods: In this study, we used yeast two-hybrid screening to identify host proteins interacting with p72 in porcine alveolar macrophages (PAMs) and verified these proteins using confocal microscopy and immunoprecipitation techniques. Results and Discussion: We validated 13 proteins that interact with p72, including CD63, B2M, YTHDF2, FTH1, SHFL, CDK5RAP3, VIM, PELO, TIMP2, PHYH, C1QC, CMAS, and ERCC1. Enrichment analysis and protein-protein interaction network analysis of these interacting proteins revealed their involvement in virus attachment, invasion, replication, assembly, and immune regulation. These findings provide new insights into the function of p72 and valuable information for future research on the interaction between ASFV and host proteins.

Calycosin (CA) inhibits proliferation, migration and invasion by suppression of CXCL10 signaling pathway in glioma.

Glioblastoma is the most common malignant tumor in the central nervous system and its occurrence and development is involved in various molecular abnormalities. C-X-C chemokine ligand 10 (CXCL10), an inflammatory chemokine, has been reported to be related to the pathogenesis of cancer while it has not yet been linked to glioma. Calycosin, a bioactive compound derived from Radix astragali, has demonstrated anticancer properties in several malignancies, including glioma. Nonetheless, its underlying mechanisms are not fully understood. This study explores CXCL10 as a potential therapeutic target for calycosin in the suppression of glioblastoma. We observed that CXCL10 expression correlates positively with glioma malignancy and inversely with patient prognosis, highlighting its potential as a glioblastoma treatment target. Furthermore, we found that calycosin inhibited proliferation, migration, and invasion in U87 and U251 glioma cells, and decreased CXCL10 expression in a dose-dependent manner, along with its downstream effectors such as NLRP3, NF-κB, and IL-1ß. Additionally, molecular docking experiments demonstrated that calycosin exhibits a notable binding affinity to CXCL10. Overexpression of CXCL10 counteracted the inhibitory effects of calycosin on cell proliferation, migration, and invasion, while CXCL10 knockdown enhanced these effects. Finally, we verified that calycosin inhibited glioma growth in a xenograft mouse model and downregulated CXCL10 and its downstream molecules. These findings suggest that targeting CXCL10 may be an effective strategy in glioblastoma treatment, and calycosin emerges as a potential therapeutic agent.

Silencing of matrix metalloprotease-12 delays the progression of castration-resistant prostate cancer by regulating autophagy and lipolysis

Abstract The complex pathogenesis of castration-resistant prostate cancer (CRPC) makes it challenging to identify effective treatment methods. Matrix metalloproteinase (MMP)-12 can degrade elastin as well as various extracellular matrix (ECM) components, which is associated with cancer progression. However, the relationship between MMP-12 and CRPC progression is poorly understood. In this study, we observed the effect of MMP-12 on the progression of CRPC and further explored its potential mechanism of action. High levels of MMP-12 were observed in patients with CRPC. We therefore developed cell co-culture and mouse models to study the function of MMP-12. Silencing MMP-12 in CRPC cells disrupted lipid utilization and autophagy marker expression via the CD36/CPT1 and P62/LC3 pathways, respectively, leading to reduced CRPC cell migration and invasion. Moreover, animal experiments confirmed that MMP-12-knockdown CRPC xenograft tumors exhibited reduced tumor growth, and the mechanisms involved the promotion of cancer cell autophagy and the inhibition of lipid catabolism. According to our results, MMP-12 played important roles in the progression of CRPC by disrupting adipocyte maturation and regulating cancer migration and invasion via the modulation of autophagy and lipid catabolism pathways.

Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.

INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Material Hardship Predicts Response Bias in Loss-Averse Decisions: The Roles of Anxiety and Cognitive Control.

Income poverty is associated with an enhanced tendency to avoid losses in economic decisions, which can be driven by a response bias (risk avoidance) and a valuation bias (loss aversion). However, the impact of non-income dimensions of poverty on these biases remains unclear. The current study tested the impact of material hardship on these biases, and the mediating effects of anxiety, depression, and cognitive control in these associations. Healthy adults (N = 188) completed questionnaire and behavioral measures of the variables. Results of regression-based analyses showed that participants who reported higher material hardship exhibited greater response bias, but not valuation bias. This effect was mediated by anxiety. Although material hardship predicted lower cognitive control, cognitive control did not mediate the association between material hardship and either type of bias. These findings suggest that material hardship may lead to economic decision-making biases because it impacts emotional states rather than cognitive control.

De Novo Atomistic Discovery of Disordered Mechanical Metamaterials by Machine Learning.

