Explore the vast range of titles available.

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.

The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40–70 SFC/106 PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50–130 SFC/106 PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response.

COVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 10 9 PFU Sad23L-nCoV-S, followed by boosting with 5 × 10 9 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 10 3.16 anti-S, 10 2.75 anti-RBD binding antibody and 10 2.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 10 1.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/10 6 cells), IL-2 (334 SFCs/10 6 cells) and intracellular IFN-γ in CD4 + /CD8 + T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials.

Common marmosets infected with GB virus-B (GBV-B) chimeras containing hepatitis C virus (HCV) core and envelope proteins (CE1E2p7) developed more severe hepatitis than those infected with HCV envelope proteins (E1E2p7), suggesting that HCV core protein might be involved in the pathogenesis of viral hepatitis. The potential role of HCV core in hepatic inflammation was investigated. Six individual cDNA libraries of liver tissues from HCV CE1E2p7 or E1E2p7 chimera-infected marmosets (three animals per group) were constructed and sequenced. By differential expression gene analysis, 30 of 632 mRNA transcripts were correlated with the immune system process, which might be associated with hepatitis. A protein-protein interaction network was constituted by STRING database based on these 30 differentially expressed genes (DEGs), showing that IL-32 might play a central regulatory role in HCV core-related hepatitis. To investigate the effect of HCV core protein on IL-32 production, HCV core expressing and mock constructs were transfected into Huh7 cells. IL-32 mRNA and secretion protein were detected at significantly higher levels in cells expressing HCV core protein than in those without HCV core expression ( < 0.01 and < 0.001, respectively). By KEGG enrichment analysis and using the specific signaling pathway inhibitor LY294002 for inhibition of PI3K, IL-32 expression was significantly reduced ( < 0.001). In conclusion, HCV core protein induces an increase of IL-32 expression via the PI3K pathway in hepatic cells, which played a major role in development of HCV-related severe hepatitis.

The failure of COVID-19 vaccines to prevent SARS-CoV-2 infection and transmission, a possibly critical reason was the lack of protective mucosal immunity in respiratory tract. Here, we evaluated the effects of mucosal and systemic immunity from a novel simian adenovirus vectored COVID-19 vaccine (Sad23L- nCoV-S) in mice in comparison with Ad5-nCoV-S by intranasal (IN) drip and intramuscular (IM) injection vaccinations. As good as the well-known Ad5-nCoV-S vaccine, a single-dose IN inoculation of 1×109 PFU Sad23L-nCoV-S vaccine induced a similar level of IgG S-binding antibody (S-BAb) and neutralizing antibody (NAb) and higher IgA in serum, while IN route raised significantly higher IgG and IgA S- BAb and NAb in bronchoalveolar lavage (BAL), and specific IFN-γ secreting T cell response in lung compared with IM route, but lower T cell response in spleen. By prime-boost vaccination regimens with different combination of IN and IM inoculations of Sad23L-nCoV-S vaccine, the IN involved vaccinations stimulated higher protective mucosal or local immunity in BAL and lung, while the IM involved immunizations induced higher systemic immunity in serum and spleen. A long-term sustained systemic and mucosal NAb and T cell immunity to SARS-CoV-2 was maintained at high levels over 32 weeks by prime-boost vaccination regimens with IN and IM routes. In conclusion, priming or boosting immunization with IN inoculation of Sad23L-nCoV-S vaccine could induced effective mucosal immunity and in combination of IM route could additionally achieve systemic immunity, which provided an important reference for vaccination regimens against respiratory virus infection. The essential goal of vaccination is to generate potent and long-term protection against diseases. Several factors including type of vector, delivery route, boosting regimen influence the outcome of prime-boost immunization approaches. The immunization regimen by constructing a novel simian adenovirus vectored COVID-19 vaccine and employing combination of intranasal and intramuscular inoculations, could elicit mucosal neutralizing antibodies against five mutant strains in the respiratory tract, and strong systemic immunity. Immune protection could last for more than 32 weeks. Vectored vaccine construction and immunization regimens have positively impacted respiratory disease prevention.

