Interface-constrained catalytic hairpin assembly permits highly sensitive SERS signaling of miRNA.

The rapid and precise monitoring of peripheral blood miRNA levels holds paramount importance for disease diagnosis and treatment monitoring. In this study, we propose an innovative research strategy that combines the catalytic hairpin assembly reaction with SERS signal congregation and enhancement. This combination can significantly enhance the stability of SERS detection, enabling stable and efficient detection of miRNA. Specifically, our paper-based SERS detection platform incorporates a streptavidin-modified substrate, biotin-labeled catalytic hairpin assembly reaction probes, 4-ATP, and primer-co-modified gold nanoparticles. In the presence of miRNA, the 4-ATP and primer-co-modified gold nanoparticles can specifically recognize the miRNA and interact with the biotin-labeled CHA probes to initiate an interfacial catalytic hairpin assembly reaction. This enzyme-free high-efficiency catalytic process can accumulate a large amount of biotin on the gold nanoparticles, which then bind to the streptavidin on the substrate with the assistance of the driving liquid, forming red gold nanoparticle stripes. These provide a multitude of hotspots for SERS, enabling enhanced signal detection. This innovative design achieves a low detection limit of 3.47 fM while maintaining excellent stability and repeatability. This conceptually innovative detection platform offers new technological possibilities and solutions for clinical miRNA detection.

Ecological risk assessment of commonly used antibiotics in aquatic ecosystems along the coast of China.

The consistent input of antibiotics into aquatic environments may pose risks to various creatures and ecosystems. However, risk assessment of pharmaceuticals and personal care products (PPCPs) in aquatic environments is frequently limited by the lack of toxicity data. To investigate the risk of commonly used antibiotics to various aquatic creatures, we focused on the distribution patterns and temporal dynamics of antibiotics in the coastal estuary area of China and performed a comprehensive ecological risk assessment for four antibiotics: erythromycin (ERY), tetracycline (TCN), norfloxacin (NOR) and sulfamethoxazole (SMX). An interspecies correlation estimation (ICE)-species sensitivity distribution (SSD) combined model was applied to predict the toxicity data of untested aquatic species, and an accurate ecological risk assessment procedure was developed to evaluate the risk level of PPCPs. The results of risk quotient assessments and probabilistic risk assessments (PRAs) suggested that four objective antibiotics in the Chinese coastal estuary area were at a low risk level. These antibiotics posed a high risk in antibiotic-related global hot spots, with probabilistic risk values for ERY, NOR, SMX, and TCN of 81.33 %, 27.08 %, 21.13 %, and 15.44 %, respectively. We applied an extrapolation method to overcome the lack of toxicity data in ecological risk assessment, enhanced the ecological reality of water quality criteria derivation and reduced the uncertainty of risk assessment for antibiotics.

Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

A Novel Event-Triggered Bipartite Consensus for PDE-Based Multiagent Systems With Switching Topologies and Antagonistic Interactions.

Unlike the traditional studies on multiagent systems (MASs), this article investigates a class of MASs with spatial properties, whose agents are modeled by partial differential equations (PDE), in addition, to make the model more comprehensive, the Markovian switching topology with partially unknown probability is taken into account. The purpose of this article is to achieve the bipartite consensus for the above PDE-based MASs. In fact, the consideration of spatial factors in MASs will exacerbate the network transmission pressure, to overcome this problem, a novel spatiotemporal event-triggered mechanism is developed. Compared with the existing event-triggered mechanism, the proposed one is not only time-dependent but also covers the influence of spatial variables on the trigger conditions, which helps to further reduce the triggering frequency. Finally, three examples are given to verify the validity of the conclusion we proposed.

Damage and reliability analysis of double-arch tunnel without a middle pilot tunnel under blast load.

