High expression levels of haem oxygenase-1 promote ferroptosis in macrophage-derived foam cells and exacerbate plaque instability.

Plaque rupture with consequent thrombosis is the leading cause of acute cardiovascular events, during which macrophage death is a hallmark. Ferroptosis is a pivotal intermediate link between early and advanced atherosclerosis. Existing evidence indicates the involvement of macrophage ferroptosis in plaque vulnerability; however, the exact mechanism remains elusive. The aim of this study was to explore key ferroptosis-related genes (FRGs) involved in plaque progression and the underlying molecular mechanisms involved. The expression landscape of FRGs was obtained from atherosclerosis-related GEO datasets. Molecular mechanism studies of ferroptosis were performed using bone marrow-derived macrophages (BMDMs) and macrophage-derived foam cells (MDFCs). Bioinformatics analysis and immunohistochemistry revealed that macrophage haem oxygenase-1 (HMOX1) is the key FRG involved in plaque destabilization. Hypoxic conditions induced a significant increase in Hmox1 expression in MDFCs but not in macrophages. In addition, the beneficial or deleterious effects of Hmox1 were dependent on the degree of Hmox1 induction. Hmox1 overexpression drove inflammatory responses and ferroptotic oxidative stress in MDFCs and aggravated the plaque burden in atherosclerotic model mice. Further mechanistic investigations demonstrated that hypoxia-mediated degradation of egl-9 family hypoxia-inducible factor 3 (Egln3) stabilized Hif1a, which subsequently promoted Hmox1 transcription. Our findings suggest that high Hmox1 expression under hypoxia is deleterious to MDFC viability and plaque stability, providing a reference for the management of acute cardiovascular events.

The synergistic effect of NiCo2S4 and carbon nanosheets for supercapacitor: Enhanced adsorption/desorption of OH- on Ni and Co active sites.

To improve the low energy density, low conductivity, and poor cycling stability of NiCo2S4 in supercapacitors, a two-step hydrothermal method was used to prepare a composite material of NiCo2S4 and carbon nanosheets (NiCo2S4/CNs). The electrochemical tests revealed a high specific capacitance of 1576 F g-1 at 1 A/g for the composite, and the NiCo2S4/CNs//AC asymmetric supercapacitor showed a energy density of 49.7 Wh kg-1 at 818 W kg-1. This study confirmed the phase transformation of NiCo2S4 during charge/discharge in alkaline solution through ex-situ X-ray diffraction (ex-situ XRD) for the first time, and proposed a potential reaction pathway. Moreover, Density Functional Theory (DFT) confirmed that the NiCo2S4/CNs heterostructure enhances OH- adsorption/desorption on Ni and Co active sites and improves electronic conductivity. In conclusion, this study advances the application of transition metal sulfide in high-performance energy storage.

Insightful analysis of physical properties, kinetics, absorption capacity, and regeneration heat duty of monoethanolamine and N-methyl-4-piperidinol blended solvent in post-combustion carbon capture.

In this study, the high potential tertiary N-methyl-4-piperidinol or MPDL (0.25-1.00 M) was blended with 5 M monoethanolamine (MEA) to formulate 5.25-6.00 M MEA-MPDL solvent and compare with the benchmark 5 M MEA. It was found that the density and the Henry's constant slightly decreased, while the viscosity increased as the MPDL concentration in the blend increased. Even though the equilibrium CO2-loaded viscosity considerably increased (by 34.3-40.2%) as the MPDL content increased, it was still in a great operating region of less than 10 mPa.s. Experimental overall reaction kinetics constant ( k ov ) was well corresponding with the zwitterion mechanism of MEA and the base-catalyze hydration mechanism of MPDL based absorption kinetics model, with %AAD of 0.56%. Interestingly, an addition of MPDL into 5 M MEA slightly enhanced k ov (1.2-3.3% increment) and considerably favored absorption capacity (13-31% elevation), and regeneration heat duty (28-47% reduction), respecting 5 M MEA. The proposed strategic blending can maintain the overall solvent reactivity at the same level of the benchmark, while obviously increase the absorption capacity and largely reduce the regeneration heat duty. This highly favors a solvent upgrading for the existing 5 M MEA based CO2 capture plant. According to the recent data, 5 M MEA + 1.00 M MPDL was suggested. Since the blend was formulated at high concentration, its corrosiveness should also be considered.

