Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS.

Vaccines are urgently needed to control the ongoing pandemic COVID-19 and previously emerging MERS/SARS caused by coronavirus (CoV) infections. The CoV spike receptor-binding domain (RBD) is an attractive vaccine target but is undermined by limited immunogenicity. We describe a dimeric form of MERS-CoV RBD that overcomes this limitation. The RBD-dimer significantly increased neutralizing antibody (NAb) titers compared to conventional monomeric form and protected mice against MERS-CoV infection. Crystal structure showed RBD-dimer fully exposed dual receptor-binding motifs, the major target for NAbs. Structure-guided design further yielded a stable version of RBD-dimer as a tandem repeat single-chain (RBD-sc-dimer) which retained the vaccine potency. We generalized this strategy to design vaccines against COVID-19 and SARS, achieving 10- to 100-fold enhancement of NAb titers. RBD-sc-dimers in pilot scale production yielded high yields, supporting their scalability for further clinical development. The framework of immunogen design can be universally applied to other beta-CoV vaccines to counter emerging threats.

Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch.

Antibody-dependent enhancement (ADE) is an important safety concern for vaccine development against dengue virus (DENV) and its antigenically related Zika virus (ZIKV) because vaccine may prime deleterious antibodies to enhance natural infections. Cross-reactive antibodies targeting the conserved fusion loop epitope (FLE) are known as the main sources of ADE. We design ZIKV immunogens engineered to change the FLE conformation but preserve neutralizing epitopes. Single vaccination conferred sterilizing immunity against ZIKV without ADE of DENV-serotype 1-4 infections and abrogated maternal-neonatal transmission in mice. Unlike the wild-type-based vaccine inducing predominately cross-reactive ADE-prone antibodies, B cell profiling revealed that the engineered vaccines switched immunodominance to dispersed patterns without DENV enhancement. The crystal structure of the engineered immunogen showed the dimeric conformation of the envelope protein with FLE disruption. We provide vaccine candidates that will prevent both ZIKV infection and infection-/vaccination-induced DENV ADE.

A genome assembly of ginger (Zingiber officinale Roscoe) provides insights into genome evolution and 6-gingerol biosynthesis.

Ginger is cultivated in tropical and subtropical regions and is one of the most crucial spices worldwide owing to its special taste and scent. Here, we present a high-quality genome assembly for 'Small Laiwu Ginger', a famous cultivated ginger in northern China. The ginger genome was phased into two haplotypes, haplotype A (1.55Gb), and haplotype B (1.44Gb). Analysis of Ty1/Copia and Ty3/Gypsy LTR retrotransposon families revealed that both have undergone multiple retrotransposon bursts about 0-1 million years ago. In addition to a recent whole-genome duplication event, there has been a lineage-specific expansion of genes involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, thereby enhancing 6-gingerol biosynthesis. Furthermore, we focused on the biosynthesis of 6-gingerol, the most important gingerol, and screened key transcription factors ZoMYB106 and ZobHLH148 that regulate 6-gingerol synthesis by transcriptomic and metabolomic analysis in the ginger rhizome at four growth stages. The results of yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase reporter gene assays showed that both ZoMYB106 and ZobHLH148 bind to the promoters of the key rate-limiting enzyme genes ZoCCOMT1 and ZoCCOMT2 in the 6-gingerol synthesis pathway and promote their transcriptional activities. The reference genome, transcriptome, and metabolome data pave the way for further research on the molecular mechanism underlying the biosynthesis of 6-gingerol. Furthermore, it provides precious new resources for the study on the biology and molecular breeding of ginger.

Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB/BQ.1.1/BF.7.

SARS-CoV-2 variants with severe immune evasion are a major challenge for COVID-19 prevention, especially the circulating Omicron XBB/BQ.1.1/BF.7 strains. Thus, the next-generation of broad-spectrum vaccines are urgently needed. Previously, we developed a COVID-19 protein subunit vaccine, ZF2001, based on the RBD-homodimer as the immunogen. To adapt SARS-CoV-2 variants, we developed chimeric RBD-heterodimers to induce broad immune responses. In this study, we further explored the concept of tandem RBD homotrimer and heterotrimer. Prototype SARS-CoV-2 RBD-homotrimer, prototype-Delta-BA.1 (PDO) RBD-heterotrimer and Delta-BA.2-BA.5 (DBA2BA5) RBD-heterotrimer were designed. Biochemical and cryo-EM structural characterization demonstrated total epitope exposure of the RBD-trimers. In mouse experiments, PDO and DBA2BA5 elicited broad SARS-CoV-2 neutralization. Potent protection against SARS-CoV-2 variants was observed in challenge assays and was correlated with neutralizing antibody titer. This study validated the design strategy of tandem RBD-heterotrimers as multivalent immunogens and presented a promising vaccine candidate, DBA2BA5, eliciting broad-spectrum immune responses, including against the circulating XBB/BF.7/BQ.1.1.