In this study, a new type of multi-arch tunnel construction method is proposed. This effort is undertaken due to the many disadvantages of the traditional multi-arch tunnel construction method. Furthermore, this method omits the construction of a middle pilot tunnel, and it has the advantages of safety, high efficiency, and being economical. When using the method of continuous arch tunneling without a middle pilot tunnel, the blasting of the first tunnel and the following tunnel has a greater impact on the surrounding rock damage, as well as on the supporting structure of the same cross-section. Therefore, this study uses LS-DYNA finite element software to construct a three-dimensional numerical model. In addition, the perimeter rock damage law and mechanical response characteristics of the supporting structure in the same cross-section of the first tunnel, as well as the following tunnel after blasting without a middle pilot tunnel, are analyzed. At the same time, the results of the study are based on optimizing the blasting program, and these are then applied to the field. Through the results, it is found that, after blasting a continuous arch tunnel without a medial pilot tunnel, the surrounding rock damage in the arch cross-region of the double-arch tunnel (where the arch top and the arch shoulder are more significant) and the effective stress of the supporting structure exceed the strength design value. In addition, the maximum adequate pressure is distributed in the medial diaphragm wall. With the optimized blasting scheme, the range of the peripheral rock damage is reduced by a maximum of 67%, and the effective stress in the supporting structure is reduced by 25.9-64.8%. The research results are of great significance in terms of improving construction safety, economic efficiency, and project quality, as well as in promoting the research and development of new work methods for double-arch tunnels.

Towards a Safer Future: Enhancing Vaccine Development to Combat Animal Coronaviruses.

Coronaviruses (CoVs) are a large class of positively stranded RNA viruses that pose a significant threat to public health, livestock farming, and wild animals. These viruses have the ability to cross species barriers and cause devastating epidemics. Animals are considered to be intermediate hosts for many coronaviruses, and many animal coronaviruses also have the potential for cross-species transmission to humans. Therefore, controlling the epidemic transmission of animal coronaviruses is of great importance to human health. Vaccination programs have proven to be effective in controlling coronaviruses infections, offering a cost-effective approach to reducing morbidity and mortality, so the re-emergence of lethal coronaviruses emphasizes the urgent need for the development of effective vaccines. In this regard, we explore the progress in animal coronavirus vaccine development, covering the latest taxonomy of the main animal coronaviruses, spillover events, diverse vaccine development platforms, potential main targets for animal coronavirus vaccine development, and primary challenges facing animal coronavirus vaccines. We emphasize the urgent need to create a "dual-effect" vaccine capable of eliciting both cellular and humoral immune responses. The goal is to highlight the contributions of veterinary scientists in this field and emphasize the importance of interdisciplinary collaboration between the veterinary and medical communities. By promoting communication and cooperation, we can enhance the development of novel and super vaccines to combat human and animal coronavirus infections in the future.

A novel intracoronary hypothermia device reduces myocardial reperfusion injury in pigs.

BACKGROUND: Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury. METHODS: This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (5 and 42 days post-MI) and a series of biomarkers/histological studies were performed. RESULTS: The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH. CONCLUSIONS: The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

TEA domain transcription factor 1(TEAD1) induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway.

Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.

Simulating behavior of perfluorooctane sulfonate (PFOS) in the mainstream of a river system with sluice regulations.

Perfluorooctane sulfonate (PFOS) is a persistent, anionic and ubiquitous contaminant that undergoes long-range transport within the environment. Its behavior has attracted wide-range academic and regulatory attention. In this article, a mass balance model was employed to simulate PFOS concentrations in the mainstream of Haihe River water system, encompassing sluices and artificial rivers. The dynamic simulation of PFOS concentrations in both sediment and freshwater took into account fluctuations in PFOS emissions, water levels and water discharge. Furthermore, the study delved into exploring the impacts of sluices and artificial rivers on the behavior of PFOS. The simulated concentrations of PFOS in steady state agreed with the measured concentrations in surveys carried out in Nov. 2019, July 2020, Oct. 2020, and June 2021. Every year, approximately 24 kg PFOS was discharged into the Bohai Sea with Chaobai New River being the largest contributor for 44 %. Moreover, the transport of PFOS in the original rivers is likely to be restricted by sluices and replaced by artificial rivers. Monte Carlo analysis showed that model predictions of PFOS concentrations in sediment were subject to greater uncertainty than those in freshwater as the former is impacted by more parameters, such as density of sediment. This study provides a scientific basis for the local government to manage and control PFOS.

Legacy and alternative per-and polyfluoroalkyl substances (PFASs) in the Bohai Bay Rim: Occurrence, partitioning behavior, risk assessment, and emission scenario analysis.