Application of magnetism in tissue regeneration: recent progress and future prospects.

Tissue regeneration is a hot topic in the field of biomedical research in this century. Material composition, surface topology, light, ultrasonic, electric field and magnetic fields (MFs) all have important effects on the regeneration process. Among them, MFs can provide nearly non-invasive signal transmission within biological tissues, and magnetic materials can convert MFs into a series of signals related to biological processes, such as mechanical force, magnetic heat, drug release, etc. By adjusting the MFs and magnetic materials, desired cellular or molecular-level responses can be achieved to promote better tissue regeneration. This review summarizes the definition, classification and latest progress of MFs and magnetic materials in tissue engineering. It also explores the differences and potential applications of MFs in different tissue cells, aiming to connect the applications of magnetism in various subfields of tissue engineering and provide new insights for the use of magnetism in tissue regeneration.

IKVAV functionalized oriented PCL/Fe3O4 scaffolds for magnetically modulating DRG growth behavior.

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3O4) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe3O4 scaffolds containing different Fe3O4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe3O4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10 F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe3O4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe3O4 composite oriented scaffolds have potential applications in neural tissue engineering.

Cerium-MOF-Derived Composite Hierarchical Catalyst Enables Energy-Efficient and Green Amine Regeneration for CO2 Capture.

The excessive energy consumed restricts the application of traditional postcombustion CO2 capture technology and limits the achievement of carbon-neutrality goals. Catalytic-rich CO2 amine regeneration has the potential to accelerate proton transfer and increase the energy efficiency in the CO2 separation process. Herein, we reported a Ce-metal-organic framework (MOF)-derived composite catalyst named HZ-Ni@UiO-66 with a hierarchical structure, which can increase the CO2 desorbed amount by 57.7% and decrease the relative heat duty by 36.5% in comparison with the noncatalytic monoethanolamine (MEA) regeneration process. The composite catalyst of the CeO2 coating from the UiO-66 precursor on the HZ-Ni carrier shows excellent stability with a long lifespan. The HZ-Ni@UiO-66 catalyst also shows a universal catalytic effect in typical blended amine systems with a large cyclic capacity. The HZ-Ni@UiO-66 catalyst effectively decreases the energy barrier of the CO2 desorption reaction to reduce the time required to reach thermodynamics, consequently saving the energy consumption generated by water evaporation. This research provides a new avenue for advancing amine regeneration with less heat duty at low temperatures.

Biomimetic-inspired piezoelectric ovalbumin/BaTiO3 scaffolds synergizing with anisotropic topology for modulating Schwann cell and DRG behavior.

The treatment of peripheral nerve injury is a clinical challenge that tremendously affected the patients' health and life. Anisotropic topographies and electric cues can simulate the regenerative microenvironment of nerve from physical and biological aspects, which show promising application in nerve regeneration. However, most studies just unilaterally emphasize the effect of sole topological- or electric- cue on nerve regeneration, while rarely considering the synergistic function of both cues simultaneously. In this study, a biomimetic-inspired piezoelectric topological ovalbumin/BaTiO3 scaffold that can provide non-invasive electrical stimulation in situ was constructed by combining piezoelectric BaTiO3 nanoparticles and surface microtopography. The results showed that the incorporation of piezoelectric nanoparticles could improve the mechanical properties of the scaffolds, and the piezoelectric output of the scaffolds after polarization was significantly increased. Biological evaluation revealed that the piezoelectric topological scaffolds could regulate the orientation growth of SCs, promote axon elongation of DRG, and upregulate the genes expression referring to myelination and axon growth, thus rapidly integrated chemical-mechanical signals and transmitted them for effectively promoting neuronal myelination, which was closely related to peripheral neurogenesis. The study suggests that the anisotropic surface topology combined with non-invasive electronic stimulation of the ovalbumin/BaTiO3 scaffolds possess a promising application prospect in the repair and regeneration of peripheral nerve injury.

