MAVS Is essential for primary CD4 + T cell immunity but not for recall T cell responses following an attenuated West Nile virus infection

ABSTRACT The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs −/− mice were more susceptible to NS4B-P38G priming than WT mice. Mavs −/− mice had a transiently reduced production of antiviral cytokines and an impaired CD4 + T cell response in peripheral organs. However, antibody and CD8 + T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs −/− dendritic cells and subsequently compromised the antigen-presenting capacity for CD4 + T cells. Interestingly, Mavs −/− mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs −/− mice exhibited equivalent levels of protective CD4 + T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8 + T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4 + T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection. IMPORTANCE The production of innate cytokines induced by the recognition of pathogen recognition receptors (PRRs) via their cognate ligands are critical for enhancing antigen-presenting cell functions and influencing T cell responses during microbial infection. The use of PRR agonists and the underlying molecular mechanisms have been the major focus in individual vaccine development. Here, we determined the role of mitochondrial antiviral-signaling protein (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the live attenuated West Nile virus (WNV) vaccine strain, the nonstructural (NS) 4B-P38G mutant. We found that MAVS is important for boosting optimal primary CD4 + T cell response during NS4B-P38G vaccination. However, MAVS is dispensable for memory T cell development and host protection during secondary wild-type WNV infection. Overall, these results may be utilized as a paradigm to aid in the rational development of other efficacious live attenuated flavivirus vaccines

Study on Wear Resistance of Nickel Cladding Layer with Imitation Shell Convex Strip Structure on the Surface of 7075 Aluminum Alloy Drill Pipe

In this study, a nickel cladding layer with a bionic convex strip structure was applied to the surface of an aluminum alloy drill pipe, and laser cladding technology was used to improve the wear resistance of the aluminum alloy drill pipe. Firstly, by observing the morphological characteristics of the shell surface, the ratio of the width of the convex strips to the spacing between the convex strips was obtained as 0.39–0.53, and thus a model of the bionic structure was constructed. Numerical simulations were performed, and the results showed that the wear of the bionic structure was reduced by 77.6% compared with that of the smooth structure. Subsequently, the cladding layers of both structures were coated on the drill pipe using nickel powder as the material, and wear tests were performed. The microstructure, composition, and hardness behavior of the cladding layers were analyzed using scanning electron microscopy, an X-ray diffractometer, and a microhardness tester. It was found that the cladding layer mainly consists of Al3Ni2, and there is a transition layer between the cladding layer and the aluminum alloy matrix, whose hardness is lower than that of Al3Ni2. In addition, the groove space can be formed between the convex strips, which effectively reduces the frequency of the debris flow. The results of the wear tests show that the wear of the cladding layer with the bionic structure is reduced by 74.0%. Similar results in numerical simulations and experiments verified that the designed cladding layer with a bionic convex strip structure can significantly improve the wear resistance of aluminum alloy drill pipes.© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Tissue memory CD4+ T cells expressing IL-7 receptor-alpha (CD127) preferentially support latent HIV-1 infection.

The primary reservoir for HIV is within memory CD4+ T cells residing within tissues, yet the features that make some of these cells more susceptible than others to infection by HIV is not well understood. Recent studies demonstrated that CCR5-tropic HIV-1 efficiently enters tissue-derived memory CD4+ T cells expressing CD127, the alpha chain of the IL7 receptor, but rarely completes the replication cycle. We now demonstrate that the inability of HIV to replicate in these CD127-expressing cells is not due to post-entry restriction by SAMHD1. Rather, relative to other memory T cell subsets, these cells are highly prone to undergoing latent infection with HIV, as revealed by the high levels of integrated HIV DNA in these cells. Host gene expression profiling revealed that CD127-expressing memory CD4+ T cells are phenotypically distinct from other tissue memory CD4+ T cells, and are defined by a quiescent state with diminished NFκB, NFAT, and Ox40 signaling. However, latently-infected CD127+ cells harbored unspliced HIV transcripts and stimulation of these cells with anti-CD3/CD28 reversed latency. These findings identify a novel subset of memory CD4+ T cells found in tissue and not in blood that are preferentially targeted for latent infection by HIV, and may serve as an important reservoir to target for HIV eradication efforts

Roadmap on energy harvesting materials

Ambient energy harvesting has great potential to contribute to sustainable development and address growing environmental challenges. Converting waste energy from energy-intensive processes and systems (e.g. combustion engines and furnaces) is crucial to reducing their environmental impact and achieving net-zero emissions. Compact energy harvesters will also be key to powering the exponentially growing smart devices ecosystem that is part of the Internet of Things, thus enabling futuristic applications that can improve our quality of life (e.g. smart homes, smart cities, smart manufacturing, and smart healthcare). To achieve these goals, innovative materials are needed to efficiently convert ambient energy into electricity through various physical mechanisms, such as the photovoltaic effect, thermoelectricity, piezoelectricity, triboelectricity, and radiofrequency wireless power transfer. By bringing together the perspectives of experts in various types of energy harvesting materials, this Roadmap provides extensive insights into recent advances and present challenges in the field. Additionally, the Roadmap analyses the key performance metrics of these technologies in relation to their ultimate energy conversion limits. Building on these insights, the Roadmap outlines promising directions for future research to fully harness the potential of energy harvesting materials for green energy anytime, anywhere