The use of alternative per- and polyfluoroalkyl substances (PFASs) has been practiced because of the restrictions on legacy PFASs. However, knowledge gaps exist on the ecological risks of alternatives and relationships between restrictions and emissions. This study systematically analyzed the occurrence characteristics, water-sediment partitioning behaviors, ecological risks, and emissions of legacy and alternative PFASs in the Bohai Bay Rim (BBR). The mean concentration of total PFASs was 46.105 ng/L in surface water and 6.125 ng/g dry weight (dw) in sediments. As an alternative for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide dimer acid (GenX) had a concentration second only to PFOA in surface water. In sediments, perfluorobutyric acid (PFBA) and GenX were the two predominant contaminants. In the water-sediment partitioning system, GenX, 9-chlorohexadecafluoro-3-oxanone-1-sulfonic acid (F-53B), and 11-chloroeicosafluoro-3-oxaundecane-1-sulfonic acid (8:2 Cl-PFESA) tended to be enriched towards sediments. The species sensitivity distribution (SSD) models revealed the low ecological risks of PFASs and their alternatives in the BBR. Moreover, predicted no-effected concentrations (PNECs) indicated that short-chain alternatives like PFBA and perfluorobutane sulfonate (PFBS) were safer for aquatic ecosystems, while caution should be exercised when using GenX and F-53B. Due to the incremental replacement of PFOA by GenX, cumulative emissions of 1317.96 kg PFOA and 667.22 kg GenX were estimated during 2004-2022, in which PFOA emissions were reduced by 59.2 % due to restrictions implemented since 2016. If more stringent restrictions are implemented from 2023 to 2030, PFOA emissions will further decrease by 85.0 %, but GenX emissions will increase by an additional 21.3 %. Simultaneously, GenX concentrations in surface water are forecasted to surge by 2.02 to 2.45 times in 2023. This study deepens the understanding of PFAS alternatives and assists authorities in developing policies to administer PFAS alternatives.

Corrigendum: Impact of intestinal microbiota on metabolic toxicity and potential detoxification of amygdalin.

[This corrects the article DOI: 10.3389/fmicb.2022.1030516.].

Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets.

Hypoxia, characterized by reduced oxygen concentration, is a significant stressor that affects the survival of aerobic species and plays a prominent role in cardiovascular diseases. From the research history and milestone events related to hypoxia in cardiovascular development and diseases, The "hypoxia-inducible factors (HIFs) switch" can be observed from both temporal and spatial perspectives, encompassing the occurrence and progression of hypoxia (gradual decline in oxygen concentration), the acute and chronic manifestations of hypoxia, and the geographical characteristics of hypoxia (natural selection at high altitudes). Furthermore, hypoxia signaling pathways are associated with natural rhythms, such as diurnal and hibernation processes. In addition to innate factors and natural selection, it has been found that epigenetics, as a postnatal factor, profoundly influences the hypoxic response and progression within the cardiovascular system. Within this intricate process, interactions between different tissues and organs within the cardiovascular system and other systems in the context of hypoxia signaling pathways have been established. Thus, it is the time to summarize and to construct a multi-level regulatory framework of hypoxia signaling and mechanisms in cardiovascular diseases for developing more therapeutic targets and make reasonable advancements in clinical research, including FDA-approved drugs and ongoing clinical trials, to guide future clinical practice in the field of hypoxia signaling in cardiovascular diseases.

The causal association between thyroid disease and gout: A Mendelian randomization study.

Observational studies have reported some associations between thyroid disease and gout, but the causal relationship between the 2 is not clear. We used Mendelian randomization (MR) Analysis to investigate the causal association between some thyroid diseases (autoimmune hypothyroidism, autoimmune hyperthyroidism, thyroid nodules, and thyroid cancer) and gout. GWAS data were used for analysis. The exposure factors were autoimmune hypothyroidism, autoimmune hyperthyroidism, thyroid nodules and thyroid cancer, and the outcome variables were gout. IVW, MR-Egger, Weighted median and Weighted mode were used for MR analysis. Cochran Q test MR-PRESSO and MR-Egger intercept analysis were used to detect heterogeneity and multi directivity. Autoimmune hypothyroidism has a causal effect on gout, IVW results show (OR = 1.13, 95% CI = 1.03-1.21, PFDR = 0.0336); Autoimmune hyperthyroidism has a causal effect on gout, IVW results show (OR = 1.07, 95% CI = 1.01-1.12, PFDR = 0.0314); Thyroid cancer has no causal effect on gout, IVW results show (OR = 1.03, 95% CI = 0.98-1.09, PFDR = 0.297); Thyroid nodules has no causal effect on gout, IVW results show (OR = 1.03, 95% CI = 0.98-1.08, PFDR = 0.225); Reverse MR Studies show that gout have no causal effect on the above thyroid diseases. Autoimmune hypothyroidism and autoimmune hyperthyroidism increase the risk of gout.

