A 10-year follow-up of high-dose ambroxol treatment combined with enzyme replacement therapy for neuropathic Gaucher disease.

High-dose ambroxol therapy combined with ERT in patients with neuropathic Gaucher disease.

Hybrid integrated thin-film lithium niobate-silicon nitride electro-optical phased array incorporating silicon nitride grating antenna for two-dimensional beam steering.

This study proposes a solid-state two-dimensional beam-steering device based on an electro-optical phased array (EOPA) in thin-film lithium niobate (TFLN) and silicon nitride (SiN) hybrid platforms, thereby eliminating the requirement for the direct etching of TFLN. Electro-optic (EO) phase modulator array comprises cascaded multimode interference couplers with an SiN strip-loaded TFLN configuration, which is designed and fabricated via i-line photolithography. Each EO modulator element with an interaction region length of 1.56 cm consumed a minimum power of 3.2 pJ/π under a half-wave voltage of 3.64 V and had an estimated modulation speed of 1.2 GHz. Subsequently, an SiN dispersive antenna with a waveguide grating was tethered to the modulator array to form an EOPA, facilitating the out-of-plane radiation of highly defined near-infrared beams. A prepared EOPA utilized EO phase control and wavelength tuning near 1550 nm to achieve a field-of-view of 22° × 5° in the horizontal and vertical directions. The proposed hybrid integrated platform can potentially facilitate low-power and high-speed beam steering.

Effect of Secondary Phase on Electroless Ni Plating Behaviour of Super Duplex Stainless Steel SAF2507 for Advanced Li-Ion Battery Case.

The development of Li-ion battery cases requires superior electrical conductivity, strength, and corrosion resistance for both cathode and anode to enhance safety and performance. Among the various battery case materials, super duplex stainless steel (SDSS), which is composed of austenite and ferrite as two-phase stainless steel, exhibits outstanding strength and corrosion resistance. However, stainless steel, which is an iron-based material, tends to have lower electrical conductivity. Nevertheless, nickel-plating SDSS can achieve excellent electrical conductivity, making it suitable for Li-ion battery cases. Therefore, this study analysed the plating behaviour of SDSS plates after nickel plating to leverage their exceptional strength and corrosion resistance. Electroless Ni plating was performed to analyse the plating behaviour, and the plating behaviour was studied with reference to different plating durations. Heat treatment was conducted at 1000 °C for one hour, followed by cooling at 50 °C/s. Post-heat treatment, the analysis of phases was executed using FE-SEM, EDS, and EPMA. Electroless Ni plating was performed at 60-300 s. The plating duration after the heat treatment was up to 300 s, and the behaviour of the materials was observed using FE-SEM. The phase analysis concerning different plating durations was conducted using XRD. Post-heat treatment, the precipitated secondary phases in SAF2507 were identified as Sigma, Chi, and CrN, approximating a 13% distribution. During the electroless Ni plating, the secondary phase exhibited a plating rate equivalent to that of ferrite, entirely plating at around 180 s. Further increments in plating time displayed growth of the plating layer from the austenite direction towards the ferrite, accompanied by a reduced influence from the substrate. Despite the differences in composition, both the secondary phase and austenite demonstrated comparable plating rates, showing that electroless Ni plating on SDSS was primarily influenced by the substrate, a finding which was primarily confirmed through phase analysis.

Review of quorum-quenching probiotics: A promising non-antibiotic-based strategy for sustainable aquaculture.

The emergence of antibiotic-resistant bacteria (ARBs) and genes (ARGs) in aquaculture underscores the urgent need for alternative veterinary strategies to combat antimicrobial resistance (AMR). These measures are vital to reduce the likelihood of entering a post-antibiotic era. Identifying environmentally friendly biotechnological solutions to prevent and treat bacterial diseases is crucial for the sustainability of aquaculture and for minimizing the use of antimicrobials, especially antibiotics. The development of probiotics with quorum-quenching (QQ) capabilities presents a promising non-antibiotic strategy for sustainable aquaculture. Recent research has demonstrated the effectiveness of QQ probiotics (QQPs) against a range of significant fish pathogens in aquaculture. QQ disrupts microbial communication (quorum sensing, QS) by inhibiting the production, replication, and detection of signalling molecules, thereby reducing bacterial virulence factors. With their targeted anti-virulence approach, QQPs have substantial promise as a potential alternative to antibiotics. The application of QQPs in aquaculture, however, is still in its early stages and requires additional research. Key challenges include determining the optimal dosage and treatment regimens, understanding the long-term effects, and integrating QQPs with other disease control methods in diverse aquaculture systems. This review scrutinizes the current literature on antibiotic usage, AMR prevalence in aquaculture, QQ mechanisms and the application of QQPs as a sustainable alternative to antibiotics.