How Does Organizational Career Management Benefit Employees? The Impact of the “Enabling” and “Energizing” Paths of Organizational Career Management on Employability and Job Burnout

Organizational career management (OCM) is believed to be a useful practice to stimulate the potential of employees. However, how this can be achieved is still under investigation. This research aims to explore the mechanisms that explain the effects of OCM by clarifying its impact on employees’ psychological states and their capability, based on a socially embedded model of thriving. To examine our hypotheses, we conducted a three-wave survey study with 272 full-time employees in China from diverse industries. The study lasted for three months and there was a one-month interval after each wave. We asked the participants to report OCM, career plateau and demographic variables at Time 1, their appraisal of learning and vitality at Time 2, and their self-perceived employability and job burnout at Time 3. We utilized regression analysis to examine our theoretical model and path analysis using the bias-corrected bootstrap method to test the significance of the indirect and moderation effects. The findings showed that OCM positively affected employees’ learning and vitality at work, which increased their self-perceived employability and subsequently decreased job burnout. Furthermore, the effects of OCM were found to be weaker for employees with a high degree of career plateau. These findings demonstrate that OCM benefits employees by “enabling” and “energizing” them to better themselves in terms of their employment and they shed light on the boundary condition of the career plateau. Therefore, organizations may provide OCM to facilitate employees’ capability and their motivation to engage in self-development, and to further enhance the effects by decreasing their perception of a career plateau

Electromechanical behavior of fiber-reinforced dielectric elastomer membrane

Based on its large deformation, light weight, and high energy density, dielectric elastomer (DE) has been used as driven muscle in many areas. We design the fiber-reinforced DE membrane by adding fibers in the membrane. The deformation and driven force direction of the membrane can be tuned by changing the fiber arrangements. The actuation in the perpendicular direction of the DE membrane with long fibers first increases and then decreases by the increasing of the fiber spacing in the perpendicular direction. The horizontal actuation of the membrane decreases by decreasing the spacing of short fibers. In the membrane-inflating structure, the radially arranged fibers will break the axisymmetric behavior of the structure. The top area of the inflated balloon without fiber will buckle up when the voltage reaches a certain level. Finite element simulations based on nonlinear field theory are conducted to investigate the effects of fiber arrangement and verify the experimental results. This work can guide the design of fiber-reinforced DE

Factors influencing postoperative length of stay in an enhanced recovery after surgery program for primary total knee arthroplasty

Abstract Background Hospital length of stay (LOS) after primary total knee arthroplasty (TKA) has decreased obviously following the implementation of enhanced recovery after surgery (ERAS) program in the last few years. However, there are still some patients that cannot be discharged at early time for a variety of reasons, and it is necessary to explore factors leading to prolonged LOS. Therefore, the purpose of this study was to identify the complete preoperative, perioperative, and postoperative factors associated with prolonged postoperative LOS (PLOS) after primary TKA in a detailed ERAS program. Methods In a consecutive series from July 2015 to March 2017, all patients who underwent unilateral elective primary TKA were included in the retrospective study. A PLOS greater than 3 days was considered a prolonged PLOS. Multivariable logistic regression analysis was performed to identify patient characteristics and relevant preoperative, perioperative, and postoperative variables that were associated with prolonged PLOS and postoperative complications. Results A total of 241 patients were included with a mean PLOS of 3.8 days. Prolonged PLOS was significantly associated with preoperative valgus deformity of the knee (OR 4.95, 95%CI 1.56–15.77, P = 0.007), increased serum level of interleukin-6 on postoperative day 1 (OR 1.01, 95%CI 1.00–1.03, P = 0.039), increased visual analogue scale pain score and serum level of C-reactive protein on postoperative day 3 (OR 2.56, 95%CI 1.28–5.13, P = 0.008; OR 1.01, 95%CI 1.00–1.03, P = 0.019), increased day to achieve 90° active knee flexion after surgery (OR 2.19, 95%CI 1.27–3.79, P = 0.005), and postoperative wound complications (OR 8.58, 95%CI 2.10–35.03, P = 0.003) and other minor complications (OR 6.04, 95%CI 2.40–15.19, P < 0.001). Preoperative pulmonary infection (OR 2.75, 95%CI 1.20–6.28, P = 0.016), American Society of Anesthesiologists score 3/4 (OR 2.14, 95%CI 1.01–4.52, P = 0.046), and utilization of catheter after surgery (OR 2.53, 95%CI 1.23–5.19, P = 0.012) were significantly associated with postoperative complications. Conclusions Multiple factors were associated with prolonged PLOS and postoperative complications after TKA in the ERAS program. It is important to recognize all the factors to try to maximize the use of medical resources and ultimately optimize the care of our patients