Downregulation of apoptotic repressor AVEN exacerbates cardiac injury after myocardial infarction.

Myocardial infarction (MI) is a leading cause of heart failure (HF), associated with morbidity and mortality worldwide. As an essential part of gene expression regulation, the role of alternative polyadenylation (APA) in post-MI HF remains elusive. Here, we revealed a global, APA-mediated, 3' untranslated region (3' UTR)-lengthening pattern in both human and murine post-MI HF samples. Furthermore, the 3' UTR of apoptotic repressor gene, AVEN, is lengthened after MI, contributing to its downregulation. AVEN knockdown increased cardiomyocyte apoptosis, whereas restoration of AVEN expression substantially improved cardiac function. Mechanistically, AVEN 3' UTR lengthening provides additional binding sites for miR-30b-5p and miR-30c-5p, thus reducing AVEN expression. Additionally, PABPN1 (poly(A)-binding protein 1) was identified as a potential regulator of AVEN 3' UTR lengthening after MI. Altogether, our findings revealed APA as a unique mechanism regulating cardiac injury in response to MI and also indicated that the APA-regulated gene, AVEN, holds great potential as a critical therapeutic target for treating post-MI HF.

Species variations in the gut microbiota of captive snub-nosed monkeys.

Introduction: Snub-nosed monkeys are species in danger of extinction due to habitat fragmentation and human activities. Captivity has been suggested as an Auxiliary Conservation Area (ASA) strategy. However, little is known about the adaptation of different species of snub-nosed monkeys to captive environments. Methods: This study compared the gut microbiota between Rhinopithecus bieti, R. brelichi, and R. roxellana under identical captive conditions to provide insights for improving captive conservation strategies. Results: The results showed that these three Rhinopithecus species shared 80.94% of their Operational Taxonomic Unit (OTU), indicating high similarity in gut microbiota composition. The predominant phyla were Firmicutes and Bacteroidetes for all three Rhinopithecus species, but differences were observed in diversity, characteristic bacterial communities, and predicted function. Significant enrichment of cellulolytic families, including Ruminococcaceae, Clostridiales vadinBB60 group, Christensenellaceae, and Erysipelotrichaceae, and pathways involved in propionate and butyrate metabolism in the gut of R. bieti suggested that it may have a superior dietary fiber utilization capacity. In contrast, Bacteroidetes, Ruminoccaceae, and Trichospiraceae were more abundant in R. brelichi and R. roxellana, and were associated with saccharide and glycan metabolic pathways. Moreover, R. brelichi and R. roxellana also had higher similarity in microbiota composition and predicted function. Discussion: In conclusion, the results demonstrate that host species are associated with the composition and function of the gut microbiota in snub-nosed monkeys. Thus, host species should be considered when formulating nutritional strategies and disease surveillance in captive snub-nosed monkeys.

Switching ETM-based neural adaptive output feedback control for nonaffine stochastic MIMO nonlinear systems subject to deferred constraint.

This article focuses on the neural adaptive output feedback control study related to nonaffine stochastic multiple-input, multiple-output nonlinear plants. First, a K-filter state observer based on a radial basis function neural network is designed to estimate the remaining unavailable states. Then, a novel adaptive command-filtered backstepping output feedback control framework is established, where an improved command filter with a fractional-order parameter is applied to conquer the calculation size problem. Specifically, the highlight of this work is that it designs a modified error compensation signal and incorporates the concept of deferred constraint to eradicate the negative effect caused by the filter errors. In addition, the network bandwidth resources, control impulse, and control accuracy are synthesized using an amended switching event-triggered mechanism. The theoretical analysis proved that the proposed control approach guarantees that the tracking error can converge to a preassigned region within a user-defined time while the violation of the deferred output constraint can be excluded. Two illustrative studies are provided to demonstrate the validity and superiority of the developed control method.

High S-doped amorphous carbon/carbon quantum dots coupled micro-frame for highly efficient potassium storage.