Architected materials design across orders of magnitude length scale intrigues exceptional mechanical responses nonexistent in their natural bulk state. However, the so-termed mechanical metamaterials, when scaling bottom down to the atomistic or microparticle level, remain largely unexplored and conventionally fall out of their coarse-resolution, ordered-pattern design space. Here, combining high-throughput molecular dynamics (MD) simulations and machine learning (ML) strategies, some intriguing atomistic families of disordered mechanical metamaterials are discovered, as fabricated by melt quenching and exemplified herein by lightweight-yet-stiff cellular materials featuring a theoretical limit of linear stiffness-density scaling, whose structural disorder-rather than order-is key to reduce the scaling exponent and is simply controlled by the bonding interactions and their directionality that enable flexible tunability experimentally. Importantly, a systematic navigation in the forcefield landscape reveals that, in-between directional and non-directional bonding such as covalent and ionic bonds, modest bond directionality is most likely to promotes disordered packing of polyhedral, stretching-dominated structures responsible for the formation of metamaterials. This work pioneers a bottom-down atomistic scheme to design mechanical metamaterials formatted disorderly, unlocking a largely untapped field in leveraging structural disorder in devising metamaterials atomistically and, potentially, generic to conventional upscaled designs.

Supramolecular assembly of blue and green halide perovskites with near-unity photoluminescence.

The metal-halide ionic octahedron is the optoelectronic unit for halide perovskites, and a crown ether-assisted supramolecular assembly approach can pack various ionic octahedra into tunable symmetries. In this work, we demonstrate near-unity photoluminescence quantum yield (PLQY) blue and green emission with the supramolecular assembly of hafnium (Hf) and zirconium (Zr) halide octahedral clusters. (18C6@K)2HfBr6 powders showed blue emission with a near-unity PLQY (96.2%), and green emission was also achieved with (18C6@K)2ZrCl4Br2 powders at a PLQY of 82.7%. These highly emissive powders feature facile low-temperature solution-based synthesis conditions and maintain high PLQY in solution-processable semiconductor inks under ambient conditions, and they were used in thin-film displays and emissive three-dimensional-printed architectures that exhibited high spatial resolution.

Dietary supplementation of benzoic acid and essential oils combination enhances intestinal resilience against LPS stimulation in weaned piglets.

BACKGROUND: The benefits of combining benzoic acid and essential oils (BAO) to mitigate intestinal impairment during the weaning process have been well established, while the detailed underlying mechanism has not been fully elucidated. Previous research has primarily focused on the reparative effects of BAO on intestinal injury, while neglecting its potential in enhancing intestinal stress resistance. METHODS: In this study, we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure. Piglets were pre-supplemented with BAO for 14 d, followed by a challenge with LPS or saline to collect blood and intestinal samples. RESULTS: Our findings demonstrated that BAO supplementation led to significant improvements in piglets' final weight, average daily gain, and feed intake/body gain ratio. Additionally, BAO supplementation positively influenced the composition of intestinal microbiota, increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota, Prevotella and Oscillospira. Furthermore, BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge. This was evidenced by elevated levels of T-AOC, SOD, and GSH, as well as decreased levels of MDA, TNF-α, and IL-6 in the plasma. Moreover, piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity, as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts. Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway. Additionally, the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO. CONCLUSIONS: In summary, our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition, reinforcing the intestinal barrier, and enhancing antioxidative and anti-inflammatory capabilities. These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

In-sample stability and postsampling analysis of 21 illicit drugs, their metabolites and cotinine in wastewater.

A thorough understanding of the degradation of chemical biomarkers in wastewater after the sampling is critical in the surveillance of illicit drug use based on the back-calculation technique. Herein, three temperatures, eight groups of matrices, and acidification were applied to simulate the preservation condition of 21 illicit drugs, their metabolites, and cotinine for a 240-day stability study. It was proved that the temperature, matrices, and acidification play vital roles in their stability in wastewater. Most of them demonstrated high stability (transformation rates < 20%) during room temperature for 45 days, and the transformation rates decreased while the storage temperature reduced. The stability of the target compounds such as cocaine (COC), 6-monoacetylmorphine (6-MAM), and amphetamine (AM) is influenced by matrices. Acidification prevented the majority of analytes from transforming, making it a feasible solution for preservation after sampling. A model that combined the effects of temperature and matrix was developed to back-calculate the concentration of target compounds during the postsampling process. The feasibility of this model was validated by correcting the loss of COC and 6-MAM from 24.2% and 16.2% to 2.98% and 2.77%. This study simulated a typical large-scale sampling and storage scenario. The effect of the temperature, pH, and matrix on in-sample stability and the postsampling analysis of selected target compounds was investigated for the first time in this study.

