Search Results (101)

Many electric vehicle (EV) batteries will retire in the next 5–10 years around the globe. These batteries are retired when no longer suitable for energy-intensive EV operations despite having 70–80% capacity left. The second-life use of these battery packs has the potential to address the increasing demand for battery energy storage systems (BESSs) for the electric grid, which will also create a robust circular economy for EV batteries. This article proposes a two-layered energy management algorithm (monthly layer and daily layer) for demand charge reduction for an industrial consumer using photovoltaic (PV) panels and BESSs made of retired EV batteries. In the proposed algorithm, the monthly layer (ML) calculates the optimal dispatch for the whole month and feeds the output to the daily layer (DL), which optimizes the BESS dispatch, BESSs’ degradation, and energy imported/exported from/to the grid. The effectiveness of the proposed algorithm is tested as a case study of an industrial load using a real-world demand charge and Real-Time Pricing (RTP) tariff. Compared with energy management with no consideration of degradation or demand charge reduction, this algorithm results in 71% less degradation of BESS and 57.3% demand charge reduction for the industrial consumer. Full article

Carsharing has long supported trip purposes typically made by private vehicles, with grocery shopping especially benefiting from the carrying capacity of a personal vehicle. BlueLA is a one-way, station-based electric vehicle (EV) carsharing service in Los Angeles aimed at improving access in low-income neighborhoods. We hypothesize that BlueLA improves grocery access for underserved households by increasing their spatial-temporal reach to diverse grocery store types. We test two hypotheses: (1) accessibility from BlueLA stations to grocery stores varies by store type, traffic conditions, and departure times; and (2) Standard (general population) and Community (low-income) members differ in perceived grocery access and station usage. Using a mixed-methods approach, we integrate walking and driving isochrones, store data (n = 5888), trip activity data (n = 59,112), and survey responses (n = 215). Grocery shopping was a key trip purpose, with 69% of Community and 61% of Standard members reporting this use. Late-night grocery access is mostly limited to convenience stores, while roundtrips to full-service stores range from 55 to 100 min and cost USD 12 to USD 20. Survey data show that 84% of Community and 71% of Standard members reported improved grocery access. The findings highlight the importance of trip timing and the potential for carsharing and retail strategies to improve food access. Full article

Background: The three commercial Enterovirus 71 (EV71) inactivated vaccines which have effectively controlled the EV71 pandemic currently rely on inherent variable in vivo potency methods for batch release. To align with 3R (Replacement, Reduction, Refinement) principles and enhance quality control, this study referred to WHO guidelines and the European Pharmacopoeia to develop in vitro relative potency (IVRP) methods. Methods: Working standards tracing to phase 3 clinical vaccines were established. Manufacture-specific IVRP methods were developed and validated per ICH Q14/Q2(R2), utilizing conformational epitope-targeting neutralizing monoclonal antibodies (MAbs). One of the MAbs (CT11F9) recognition sites was clarified with Cryo-EM. Subsequently, the performance of IVRP was assessed using varied concentrations and heat-treated vaccines. The correlation between IVRP and in vivo methods was analyzed, followed by setting IVRP specifications. Results: The manufacturer-specific working standard exhibited ED50 values comparable to those of related phase 3 clinical vaccines. All IVRP methods achieved a relative bias/precision/total error ≤ 15%. The IVRP methods correlated with in vivo methods (p < 0.05, r > 0.9) can discriminate EV71 antigen concentrations (p < 0.01, r > 0.99) and indicate the stability of the vaccines. Cryo-EM was adopted to identify the epitopes recognized by CT11F9, revealing that this neutralizing antibody recognizes a conformational epitope spanning VP1-3 of the same protomer. Using 31–47 batches of commercial vaccines, IVRP specifications were proposed as 0.56–1.35, 0.58–1.40, and 0.54–1.50. Conclusions: Based on conformational epitope-targeting neutralizing MAbs, manufacturer-specific IVRP methods, which were sensitive to process variations and correlated with in vivo results, have been established. IVRP methods provide a reliable, animal-free alternative for EV71 vaccine batch release. Full article

Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD), leading to a serious health threat to young children. Probiotics are effective at treating or preventing gastrointestinal infections, especially viral infections. Probiotics against EV71 are mainly traditional lactic acid-producing bacteria, and most of them have been proven to be effective only in vitro. Here, we report that the marine bacterium Paraliobacillus zengyii X-1125 (P. zengyii) has promising anti-EV71 activity. The antiviral effect of P. zengyii against EV71 was assessed in different cell lines, and the viral RNA levels and titers were obviously reduced after treatment with P. zengyii. Furthermore, we established an EV71-infected mouse model to evaluate its antiviral efficacy in vivo. The oral administration of P. zengyii significantly decreased the viral loads in the hindlimb muscles, spleens, and ileums. Further research revealed that P. zengyii enhances the expression of type I interferon (IFN-I) in EV71-infected cells. Similarly, transcriptome analysis indicated that the expression of interferon-stimulated genes (ISGs) in EV71-infected mice significantly increased after P. zengyii treatment. Taken together, the results of this study indicated that P. zengyii markedly reduces EV71 infection by regulating the IFN response both in vivo and in vitro, providing a potential means to work against EV71 infection. Full article

Background/Objectives: Enterovirus 71 (EV71) and coxsackieviruses A16 (CA16), A10 (CA10), and A6 (CA6) are the primary pathogens that cause hand, foot, and mouth disease (HFMD). Currently, many manufacturers are developing bivalent, trivalent, and tetravalent vaccines that target these antigens. Cell-based neutralization assay (CBNA), the gold standard for detecting neutralizing antibodies (NtAbs), which are used as indicators of HFMD vaccine efficacy, has several limitations. We aimed to develop a novel assay for detecting NtAbs against a quadrivalent HFMD vaccine. Methods: We developed a four-color pseudovirus-based neutralization assay (PBNA), utilizing fluorescent reporter genes, to rapidly evaluate neutralizing antibodies against EV71, CA16, CA10, and CA6 in multivalent vaccines and compared it with CBNA. Results: PBNA could rapidly and simultaneously detect NtAbs against the four serotypes and required lesser amounts of sera compared to CBNA. A good consistency in determining NtAb titers was observed for PBNA and CBNA. Conclusions: PBNA provides a robust tool for evaluating the efficacy of multivalent HFMD vaccines and conducting seroepidemiological studies. Full article

Hand, Foot, and Mouth Disease (HFMD) is a viral illness caused by enterovirus infections. While the introduction of the enterovirus 71 (EV71) vaccine has significantly reduced the number of EV71-related cases, the continued spread of Coxsackievirus A16 (CVA16) remains a major public health threat. Previous studies have shown that human SCARB2 (hSCARB2) knock-in (KI) mice, generated using embryonic stem cell (ESC) technology, are susceptible to CVA16. However, these models have failed to reproduce the clinical pathology and neurotoxicity after CVA16 infection. Therefore, there is an urgent need for a more reliable and effective animal model to study CVA16. In this study, we successfully created a hSCARB2 KI mouse model targeting the ROSA26 locus using CRISPR/Cas9 gene editing technology. The application of CRISPR/Cas9 enabled stable and widespread expression of hSCARB2 in the model. After infection, the KI mice exhibited a clinical pathology that closely mimics human infection, with prominent limb weakness and paralysis. The virus was detectable in multiple major organs of the mice, with peak viral load observed on day 7 post-infection, gradually clearing thereafter. Further analysis revealed widespread neuronal necrosis and infiltration of inflammatory cells in the brain and spinal cord of the KI mice. Additionally, significant activation of astrocytes (GFAP-positive) and microglia (IBA1-positive) was observed in the brain, suggesting that CVA16 infection may induce limb paralysis by attacking neuronal cells. Overall, this model effectively replicates the neuropathological changes induced by CVA16 infection and provides a potential experimental platform for studying CVA16-associated pathogenesis and neurotoxicity. Full article