Iodine intercalation-assisted alkali activation constructs coal-based porous carbon for high-performance supercapacitors.

Supercapacitors have the advantages of fast charging and discharging speeds, high power density, long cycle life, and wide operating temperature range. They are widely used in portable electronic equipment, rail transit, industry, military, aerospace, and other fields. The design and preparation of low-cost, high-performance electrode materials still pose a bottleneck that hinders the development of supercapacitors. In this paper, coal was used as the raw material, and the coal-based porous carbon electrode material was constructed using the iodine intercalation-assisted activation method and used for supercapacitors. The CK-700 electrode exhibits excellent charge storage performance in a 6 M potassium hydroxide (KOH) electrolyte, with a maximum specific capacitance of 350 F/g at a current density of 0.5 A/g. In addition, it has an excellent rate performance (310 F/g at 1 A/g) and cycle stability (capacitance retention up to 91.7 % after 30000 cycles). This work provides a method for realizing high-quality, high-yield and low-cost preparation of coal-based porous carbon, and an idea for improving the performance of supercapacitors.

Cell culture on suspended fiber for tissue regeneration: A review.

Cell culturing is a cornerstone of tissue engineering, playing a crucial role in tissue regeneration, drug screening, and the study of disease mechanisms. Among various culturing techniques, 3D culture systems, particularly those utilizing suspended fiber scaffolds, offer a more physiologically relevant environment than traditional 2D monolayer cultures. These 3D scaffolds enhance cell growth, differentiation, and proliferation by mimicking the in vivo cellular milieu. This review focuses on the critical role of suspended fiber scaffolds in tissue engineering. We compare the effectiveness of 3D suspended fiber scaffolds with 2D culture systems, discussing their respective benefits and limitations in the context of tissue regeneration. Furthermore, we explore the preparation methods of suspended fiber scaffolds and their potential applications. The review concludes by considering future research directions for optimizing suspended fiber scaffolds to address specific challenges in tissue regeneration, underscoring their significant promise in advancing tissue engineering and regenerative medicine.

Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.

Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.

A Novel Zn(II) Coordination Polymer: Fluorescence Performances, Molecular Docking and Loaded with Bleomycin-Hydrogels on Hemangiomas.

In this study, we successfully synthesized an innovative 1D-Zn(II) coordination polymer, denoted as [Zn(L)(H2O)2]n, employing the Schiff base {4-[(2-hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid} (H2L). The Schiff base was obtained through the reaction of 4-aminobenzoic acid and o-vanillin under slow volatilization conditions. The resulting compound exhibits remarkable green fluorescence emission properties, indicating its potential as a novel fluorescent and sensing material. Hydrogels based on hyaluronic acid (HA) and carboxymethyl chitosan (CMCS), denoted as HA/CMCS hydrogels, were synthesized using a chemical method. Additionally, we utilized bleomycin as a model drug to synthesize a novel bleomycin metal gel and assessed its anti-hemangioma activity. Molecular docking simulations revealed that the Zn complex can form stable bonds with the key target, involving the methoxy and carboxyl groups on the Zn complex.

The improvement of tyrosol bioavailability by encapsulation into liposomes using pH-driven method.

To improve the poor water solubility and oral bioavailability of tyrosol, novel tyrosol liposomes (Tyr-LPs) were prepared by pH-driven method. Fourier transform infrared (FTIR) absorption spectra and X-ray diffraction (XRD) analysis indicated that Tyr-LPs were successfully encapsulated and tyrosol was in an amorphous state in liposomes. When tyrosol content in Tyr-LP was 1.33 mg/ml and the Tyr:LP (mass ratio) = 1:2, favorable dispersibility of Tyr-LP was exhibited, with an instability index of 0.049 ± 0.004, PDI of 0.274 ± 0.003, and the EE of 94.8 ± 2.5 %. In vivo pharmacokinetic studies showed that after oral administration of tyrosol or Tyr-LP (Tyr:LP = 1:2), concentration-versus-time curve (AUC0-720mins) and maximum concentration (Cmax) values of Tyr-LP was respectively 1.5-fold (P < 0.01) and 2.25-fold (P < 0.01) higher than tyrosol, which indicated that the oral bioavailability of tyrosol was effectively improved in Tyr-LPs. Our study thereby provides theoretical support for the application of Tyr-LP for optimal delivery of tryosol.

