All-Single Bonds Fused N18 Macro-Rings and N8 Cagelike Building Blocks Stabilized in Lanthanum Supernitrides.

Single-bonded polymeric nitrogen has gained tremendous research interest because of its unique physical properties and great potential applications. Despite much progress in theoretical predictions, it is still challenging to experimentally synthesize polynitrogen compounds with novel all-single-bonded units. Herein, we have synthesized two brand-new lanthanum supernitrides LaN8, through a direct reaction between La and N2 in laser-heated diamond anvil cells at megabar pressures. Our experiments and calculations revealed that two LaN8 phases had the R-3 and P4/n symmetry characterized by a unique 2D network with N18 macro-rings and cagelike N8 building blocks, respectively. Differing from known polynitrogen structures, these two polymers were composed of single-bonded nitrogen atoms belonging to sp3 and sp2 hybridizations. In particular, P4/n LaN8 possessed the longest N-N bond length among all of the experimentally reported metal nitrides, potentially being a high-energy-density material. The present study opens a fresh, promising avenue for the rational design and discovery of new supernitrides with unique nitrogen structures via the high-pressure treatment.

In vivo dendritic cell reprogramming for cancer immunotherapy.

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells, induced tumor regressions, and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

Pressure Strategy To Improve H Atomic Utilization via Optimized Decomposition Pathway in Solid Hydrazine Borane.

Hydrazine borane (N2H4BH3, HB), a typical B-N-H compound with very high hydrogen content (15.4 wt %), is regarded as an efficient hydrogen storage material. However, during the pyrolysis at ambient pressure, solid HB decomposes, losing ∼30 wt %, which is rationalized by the evolution of hydrazine (N2H4). Here, high pressure is introduced as an analogous catalyst role that enable to optimize the decomposition pathway of solid HB. This approach improves the H atomic utilization to over 95%. Energy-dispersive spectroscopy (EDS) analysis indicates that pressure inhibits the production of N2H4, in-situ high-pressure-high-temperature Raman and in-situ high-pressure Infrared (IR) spectra, Density functional theory (DFT) calculation, and Hirshfeld analysis reveal that this inhibition is a consequence of pressure-enhanced dihydrogen and BN bonds. The superior hydrogen release properties of HB under high pressure make it a candidate for use in the synthesis of superconductor CeH9 as a hydrogen source.

Transcriptome analysis reveals high concentration of resveratrol promotes lipid synthesis and induces apoptosis in Siberian sturgeon (Acipenser baerii).

Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45ß and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.

Changes in soil properties and microbial activity unveil the distinct impact of polyethylene and biodegradable microplastics on chromium uptake by peanuts.

Microplastics (MPs) are emerging persistent pollutants, and heavy metals are typical environmental pollutants, with their coexistence potentially compounding pollution and ecological risks. However, the interactive impacts and the relevant mechanisms of heavy metal and different types of MPs in plant-soil systems are still unclear. This study investigated the differential impacts of polyethylene MPs (PE MPs) and biodegradable polybutylene adipate MPs (PBAT MPs) on chromium (Cr) uptake in peanuts, focusing on plant performance and rhizosphere soil microenvironment. Compared with nondegradable PE-MPs, biodegradable PBAT MPs produced less significant influences on plant phytotoxicity, soil Cr bioavailability, and soil properties such as pH, CEC, DOC, and MBC, with the exception of MBN in Cr-contaminated soils. Compared to the control, soil pH and cation exchange capacity (CEC) decreased by MPs, while soil-soluble carbon (DOC), microbial biomass carbon, and nitrogen (MBC and MBN) increased by MPs. Compared to the control, soil-bioavailable Cr increased by 11.8-177.8% under PE MPs treatments, while increased by 5.1-156.9% under PBAT MPs treatments. The highest Cr content in shoots and roots was observed at 500.0 mg·kg-1 Cr level, which increased by 53.1% and 79.2% under 5% PE MPs treatments, respectively, as well as increased by 38.3% and 60.4% under 5% PBAT MPs treatments, respectively, compared with the control. The regression path analysis indicated that pH, MBC, MBN, and soil-bioavailable Cr played a vital role in the changes of soil properties and Cr uptake by peanuts induced by MPs. Soil bacterial community analysis revealed that Nocardioides, Proteobacteria, and Sphingomonas were reduced by the inhibition of MPs, which affected Cr uptake by peanuts. These results indicated that the peanut soil microenvironment was affected by PBAT and PE MPs, altering the Cr bioavailability and plant Cr uptake in Cr-contaminated soil.