International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis.

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results.Abbreviation: 3-MA:3-methyladenine; 4HNE: 4-hydroxynonenal; ACD: accidentalcell death; ADF: autophagy-dependentferroptosis; ARE: antioxidant response element; BH2:dihydrobiopterin; BH4: tetrahydrobiopterin; BMDMs: bonemarrow-derived macrophages; CMA: chaperone-mediated autophagy; CQ:chloroquine; DAMPs: danger/damage-associated molecular patterns; EMT,epithelial-mesenchymal transition; EPR: electronparamagnetic resonance; ER, endoplasmic reticulum; FRET: Försterresonance energy transfer; GFP: green fluorescent protein;GSH: glutathione;IF: immunofluorescence; IHC: immunohistochemistry; IOP, intraocularpressure; IRI: ischemia-reperfusion injury; LAA: linoleamide alkyne;MDA: malondialdehyde; PGSK: Phen Green™ SK;RCD: regulatedcell death; PUFAs: polyunsaturated fatty acids; RFP: red fluorescentprotein;ROS: reactive oxygen species; TBA: thiobarbituricacid; TBARS: thiobarbituric acid reactive substances; TEM:transmission electron microscopy.

Recent advances in the role of interfacial liquids in electrochemical reactions.

The interfacial liquid, situated in proximity to an electrode or catalyst, plays a vital role in determining the activity and selectivity of crucial electrochemical reactions, including hydrogen evolution, oxygen evolution/reduction, and carbon dioxide reduction. Thus, there has been a growing interest in better understanding the behavior and the catalytic effect of its constituents. This minireview examines the impact of interfacial liquids on electrocatalysis, specifically the effects of water molecules and ionic species present at the interface. How the structure of interfacial water, distinct from the bulk, can affect charge transfer kinetics and transport of species is presented. Furthermore, how cations and anions (de)stabilize intermediates and transition states, compete for adsorption with reaction species, and act as local environment modifiers including pH and the surrounding solvent structure are described in detail. These effects can promote or inhibit reactions in various ways. This comprehensive exploration provides valuable insights for tailoring interfacial liquids to optimize electrochemical reactions.

Two intestinal microbiota-derived metabolites, deoxycholic acid and butyrate, synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis.

BACKGROUND: Necrotic enteritis (NE) is a major enteric disease in poultry, yet effective mitigation strategies remain elusive. Deoxycholic acid (DCA) and butyrate, two major metabolites derived from the intestinal microbiota, have independently been shown to induce host defense peptide (HDP) synthesis. However, the potential synergy between these two compounds remains unexplored. METHODS: To investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function, we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate (NaB), either individually or in combination, for 24 h. Subsequently, we performed RNA isolation and reverse transcription-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function. To further determine the synergy between DCA and NaB in enhancing NE resistance, we conducted two independent trials with Cobb broiler chicks. In each trial, the diet was supplemented with DCA or NaB on the day-of-hatch, followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14, respectively. We recorded animal mortality after infection and assessed intestinal lesions on d 17. The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing. RESULTS: We found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants. Additionally, the gene for claudin-1, a major tight junction protein, also exhibited synergistic induction in response to DCA and NaB. Furthermore, dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE. Notably, the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides, Faecalibacterium, and Cuneatibacter, with lactobacilli becoming the most dominant species. However, supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels. CONCLUSIONS: DCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance, with potential for further development as cost-effective antibiotic alternatives.