ABSTRACT COVID-19 vaccines are being developed urgently worldwide, among which single-shot adenovirus vectored vaccines represent a major approach. Here, we constructed two novel adenovirus vectored COVID-19 vaccine candidates on simian adenovirus serotype 23 (Sad23L) and human adenovirus serotype 49 vectors (Ad49L) carrying the full-length gene of SARS-CoV-2 spike protein (S), designated Sad23L-nCoV-S and Ad49L-nCoV-S vaccines, respectively. The immunogenicity elicited by these two vaccine strains was individually evaluated in mice. Specific humoral and cellular immune responses were proportionally observed in a dose-dependent manner, and stronger response was obtained by boosting. Furthermore, five rhesus macaques were intramuscularly injected with a dose of 5×109 PFU Sad23L-nCoV-S vaccine for prime vaccination, followed by boosting with 5×109 PFU of Ad49L-nCoV-S vaccine at 4-week interval. Three macaques were injected with Sad23L-GFP and Ad49L-GFP vectorial viruses as negative controls. Both mice and macaques tolerated well the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost vaccination regimen induced high titers of 103.16 S-binding antibody (S-BAb), 102.75 cell receptor binding domain (RBD)-BAb and 102.38 neutralizing antibody (NAb) to pseudovirus a week after boosting injection, followed by sustained high levels over 10 weeks of observation. Robust IFN-γ secreting T-cell response (712.6 SFCs/106 cells), IL-2 secreting T-cell response (334 SFCs/106 cells) and intracellular IFN-γ expressing CD4+/CD8+ T cell response (0.39%/0.55%) to S peptides were detected in the vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S vaccines can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials. Competing Interest Statement S.L., P.Z., B.L., and C.L.L. were partly sponsored by BRK company. All other authors declare that they have no competing interests.

With the rapid development of the Industrial Internet of Things in rotating machinery, the amount of data sampled by mechanical vibration wireless sensor networks (MvWSNs) has increased significantly, straining bandwidth capacity. Concurrently, the safety requirements for rotating machinery have escalated, necessitating enhanced real-time data processing capabilities. Conventional methods, reliant on experiential approaches, have proven inefficient in meeting these evolving challenges. To this end, a fault detection method for rotating machinery based on mobileNet in MvWSNs is proposed to address these intractable issues. The small and light deep learning model is helpful to realize nearly real-time sensing and fault detection, lightening the communication pressure of MvWSNs. The well-trained deep learning is implanted on the MvWSNs sensor node, an edge computing platform developed via embedded STM32 microcontrollers (STMicroelectronics International NV, Geneva, Switzerland). Data acquisition, data processing, and data classification are all executed on the computing- and energy-constrained sensor node. The experimental results demonstrate that the proposed fault detection method can achieve about 0.99 for the DDS dataset and an accuracy of 0.98 in the MvWSNs sensor node. Furthermore, the final transmission data size is only 0.1% compared to the original data size. It is also a time-saving method that can be accomplished within 135 ms while the raw data will take about 1000 ms to transmit to the monitoring center when there are four sensor nodes in the network. Thus, the proposed edge computing method shows good application prospects in fault detection and control of rotating machinery with high time sensitivity.