Toxicological effects of Honokiol on zebrafish and its underlying mechanism.

The compound Honokiol, derived from the bark of Magnolia officinalis, possesses the ability to induce apoptosis and inhibit cellular damage caused by reactive oxygen species. The objective of this study was to investigate the toxicological and histopathological effects of Honokiol on zebrafish (Danio rerio) through conducting a semistatic acute toxicity test involving immersion in an Honokiol-containing solution. The results showed that the toxic effects of Honokiol on zebrafish were primarily manifested in the liver and gills. When exposed to 0.6 mg/L of Honokiol, it could lead to liver hemorrhage as well as swelling and necrosis of gill tissues, and high concentrations of Honokiol could trigger inflammatory responses. Additionally, research found that Honokiol could induce apoptosis in liver and gill tissues through the P53 pathway and possessed the ability to enhance antioxidation. The present findings significantly contribute to a more profound understanding of the toxic impact of Honokiol and its underlying mechanism, thereby providing a valuable reference for the future safe utilization of Honokiol and related pharmaceutical advancements.

Bioelectrical Impedance Analysis to Assess Energy Expenditure in Critically Ill Patients: A Cross-Sectional Study.

BACKGROUND: Evaluating energy expenditure is important for establishing optimal goals for nutrition treatment. However, indirect calorimetry, the reference standard for measuring energy expenditure, is difficult to apply widely in clinical practice. OBJECTIVE: To test the consistency of bioelectrical impedance analysis (BIA) relative to indirect calorimetry for evaluating energy expenditure in critically ill patients. METHODS: A cross-sectional study of 140 critically ill adult patients was conducted. Within 24 hours of a patient being transferred to the intensive care unit, trained researchers assessed the patient's energy expenditure by use of BIA and indirect calorimetry simultaneously. Consistency of the 2 measurements was detected by intraclass correlation coefficients with a 2-way random-effects model. Factors affecting consistency were analyzed. RESULTS: Median energy expenditure measured by indirect calorimetry was 1430.0 kcal/d (IQR, 1190.5-1650.8 kcal/d). Median energy expenditure measured by BIA was 1407.0 kcal/d (IQR, 1248.5-1563.5 kcal/d). The correlation coefficient between indirect calorimetry and BIA was 0.813 (95% CI, 0.748-0.862; P < .001). The consistency of the 2 measurements was lower in patients with comorbidities than in those without (P = .004). CONCLUSIONS: Results of BIA were highly consistent with indirect calorimetry assessments of energy expenditure in critically ill patients. Few factors except comorbidity affect the accuracy of BIA when assessing energy expenditure. Therefore, as a low-cost, easy-to-use, and noninvasive method, BIA is a valuable clinical tool for assessing energy expenditure in critically ill patients.

Reprogramming human B cells with custom heavy-chain antibodies.

The immunoglobulin locus of B cells can be reprogrammed by genome editing to produce custom or non-natural antibodies that are not induced by immunization. However, current strategies for antibody reprogramming require complex expression cassettes and do not allow for customization of the constant region of the antibody. Here we show that human B cells can be edited at the immunoglobulin heavy-chain locus to express heavy-chain-only antibodies that support alterations to both the fragment crystallizable domain and the antigen-binding domain, which can be based on both antibody and non-antibody components. Using the envelope protein (Env) from the human immunodeficiency virus as a model antigen, we show that B cells edited to express heavy-chain antibodies to Env support the regulated expression of B cell receptors and antibodies through alternative splicing and that the cells respond to the Env antigen in a tonsil organoid model of immunization. This strategy allows for the reprogramming of human B cells to retain the potential for in vivo amplification while producing molecules with flexibility of composition beyond that of standard antibodies.

Defense against Paramecium predation via long filament morphology favors the survival of Raphidiopsis raciborskii populations.