Unique Changes in the Lung Microbiome following the Development of Chronic Lung Allograft Dysfunction.

The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung microbiome-immune interaction may be critical in developing CLAD. In this context, examining alterations in the microbiome and immune cells of the lungs following CLAD, in comparison to the lung condition immediately after transplantation, can offer valuable insights. Four adult patients who underwent lung retransplantation between January 2019 and June 2020 were included in this study. Lung tissues were collected from the same four individuals at two different time points: at the time of the first transplant and at the time of the explantation of CLAD lungs at retransplantation due to CLAD. We analyzed whole-genome sequencing using the Kraken2 algorithm and quantified the cell fractionation from the bulk tissue gene expression profile for each lung tissue. Finally, we compared the differences in lung microbiome and immune cells between the lung tissues of these two time points. The median age of the recipients was 57 years, and most (75%) had undergone lung transplants for idiopathic pulmonary fibrosis. All patients were administered basiliximab for induction therapy and were maintained on three immunosuppressants. The median CLAD-free survival term was 693.5 days, and the median time to redo the lung transplant was 843.5 days. Bacterial diversity was significantly lower in the CLAD lungs than at transplantation. Bacterial diversity tended to decrease according to the severity of the CLAD. Aerococcus, Caldiericum, Croceibacter, Leptolyngbya, and Pulveribacter genera were uniquely identified in CLAD, whereas no taxa were identified in lungs at transplantation. In particular, six taxa, including Croceibacter atlanticus, Caldiserium exile, Dolichospermum compactum, Stappia sp. ES.058, Kinetoplastibacterium sorsogonicusi, and Pulveribacter suum were uniquely detected in CLAD. Among immune cells, CD8+ T cells were significantly increased, while neutrophils were decreased in the CLAD lung. In conclusion, unique changes in lung microbiome and immune cell composition were confirmed in lung tissue after CLAD compared to at transplantation.

Assessing the impact of mRNA vaccination in chronic inflammatory murine model.

The implications of administration of mRNA vaccines to individuals with chronic inflammatory diseases, including myocarditis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), are unclear. We investigated mRNA vaccine effects in a chronic inflammation mouse model implanted with an LPS pump, focusing on toxicity and immunogenicity. Under chronic inflammation, mRNA vaccines exacerbated cardiac damage and myocarditis, inducing mild heart inflammation with heightened pro-inflammatory cytokine production and inflammatory cell infiltration in the heart. Concurrently, significant muscle damage occurred, with disturbances in mitochondrial fusion and fission factors signaling impaired muscle repair. However, chronic inflammation did not adversely affect muscles at the vaccination site or humoral immune responses; nevertheless, it partially reduced the cell-mediated immune response, particularly T-cell activation. These findings underscore the importance of addressing mRNA vaccine toxicity and immunogenicity in the context of chronic inflammation, ensuring their safe and effective utilization, particularly among vulnerable populations with immune-mediated inflammatory diseases.

Diagnostic performance of cross-priming amplification-based lateral flow assay (CPA-LFA) and real-time PCR for koi herpesvirus (KHV) detection.

Epizootics of Koi herpesvirus (KHV) cause mass mortality in koi carp (Cyprinus rubrofuscus) and common carp (Cyprinus carpio) worldwide. Rapid and accurate virus detection technology is crucial for preventing pathogen spread and minimizing damage. Although several diagnostic assays have been developed for KHV, the analytical and diagnostic performance of the detection methods has not been evaluated. In this study, we developed and validated the diagnostic performance of two molecular diagnostic assays, cross-priming amplification-based lateral flow assay (CPA-LFA) and TaqMan probe-based real-time polymerase chain reaction (PCR). To detect KHV, primers and probe were designed based on the thymidine kinase (TK) genes. The detection limits of developed CPA-LFA and real-time PCR assays were determined to be 675.69 copies/µL and 8.384 copies/µL, respectively. The diagnostic sensitivity and specificity of the developed assay were determined using fish samples (n = 179). CPA-LFA was found to be 93.67% and 100%, respectively, and real-time PCR was found to be 100% and 100%, respectively. Therefore, the newly developed CPA-LFA and real-time PCR assays accurately and rapidly detect KHV. CPA-LFA is particularly suitable for point-of-care diagnosis because of its simple diagnostic process, and real-time PCR analysis is most suitable for precise diagnosis because it can detect low viral loads.

