Characteristics of Aqueous Chemical Species Generation in Plasma-Facing Liquid Systems Using Helium Jet Plasma.

Plasma-facing liquids (PFLs) facilitate the storage of reactive O and N species (RONS), including H2O2 and NO2 -, which remain in the PFL after plasma treatment, and they can continuously influence the target immersed in the liquid. However, their behaviors and levels of generation and extinction depend strongly on the plasma characteristics and liquid condition. Therefore, understanding the effects of the liquid type on the plasma discharge characteristics and the RONS generated via plasma discharge is necessary. We compared the RONS generation and storage trends of deionized H2O and a high-conductivity PFL, RPMI 1640, which is a well-known cell culture medium commonly used to culture mammalian cells. RPMI 1640 acted as an electrode and enhanced the plasma discharge power by supplying abundant radicals and RONS. The production of gaseous hydroxyl radicals and NO markedly increased, which facilitated H2O2 and NO2 - production in the PFL for the first 200 s, and then the increase in the RONS concentration stagnated. With respect to storage, as the components within RMPI 1640 exhibited high reaction constants for their reactions with H2O2, H2O2 elimination was completed in <30 min. Unlike H2O2, the concentration of NO2 - in the PFL was unchanged.

Behavioral and neuropathological features of Alzheimer's disease are attenuated in 5xFAD mice treated with intranasal GHK peptide.

Efforts to find disease modifying treatments for Alzheimer's disease (AD) have met with limited success in part because the focus has been on testing drugs that target a specific pathogenic mechanism. Multiple pathways have been implicated in the pathogenesis of AD. Hence, the probability of more effective treatment for AD is likely increased by using an intervention that targets more than one pathway. The naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine), as a GHK-Cu complex, supports angiogenesis, remodeling, and tissue repair, has anti-inflammatory and antioxidant properties, and has been shown to improve cognitive performance in aging mice. In order to test GHK-Cu as a neurotherapeutic for AD, male and female 5xFAD transgenic mice on the C57BL/6 background at 4 months of age were given 15 mg/kg GHK-Cu intranasally 3 times per week for 3 months until 7 months of age. Results showed that intranasal GHK-Cu treatment delayed cognitive impairment, reduced amyloid plaques, and lowered inflammation levels in the frontal cortex and hippocampus. These observations suggest additional studies are warranted to investigate the potential of GHK-Cu peptide as a promising treatment for AD.

Intranasal GHK peptide enhances resilience to cognitive decline in aging mice.

Brain aging and cognitive decline are aspects of growing old. Age-related cognitive impairment entails the early stages of cognitive decline, and is extremely common, affecting millions of older people. Investigation into early cognitive decline as a treatable condition is relevant to a wide range of cognitive impairment conditions, since mild age-related neuropathology increases risk for more severe neuropathology and dementia associated with Alzheimer's Disease. Recent studies suggest that the naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine) in its Cu-bound form, has the potential to treat cognitive decline associated with aging. In order to test this concept, male and female C57BL/6 mice, 20 months of age, were given intranasal GHK-Cu, 15 mg/kg daily, for two months. Results showed that mice treated with intranasal GHK-Cu had an enhanced level of cognitive performance in spatial memory and learning navigation tasks, and expressed decreased neuroinflammatory and axonal damage markers compared to mice treated with intranasal saline. These observations suggest that GHK-Cu can enhance resilience to brain aging, and has translational implications for further testing in both preclinical and clinical studies using an atomizer device for intranasal delivery.

Cytokine receptor γc effectuates the generation of proinflammatory innate CD8 T cells by non-classical MHC-I molecules.

Innate CD8 T cells correspond to a population of terminally differentiated effector T cells that phenotypically appear as antigen-experienced memory cells and functionally resemble proinflammatory CD8 T cells, expressing copious amounts of IFNγ. Innate CD8 T cells, however, are distinct from conventional effector-memory CD8 T cells as they acquire functional maturity during their generation in the thymus. Understanding the molecular mechanisms that drive their thymic development and differentiation is an intensely studied subject in T cell immunity, and here we identified the cytokine receptor γc as a critical mediator of innate CD8 T cell generation that promotes their selection even in the absence of classical MHC-I molecules. Consequently, overexpression of γc resulted in a dramatic increase of innate CD8 T cells in KbDb-deficient mice. We mapped its underlying mechanism to the expansion of IL-4-producing invariant NKT cells, so that it is the increased availability of intrathymic IL-4 which augments the selection of innate CD8 T cells. Collectively, these results unravel the selection of innate CD8 T cells being mediated by non-classical MHC-I molecules and being modulated by the abundance of the γc cytokine, IL-4.

Recent catalytic applications of MXene-based layered nanomaterials.

