Key Switch Research Articles

Design of Stimuli‐Responsive Peptides and Proteins

AbstractStimuli‐responsive peptides and proteins are an exciting class of smart biomaterials for various applications and have received significant attention over the past decades. A wide variety of stimuli such as temperature, pH, ions, enzymes, magnetic field, redox, etc., are explored. This article provides a review of five intensively studied types of stimuli‐responsive peptides and proteins, their design principles and applications, including temperature‐, pH‐, light‐, metal ion‐, and enzyme‐responsive with an emphasis on the key design concepts and switch function. Moreover, typical examples of their applications are discussed to provide a better understanding of the design concept and underlying methodology. This review will facilitate and inspire future innovation toward new peptide‐ and protein‐based materials and their diverse applications.

DUSP9 alleviates hepatic ischemia/reperfusion injury by restraining both mitogen-activated protein kinase and IKK in an apoptosis signal-regulating kinase 1-dependent manner.

Hepatic ischemia/reperfusion (I/R) injury occurs frequently in various liver operations and diseases, but its effective treatment remains inadequate because the key switch that leads to hepatic explosive inflammation has not been well disclosed. Dual specificity phosphatase 9 (DUSP9) is widely involved in the innate immune response of solid organs and is sometimes regulated by ubiquitin. In the present study, we find that DUSP9 is reduced in mouse hepatic I/R injury. DUSP9 enrichment attenuates hepatic inflammation both in vivo and in vitro as revealed by western blot analysis and qRT-PCR. In contrast, DUSP9 depletion leads to more severe I/R injury. Mechanistically, DUSP9 inhibits the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) by directly binding to ASK1, thereby decreasing tumor necrosis factor receptor-associated factor 6 (TRAF6), K63 ubiquitin and the phosphorylation of p38/JNK1 instead of ERK1. The present study documents a novel role of DUSP9 in hepatic I/R injury and implies the potential of targeting the DUSP9/ASK1 axis towards mitogen-activated protein kinase and TRAF6/inhibitor of κB kinase pathways.

Reconstitution of a Reversible Membrane Switch via Prenylation by One-Pot Cell-Free Expression.

Reversible membrane targeting of proteins is one of the key regulators of cellular interaction networks, for example, for signaling and polarization. So-called "membrane switches" are thus highly attractive targets for the design of minimal cells but have so far been tricky to reconstitute in vitro. Here, we introduce cell-free prenylated protein synthesis (CFpPS), which enables the synthesis and membrane targeting of proteins in a single reaction mix including the prenylation machinery. CFpPS can confer membrane affinity to any protein via addition of a 4-peptide motif to its C-terminus and offers robust production of prenylated proteins not only in their soluble forms but also in the direct vicinity of biomimetic membranes. Thus, CFpPS enabled us to reconstitute the prenylated polarity hub Cdc42 and its regulatory protein in vitro, implementing a key membrane switch. We propose CFpPS to be a versatile and effective platform for engineering complex features, such as polarity induction, in synthetic cells.

A Blockchain-Based Data Sharing System with Enhanced Auditability

Cloud platforms provide a low-cost and convenient way for users to share data. One important issue of cloud-based data sharing systems is how to prevent the sensitive information contained in users’ data from being disclosed. Existing studies often utilize cryptographic primitives, such as attribute-based encryption and proxy re-encryption, to protect data privacy. These approaches generally rely on a centralized server which may cause a single point of failure problem. Blockchain is known for its ability to solve such a problem. Some blockchain-based approaches have been proposed to realize privacy-preserving data sharing. However, these approaches did not fully explore the auditability provided by the blockchain. The dishonest cloud server can share data with a requester without notifying the data owner or being logged by the blockchain. In this paper, we propose a blockchain-based privacy-preserving data sharing system with enhanced auditability. The proposed system follows the idea of hybrid encryption to protect data privacy. The data to be shared are encrypted with a symmetric key, and the symmetric key is encrypted with a joint public key which is the sum of multiple blockchain nodes’ public keys. Only if a data requester is authorized, the blockchain nodes will be triggered to execute a verifiable key switch protocol. By using the output of the protocol, the data requester can get the plaintext of the symmetric key. The blockchain nodes participate in both the authorization process and the key switch process, which means the behavior of the data requester is witnessed by multi-parties and is auditable. We implement the proposed system on Hyperledger Fabric. The simulation results show that the performance overhead is acceptable.