MKK3 Cascade Regulates Seed Dormancy Through a Negative Feedback Loop Modulating ABA Signal in Rice.

BACKGROUND: With the increasing frequency of climatic anomalies, high temperatures and long-term rain often occur during the rice-harvesting period, especially for early rice crops in tropical and subtropical regions. Seed dormancy directly affects the resistance to pre-harvest sprouting (PHS). Therefore, in order to increase rice production, it is critical to enhance seed dormancy and avoid yield losses to PHS. The elucidation and utilization of the seed dormancy regulation mechanism is of great significance to rice production. Preliminary results indicated that the OsMKKK62-OsMKK3-OsMPK7/14 module might regulate ABA sensitivity and then control seed dormancy. The detailed mechanism is still unclear. RESULTS: The overexpression of OsMKK3 resulted in serious PHS. The expression levels of OsMKK3 and OsMPK7 were upregulated by ABA and GA at germination stage. OsMKK3 and OsMPK7 are both located in the nucleus and cytoplasm. The dormancy level of double knockout mutant mkk3/mft2 was lower than that of mkk3, indicating that OsMFT2 functions in the downstream of MKK3 cascade in regulating rice seeds germination. Biochemical results showed that OsMPK7 interacted with multiple core ABA signaling components according to yeast two-hybrid screening and luciferase complementation experiments, suggesting that MKK3 cascade regulates ABA signaling by modulating the core ABA signaling components. Moreover, the ABA response and ABA responsive genes of mpk7/14 were significantly higher than those of wild-type ZH11 when subjected to ABA treatment. CONCLUSION: MKK3 cascade mediates the negative feedback loop of ABA signal through the interaction between OsMPK7 and core ABA signaling components in rice.

Abnormalities in brain structure following childhood unpredictability: a mechanism underlying depressive and anxiety symptoms.

BACKGROUND: Childhood adversity is associated with abnormalities in brain structure, but this association has not been tested for childhood unpredictability, one form of adversity. We studied whether abnormalities in gray matter volume (GMV) could be a mechanism linking childhood unpredictability and psychopathology, over and above the effect of childhood trauma. METHODS: Participants were 158 right-handed healthy young adults (aged 17-28 years, M = 22.07, s.d. = 2.08; 66.46% female) who underwent structural magnetic resonance imaging measurements and provided retrospective reports of childhood unpredictability. The anxiety and depression subscales of the self-report Brief Symptom Inventory-53 were used to index psychopathology. RESULTS: Whole-brain voxel-based morphometric analyses showed that after controlling for the effect of childhood trauma, childhood unpredictability was correlated with greater GMV in bilateral frontal pole, bilateral precuneus, bilateral postcentral gyrus, right hemisphere of fusiform, and lingual gyrus, and left hemisphere of ventrolateral prefrontal cortex as well as occipital gyrus. Greater GMV in bilateral frontal pole, bilateral precuneus, and bilateral postcentral gyrus mediated associations between unpredictability and symptoms of depression and anxiety. CONCLUSIONS: The findings suggest that childhood unpredictability could exact unique effects on neural development, over and above the effect of childhood trauma. These findings are relevant for understanding the occurrence of psychopathology following childhood unpredictability and have implications for intervention.

Exogenous alpha-linolenic acid and Vibrio parahaemolyticus induce EPA and DHA levels mediated by delta-6 desaturase to enhance shrimp immunity.

Globally, penaeid shrimp are the most farmed and traded aquatic organisms, although they are easily susceptible to microbial pathogens. Moreover, there is a desire to increase the nutritional value of shrimp, especially the levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which also possess immunomodulatory and anti-inflammatory properties. Some aquatic animals can synthesize EPA and DHA from dietary plant-sourced alpha-linolenic acid (ALA), but penaeid shrimps' ability to synthesize these n-3 PUFAs is unknown. Here, molecular biology techniques, including gas chromatography-mass spectrometry, qPCR, ELISA, etc., were used to demonstrate that exogenous ALA or Vibrio parahaemolyticus could modulate EPA and DHA levels and immune genes in Penaeus vannamei by inducing key enzymes involved in n-3 PUFAs biosynthesis, such as delta desaturases and elongation of very long-chain fatty acid (ELOVLs). Most importantly, knockdown or inhibition of ∆6 desaturase significantly decreased EPA and DHA levels and immune gene expression even with exogenous ALA treatment, consequently affecting shrimp antibacterial immunity and survival. This study provides new insight into the potential of P. vannamei to synthesize n-3 PUFAs from exogenous ALA or upon bacteria challenge, which could be leveraged to increase their nutritional content and antimicrobial immunity.