Development of ovalbumin implants with different spatial configurations for treatment of peripheral nerve injury.

Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 µL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.

Mzb1 Attenuates Atherosclerotic Plaque Vulnerability in ApoE-/- Mice by Alleviating Apoptosis and Modulating Mitochondrial Function.

In this study, we investigated the protective role of Mzb1 in atherosclerotic plaque vulnerability. To explore the impact of Mzb1, we analyzed Mzb1 expression, assessed apoptosis, and evaluated mitochondrial function in atherosclerosis (AS) mouse models and human vascular smooth muscle cells (HVSMCs). We observed a significant decrease in Mzb1 expression in AS mouse models and ox-LDL-treated HVSMCs. Downregulation of Mzb1 increased ox-LDL-induced apoptosis and cholesterol levels of HVSMCs, while Mzb1 overexpression alleviated these effect. Mzb1 was found to enhance mitochondrial function, as evidenced by restored ATP synthesis, mitochondrial membrane potential, and reduced mtROS production. Moreover, Mzb1 overexpression attenuated atherosclerotic plaque vulnerability in ApoE-/- mice. Our findings suggest that Mzb1 overexpression regulates the AMPK/SIRT1 signaling pathway, leading to the attenuation of atherosclerotic plaque vulnerability. This study provides compelling evidence for the protective effect of Mzb1 on atherosclerotic plaques by alleviating apoptosis and modulating mitochondrial function in ApoE-/- mice.

Parental readiness for hospital discharge and the relationship with growth and development of infant in China.

PURPOSE: This study aimed to evaluate the associations between parental readiness for discharge and neonatal growth. DESIGN AND METHODS: This cross-sectional study included 549 newborns whose parents filled out the Newborn-Parental Readiness for Discharge Scale (N-PRDS).Additionally, data on birth weight, length, and head circumference were collected.The total N-PRDS scores were divided into three levels in terms of readiness: low, intermediate, and high readiness. Parents and infants were followed up 42 days after the birth, and the weight, length, and head circumference of the newborns were measured at the hospital. RESULTS: A total of 306 data were obtained. The generalized linear mixed model (GLMM) showed that time and parental readiness had an interaction effect on the weight, length and head circumference of infants. The difference in weight between infants under the high and low readiness conditions at 42 days increased by 0.357 kg compared to the difference at birth. The difference in length between high readiness infants and low readiness infants at 42 days increased by 2.155 cm compared to the difference at birth. The difference between the infants' head circumference under the high and low readiness conditions at 42 days was 0.873 cm higher than that at birth. CONCLUSIONS: High readiness for discharge could promote an increase in infant weight, length,and head circumference at 42 days after birth. PRACTICE IMPLICATIONS: Nurses should assess parental readiness prior to the discharge of newborns by using the N-PRDS and provide discharge guidance and education to newborns' parents based on the outcomes of this scale.

Suppression of endoplasmic reticulum stress by 4-PBA enhanced atherosclerotic plaque stability via up-regulating CLOCK expression.

