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Abstract The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules. Graphic Abstract

Abstract Take-home exam (THE) use has been reported in various disciplines, but research on THE use in language modules in higher education appears to be scarce. The current study employed surveys and interviews to examine how the shift to written THE, in place of the traditional in-class exam (ICE) during the pandemic, impacted language learning and teaching on the China campus of a British university. Additionally, correlation analyses were conducted with ranking data of students from the same cohort under THE and ICE to explore patterns in student performance under these exam conditions. In surveys and interviews, teachers reported that their teaching foci did not change under THE, while many students reported that their learning practices were different under THE and ICE. Students also exhibited a tendency to spend more time practicing skills that they expected to be assessed in the exam. Overall, both teachers and students expressed preference for ICE, with many raising concerns about fairness issues in THE. Furthermore, correlation analyses showed that, overall, for a given group of students, written ICE rankings exhibited strong correlations with each other but written THE rankings did not, suggesting relative instability of THE results. However, when written THE and oral ICE results from the same module are combined, the resultant rankings strongly correlated with pure ICE rankings. This indicates that combining ICE and THE components for assessment could help mitigate some perceived shortcomings, including the instability issue, of THE used alone.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Starting from a manifestly Lorentz-invariant chiral Lagrangian, we present a model-free prediction for the transition amplitude of the process nn→ppe−e− induced by light Majorana neutrinos, which is a key process of the neutrinoless double beta decay (0νββ) in heavy nuclei employed in large-scale searches. Contrary to the nonrelativistic case, we show that the transition amplitude can be renormalized at leading order without any uncertain contact operators. The predicted amplitude defines a stringent benchmark for the previous estimation with model-dependent inputs, and greatly reduces the uncertainty of 0νββ transition operator in the calculations of nuclear matrix elements. Generalizations of the present framework could also help to address the uncertainties in 0νββ decay induced by other mechanisms. In addition, the present work motivates a relativistic ab initio calculation of 0νββ decay in light and medium-mass nuclei.

Abstract Robot calligraphy visually reflects the motion capability of robotic manipulators. While traditional researches mainly focus on image generation and the writing of simple calligraphic strokes or characters, this article presents a generative adversarial network (GAN)‐based motion learning method for robotic calligraphy synthesis (Gan2CS) that can enhance the efficiency in writing complex calligraphy words and reproducing classic calligraphy works. The key technologies in the proposed approach include: (1) adopting the GAN to learn the motion parameters from the robot writing operation; (2) converting the learnt motion data into the style font and realising the transition from static calligraphy images to dynamic writing demonstration; (3) reproducing high‐precision calligraphy works by synthesising the writing motion data hierarchically. In this study, the motion trajectories of sample calligraphy images are firstly extracted and converted into the robot module. The robot performs the writing with motion planning, and the writing motion parameters of calligraphy strokes are learnt with GANs. Then the motion data of basic strokes is synthesised based on the hierarchical process of ‘stroke‐radical‐part‐character’. And the robot re‐writes the synthesised characters whose similarity with the original calligraphy characters is evaluated. Regular calligraphy characters have been tested in the experiments for method validation and the results validated that the robot can actualise the robotic calligraphy synthesis of writing motion data with GAN.

Abstract Object Constraint Language (OCL) is one kind of lightweight formal specification, which is widely used for software verification and validation in NASA and Object Management Group projects. Although OCL provides a simple expressive syntax, it is hard for the developers to write correctly due to lacking knowledge of the mathematical foundations of the first‐order logic, which is approximately half accurate at the first stage of development. A deep neural network named DeepOCL is proposed, which takes the unrestricted natural language as inputs and automatically outputs the best‐scored OCL candidates without requiring a domain conceptual model that is compulsively required in existing rule‐based generation approaches. To demonstrate the validity of our proposed approach, ablation experiments were conducted on a new sentence‐aligned dataset named OCLPairs. The experiments show that the proposed DeepOCL can achieve state of the art for OCL statement generation, scored 74.30 on BLEU, and greatly outperformed experienced developers by 35.19%. The proposed approach is the first deep learning approach to generate the OCL expression from the natural language. It can be further developed as a CASE tool for the software industry.

Abstract Rift Valley fever virus (RVFV) is listed as a priority pathogen by the World Health Organization (WHO) because it causes serious and fatal disease in humans, and there are currently no effective countermeasures. Therefore, it is urgent to develop a safe and efficacious vaccine. Here, we developed six nucleotide-modified mRNA vaccines encoding different regions of the Gn and Gc proteins of RVFV encapsulated in lipid nanoparticles, compared their ability to induce immune responses in mice and found that mRNA vaccine encoding the full-length Gn and Gc proteins had the strongest ability to induce cellular and humoral immune responses. IFNAR(−/−) mice vaccinated with mRNA-GnGc were protected from lethal RVFV challenge. In addition, mRNA-GnGc induced high levels of neutralizing antibodies and cellular responses in rhesus macaques, as well as antigen-specific memory B cells. These data demonstrated that mRNA-GnGc is a potent and promising vaccine candidate for RVFV.