Raphidiopsis blooms are notorious for cyanotoxin formation and strong invasiveness, threatening the stability of aquatic ecosystems and human health. The protozoa Paramecium can potentially serve as an organism for controlling Raphidiopsis blooms owing to its grazing effect. However, the grazing ability of Paramecium is largely determined by the size of the prey, and the population of Raphidiopsis consists of filaments of varying lengths and sizes. The selective grazing behavior of Paramecium toward short-length or small-sized filaments in the Raphidiopsis population, as opposed to long filaments, remains unclear. Therefore, in this study, we co-cultured the predator Paramecium sp. with different initial abundances and the prey Raphidiopsis raciborskii to explore this knowledge gap. Our results suggested that: (1) the population of R. raciborskii declined under the selective grazing effect of Paramecium sp. on short filaments, whereas R. raciborskii with long filaments survived; (2) the growth of Paramecium sp. feeding on the same abundance of R. raciborskii was reduced at higher initial abundances, whereas its carrying capacity exhibited an opposite trend; (3) under ingestion by Paramecium sp., the morphology of R. raciborskii developed in the direction of becoming larger, and higher initial abundances of Paramecium sp. intensified this process; (4) increasing initial abundance of Paramecium sp. aggravated the decline of R. raciborskii photosynthetic activity. Therefore, the grazing effect of Paramecium sp. on R. raciborskii mainly affects filaments of short length or small size. Collectively, these results clarify the inter-species interaction between the protozoa Paramecium and filamentous cyanobacteria Raphidiopsis, including population dynamics and morphological and physiological changes in the predator and prey. Such insights into the interactions between Paramecium and R. raciborskii may have implications for the biological control of blooms caused by filamentous cyanobacteria.

Destructive Cryptococcal Osteomyelitis Mimicking Tuberculous Spondylitis.

BACKGROUND Cryptococcosis is an opportunistic fungal infection that typically occurs in patients with compromised immune systems, primarily affecting the respiratory and central nervous systems. However, cryptococcal osteomyelitis is a rare manifestation of cryptococcal infection, characterized by nonspecific clinical features. Here, we present a case of vertebral cryptococcal osteomyelitis in a middle-aged woman and discuss diagnostic approaches. CASE REPORT A 56-year-old woman presented with lower back pain and limited mobility, without fever, and with a history of pulmonary tuberculosis. Physical examination revealed enlarged lymph nodes and tenderness in the thoracic vertebrae. A computed tomography-guided biopsy confirmed granulomatous inflammation caused by Cryptococcus, with abundant 10 µm spherical microbial spores. After 4 weeks of treatment with amphotericin B and fluconazole, symptoms and lesions improved. Upon discharge, the patient was prescribed oral fluconazole. Follow-up examinations showed a stable condition and a negative serum cryptococcal capsular polysaccharide antigen test. CONCLUSIONS Given the rarity and lack of specificity of clinical features of cryptococcal spondylitis, clinicians encountering similar presentations should consider tuberculous spondylitis and spinal tumors as differential diagnoses. Additionally, tissue biopsy of the affected vertebral bodies should be performed early to establish the type of vertebral infection, aiding in diagnosis, treatment, and prognosis.

Research Progress on the Mechanism of Lysosome in Myocardial Ischemia-Reperfusion Injury Based on Autophagy.

In recent years, the interaction of intracellular organelles such as mitochondria and lysosomal functions has attracted increasing attention. Recent evidence suggests that mitochondrion-lysosomal contact plays a key role in regulating lysosomal biogenesis and maintaining cellular homeostasis. Myocardial ischemia and reperfusion will lead to corresponding changes in the autophagy flux in cardiomyocytes, and lysosomes are a key link in the process of autophagy, and the fusion of lysosomes and autophagosomes is an essential link in the occurrence of autophagy. Therefore, the function and homeostasis of lysosomes also undergo different changes during myocardial ischemia and reperfusion. Lysosomal-related biological factors and membrane proteins also play different roles. This article will review the mechanism of lysosomes in myocardial ischemia-reperfusion injury and the research progress of lysosomal-related proteins.

Discovering novel derivatives of STAT3 and HDAC inhibitors with anti-tumor activity.

In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual-target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS-275. Among them, compound 24 (IC50 = 8.22 ± 0.27 µM) showed better anti-tumor activity than the clinical Class I HDAC inhibitor MS-275 (IC50 = 14.65 ± 0.24 µM) in MCF-7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3-HDAC pathway inhibitor achieved with a single molecule.