Multimetal-Based Metal-Organic Framework System for the Sensitive Detection of Heart-Type Fatty Acid Binding Protein in Electrochemiluminescence Immunoassay.

In this work, an electrochemiluminescence (ECL) quenching system using multimetal-organic frameworks (MMOFs) was proposed for the sensitive and specific detection of heart-type fatty acid-binding protein (H-FABP), a marker of acute myocardial infarction (AMI). Bimetallic MOFs containing Ru and Mn as metal centers were synthesized via a one-step hydrothermal method, yielding RuMn MOFs as the ECL emitter. The RuMn MOFs not only possessed the strong ECL performance of Ru(bpy)32+ but also maintained high porosity and original metal active sites characteristic of MOFs. Moreover, under the synergistic effect of MOFs and Ru(bpy)32+, RuMn MOFs have more efficient and stable ECL emission. The trimetal-based MOF (FePtRh MOF) was used as the ECL quencher because of the electron transfer between FePtRh MOFs and RuMn MOFs. In addition, active intramolecular electron transfer from Pt to Fe or Rh atoms also occurred in FePtRh MOFs, which could promote intermolecular electron transfer and improve electron transfer efficiency to enhance the quenching efficiency. The proposed ECL immunosensor demonstrated a wide dynamic range and a low detection limit of 0.01-100 ng mL-1 and 6.8 pg mL-1, respectively, under optimal conditions. The ECL quenching system also presented good specificity, stability, and reproducibility. Therefore, an alternative method for H-FABP detection in clinical diagnosis was provided by this study, highlighting the potential of MMOFs in advancing ECL technology.

Salidroside inhibits the ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signalling pathway.

OBJECTIVE: The present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. MATERIALS AND METHODS: After we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. RESULTS: Remarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. CONCLUSIONS: Salidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.

Unveiling the impact of low-frequency electrical stimulation on network synchronization and learning behavior in cultured hippocampal neural networks.

Understanding the dynamics of neural networks and their response to external stimuli is crucial for unraveling the mechanisms associated with learning processes. In this study, we hypothesized that electrical stimulation (ES) would lead to significant alterations in the activity patterns of hippocampal neuronal networks and investigated the effects of low-frequency ES on hippocampal neuronal populations using the microelectrode arrays (MEAs). Our findings revealed significant alterations in the activity of hippocampal neuronal networks following low-frequency ES trainings. Post-stimulation, the neural activity exhibited an organized burst firing pattern characterized by increased spike and burst firings, increased synchronization, and enhanced learning behaviors. Analysis of peri-stimulus time histograms (PSTHs) further revealed that low-frequency ES (1Hz) significantly enhanced neural plasticity, thereby facilitating the learning process of cultured neurons, whereas high-frequency ES (>10Hz) impeded this process. Moreover, we observed a substantial increase in correlations and connectivity within neuronal networks following ES trainings. These alterations in network properties indicated enhanced synaptic plasticity and emphasized the positive impact of low-frequency ES on hippocampal neural activities, contributing to the brain's capacity for learning and memory.

Optimizing Droplet-Based Electricity Generator via a Low Sticky Hydrophobic Droplet-Impacted Surface.

Droplet-based electricity generators (DEGs) are increasingly recognized for their potential in converting renewable energy sources. This study explores the interplay of surface hydrophobicity and stickiness in improving DEG efficiency. It find that the high-performance C-WaxDEGs leverage both these properties. Specifically, DEGs incorporating polydimethylsiloxane (PDMS) with carnauba wax (C-wax) exhibit increased output as surface stickiness decreases. Through experimental comparisons, PDMS with 1wt.% C-wax demonstrated a significant power output increase from 0.07 to 1.2 W m- 2, which attribute to the minimized adhesion between water molecules and the polymer surface, achieved by embedding C-wax into PDMS surface to form microstructures. This improvement in DEG performance is notable even among samples with similar surface potentials and contact angles, suggesting that C-wax's primary contribution is in reducing surface stickiness rather than altering other surface properties. The further investigations into the C-WaxDEG variant with 1wt.% C-wax PDMS uncover its potential as a sensor for water quality parameters such as temperature, pH, and heavy metal ion concentration. These findings open avenues for the integration of C-WaxDEGs into flexible electronic devices aimed at environmental monitoring.

Tunable-bias based optical neural network for reinforcement learning in path planning.