Light‐Mediated Multi‐Level Flexible Copper Iodide Resistive Random Access Memory for Forming‐Free, Ultra‐Low Power Data Storage Application

AbstractThis study demonstrates the efficacy of an emerging p‐type copper iodide (CuI) semiconductor in a flexible, low‐voltage resistive random‐access memory (RRAM), which can be readily integrated with metal‐oxide n‐type counterparts for complementary circuit systems. Herein, CuI RRAM devices are implemented via a room‐temperature solid iodination process, exhibiting a consistent On/Off ratio (≈104), excellent endurance of more than ≈103 cycles, together with a long retention period (> 5 × 104 s). Furthermore, a scheme of light‐mediated multi‐level data storage is demonstrated using blue light illumination (λ = 455 nm), to exploit possible photonic memristive functionality through notable photo‐response of CuI. In addition, the current conduction and resistive switching behaviors are systematically studied via low‐temperature measurements from 203 to 343 K, validating thermal stability and the governing key switching mechanism in CuI RRAM devices. The longstanding problem with CuI device longevity is effectively addressed via PMMA encapsulation, resulting in a 15‐fold improvement in the lifespan of devices even in air, as compared with non‐passivated devices. These findings suggest that flexible optoelectronic systems, combined with reliable, ultra‐low power CuI RRAM devices with photo memristive functionality, can leverage the enhancement of multifunctional selectors required in process‐in‐memories and the synaptic elements of neuromorphic applications.

EPCO-13. IDENTIFYING REGULATORS OF GLIOMA CELL STATE DIVERSITY AND EVOLUTION VIA JOINT SINGLE NUCLEUS RNA AND CHROMATIN ACCESSIBILITY

Abstract Glioma cellular heterogeneity and plasticity represent fundamental obstacles to effective therapies. Understanding the determinants that govern glioma cell diversity and adaptability is critical to overcoming treatment resistance. Recent single cell DNA methylation studies have demonstrated that dynamic epigenetic alterations facilitate glioma cell state shifts and stress response. However, information regarding other modes of epigenetic gene regulation, such as chromatin accessibility, and how therapy shapes cellular heterogeneity remains limited. To determine the critical regulators of glioma cell state plasticity under treatment, we profiled 36 tumors (n = 23 adult patients) with joint single nucleus RNA and ATACseq including 13 longitudinal initial – recurrent pairs that yielded a total of 79,945 cells (37,883 malignant cells). We identified chromatin peaks that were uniquely open in glioma cells (n = 14,462 peaks, FDR < 0.05) compared with tumor microenvironmental cells including neuronal, perivascular, glial, and immune populations. Among malignant cells, differentiated-like cells exhibited more recurrent regions of accessibility than stem-like cells. These populations could be further delineated by differential peak enrichment of transcription factor binding sites in the stem-like (TCF12, ASCL1), differentiated-like (SMARCC1, JUN), and proliferating stem-like (E2F4) malignant cells nominating these transcription factors as master regulators. We confirmed that these cell state-specific open chromatin peaks overlapped enhancer regions via single nucleus multiomics and bulk H3K27ac profiling in 3 patient-derived cell lines. We further demonstrated that there are cell state-specific chromatin changes at recurrence with a trend toward a more open chromatin state that was associated with coordinated transcriptional changes. Finally, we incorporated matched longitudinal whole genome sequencing data to evaluate mutational profiles and differentiate between predominantly epigenetically driven changes and epigenomic co-evolution with the genome. Together, these findings define the key epigenetic switches that shape glioma cell states and facilitate plasticity during tumor progression.