Hand-foot-and-mouth disease (HFMD) caused by Enterovirus 71 (EV71) is highly infectious and can lead to serious neurological complications. This study proposed to evaluate the seroprevalence of EV71 in children of two states of western India by estimating neutralizing antibodies (nAbs) to EV71 genotypes D, G, and C isolated in India, using micro-neutralization assay. Among the serum samples of 612 children tested, 213 (34.80%, 95% CI: 31.00–38.73) and 312 (51.00%, 95% CI: 47.00–55.00) were positive for nAbs to EV71 BrCr and indigenous genotype D, respectively, with a significant rise with age for genotype D. However, compared to other age groups, only 23.2% of children aged 1–5 years showed nAbs to EV71 genotype D with a considerably lower Geometric Mean Titer, indicating the susceptibility of this age group to EV71 infection. Our study confirms the circulation of EV71 in India with relatively high susceptibility of children up to 5 years to EV71 infections. Full article

Enterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this study, we successfully infected mice of different ages using a mouse-adapted EV71 strain, resulting in disease and mortality. We compared immune system responses between infected and uninfected mice of different ages to identify key pathogenic targets during EV71 infection. Our findings revealed that the level of Group 3 Innate Lymphoid Cells (ILC3s) in mice negatively correlated with the severity of disease induced by EV71 infection. We conducted anti-ILC3 cytokine injections and cytokine neutralizing antibody experiments on 14-day-old EV71-infected mice. The results showed that the cytokine IL-17 secreted by ILC3 cells had a mild protective effect, while IL-22 promoted inflammatory responses. Our research demonstrates that ILC3 cells play a dual role in EV71 infection. These findings not only clarify key immune factors in the progression of EV71-induced disease but also provide a promising approach for the early diagnosis and treatment of severe EV71 infections. Full article

Human enterovirus 71 (EV-A71), a member of the Picornaviridae family, is predominantly associated with hand, foot, and mouth disease in infants and young children. Additionally, EV-A71 can cause severe neurological complications, including aseptic meningitis, brainstem encephalitis, and fatalities. The molecular mechanisms underlying these symptoms are complex and involve the viral tissue tropism, evasion from the host immune responses, induction of the programmed cell death, and cytokine storms. This review article delves into the EV-A71 life cycle, with a particular emphasis on recent advancements in understanding the virion structure, tissue tropism, and the interplay between the virus and host regulatory networks during replication. The comprehensive review is expected to contribute to our understanding of EV-A71 pathogenesis and inform the development of antiviral therapies and vaccines. Full article

Background: The impact of respiratory viral infections associated with Kawasaki Disease (KD) cases on KD’s clinical presentation and initial response to treatment has not been clearly determined. Objective: This study aimed to evaluate respiratory viral infections using FilmArray Respiratory Panel (FARP) testing and analyze the effect of the concurrent presence of pathogens on clinical presentations of KD. Methods: Between January 2021 and June 2023, we conducted a retrospective, single-center observational study of 105 Japanese children with KD. KD was diagnosed and treated according to RAISE study guidelines, and the cases’ clinical information was assessed. FARP testing was performed in 71 out of 105 KD cases with fever and/or respiratory symptoms. Results: In 38 (53.5%) out of 71 cases, at least one virus was detected. The FARP-positive cases tended to have a higher frequency of Kobayashi scores (K-scores) ≥ 5 than the negative cases (42.1% vs. 21.2%), and lower initial treatment failure (7.89% vs. 21.2%). The most common virus detected was rhino/enterovirus (RV/EV: 27 cases), followed by seven cases of respiratory syncytial virus (RSV). RV/EV-positive KD cases did not differ significantly in their clinical data or the frequency of K-scores ≥ 5, and RSV-positive cases showed significantly elevated liver enzyme (AST:59 U/L (43.5–150.5) vs. 35 U/L (27–41), ALT:40 U/L (28.5–244.5) vs. 18 U/L (14–27)) and CRP levels (12 mg/dL (7.3–14.2) vs. 6.5 mg/dL (4.1–8.5)), and an increased frequency of K-scores ≥ 5 (71.4% vs. 21.2%) compared to FARP-negative cases. KD cases that were also RSV-positive or RV/EV-positive showed favorable responses to initial treatments. Conclusions: Concurrent respiratory virus infection could affect the clinical manifestation and initial treatment response of KD. Full article