Owing to the high integration, reconfiguration and strong robustness, Mach-Zehnder interferometers (MZIs) based optical neural networks (ONNs) have been widely considered. However, there are few works adding bias, which is important for neural networks, into the ONNs and systematically studying its effect. In this article, we propose a tunable-bias based optical neural network (TBONN) with one unitary matrix layer, which can improve the utilization rate of the MZIs, increase the trainable weights of the network and has more powerful representational capacity than traditional ONNs. By systematically studying its underlying mechanism and characteristics, we demonstrate that TBONN can achieve higher performance by adding more optical biases to the same side beside the inputted signals. For the two-dimensional dataset, the average prediction accuracy of TBONN with 2 biases (97.1%) is 5% higher than that of TBONN with 0 biases (92.1%). Additionally, utilizing TBONN, we propose a novel optical deep Q network (ODQN) algorithm to complete path planning tasks. By implementing simulated experiments, our ODQN shows competitive performance compared with the conventional deep Q network, but accelerates the computation speed by 2.5 times and 4.5 times for 2D and 3D grid worlds, respectively. Further, a more noticeable acceleration will be obtained when applying TBONN to more complex tasks. Also, we demonstrate the strong robustness of TBONN and the imprecision elimination method by using on-chip training.

Generation of 583 fs optical pulses at 10†GHz from a regeneratively mode-locked fiber laser combining nonlinear polarization evolution.

A regeneratively mode-locked erbium fiber laser was numerically investigated and experimentally demonstrated, which was able to generate a 583 fs pulse train at 10 GHz via intracavity pulse compression with nonlinear polarization evolution (NPE). To excite the NPE at such a high repetition rate, a dispersion map was intentionally introduced to obtain short pulses accompanied by high peaks through soliton-like pulse shaping. Numerical simulations indicated that steady-state oscillation with pulses below 1 ps can be successfully established using this laser configuration. Experimentally, we obtained a pulse duration of 583 fs and a 3 dB spectral width of 4.5 nm at an average output power of 15.6 mW. Simultaneously, supermode suppression of more than 80 dB was also obtained from the appropriate biased NPE.

Ultra-high-speed four-dimensional hyperspectral imaging.

We propose, to the best of our knowledge, a novel deep learning-enabled four-dimensional spectral imaging system composed of a reflective coded aperture snapshot spectral imaging system and a panchromatic camera. The system simultaneously captures a compressively coded hyperspectral measurement and a panchromatic measurement. The hyperspectral data cube is recovered by the U-net-3D network. The depth information of the scene is then acquired by estimating a disparity map between the hyperspectral data cube and the panchromatic measurement through stereo matching. This disparity map is used to align the hyperspectral data cube and the panchromatic measurement. A designed fusion network is used to improve the spatial reconstruction of the hyperspectral data cube by fusing aligned panchromatic measurements. The hardware prototype of the proposed system demonstrates high-speed four-dimensional spectral imaging that allows for simultaneously acquiring depth and spectral images with an 8 nm spectral resolution between 450 and 700 nm, 2.5 mm depth accuracy, and a 1.83 s reconstruction time.

Intracavity spatially modulated metasurfaces for a wavelength-tunable figure-9 vortex fiber laser.

Intracavity optical metasurfaces with compact and flexible light manipulation capabilities, effectively enrich the implementation of miniaturized and user-friendly orbital angular momentum (OAM) laser sources. Here we demonstrate a wavelength-tunable figure-9 Yb-doped vortex fiber laser solely with standard non-polarization-maintaining single-mode fibers, which utilizes a gap-surface plasmon (GSP) metasurface as the intracavity mode regulation component to generate OAM beams, extending the avenues and related applications for cost-effective OAM laser sources. Gained by the broadband operation range of the metasurface, the figure-9 fiber laser could emit OAM light with center wavelength tunable from 1020 nm to 1060 nm and of high mode purity (about 90%). OAM beams with different topological charges such as l = ±1 have been obtained by changing the metasurface design. The proposed fiber laser with the intracavity GSP metasurface provides a reliable and customized output of OAM beams at the laser source, holding great promise for a wide range of applications in optical communications, sensing, and super-resolution imaging.

Dual-polarization RF channelizer based on microcombs.