Structural basis of the key residue W320 responsible for Hsp90 conformational change

The 90-kDa heat shock protein (Hsp90) is a homodimeric molecular chaperone with ATPase activity, which has become an intensely studied target for the development of drugs for the treatment of cancer, neurodegenerative and infectious diseases. The equilibrium between Hsp90 dimers and oligomers is important for modulating its function. In the absence of ATP, the passive chaperone activity of Hsp90 dimers and oligomers has been shown to stabilize client proteins as a holdase, which enhances substrate binding and prevents irreversible aggregation and precipitation of the substrate proteins. In the presence of ATP and its associated cochaperones, Hsp90 homodimers act as foldases with the binding and hydrolysis of ATP driving conformational changes that mediate client folding. Crystal structures of both wild type and W320A mutant Hsp90αMC (middle/C-terminal domain) have been determined, which displayed a preference for hexameric and dimeric states, respectively. Structural analysis showed that W320 is a key residue for Hsp90 oligomerization by forming intermolecular interactions at the Hsp90 hexameric interface through cation-π interactions with R367. W320A substitution results in the formation of a more open conformation of Hsp90, which has not previously been reported, and the induction of a conformational change in the catalytic loop. The structures provide new insights into the mechanism by which W320 functions as a key switch for conformational changes in Hsp90 self-oligomerization, and binding cochaperones and client proteins. Communicated by Ramaswamy H. Sarma

Identifying ligand-binding specificity of the oligopeptide receptor OppA from Bifidobacterium longum KACC91563 by structure-based molecular modeling

As a ATP-binding cassette (ABC) transporter the OppA receptor plays key roles in protecting the host organism and transporting nutrients across the intestine by the oligopeptide transporter from symbiotic bacteria and directs maturation of the host immune system. Among lactic acid bacteria, Bifidobacterium longum KACC91563, isolated from fecal samples of healthy Korean neonates, has the capability to alleviate food allergy effects. Operating as a peptide importer, the extracellular OppA receptor from gram-positive B. longum KACC91563 translocates nutrients, specifically peptides, from the outside environment of the intestinal tract to the inside of symbiotic cells. In the present study we attempt to explicate the relationship between the substrate’s specificity from the OppA importer and the probiotic effects of B. longum KACC91563 in the host intestine. It was first identified in this study the specialized structure–function relationship from the OppA importer of B. longum KACC91563 with its structural and functional determinants. This could provide insights into substrate specificity of unique immunological properties and a key switch for the substrate’s metabolism to reprogramming immune responses in the host intestine by structure-based molecular modeling. The probiotic effects of oligopeptide substrate (such as a proline-rich peptide containing at least one branched residue of leucine, isoleucine, and valine) and its metabolism for the OppA from B. longum KACC91563 are attributed to enhancement of the epithelial barrier by several different strain specific pathways to prevent the strong adhesion of pathogens.

Role of CXCR3 in fibrotic tissue responses.

Development of fibrosis leads to end stage diseases that defy treatments across all organs. This ensues as chronic inflammation is not dampened by physiologic processes that issue in the resolution phase of wound healing. Thus, these conditions can be considered diseases of "failure to heal". In the absence of broadly viable treatments, it is proposed to examine key switches in wound healing resolution to seek insights into novel approaches. Signaling through the GPCR CXCR3 has been shown to be one such critical player in this physiologic transition that limits and even reverses early fibrosis. As such, a number of investigators and early stage technology companies have posited that triggering this signaling network would limit fibrosis. While there are some conflicting results, a consensus is emerging that pharmacologic interventions that promote signaling through this pathway represent innovative ways to limit fibrotic diseases.

Divergence of flowering-related genes to control flowering in five Euphorbiaceae genomes.