In the context of agricultural modernization and intelligentization, automated fruit recognition is of significance for improving harvest efficiency and reducing labor costs. The variety of fruits commonly planted in orchards and the fluctuations in market prices require farmers to adjust the types of crops they plant flexibly. However, the differences in size, shape, and color among different types of fruits make fruit recognition quite challenging. If each type of fruit requires a separate visual model, it becomes time-consuming and labor intensive to train and deploy these models, as well as increasing system complexity and maintenance costs. Therefore, developing a general visual model capable of recognizing multiple types of fruits has great application potential. Existing multi-fruit recognition methods mainly include traditional image processing techniques and deep learning models. Traditional methods perform poorly in dealing with complex backgrounds and diverse fruit morphologies, while current deep learning models may struggle to effectively capture and recognize targets of different scales. To address these challenges, this paper proposes a general fruit recognition model based on the Multi-Scale Attention Network (MSA-Net) and a Hough Transform localization compensation mechanism. By generating multi-scale feature maps through a multi-scale attention mechanism, the model enhances feature learning for fruits of different sizes. In addition, the Hough Transform ellipse detection compensation mechanism uses the shape features of fruits and combines them with MSA-Net recognition results to correct the initial positioning of spherical fruits and improve positioning accuracy. Experimental results show that the MSA-Net model achieves a precision of 97.56, a recall of 92.21, and an mAP@0.5 of 94.81 on a comprehensive dataset containing blueberries, lychees, strawberries, and tomatoes, demonstrating the ability to accurately recognize multiple types of fruits. Moreover, the introduction of the Hough Transform mechanism reduces the average localization error by 8.8 pixels and 3.5 pixels for fruit images at different distances, effectively improving the accuracy of fruit localization.

High-entropy oxides (HEOs) and medium-entropy oxides (MEOs) are new types of single-phase solid solution materials. MEOs have rarely been reported as positive electrode material for sodium-ion batteries (SIBs). In this study, we first proposed the concept of the application of MEOs in SIBs. P2-type 3-cation oxide Na 2/3 Ni 1/3 Mn 1/3 Fe 1/3 O 2 (NaNMF) and 4-cation oxide Na 2/3 Ni 1/3 Mn 1/3 Fe 1/3− x Al x O 2 (NaNMFA) were prepared using the solid-state method, rather than the doping technology. In addition, the importance of the concept of entropy stabilization in material performance and battery cycling was demonstrated by testing 3-cation (NaNMF) and 4-cation (NaNMFA) oxides in the same system. Thus, NaNMFA can provide a reversible capacity of about 125.6 mAh·g −1 in the voltage range of 2–4.2 V, and has enhanced cycle stability. The capacity and decay law of the MEO batteries indicate that the configurational entropy (1.28 R (NaNMFA) > 1.10 R (NaNMF)) of the cationic system, is the main factor affecting the structural and cycle stability of the electrode material. This work emphasizes that the rational design of MEOs with novel structures and different electrochemically active elements may be the strategy for exploring high-performance SIB cathode materials in next-generation energy storage devices.

Lithium–oxygen batteries have attracted considerable attention in recent years due to their high energy density and potential applications. However, the slow kinetics of the cathode reaction and the unstable products in lithium–oxygen batteries have limited their practical applications. Metal–organic frameworks (MOFs) and their derivatives have emerged as a novel class of functional materials, thus becoming ideal candidates for the cathode of lithium–oxygen batteries. This is due to their high specific surface area, structural tunability, and abundant active sites. This paper presents a review of the research progress made in the field of MOFs and their derivatives in the cathode of lithium–oxygen batteries. It provides a summary of the design and synthesis strategies employed in the development of MOF-based catalysts, with a particular focus on the application of primary MOFs materials, MOF-derived materials and MOF composite materials in Li-O2 batteries. Additionally, it analyses the catalytic mechanism of MOFs and their derivatives in the ORR/OER. The comprehensive analysis demonstrates that MOFs and their derivatives are ideal candidates for the cathodes of lithium–oxygen batteries due to their high specific surface area, structural tunability, and abundant active sites. However, the electrical conductivity of MOFs is usually low and needs to be enhanced by composites or derivative materials. This paper reviews the research progress on MOFs and their derivatives in lithium–oxygen battery cathodes, focuses on the design and synthesis strategies of MOF-based catalysts, and discusses their catalytic mechanisms in the ORR/OER.