Abstract Objectives Advanced cancer patients face various symptoms, which can cause physical and psychological distress. As a multidimensional construct, spiritual well-being (SWB) may be an inner resource for dealing with these problems. Our study explored the impact of different dimensions of SWB on physical and psychological symptoms in advanced cancer patients admitted to a palliative care unit. Methods This cross-sectional study was conducted among 108 advanced cancer patients in the Hospice Ward, Shengjing Hospital of China Medical University. Patients completed questionnaires on SWB and cancer-related symptoms (insomnia, fatigue, pain, depression and anxiety) at the time of admission. Linear regression analysis was applied to determine the relationship between SWB (meaning, peace and faith) and symptom distress. Results SWB accounted for an additional variance of cancer-related symptoms (17.8% to 44.4%). Meaning was negatively associated with insomnia (β = -0.516, p < 0.001) and fatigue (β = -0.563, p < 0.001). Peace and faith were related to lower psychological symptoms, while meaning represented a positive effect on anxiety (β = 0.275, p = 0.036). Higher peace was associated with lower cancer pain (β = -0.422, p < 0.001). Conclusions Our findings suggested that achieving peace and faith appeared to function consistently as a positive resource for advanced cancer patients on depression, anxiety and pain, while meaning may serve to facilitate or hinder positive adjustment. Future studies should focus on the potential clinical implications by identifying the distinct dimension of SWB as symptom management targets in the palliative care practice.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Abstract Combined sewer overflows represent significant risks to human health as untreated water is discharged to the environment. Municipalities, such as the Metropolitan Sewer District of Greater Cincinnati (MSDGC), recently began collecting large amounts of water‐related data and considering the adoption of deep learning (DL) solutions like recurrent neural network (RNN) for predicting overflow events. Clearly, assessing the DL's fitness for the purpose requires a systematic understanding of the problem context. In this study, we propose a requirements engineering framework that uses the problem frames to identify and structure the stakeholder concerns, analyses the physical situations in which the high‐quality data assumptions may not hold, and derives the software testing criteria in the form of metamorphic relations that incorporate both input transformations and output comparisons. Applying our framework to MSDGC's overflow prediction problem enables a principled way to evaluate different RNN solutions in meeting the requirements.

Abstract Capacitive deionization (CDI) is a green and pollution‐free emerging technology that can be used for ions removal and recovery from water. However, the traditional electro‐adsorption process to achieve ions removal faces the challenges of non‐selectivity, low efficiency and difficult ion recovery. In recent years, the conversion reaction has attracted wide attention due to its high selectivity, reversibility and excellent desalination ability for ions removal and recovery. This concept article will focus on the connotation and representative applications of conversion reactions that can be used for ion‐selective removal and recovery and put forward the perspectives and outlooks of conversion reactions.

Abstract Background Although palliation of psycho-spiritual distress is of great importance in terminally ill cancer patients, there is a little information about screening patients who benefit from palliative care and identifying the cancer care targets. This study explored the relationship of pain management and positive expectations with depression, anxiety and spiritual well-being (SWB) in terminal cancer patients admitted to a palliative care unit. Methods Eighty-four terminal cancer inpatients were recruited from the Hospice Ward, Shengjing Hospital of China Medical University. Optimism and general self-efficacy (GSE) were evaluated at admission. Patients completed self-report questionnaires on SWB, depression, anxiety and pain both on admission and one week later. The repeated designed analysis of variance was used to explore the correlates of depression, anxiety and SWB (meaning, peace, faith). Results In our sample, only cancer pain diminished significantly one week later. For depression (p = 0.041) and faith (p = 0.013), there was a significant pain group (relieved vs. not relieved) × time interaction effect, such that those with satisfied pain control experienced the improved psycho-spiritual outcomes at 1 week. The relationship between positive expectations, peace and faith was also statistically significant, indicating that the improvement of peace or faith was significant in the low group of optimism and GSE. Conclusions Our findings indicated that pain management lied at the center of depression and SWB, meaning that effective pain management may reduce depression, and improve SWB among terminal cancer patients. Moreover, positive expectations, especially for optimism, may be the new target for SWB-related intervention research. Palliative care nurse should require the identification of terminal cancer patients who may more benefit from short-term palliative care, and target them with effective cancer care.