Reproductive growth and vegetative growth are a pair of main contradictions in the process of plant growth. Flowering, as part of reproductive growth, is a key switch in the life cycle of higher plants, which affects the yield and economic benefits of plants to a certain extent. The Euphorbiaceae species, including castor bean (Ricinus communis), physic nut (Jatropha curcas), tung tree (Vernicia fordii), cassava (Manihot esculenta), and rubber tree (Hevea brasiliensis), have important economic values because they are raw materials for the production of biodiesel, rubber, etc. The flowering mechanisms are still excluded in the Euphorbiaceae species. The flowering-related genes of Arabidopsis thaliana (Arabidopsis) were used as a reference to determine the orthologs of these genes in Euphorbiaceae genomes. The result showed that 146, 144, 114, 114, and 149 of 207 A. thaliana genes were respectively matched to R. communis, V. fordii, J. curcas, H. brasiliensis, and M. esculenta. These identified genes were clustered into seven pathways including gibberellins, floral meristem identity (FMI), vernalization, photoperiod, floral pathway integrators (FPIs), and autonomous pathways. Then, some key numbers of flowering-related genes are widely conserved in the Euphorbiaceae genomes including but not limited to FPI genes LFY, SOC1, FT, and FMI genes AG, CAL, and FUL. However, some genes, including FRI, FLC, and GO, were missing in several or all five Euphorbiaceae species. In this study, we proposed the putative mechanisms of flowering-related genes to control flowering and provided new candidate flowering genes for using marker-assisted breeding to improve variety quality.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.

Astrocytic NDRG2-PPM1A interaction exacerbates blood-brain barrier disruption after subarachnoid hemorrhage.

Blood-brain barrier (BBB) injury critically exacerbates the poor prognosis of patients with subarachnoid hemorrhage (SAH). The massively increased matrix metalloproteinases 9 (MMP-9) plays a deleterious role in BBB. However, the main source and mechanism of MMP-9 production after SAH remain unclear. We reported that the increased MMP-9 was mainly derived from reactive astrocytes after SAH. Ndrg2 knockout in astrocytes inhibited MMP-9 expression after SAH and attenuated BBB damage. Astrocytic Ndrg2 knockout decreased the phosphorylation of Smad2/3 and the transcription of MMP-9. Notably, cytoplasmic NDRG2 bound to the protein phosphatase PPM1A and restricted the dephosphorylation of Smad2/3. Accordingly, TAT-QFNP12, a novel engineered peptide that could block the NDRG2-PPM1A binding and reduce Smad2/3 dephosphorylation, decreased astrocytic MMP-9 production and BBB disruption after SAH. In conclusion, this study identified NDRG2-PPM1A signaling in reactive astrocytes as a key switch for MMP-9 production and provided a novel therapeutic avenue for BBB protection after SAH.

NRF-2/HO-1 Pathway-Mediated SHOX2 Activation Is a Key Switch for Heart Rate Acceleration by Yixin-Fumai Granules.

Population aging has led to increased sick sinus syndrome (SSS) incidence; however, no effective and safe medical therapy has been reported thus far. Yixin-Fumai granules (YXFMs), a Chinese medicine granule designed for bradyarrhythmia treatment, can effectively increase SSS patients' heart rate. Senescence-induced sinoatrial node (SAN) degeneration is an important part of SSS pathogenesis, and older people often show high levels of oxidative stress; reactive oxygen species (ROS) accumulation in the SAN causes abnormal SAN pacing or conduction functions. The current study observed the protective effects of YXFMs on senescent SAN and explored the relationship between the NRF-2/HO-1 pathway, SHOX2, and T-type calcium channels. We selected naturally senescent C57BL/6 mice with bradycardia to simulate SSS; electrocardiography, Masson's trichrome staining, and DHE staining were used to assess SAN function and tissue damage. Immunofluorescence staining and Western blotting were used to assay related proteins. In vitro, we treated human-induced pluripotent stem cell-derived atrial myocytes (hiPSC-AMs) and mouse atrial myocyte-derived cell line HL-1 with D-galactose to simulate senescent SAN-pacemaker cells. CardioExcyte96 was used to evaluate the pulsatile function of the hiPSC-AMs, and the mechanism was verified by DCFH-DA, immunofluorescence staining, RT-qPCR, and Western blotting. The results demonstrated that YXFMs effectively inhibited senescence-induced SAN hypofunction, and this effect possibly originated from scavenging of ROS and promotion of NRF-2, SHOX2, and T-type calcium channel expression. In vitro experiment results indicated that ML385, si-SHOX2, LDN193189, and Mibefradil reversed YXFMs' effects. Moreover, we, for the first time, found that ROS accumulation may hinder SHOX2 expression; YXFMs can activate SHOX2 through the NRF-2/HO-1 pathway-mediated ROS scavenging and then regulate CACNA1G through the SHOX2/BMP4/GATA4/NKX2-5 axis, improve T-type calcium channel function, and ameliorate the SAN dysfunction. Finally, through network pharmacology and molecular docking, we screened for the most stable YXFMs compound that docks to NRF-2, laying the foundation for future studies.