TIMP-1 Promotes Expression of MCP-1 and Macrophage Migration by Inducing Fli-1 in Experimental Liver Fibrosis.

Background and Aims: Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a role in the excessive generation of extracellular matrix in liver fibrosis. This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1 (MCP-1) expression and promotes hepatic macrophage recruitment. Methods: Liver fibrosis was triggered through carbon tetrachloride, and an adeno-associated virus containing small interfering RNA targeting TIMP-1 (siRNA-TIMP-1) was administered to both rats and mice. We assessed the extent of fibrosis and macrophage recruitment. The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays, luciferase reporter assays, the use of pharmacological modulators, and an analysis of extracellular vesicles (EVs). Results: siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis, reducing macrophage migration and MCP-1 expression. Co-culturing macrophages with hepatic stellate cells (HSCs) post-TIMP-1 downregulation inhibited macrophage migration. In siRNA-TIMP-1-treated HSCs, microRNA-145 (miRNA-145) expression increased, while the expression of Friend leukemia virus integration-1 (Fli-1) and MCP-1 was inhibited. Downregulation of Fli-1 led to decreased MCP-1 expression, whereas Fli-1 overexpression increased MCP-1 expression within HSCs. Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1, while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs. miRNA-145 bound directly to the 3'-UTR of Fli-1, and miRNA-145-enriched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment. Conclusions: TIMP-1 induces Fli-1 expression through miRNA-145, subsequently increasing MCP-1 expression and macrophage recruitment. MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

[Analysis of a child with developmental disorder and epilepsy due to a homozygous variant of SLC25A12 gene].

OBJECTIVE: To explore the genetic basis for a child featuring global developmental delay and epilepsy. METHODS: A child who had presented at Guangzhou Women and Children's Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c.115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+PM3_Supporting+PP3_Moderate+PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. CONCLUSION: The homozygous c.115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.

Identification of TonB-dependent siderophore receptor inhibitors against Flavobacterium columnare using a structure-based high-throughput virtual screening method.

TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.

Photocatalytic Synthesis of Ammonia from Hollow Coral-Like Graphitic Carbon Nitride/FeOCl Loaded with Fe-1T MoS2 Nanosheets as Cocatalysts.

Photocatalytic ammonia synthesis (PAS) represents an emerging environmentally friendly approach to ammonia production. In this work, we employed Fe doping to modify the cocatalyst 1T MoS2, enhancing the active N2 sites on Fe-1T MoS2 by inducing defects on the surface of 1T MoS2. Afterward, Fe-1T MoS2 was loaded onto a hollow coral-like graphitic carbon nitride (CCN)/FeOCl composite. Under simulated sunlight, the efficiency of 5% Fe-1T MoS2@CCN/FeOCl (Fe-MCN/FeOCl) reached 367.62 µmol g-1 h-1, surpassing 1T MoS2@CCN(MCN) by 3.2 times, CCN by 16.9 times, and g-C3N4 by 32.5 times, where 5% means the doping amount of Fe in 1T MoS2. The good performance of Fe MCN/FeOCl should be attributed to the Fe doping in Fe-MCN/FeOCl which not only increases the separation efficiency of active sites and charge carriers, but also reduces the sample impedance significantly through the heterojunction formed between CCN and FeOCl. This work also presents a method for creating more efficient and stable photocatalysts for ammonia synthesis.

Superconducting ternary hydrides: progress and challenges.

Since the discovery of the high-temperature superconductors H3S and LaH10 under high pressure, compressed hydrides have received extensive attention as promising candidates for room-temperature superconductors. As a result of current high-pressure theoretical and experimental studies, it is now known that almost all the binary hydrides with a high superconducting transition temperature (T c) require extremely high pressure to remain stable, hindering any practical application. In order to further lower the stable pressure and improve superconductivity, researchers have started exploring ternary hydrides and had many achievements in recent years. Here, we discuss recent progress in ternary hydrides, aiming to deepen the understanding of the key factors regulating the structural stability and superconductivity of ternary hydrides, such as structural motifs, bonding features, electronic structures, electron-phonon coupling, etc. Furthermore, the current issues and challenges of superconducting ternary hydrides are presented, together with the prospects and opportunities for future research.