A reproducible ensemble machine learning approach to forecast dengue outbreaks.

Dengue fever, a prevalent and rapidly spreading arboviral disease, poses substantial public health and economic challenges in tropical and sub-tropical regions worldwide. Predicting infectious disease outbreaks on a countrywide scale is complex due to spatiotemporal variations in dengue incidence across administrative areas. To address this, we propose a machine learning ensemble model for forecasting the dengue incidence rate (DIR) in Brazil, with a focus on the population under 19 years old. The model integrates spatial and temporal information, providing one-month-ahead DIR estimates at the state level. Comparative analyses with a dummy model and ablation studies demonstrate the ensemble model's qualitative and quantitative efficacy across the 27 Brazilian Federal Units. Furthermore, we showcase the transferability of this approach to Peru, another Latin American country with differing epidemiological characteristics. This timely forecast system can aid local governments in implementing targeted control measures. The study advances climate services for health by identifying factors triggering dengue outbreaks in Brazil and Peru, emphasizing collaborative efforts with intergovernmental organizations and public health institutions. The innovation lies not only in the algorithms themselves but in their application to a domain marked by data scarcity and operational scalability challenges. We bridge the gap by integrating well-curated ground data with advanced analytical methods, addressing a significant deficiency in current practices. The successful transfer of the model to Peru and its consistent performance during the 2019 outbreak in Brazil showcase its scalability and practical application. While acknowledging limitations in handling extreme values, especially in regions with low DIR, our approach excels where accurate predictions are critical. The study not only contributes to advancing DIR forecasting but also represents a paradigm shift in integrating advanced analytics into public health operational frameworks. This work, driven by a collaborative spirit involving intergovernmental organizations and public health institutions, sets a precedent for interdisciplinary collaboration in addressing global health challenges. It not only enhances our understanding of factors triggering dengue outbreaks but also serves as a template for the effective implementation of advanced analytical methods in public health.

Contrasting views on the role of AMPK in autophagy.

Efficient management of low energy states is vital for cells to maintain basic functions and metabolism and avoid cell death. While autophagy has long been considered a critical mechanism for ensuring survival during energy depletion, recent research has presented conflicting evidence, challenging the long-standing concept. This recent development suggests that cells prioritize preserving essential cellular components while restraining autophagy induction when cellular energy is limited. This essay explores the conceptual discourse on autophagy regulation during energy stress, navigating through the studies that established the current paradigm and the recent research that has challenged its validity while proposing an alternative model. This exploration highlights the far-reaching implications of the alternative model, which represents a conceptual departure from the established paradigm, offering new perspectives on how cells respond to energy stress.

Draft genome sequence of multiple antibiotic-resistant Vibrio harveyi isolated from diseased olive flounder (Paralichthys olivaceus) farmed in South Korea.

Vibrio harveyi strain 22FBVib0145 was isolated from a diseased olive flounder farmed in Jeju, Korea. Here, we report the draft genome sequence of this strain. It is 6,238,277 bp in length with a G + C content of 44.8%.

Right lower lung midline herniation as a rare complication in an infant with heart-lung transplantation: A case report.

BACKGROUND: Lung herniation is a rare complication of heart-lung transplantation that can be fatal owing to vascular compromise and airway obstruction. To date, only five cases of lung herniation related to heart-lung transplantation have been reported in the literature; however, to the best of our knowledge, this is the first worldwide report of heart-lung transplantation-related lung herniation in an infant. METHODS: We describe the case of lung herniation as a rare heart-lung transplantation-related complication in an infant. A 12-month-old female baby developed severe bronchopulmonary dysplasia with severe pulmonary hypertension, and she underwent extracorporeal membrane oxygenation for cardiac collapse and lung support. Then, we performed heart-lung transplantation to manage the irreversible deterioration of her lung function. After the heart-lung transplantation, we found the radiological abnormalities persisted on follow-up chest radiographs until the 13th postoperative day diagnosed as lung herniation of the right lower lobe on chest computed tomography. RESULTS: After the relocation of the herniated lung, the clinical condition of the patient improved, and the patient is currently growing without any respiratory symptoms. CONCLUSIONS: In this case report, we emphasize that clinical awareness and high suspicion of this rare complication are needed for early diagnosis and proper treatment to prevent post-transplantation morbidity and mortality related to potential ischemic injury.