A probabilistic public key encryption switching scheme for secure cloud storage

The high demand for user-centric applications such as secure cloud storage laid the foundation for the development of user-centric security schemes with multiple security features in recent years. But, the current state-of-art techniques primarily emphasized only one type of security feature i.e., either homomorphism or non-malleability. To fill this gap and provide a common platform for both homomorphic and non-malleable cloud applications, we have introduced a new public key-based probabilistic encryption switching method. The proposed scheme generates {mathcal {O}}(m+2 log N) bits of ciphertext where min {mathbb {N}} and m<n, nin {mathbb {N}} is the plaintext size, N is the RSA composite. The superior performance of the proposed scheme has been tested in comparison to existing methods and is reported in this paper.

Efficient Batch Fully Homomorphic Encryption with a Shorter Key from Ring-LWE

Fully homomorphic encryption allows users to use the computing resources of cloud servers for the computation of encrypted data without worrying about data leakage. The fully homomorphic encryption approach has problems with excessive noise and the expansion of the ciphertext dimension after the homomorphic evaluation. The key switching technology effectively solves the problem of the ciphertext dimension expansion. The generated evaluation key is a masked secret key that must be shared between the data owner and the computational entity, so the security must be guaranteed. In the RLWE-based FHE scheme, the efficiency improvement of the key switching depends on the circular security assumption, meaning the security needs to be improved. To solve the above problems, we select the secret key from the noise distribution with variable parameters so that the evaluation key and the initial noise of the encryption scheme are smaller. Specifically, the secret key is replaced after each homomorphic evaluation to ensure the security. We use the “modulus scaling” method to control the noise generated by itself, rather than the BitDecomp technology, which is complex when applied to polynomials. Finally, we combine the packing technology that relies on the polynomial CRT (Chinese remainder theorem) to design a batch-leveled fully homomorphic encryption scheme. We analyze the scheme’s noise, security proof, and specific security parameters. Compared with the FV12 scheme, our scheme is more secure. Compared with the MB18 scheme, our evaluation key size is smaller.

Research on efficient and accurate computing strategies for complex optimal control problems

In this study, grid refinement strategies are studied to improve computing accuracy and efficiency of the complex optimal control problems. Firstly, a solution method based on multiple variable time nodes was proposed for the optimal control problem with Bang-Bang characteristics. The problem was transformed into the Mayer formula by adding relaxed variables to eliminate integral terms. And the implementation procedure for the algorithm was also defined. Then, for optimal control problems with continuous slope changes and key switching points, a slope-based adaptive grid refinement strategy was also proposed. The time grids were able to automatically increase or decrease based on the slope information, and a new technique was used to judge the switching points and refine the corresponding time grids. Finally, the performances of the proposed methods were verified with six classical examples. The results demonstrate that they comprehensively surpass traditional methods in computing accuracy and efficiency.

Estimation of Extrinsic Parameters With Trifocal Tensor for Intelligent Vehicle-Mounted Cameras

In this article, the extrinsic parameter estimation of a camera mounted on an intelligent vehicle is addressed. The trifocal tensor is utilized to construct vision dynamics which relates image coordinates, velocity signals, and extrinsic parameters. Artificial visual patterns such as chessboards and planar reference objects used in homography-based methods are no longer required. An auxiliary tensor decouples the rotational extrinsic parameters from the translational ones. A key frame strategy is adopted to deal with the field of view constraint and an unknown distance is eliminated from the vision dynamics to counter the scale change caused by key frame switching. The Lyapunov method is used to design nonlinear observers, which estimate the extrinsic parameters at each time step based all collected valid historical data. Performance of the proposed method is verified by both simulation and experimental results.

The Regulatory Roles of Mitochondrial Calcium and the Mitochondrial Calcium Uniporter in Tumor Cells.