Ruthenium and Iodine Anion Cocatalyzed Cascade Dihalogenation and Cyclization of Internal Alkyne-Tethered Cyclohexadienones with 1,2-Dihaloethanes.

We have established an efficient ruthenium(II) and iodine anion cocatalyzed dihalogenation and cascade cyclization of internal alkyne-tethered cyclohexadienones, which stereoselectively afforded numerous dihalogenation products with a bioactive hydrobenzofuran skeleton in high yields under mild conditions. In this transformation, the reaction pathway was determined by the concentration of electrophilic iodine reagent, which also provided a strategy for control of the reaction selectivity. Furthermore, this method features the use of 1,2-dihaloroethane as the halogen source via iodine anion catalyst.

Exploitation of multiple host-derived nutrients by the yellow catfish epidermal environment facilitates Vibrio mimicus to sustain infection potency and susceptibility.

Infection with Vibrio mimicus in the Siluriformes has demonstrated a rapid and high infectivity and mortality rate, distinct from other hosts. Our earlier investigations identified necrosis, an inflammatory storm, and tissue remodeling as crucial pathological responses in yellow catfish (Pelteobagrus fulvidraco) infected with V. mimicus. The objective of this study was to further elucidate the impact linking these pathological responses within the host during V. mimicus infection. Employing metabolomics and transcriptomics, we uncovered infection-induced dense vacuolization of perimysium; Several genes related to nucleosidase and peptidase activities were significantly upregulated in the skin and muscles of infected fish. Concurrently, the translation processes of host cells were impaired. Further investigation revealed that V. mimicus completes its infection process by enhancing its metabolism, including the utilization of oligopeptides and nucleotides. The high susceptibility of yellow catfish to V. mimicus infection was associated with the composition of its body surface, which provided a microenvironment rich in various nucleotides such as dIMP, dAMP, deoxyguanosine, and ADP, in addition to several amino acids and peptides. Some of these metabolites significantly boost V. mimicus growth and motility, thus influencing its biological functions. Furthermore, we uncovered an elevated expression of gangliosides on the surface of yellow catfish, aiding V. mimicus adhesion and increasing its infection risk. Notably, we observed that the skin and muscles of yellow catfish were deficient in over 25 polyunsaturated fatty acids, such as Eicosapentaenoic acid, 12-oxo-ETE, and 13-Oxo-ODE. These substances play a role in anti-inflammatory mechanisms, possibly contributing to the immune dysregulation observed in yellow catfish. In summary, our study reveals a host immune deviation phenomenon that promotes bacterial colonization by increasing nutrient supply. It underscores the crucial factors rendering yellow catfish highly susceptible to V. mimicus, indicating that host nutritional sources not only enable the establishment and maintenance of infection within the host but also aid bacterial survival under immune pressure, ultimately completing its lifecycle.

Preparation and evaluation of microencapsulated delivery system of recombinant interferon alpha protein from rainbow trout.

Diseases caused by viruses pose a significant risk to the health of aquatic animals, for which there are presently no efficacious remedies. Interferon (IFN) serving as an antiviral agent, is frequently employed in clinical settings. Due to the unique living conditions of aquatic animals, traditional injection of interferon is cumbersome, time-consuming and labor-intensive. This study aimed to prepare IFN microcapsules through emulsion technique by using resistant starch (RS) and carboxymethyl chitosan (CMCS). Optimization was achieved using the Box-Behnken design (BBD) response surface technique, followed by the creation of microcapsules through emulsification. With RS at a concentration of 1.27 %, a water­oxygen ratio of 3.3:7.4, CaCl2 at 13.67 %, CMCS at 1.04 %, the rate of encapsulation can escalate to 80.92 %. Rainbow trout infected with Infectious hematopoietic necrosis virus (IHNV) and common carp infected with Spring vireemia (SVCV) exhibited a relative survival rate (RPS) of 65 % and 60 % after treated with IFN microcapsules, respectively. Moreover, the microcapsules effectively reduced the serum AST levels and enhanced the expression of IFNα, IRF3, ISG15, MX1, PKR and Viperin in IHNV-infected rainbow trout and SVCV-infected carp. In conclusion, this integrated IFN microcapsule showed potential as an antiviral agent for treatment of viral diseases in aquaculture.