Due to increasing mobility and energy conservation needs, improving bus and coach safety without adding weight is essential. Many crashes with fatal outcomes for vehicle occupants are associated with the rollover of the vehicle, revealing the structural weakness of the steel pillars between windows, which must resist high levels of bending during rollovers. This study aims to reinforce these pillars with expired carbon fiber prepreg from the aircraft industry, improving safety and reducing environmental waste. To manufacture the pillars, shot-blasted hollow S275 steel tubes with a side length of 25 mm and a thickness of 1.5 mm were used. Bidirectional GG600T woven carbon fiber, CF, and aircraft-grade recycled carbon fiber-reinforced plastic, rCFRP, prepreg M21EV/IMA/3 were used as composite reinforcements. The first composite was made from a CF weave using the rigid epoxy resin Sicomin^® 8500/Sicomin^® SD8601. The rCFRP composite was frayed, and a new composite was made with the same rigid epoxy resin. Both composites were joined to the steel tube using a tough structural adhesive (SikaPower^® 1277). A third composite was obtained using the frayed rCFRP and the structural adhesive as a polymer matrix. All composites were treated with an APPT (atmospheric-pressure plasma torch) before being joined to the steel pillar with the structural adhesive. The comparison of the three reinforcements showed that the steel reinforced with the recycled prepreg composite manufactured with the rigid adhesive performed best, with a 50% increase in specific bending strength and only a 32% increase in weight. It also absorbed 71% more energy, which shows that this novel option for upcycling can noticeably increase the crashworthiness of structures. Full article

Background: Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)—hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. Methods: The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 − OR) × 100%. Results: According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2–80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4–87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. Conclusion: The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71. Full article

This study was conducted to efficiently produce virus-like particles (VLPs) of enterovirus 71 (EV71), a causative virus of hand, foot, and mouth disease (HFMD). The expression level of the P1 precursor, a structural protein of EV71, was modified to increase VLP production, and the optimal expression level and duration of the 3CD protein for P1 cleavage were determined. The expression level and duration of 3CD were controlled by the p10 promoter, which was weakened by repeated burst sequence (BS) applications, as well as the OpIE2 promoter, which was weakened by the insertion of random untranslated region sequences of various lengths. The cleavage and production efficiency of the P1 precursor were compared based on the expression time and level of 3CD, revealing that the p10-BS5 promoter with four repeated BSs was the most effective. When P1 and 3CD were expressed using the hyperexpression vector and the p10-BS5 promoter, high levels of structural protein production and normal HFMD-VLP formation were observed, respectively. This study suggests that the production efficiency of HFMD-VLPs can be significantly enhanced by increasing the expression of the P1 precursor and controlling the amount and duration of 3CD expression. Full article

Hand, foot, and mouth disease (HFMD) is a contagious viral infection predominantly affecting infants and young children, caused by multiple enteroviruses, including Enterovirus 71 (EV71), Coxsackievirus A16 (CA16), Coxsackievirus A10 (CA10), and Coxsackievirus A6 (CA6). The high pathogenicity of HFMD has garnered significant attention. Currently, there is no specific treatment or broad-spectrum preventive measure available for HFMD, and existing monovalent vaccines have limited impact on the overall incidence or prevalence of the disease. Consequently, with the emergence of new viral strains driven by vaccine pressure, there is an urgent need to develop strategies for the rapid response and control of new outbreaks. In this study, we demonstrated the broad protective effect of maternal antibodies against three types of HFMD by immunizing mother mice with a trivalent inactivated vaccine targeting EV71, CA16, and CA10, using a neonatal mouse challenge model. Based on the feasibility of maternal antibodies as a form of passive immunization to prevent HFMD, we prepared a multivalent antiviral milk by immunizing dairy cows with the trivalent inactivated vaccine to target multiple HFMD viruses. In the neonatal mouse challenge model, this immunized milk exhibited extensive passive protection against oral infections caused by the three HFMD viruses. Compared to vaccines, this strategy may offer a rapid and broadly applicable approach to providing passive immunity for the prevention of HFMD, particularly in response to the swift emergence and spread of new variants. Full article

Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia–Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic α-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule. Full article