Using exergame-based exercise to prevent and postpone the loss of muscle mass, muscle strength, cognition, and functional performance among elders in rural long-term care facilities: A protocol for a randomized controlled trial

ObjectiveElderly individuals in long-term care facilities (LTCFs) have a higher prevalence of sarcopenia than those in the community. Exercise is the gold standard for preventing and treating sarcopenia. Regarding exercise, multicomponent exercises, including progressive resistance training (PRT), are beneficial. However, developing routine, structured exercise programs for the elderly in LTCFs is difficult because of a shortage of healthcare providers, particularly in rural regions. Exergame-based exercises can increase a player’s motivation and reduce staff time for an intervention. Nintendo Switch RingFit Adventure (RFA) is a novel exergame that combines resistance, aerobic, and balance exercises. In this study, we aim to investigate the clinical effectiveness of RFA on muscle and functional performance parameters among the elderly in LTCFs.MethodsThe EXPPLORE (using EXergame to Prevent and Postpone the LOss of muscle mass, muscle strength, and functional performance in Rural Elders) trial is a single-center randomized controlled trial involving elderly individuals (≥60 years) living in LTCFs in rural southern Taiwan. The participants will be equally randomized to the intervention group (exergame-based exercise plus standard care) or the control group (standard care alone). Both groups will receive standard care except that the intervention group will receive exergame-based exercises at the time previously scheduled for sedentary activities in the LTCFs. The exergame-based exercise will be performed using RFA in the sitting position with a specialized design, including arm fit skills and knee assist mode. Each session of the exercise lasts 30 mins and will be performed two times per week for 12 weeks. The primary outcomes will be the osteoporotic fracture index, appendicular skeletal muscle mass index, dominant handgrip strength, and gait speed. Meanwhile, the secondary outcomes will be the dexterity and agility, muscle strength and thickness, range of motion of the joints of the dominant upper extremity, Kihon checklist, Medical Outcomes Study 36-Item Short-Form Health Survey, and Brain Health Test.DiscussionThis trial will provide valuable knowledge on whether exergames using RFA can counteract physical decline and improve quality of life and cognition among the elderly in LTCFs.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT05360667]

Engineering psychrophilic polymerase for nanopore long-read sequencing

Unveiling the potential application of psychrophilic polymerases as candidates for polymerase-nanopore long-read sequencing presents a departure from conventional choices such as thermophilic Bacillus stearothermophilus (Bst) renowned for its limitation in temperature and mesophilic Bacillus subtilis phage (phi29) polymerases for limitations in strong exonuclease activity and weak salt tolerance. Exploiting the PB-Bst fusion DNA polymerases from Psychrobacillus (PB) and Bacillus stearothermophilus (Bst), our structural and biochemical analysis reveal a remarkable enhancement in salt tolerance and a concurrent reduction in exonuclease activity, achieved through targeted substitution of a pivotal functional domain. The sulfolobus 7-kDa protein (Sso7d) emerges as a standout fusion domain, imparting significant improvements in PB-Bst processivity. Notably, this study elucidates additional functional sites regulating exonuclease activity (Asp43 and Glu45) and processivity using artificial nucleotides (Glu266, Gln283, Leu334, Glu335, Ser426, and Asp430). By disclosing the intricate dynamics in exonuclease activity, strand displacement, and artificial nucleotide-based processivity at specific functional sites, our findings not only advance the fundamental understanding of psychrophilic polymerases but also provide novel insights into polymerase engineering

A network access control framework for 6LoWPAN networks

Low power over wireless personal area networks (LoWPAN), in particular wireless sensor networks, represent an emerging technology with high potential to be employed in critical situations like security surveillance, battlefields, smart-grids, and in e-health applications. The support of security services in LoWPAN is considered a challenge. First, this type of networks is usually deployed in unattended environments, making them vulnerable to security attacks. Second, the constraints inherent to LoWPAN, such as scarce resources and limited battery capacity, impose a careful planning on how and where the security services should be deployed. Besides protecting the network from some well-known threats, it is important that security mechanisms be able to withstand attacks that have not been identified before. One way of reaching this goal is to control, at the network access level, which nodes can be attached to the network and to enforce their security compliance. This paper presents a network access security framework that can be used to control the nodes that have access to the network, based on administrative approval, and to enforce security compliance to the authorized nodes

Dectin-1 signaling coordinates innate and adaptive immunity for potent host defense against viral infection

BackgroundMost commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.ObjectivesTo address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.MethodsWe demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.Resultsβ-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.ConclusionOur study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines

Upregulation of Pd-L1 by Sars-Cov-2 Promotes Immune Evasion

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity

Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model

<p>Abstract</p> <p>Background</p> <p>The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto-oncogenes, such as <it>c-myc</it>, as well as the inactivation of certain tumor suppressors, such as <it>p16</it>. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis.</p> <p>Methods</p> <p>Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of <it>p16 </it>and <it>c-myc </it>mRNA was examined by Real-time PCR (Q-PCR). The DNA methylation status within the <it>p16 </it>and <it>c-myc </it>promoter was analyzed using methylation-specific PCR.</p> <p>Results</p> <p>Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (<it>P < 0.05</it>). Although the frequency of <it>p16 </it>promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (<it>P > 0.05</it>). Betaine supplementation attenuated the down-regulation of <it>p16 </it>and inhibited the up-regulation of <it>c-myc </it>induced by DEN in a dose-dependent manner (<it>P </it>< 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (<it>P < 0.05</it>). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups.</p> <p>Conclusion</p> <p>Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels.</p