Mitochondria, as the main site of cellular energy metabolism and the generation of oxygen free radicals, are the key switch for mitochondria-mediated endogenous apoptosis. Ca2+ is not only an important messenger for cell proliferation, but it is also an indispensable signal for cell death. Ca2+ participates in and plays a crucial role in the energy metabolism, physiology, and pathology of mitochondria. Mitochondria control the uptake and release of Ca2+ through channels/transporters, such as the mitochondrial calcium uniporter (MCU), and influence the concentration of Ca2+ in both mitochondria and cytoplasm, thereby regulating cellular Ca2+ homeostasis. Mitochondrial Ca2+ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis. In particular, MCU and its regulatory proteins represent a new era in the study of MCU-mediated mitochondrial Ca2+ homeostasis in tumors. Through an in-depth analysis of the close correlation between mitochondrial Ca2+ and energy metabolism, autophagy, and apoptosis of tumor cells, we can provide a valuable reference for further understanding of how mitochondrial Ca2+ regulation helps diagnosis and therapy.

Colorless, partially directionless, and contentionless architecture for high-degree ROADMs

With the rapid growth of Internet traffic, there can be multiple pairs of bi-directional fibers on a network link. This leads to the need for high-degree reconfigurable optical add/drop multiplexers (ROADMs) in an optical network. However, this high-degree requirement poses new challenges to ROADMs since it is challenging and expensive for a wavelength selective switch (WSS), a key switching component in a ROADM, to expand its size. Therefore, a common strategy is to use small-size WSSs to build a high-degree ROADM. In this paper, we design a novel colorless, partially directionless, and contentionless (CpDC) ROADM architecture, in which the sizes of WSSs can be significantly reduced by partially sacrificing the directionless feature of a ROADM. The partially directionless feature may degrade the switching performance of a ROADM. Thus, to tackle this issue, we also propose an interconnection pattern for the ROADM backplane to effectively connect fiber links and add/drop modules. An analytical model is developed to evaluate the lightpath blocking performance of a single CpDC ROADM. Efficient routing, fiber, wavelength, and add/drop port assignment (RFWPA) algorithms (i.e., the shortest-path-based and waveplane-based algorithms) are also developed for lightpath establishment in an optical network made up of CpDC ROADMs, in which two wavelength selection strategies [i.e., non-interconnection aware (NIA) and interconnection aware (IA)] are further proposed. Simulation studies show that, while these achieve almost the same lightpath blocking performance as conventional CDC ROADMs, CpDC ROADMs are more effective from considerations of cost, insertion loss, and node volume. The waveplane-based RFWPA algorithm with the IA strategy is also found to be the most effective for lightpath provisioning in an optical network made up of CpDC ROADMs.

Selenium Nanoparticles (SeNPs) Immunomodulation Is More Than Redox Improvement: Serum Proteomics and Transcriptomic Analyses.

Selenium nanoparticles (SeNPs) are a novel elemental form selenium and often reported to possess beneficial bioactivities such as anticancer, promoting bone growth and immunomodulation. Our previous study demonstrated that chitosan-stabilized SeNPs have strong activity in immunomodulation. However, the mechanism underlying the immunomodulation of SeNPs is still unknown. The aim of this study is to identify the molecular mechanisms involved in SeNP-induced immunomodulation. Using zebrafish, as a common immunological animal model with a highly conserved molecular mechanism with other vertebrates, we conducted serum proteomic and tissue transcriptome analyses on individuals fed with SeNP in healthy or disease conditions. We also compared differences between SeNPs and an exogenous antioxidant Trolox in immune activity and redox regulation. Our results suggest that the immunomodulation activity was highly related to antioxidant activity and lipid metabolism. Interestingly, the biological functions enhanced by SeNP were almost identical in the healthy and disease conditions. However, while the SeNP was suppressing ROS in healthy individuals, it promoted ROS formation during disease condition. This might be related to the defense mechanism against pathogens. SOD and NFkβ appeared to be the key molecular switch changing effect of SeNPs when individuals undergo infection, indicating the close relationship between immune and redox regulation.