To improve the cushioning performance of soft-landing systems, a novel origami-inspired combined cushion airbag is proposed. The geometry size, initial pressure, and exhaust vent area of the cushion airbags are designed preliminarily using a theoretical model. The finite element models, including the returnable spacecraft and cushion airbags, are established via the control volume method (CVM) to analyze the impact dynamic behavior and cushioning performance during the landing attenuation process. The cushioning performance of the cushion airbags in complex landing environments are studied to investigate the influence of horizontal velocity, lateral velocity and nonhorizontal landing surfaces. Four design parameters of the cushion airbags, including the initial pressure, venting threshold pressure, exhaust vent area and polygon edge number, are employed to study their influence on the cushioning performance. A multi-objective optimization model of the cushion airbags based on the neural network and multi-objective water cycle algorithm is established to realize the rapid optimization design. The Pareto front of the maximum overload and specific energy absorption is obtained. The analysis results show that the maximum overload of the proposed combined cushion airbags is 7.30 g. The system with the anti-rollover design can avoid rollover and achieve outstanding cushioning performance in complex landing environments. The maximum overload of the returning spacecraft is decreased by 16.4% from 7.30 g to 6.10 g after multi-objective optimizations. This study could provide the technical support for the soft-landing system design of returnable spacecrafts.

IntroductionThe SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required.MethodsWe have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. ResultsThe aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. DiscussionOur findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.

Continuous generation of reactive oxygen species is desirable in the advanced oxidation process. Here, the authors report a self-cycled photoFenton-like with a scalable artificial leaf for production of H2O2 from water with solar-to-H2O2 efficiency of 1.46%.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Graphitic carbon nitride (g-C3N4) photocatalysis for water splitting is harvested as a fascinating way for addressing the global energy crisis. At present, numerous research subjects have been achieved to design and develop g-C3N4 photocatalysis, and the photocatalytic system still suffers from low efficiency that is far from practical applications. Here, there is an inspiring review on the latest progress of the doping strategies to modify g-C3N4 for enhancing the efficiency of photocatalytic water splitting, including non-metal doping, metal doping, and molecular doping. Finally, the review concludes a summary and highlights some perspectives on the challenges and future research of g-C3N4 photocatalysts.

Second language (L2) listening is a common challenge for language learners. It remains largely unknown how bilinguals process L2 listening. The literature has suggested an interactive model of L2 listening processing. However, few studies have examined the model from an experimental approach. The current study tried to provide empirical evidence for the interactive model of L2 listening processing in bilinguals by exploring the relationships among English spoken word segmentation (SWS), cognitive inhibition, cognitive flexibility, and L2 listening proficiency. The results showed positive associations among SWS, cognitive inhibition, cognitive flexibility, and L2 listening proficiency. Mediation analysis suggested that SWS might have a positive influence on L2 listening proficiency both directly and indirectly through cognitive inhibition and cognitive flexibility, respectively. These results imply that both bottom-up (reflected at SWS) and top-down (reflected at cognitive inhibition and flexibility) processes are engaged in bilinguals’ L2 listening processing.

Titanium alloy radiation rods have excellent physical and chemical properties compared to other materials, and are commonly used for ultrasonic casting of 2A14 aluminum alloy. However, titanium alloys are chemically corroded in high-temperature aluminum melts for a long time, making it difficult to precisely regulate the elemental composition during casting. In order to better understand the high-temperature chemical corrosion mechanism of titanium alloy radiation rods, this research looks into the corrosion morphology, weight loss, surface roughness, and reaction layer. The study’s findings suggest that the rate of chemical corrosion of titanium alloy in high-temperature aluminum melt is often inversely correlated with the degree of roughness, with the degree of roughness changing nonlinearly during the corrosion process. Titanium alloy weight loss rates with roughness Ra0.4 μ m, Ra7.2 μ m, Ra9.5 μ m and Ra9.8 μ m are 0.16 mg per min, 0.25 mg per min, 0.37 mg per min and 0.29 mg per min, respectively. The corrosion product of the chemical corrosion process is TiAl _3 , which is granular. Under varying roughness conditions, the solid-liquid interface of Al/Ti emerges reactants after 4 min, and the TiAl _3 reaction layer arises after 12 min. Furthermore, the reaction layer with little roughness is flat and compact, whereas the reaction layer with great roughness is loose and contains many faults. At the same time, the growth rate of the reaction layer decreases slightly. And the greater the surface roughness, the greater the TiAl _3 reaction layer grows at the titanium alloy matrix.

Take-home exam (THE) use has been reported in various disciplines, but research on THE use in language modules in higher education appears to be scarce. The current study employed surveys and interviews to examine how the shift to written THE, in place of the traditional in-class exam (ICE) during the pandemic, impacted language learning and teaching on the China campus of a British university. Additionally, correlation analyses were conducted with ranking data of students from the same cohort under THE and ICE to explore patterns in student performance under these exam conditions. In surveys and interviews, teachers reported that their teaching foci did not change under THE, while many students reported that their learning practices were different under THE and ICE. Students also exhibited a tendency to spend more time practicing skills that they expected to be assessed in the exam. Overall, both teachers and students expressed preference for ICE, with many raising concerns about fairness issues in THE. Furthermore, correlation analyses showed that, overall, for a given group of students, written ICE rankings exhibited strong correlations with each other but written THE rankings did not, suggesting relative instability of THE results. However, when written THE and oral ICE results from the same module are combined, the resultant rankings strongly correlated with pure ICE rankings. This indicates that combining ICE and THE components for assessment could help mitigate some perceived shortcomings, including the instability issue, of THE used alone.