Endoplasmic reticulum (ER) stress refers to a condition where the normal functioning of the ER is disrupted due to a variety of cellular stress factors. As a result, there is an accumulation of unfolded and misfolded proteins within the ER. Numerous studies have shown that ER stress can exacerbate inflammatory reactions and contribute to the development of various inflammatory diseases. However, the role of ER stress in the stability of atherosclerotic plaques remains poorly understood. In this study, we aimed to explore the potential impact of a specific ER stress inhibitor known as 4-phenyl butyric acid (4-PBA) on atherosclerosis in mice. The mice were fed a high-fat diet, and treatment with 4-PBA significantly improved the stability of the atherosclerotic plaques. This was evidenced by a reduction in oxidative stress and an increase in circadian locomotor output cycles kaput (CLOCK) protein and mRNA expression within the plaques. Additionally, 4-PBA reduced the expression of ER stress-related proteins and decreased apoptosis in the atherosclerotic plaques. In vitro investigation, we observed the effect of 4-PBA on vascular smooth muscle cells (VSMCs) that were exposed to oxidized low-density lipoprotein (ox-LDL), a significant contributor to the development of atherosclerosis. 4-PBA reduced reactive oxygen species (ROS) production and attenuated apoptosis, GRP78 and CHOP protein expression in ox-LDL-Induced VSMCs via up-regulating CLOCK expression. However, when the short hairpin RNA against CLOCK (sh-CLOCK) was introduced to the VSMCs, the protective effect of 4-PBA was abolished. This suggests that the up-regulation of CLOCK expression is crucial for the beneficial effects of 4-PBA on atherosclerotic plaque stability. This finding suggests that targeting ER stress and modulating CLOCK protein levels might be a promising way to enhance the stability of atherosclerotic plaques.

Piezoelectric materials for neuroregeneration: a review.

The purpose of nerve regeneration via tissue engineering strategies is to create a microenvironment that mimics natural nerve growth for achieving functional recovery. Biomaterial scaffolds offer a promising option for the clinical treatment of large nerve gaps due to the rapid advancement of materials science and regenerative medicine. The design of biomimetic scaffolds should take into account the inherent properties of the nerve and its growth environment, such as stiffness, topography, adhesion, conductivity, and chemical functionality. Various advanced techniques have been employed to develop suitable scaffolds for nerve repair. Since neuronal cells have electrical activity, the transmission of bioelectrical signals is crucial for the functional recovery of nerves. Therefore, an ideal peripheral nerve scaffold should have electrical activity properties similar to those of natural nerves, in addition to a delicate structure. Piezoelectric materials can convert stress changes into electrical signals that can activate different intracellular signaling pathways critical for cell activity and function, which makes them potentially useful for nerve tissue regeneration. However, a comprehensive review of piezoelectric materials for neuroregeneration is still lacking. Thus, this review systematically summarizes the development of piezoelectric materials and their application in the field of nerve regeneration. First, the electrical signals and natural piezoelectricity phenomenon in various organisms are briefly introduced. Second, the most commonly used piezoelectric materials in neural tissue engineering, including biocompatible piezoelectric polymers, inorganic piezoelectric materials, and natural piezoelectric materials, are classified and discussed. Finally, the challenges and future research directions of piezoelectric materials for application in nerve regeneration are proposed.

Surface topologized ovalbumin scaffolds containing YIGSR peptides for modulating Schwann cell behavior.

Peripheral nerve injuries (PNI) currently have limited therapeutic efficacy, and functional scaffolds have been shown to be effective for treating PNI. Ovalbumin (OVA) is widely used as a natural biomaterial for repairing damaged tissues due to its excellent biocompatibility and the presence of various bioactive components. However, there are few reports on the repair of PNI by ovalbumin. In this study, a novel bionic functionalized topological scaffold based on ovalbumin and grafted with tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide was constructed by micro-molding method and surface-biomodification technology. The scaffolds were subjected to a series of evaluations in terms of morphology, mechanics, hydrophilicity, and biocompatibility, and the related molecular mechanisms were further penetrated. The results showed that the scaffolds prepared in this study had aligned ridge/groove structure, good mechanical properties and biocompatibility, and could be used as carriers to slowly release YIGSR, which effectively promoted the proliferation, migration and elongation of Schwann Cells (SCs), and significantly up-regulated the gene expression related to proliferation, apoptosis, migration and axon regeneration. Therefore, the bionic functional topological scaffold has significant application potential for promoting peripheral nerve regeneration and provides a new therapeutic option for repairing PNI.

A Randomized, Double-Blind, Controlled Phase III Clinical Trial to Evaluate the Immunogenicity and Safety of a Lyophilized Human Rabies Vaccine (Vero Cells) in Healthy Participants Aged 10-60 Years Following Essen and Zagreb Vaccination Procedures.

OBJECTIVE: In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10-60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable. METHOD: A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated. RESULTS: The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10-18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed. CONCLUSION: The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.