We report a dual-polarization radio frequency (RF) channelizer based on microcombs. Two high-Q micro-ring resonators (MRRs) with slightly different free spectral ranges (FSRs) are used: one MRR is pumped to yield soliton crystal microcombs ("active"), and the other MRR is used as a "passive" periodic optical filter supporting dual-polarization operation to slice the RF spectrum. With the tailored mismatch between the FSRs of the active and passive MRRs, wideband RF spectra can be channelized into multiple segments featuring digital-compatible bandwidths via the Vernier effect. Due to the use of dual-polarization states, the number of channelized spectral segments, and thus the RF instantaneous bandwidth (with a certain spectral resolution), can be doubled. In our experiments, we used 20 microcomb lines with ∼ 49 GHz FSR to achieve 20 channels for each polarization, with high RF spectra slicing resolutions at 144 MHz (TE) and 163 MHz (TM), respectively; achieving an instantaneous RF operation bandwidth of 3.1 GHz (TE) and 2.2 GHz (TM). Our approach paves the path towards monolithically integrated photonic RF receivers (the key components - active and passive MRRs are all fabricated on the same platform) with reduced complexity, size, and unprecedented performance, which is important for wide RF applications with digital-compatible signal detection.

A new chromosome-scale genome of wild Brassica oleracea provides insights into the domestication of Brassica crops.

The cultivated diploid Brassica oleracea is an important vegetable crop, but the genetic basis of its domestication remains largely unclear in the absence of high-quality reference genomes of wild B. oleracea. Here, we report the first chromosome-level assembly of the wild Brassica oleracea L. W03 genome (total genome size, 630.7 Mb; scaffold N50, 64.6 Mb). Using the newly assembled W03 genome, we constructed a gene-based B. oleracea pangenome and identified 29 744 core genes, 23 306 dispensable genes, and 1896 private genes. We re-sequenced 53 accessions, representing six potential wild B. oleracea progenitor species. The results of the population genomic analysis showed that the wild B. oleracea populations had the highest level of diversity and represents the most closely related population to modern-day horticultural B. oleracea. In addition, the WUSCHEL gene was found to play a decisive role in domestication and to be involved in cauliflower and broccoli curd formation. We also illustrate the loss of disease-resistance genes during selection for domestication. Our results provide new insights into the domestication of B. oleracea and will facilitate the future genetic improvement of Brassica crops.

Virtual-State Model for Analyzing Electro-Optical Modulation in Ring Resonators.

Ring resonators play a crucial role in optical communication and quantum technology applications. However, these devices lack a simple and intuitive theoretical model to describe their electro-optical modulation. When the resonance frequency is rapidly modulated, the filtering and modulation within a ring resonator become physically intertwined, making it difficult to analyze the complex physical processes involved. We address this by proposing an analytical solution for electro-optic ring modulators based on the concept of a "virtual state." This approach equates a lightwave passing through a dynamic ring modulator to one excited to a virtual state by a cumulative phase and then returning to the real state after exiting the static ring. Our model simplifies the independent analysis of the intertwined physical processes, enhancing its versatility in analyzing various incident signals and modulation formats. Experimental results, including resonant and detuning modulation, align with the numerical simulation of our model. Notably, our findings indicate that the dynamic modulation of the ring resonator under detuning driving approximates phase modulation.

Corrosion Properties and Passive Film Interface of Inconel 718 in NaNO3 Solution for Laser-Assisted Electrochemical Machining.

Laser-assisted electrochemical machining (ECM) is an ideal manufacturing method for Inconel 718 (IN718) because of the method's high efficiency and good surface quality, and the basis for and key to laser-assisted ECM is its anodic electrochemical dissolution behavior. In this study, IN718 in a 10 wt % NaNO3 solution was subjected to innovative electrochemical testing and laser-assisted ECM experiments to investigate its corrosion properties and the passive film characteristics formed on its surface. The passivation-related behaviors and structures of the passive film were investigated based on open-circuit potentials, dynamic polarization, potentiostatic polarization, and electrochemical impedance spectroscopy. It was found that there was obvious active-passive-transpassive transition behavior, and the structure of the passive film in laser-assisted ECM exhibited pores and defects, resulting in weak corrosion resistance, compared with IN718 under ECM without laser irradiation. The chemical composition of the passive film was obtained by X-ray photoelectron spectroscopy. The results showed that the passive film was composed mainly of a mixture of NiO, Ni(OH)2, Cr2O3, CrO3, Fe2O3, α-Fe2O3, α-FeOOH, Nb2O5, NbO, MoO3, MoO2, and TiO2. The passive film formed by laser-assisted ECM was rich in NiO and TiO2 and lacked Cr2O3 and MoO3, which validated its pores and defect structures. A corresponding schematic model was also proposed to characterize the interface structure between the IN718 substrate and the passive film. Laser-assisted ECM tests were performed under different current densities and machining times, and the corrosion morphology of IN718 was identified. Corrosion pits and a loose product layer appeared on the machined surface at low current densities, and the dissolution mechanism was pitting. The quantity and depth of the corrosion pits dispersed on the machined surface clearly decreased as the current density increased. Finally, a quantitative corrosion model was established to characterize the dissolution behavior of IN718 in NaNO3 solution during laser-assisted ECM.