Anode materials with excellent rate capability, capacity, and cycle life have been a challenge in obtaining cost-effective K-ion batteries (KIBs). Based on the concept of waste recycling, we prepared the S-doped (21.5%) amorphous carbon/carbon quantum dots coupled micro-frame (SCMF) by combining chemical exfoliation and S/Se-assisted carbonization. SCMF exhibited the advantages of integrating amorphous carbon and carbon quantum dots (CQDs). The CQDs serve as fast electron channels, while amorphous carbon can accommodate more large-size K-ions and mitigate volume expansion. In KIBs, SCMF maintained a high reversible capacity (414.0 mAh g-1, after 100 cycles at 100 mA g-1), a good rate capability (224.0 mAh g-1, 2000 mA g-1), and excellent capacity retention (208.9 mAh g-1, after 2000 cycles at 1000 mA g-1). The molecular dynamic simulation revealed that CQDs provided fast electron transport channels and that C, O and S atoms had suitable interactions with K, facilitating potassium storage. Moreover, the potassium-ion capacitor (PIC) assembled from SCMF and activated carbon exhibited stable electrochemical performance, proving its potential for application. The research provided valuable insights into the reuse of biomass waste in new secondary batteries.

A novel mouse model of heart failure with preserved ejection fraction after chronic kidney disease induced by retinol through JAK/STAT pathway.

Heart failure is the leading cardiovascular comorbidity in chronic kidney disease (CKD) patients. Among the types of heart failure according to ejection fraction, heart failure with preserved ejection fraction (HFpEF) is the most common type of heart failure in CKD patients. However, the specific animal model of HFpEF afer CKD is currently missing. In this study, we determined the heart failure characteristics and dynamic progression in CKD mice. Based on these features, we established the practical HFpEF after CKD mouse model using 5/6 subtotal nephrectomy and retinol administration. Active apoptosis, impaired calcium handling, an imbalance between eNOS and oxidative stress and engaged endoplasmic reticulum stress were observed in our model. RNSseq revealed distinct gene expression patterns between HFpEF after CKD and metabolic induced-HFpEF. Furthermore, we revealed the potential mechanism of the pro-HFpEF effect of retinol. Serum accumulation of retinol in CKD prompts myocardial hypertrophy and fibrosis by activating JAK2 and phosphorylating STAT5. Finally, using small molecule inhibitor AC-4-130, we found STAT5 phosphorylation inhibitor may be a potential intervention target for HFpEF after CKD. In conclusion, we provide a novel animal model and a potential drug target for HFpEF intervention in CKD.

High-precision prediction of blood glucose concentration utilizing Fourier transform Raman spectroscopy and an ensemble machine learning algorithm.

Raman spectroscopy has gained popularity in analyzing blood glucose levels due to its non-invasive identification and minimal interference from water. However, the challenge lies in how to accurately predict blood glucose concentrations in human blood using Raman spectroscopy. This paper researches a novel integrated machine learning algorithm called Bagging-ABC-ELM. The optimal input weights and biases of extreme learning machine (ELM) model are obtained by artificial bee colony (ABC) algorithm. The bagging algorithm is used to obtain a better the stability of the model and higher performance than ELM algorithm. The results show that the mean value of coefficient of determination is 0.9928, and root mean square error is 0.1928. Compared to other regression models, the Bagging-ABC-ELM model exhibited superior prediction accuracy, robustness, and generalization capability. The Bagging-ABC-ELM model presents a promising alternative for analyzing blood glucose levels in clinical and research settings.

A roadmap for developing Venezuelan equine encephalitis virus (VEEV) vaccines: Lessons from the past, strategies for the future.

Venezuelan equine encephalitis (VEE) is a zoonotic infectious disease caused by the Venezuelan equine encephalitis virus (VEEV), which can lead to severe central nervous system infections in both humans and animals. At present, the medical community does not possess a viable means of addressing VEE, rendering the prevention of the virus a matter of paramount importance. Regarding the prevention and control of VEEV, the implementation of a vaccination program has been recognized as the most efficient strategy. Nevertheless, there are currently no licensed vaccines or drugs available for human use against VEEV. This imperative has led to a surge of interest in vaccine research, with VEEV being a prime focus for researchers in the field. In this paper, we initially present a comprehensive overview of the current taxonomic classification of VEEV and the cellular infection mechanism of the virus. Subsequently, we provide a detailed introduction of the prominent VEEV vaccine types presently available, including inactivated vaccines, live attenuated vaccines, nucleic acid, and virus-like particle vaccines. Moreover, we emphasize the challenges that current VEEV vaccine development faces and suggest urgent measures that must be taken to overcome these obstacles. Notably, based on our latest research, we propose the feasibility of incorporation codon usage bias strategies to create the novel VEEV vaccine. Finally, we prose several areas that future VEEV vaccine development should focus on. Our objective is to encourage collaboration between the medical and veterinary communities, expedite the translation of existing vaccines from laboratory to clinical applications, while also preparing for future outbreaks of new VEEV variants.