Development of High Efficiency, Spray-Coated Perovskite Solar Cells and Modules Using Additive-Engineered Porous PbI2 Films.

The development of anti-solvent free, scalable, and printable perovskite film is crucial to realizing the low-cost roll-to-roll development of perovskite solar cells (PSCs). Herein, large-area perovskite film fabrication is explored using a spray-assisted sequential deposition technique. How propylene carbonate (PC) solvent additive affects the transformation of lead halide (PbI2 ) into perovskite at room temperature is investigated. The result shows that PC-modified perovskite films exhibit a uniform, pinhole-free morphology with oriented grains compared with pristine perovskite films. The PC-modified perovskite film also has a prolonged fluorescence lifetime that indicates lower carrier recombination. The champion PSC devices based on PC-modified perovskite film realize a power conversion efficiency (PCE) of 20.5% and 19.3% at an active area (A) of 0.09 cm2 and 1 cm2 , respectively. The fabricated PSCs are stable and demonstrate ≥85% PCE retention following 60 days of exposure to ambient conditions. Furthermore, perovskite solar modules (A ≈ 13 cm2 ) that yield a PCE of 15.8% are fabricated. These results are among the best reported for the state-of-art spray-coated PSCs. Spray deposition coupled with a PC additive is highly promising for economical and high-output preparation of PSCs.

Intranasal immunization with the recombinant measles virus encoding the spike protein of SARS-CoV-2 confers protective immunity against COVID-19 in hamsters.

BACKGROUND: As the nasal mucosa is the initial site of infection for COVID-19, intranasal vaccines are more favorable than conventional vaccines. In recent clinical studies, intranasal immunization has been shown to generate higher neutralizing antibodies; however, there is a lack of evidence on sterilizing immunity in the upper airway. Previously, we developed a recombinant measles virus encoding the spike protein of SARS-CoV-2 (rMeV-S), eliciting humoral and cellular immune responses against SARS-CoV-2. OBJECTIVES: In this study, we aim to provide an experiment on nasal vaccines focusing on a measles virus platform as well as injection routes. STUDY DESIGN: Recombinant measles viruses expressing rMeV-S were prepared, and 5 × 105 PFUs of rMeV-S were administered to Syrian golden hamsters via intramuscular or intranasal injection. Subsequently, the hamsters were challenged with inoculations of 1 × 105 PFUs of SARS-CoV-2 and euthanized 4 days post-infection. Neutralizing antibodies and RBD-specific IgG in the serum and RBD-specific IgA in the bronchoalveolar lavage fluid (BALF) were measured, and SARS-CoV-2 clearance capacity was determined via quantitative reverse-transcription PCR (qRT-PCR) analysis and viral titer measurement in the upper respiratory tract and lungs. Immunohistochemistry and histopathological examinations of lung samples from experimental hamsters were conducted. RESULTS: The intranasal immunization of rMeV-S elicits protective immune responses and alleviates virus-induced pathophysiology, such as body weight reduction and lung weight increase in hamsters. Furthermore, lung immunohistochemistry demonstrated that intranasal rMeV-S immunization induces effective SARS-CoV-2 clearance that correlates with viral RNA content, as determined by qRT-PCR, in the lung and nasal wash samples, SARS-CoV-2 viral titers in lung, nasal wash, BALF samples, serum RBD-specific IgG concentration, and RBD-specific IgA concentration in the BALF. CONCLUSION: An intranasal vaccine based on the measles virus platform is a promising strategy owing to the typical route of infection of the virus, the ease of administration of the vaccine, and the strong immune response it elicits.