Predictive factors of medium-giant coronary artery aneurysms in Kawasaki disease.

BACKGROUND: We aimed to examine predictive measures for medium and giant coronary artery aneurysms (CAA) in Kawasaki disease (KD) patients. METHODS: Patients who were diagnosed with KD from 2015 to 2021 were retrospectively reviewed. The clinical and laboratory data were compared between medium-giant group and non-medium-giant group. RESULTS: A total of 1331 KD patients were investigated, of whom 63 patients (4.7%) developed medium-giant CAA including 27 patients (2%) with giant CAA. Sex, age, fever duration, intravenous immunoglobulin (IVIG) resistance, platelet count, and albumin level independently predicted medium or giant CAA by multivariate logistic regression analysis. Male, age, duration of fever, IVIG resistance, platelet count, hemoglobin, and erythrocyte sedimentation rate were independent predictors for giant CAA. The two new scoring systems using these factors in identifying patients with medium-giant CAA and giant CAA had respectively sensitivities of 86.89% and 92.59%, and specificities of 81.65% and 87.93%. Validation in 2021 dataset (193 KD patients) showed comparable sensitivity and specificity to development dataset. CONCLUSIONS: Male, age, fever duration, IVIG resistance, platelet count, albumin, hemoglobin, and erythrocyte sedimentation rate might be significant predictors of medium and giant CAA. The sensitivity and specificity in our risk prediction model were higher than in previous research. IMPACT: This is the first study to search for risk factors and establish a prediction model for the development of medium-giant CAA in the Chinese population using z-scores and absolute inner diameter values based on large sample sizes. The sensitivity and specificity in our model were higher than in previous studies. Our research could help clinicians better predict medium-giant CAA and choose more appropriate treatment.

Nano-Cu Derived from a Copper Nitride Precatalyst for Reductive Coupling of Nitroaromatics to Azo Compounds.

The study of structural reconstruction is vital for the understanding of the real active sites in heterogeneous catalysis and guiding the improved catalyst design. Herein, we applied a copper nitride precatalyst in the nitroarene reductive coupling reaction and made a systematic investigation on the dynamic structural evolution behaviors and catalytic performance. This Cu3N precatalyst undergoes a rapid phase transition to nanostructured Cu with rich defective sites, which act as the actual catalytic sites for the coupling process. The nitride-derived defective Cu is very active and selective for azo formation, with 99.6% conversion of nitrobenzene and 97.1% selectivity to azobenzene obtained under mild reaction conditions. Density functional theory calculations suggest that the defective Cu sites play a role for the preferential adsorption of nitrosobenzene intermediates and significantly lowered the activation energy of the key coupling step. This work not only proposes a highly efficient noble-metal-free catalyst for nitroarenes coupling to valuable azo products but also may inspire more scientific interest in the study of the dynamic evolution of metal nitrides in different catalytic reactions.

Genetically engineering of Saccharomyces cerevisiae for enhanced oral delivery vaccine vehicle.

As a series of our previous studies reported, recombinant yeast can be the oral vaccines to deliver designed protein and DNA, as well as functional shRNA, into dendritic cells (DCs) in mice for specific immune regulation. Here, we report the further optimization of oral yeast-based vaccine from two aspects (yeast characteristics and recombinant DNA constitution) to improve the effect of immune regulation. After screening four genes in negative regulation of glucan synthesis in yeast (MNN9, GUP1, PBS2 and EXG1), this research combined HDR-based genome editing technology with Cre-loxP technology to acquire 15 gene-knockout strains without drug resistance-gene to exclude biosafety risks; afterward, oral feeding experiments were performed on the mice using 15 oral recombinant yeast-based vaccines constructed by the gene-knockout strains harboring pCMV-MSTN plasmid to screen the target strain with more effective inducing mstn-specific antibody which in turn increasing weight gain effect. And subsequently based on the selected gene-knockout strain, the recombinant DNA in the oral recombinant yeast-based vaccine is optimized via a combination of protein fusion expression (OVA-MSTN) and interfering RNA technology (shRNA-IL21), comparison in terms of both weight gain effect and antibody titer revealed that the selected gene-knockout strain (GUP1ΔEXG1Δ) combined with specific recombinant DNA (pCMV-OVA-MSTN-shIL2) had a better effect of the vaccine. This study provides a useful reference to the subsequent construction of a more efficient oral recombinant yeast-based vaccine in the food and pharmaceutical industry.