Highly Reliable 3D Channel Memory and Its Application in a Neuromorphic Sensory System for Hand Gesture Recognition.

Brain-inspired neuromorphic computing systems, based on a crossbar array of two-terminal multilevel resistive random-access memory (RRAM), have attracted attention as promising technologies for processing large amounts of unstructured data. However, the low reliability and inferior conductance tunability of RRAM, caused by uncontrollable metal filament formation in the uneven switching medium, result in lower accuracy compared to the software neural network (SW-NN). In this work, we present a highly reliable CoOx-based multilevel RRAM with an optimized crystal size and density in the switching medium, providing a three-dimensional (3D) grain boundary (GB) network. This design enhances the reliability of the RRAM by improving the cycle-to-cycle endurance and device-to-device stability of the I-V characteristics with minimal variation. Furthermore, the designed 3D GB-channel RRAM (3D GB-RRAM) exhibits excellent conductance tunability, demonstrating high symmetricity (624), low nonlinearity (ßLTP/ßLTD ∼ 0.20/0.39), and a large dynamic range (Gmax/Gmin ∼ 31.1). The cyclic stability of long-term potentiation and depression also exceeds 100 cycles (105 voltage pulses), and the relative standard deviation of Gmax/Gmin is only 2.9%. Leveraging these superior reliability and performance attributes, we propose a neuromorphic sensory system for finger motion tracking and hand gesture recognition as a potential elemental technology for the metaverse. This system consists of a stretchable double-layered photoacoustic strain sensor and a crossbar array neural network. We perform training and recognition tasks on ultrasonic patterns associated with finger motion and hand gestures, attaining a recognition accuracy of 97.9% and 97.4%, comparable to that of SW-NN (99.8% and 98.7%).

Process Parameter Optimization for Laser Powder Bed Fusion of Fe-Si Alloy Considering Surface Morphology and Track Width of Single Scan Track.

A laser power bed fusion (L-PBF) manufacturing process was optimized by analyzing the surface morphology and track width w of single scan tracks (SSTs) on Fe-3.4wt.%Si. An SST was evaluated under process conditions of laser power P, scan speed V, and energy density E = P/V. The SST surface shape was mainly affected by E; desirable thin and regular tracks were obtained at E = 0.3 and 0.4 J/mm. An L-PBF process window was proposed considering the optimal w of SST, and the appropriate range of E for the alloy was identified to be 0.24 J/mm to 0.49 J/mm. w showed a strong relationship with E and V, and an analytic model was suggested. To verify the process window derived from the appropriate w of SST, cubic samples were manufactured with the estimated optimal process conditions. Most samples produced had a high density with a porosity of <1%, and the process window derived from SST w data had high reliability. This study presents a comprehensive approach to enhancing additive manufacturing for Fe-3.4Si alloy, offering valuable insights for achieving high-quality samples without the need for time-intensive procedures.

mRNA-HPV vaccine encoding E6 and E7 improves therapeutic potential for HPV-mediated cancers via subcutaneous immunization.

The E6 and E7 proteins of specific subtypes of human papillomavirus (HPV), including HPV 16 and 18, are highly associated with cervical cancer as they modulate cell cycle regulation. The aim of this study was to investigate the potential antitumor effects of a messenger RNA-HPV therapeutic vaccine (mHTV) containing nononcogenic E6 and E7 proteins. To achieve this, C57BL/6j mice were injected with the vaccine via both intramuscular and subcutaneous routes, and the resulting effects were evaluated. mHTV immunization markedly induced robust T cell-mediated immune responses and significantly suppressed tumor growth in both subcutaneous and orthotopic tumor-implanted mouse model, with a significant infiltration of immune cells into tumor tissues. Tumor retransplantation at day 62 postprimary vaccination completely halted progression in all mHTV-treated mice. Furthermore, tumor expansion was significantly reduced upon TC-1 transplantation 160 days after the last immunization. Immunization of rhesus monkeys with mHTV elicited promising immune responses. The immunogenicity of mHTV in nonhuman primates provides strong evidence for clinical application against HPV-related cancers in humans. All data suggest that mHTV can be used as both a therapeutic and prophylactic vaccine.