The urgent issues related to the catalytic processes and energy applications have accelerated the development of hybrid and smart materials. MXenes are a new family of atomic layered nanostructured materials that require considerable research. Tailorable morphologies, strong electrical conductivity, great chemical stability, large surface-to-volume ratios, tunable structures, among others are some significant characteristics that make MXenes appropriate for various electrochemical reactions, including dry reforming of methane, hydrogen evolution reaction, methanol oxidation reaction, sulfur reduction reaction, Suzuki-Miyaura coupling reaction, water-gas shift reaction, and so forth. MXenes, on the other hand, have a fundamental drawback of agglomeration, as well as poor long-term recyclability and stability. One possibility for overcoming the restrictions is the fusion of nanosheets or nanoparticles with MXenes. Herein, the relevant literature on the synthesis, catalytic stability and reusability, and applications of several MXene-based nanocatalysts are deliberated including the merits and cons of the newer MXene-based catalysts.

Regenerative Potential of Bone Morphogenetic Protein 7-Engineered Mesenchymal Stem Cells in Ligature-Induced Periodontitis.

Periodontitis is an oral disease caused by bacterial infection that has stages according to the severity of tissue destruction. The advanced stage of periodontitis presents irreversible destruction of soft and hard tissues, which finally results in loss of teeth. When conventional treatment modalities show limited results, tissue regeneration therapy is required in patients with advanced periodontitis. In the present study, we aimed to evaluate the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) delivering bone morphogenetic protein 7 (BMP7) on tissue regeneration in a periodontitis model. BMP7 is a member of the BMP family that shows bone-forming ability; however, BMPs rapid clearing and degradation and unproven efficacy make it difficult to apply it in clinical dentistry. To overcome this, we established BMP7-expressing engineered BM-MSCs (BMP7-eBMSCs) that showed superior osteogenic differentiation potential when subcutaneously transplanted with a biphasic calcium phosphate scaffold into immunocompromised mice. Furthermore, the efficacy of BMP7-eBMSC transplantation for periodontal tissue regeneration was evaluated in a rat ligature-induced periodontitis model. Upon measuring two-dimensional and three-dimensional amounts of regenerated alveolar bone using microcomputed tomography, the amounts were found to be significantly higher in the BMP7-eBMSC transplantation group than in the eBMSC transplantation group. Most importantly, fibrous periodontal ligament (PDL) tissue regeneration was also achieved upon BMP7-eBMSC transplantation, which was evaluated by calculating the modified relative connective tissue attachment. The amount of connective tissue attachment in the BMP7-eBMSC transplantation group was significantly higher than that in the ligature-induced periodontitis group, although the increase was comparable between the BMP7-eBMSC and human PDL stem cell transplantation groups. Taken together, our results suggested that sustainable release of BMP7 induces periodontal tissue regeneration and that transplantation of BMP7-eBMSCs is a feasible treatment option for periodontal regeneration. Impact Statement Periodontitis is the second most common human dental disease affecting chronic systemic diseases. Despite the tremendous efforts trying to cure the damaged periodontal tissues using tissue engineering technologies, a definitive regenerative method has not been in consensus. Researchers are seeking more feasible and abundant source of mesenchymal stem cells (MSCs), and furthermore, how to use reliable growth factors under more efficient control are the issues to be solved. In this study, we aimed to evaluate the effect of bone morphogenetic protein 7 (BMP7) gene delivering bone marrow-derived MSCs on periodontal tissue regeneration to evaluate the efficacy of BMP7 and engineered BMSCs for periodontal tissue regeneration.

Modeling resilience to sleep disruption to study resistance to Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative condition with unknown etiology and no cure. Therefore, it is imperative to learn more about the underlying risk factors. Since AD is an age-related disease, one approach is to look at factors associated with aging. One example is sleep disruption, which increases with age and accelerates the progression of cognitive decline. However, some people with sleep loss experience little or no cognitive impairment and are considered resilient. The concept that resilience to sleep disruption increases resistance to AD can be modeled in aging mice with or without cognitive impairment to determine resistance or susceptibility to AD. Given that sleep disruption is a relevant and rising health concern, it is essential to gain a better understanding of resilience, and factors associated with resistance to AD, in order to develop successful intervention strategies.

Effects of Dielectric Barrier on Water Activation and Phosphorus Compound Digestion in Gas-Liquid Discharges.

To generate a stable and effective air-liquid discharge in an open atmosphere, we investigated the effect of the dielectric barrier on the discharge between the pin electrode and liquid surface in an atmospheric-pressure plasma reactor. The atmospheric-pressure plasma reactor used in this study was based on a pin-plate discharge structure, and a metal wire was used as a pin-type power electrode. A plate-type ground electrode was placed above and below the vessel to compare the pin-liquid discharge and pin-liquid barrier discharge (PLBD). The results indicated that the PLBD configuration utilizing the bottom of the vessel as a dielectric barrier outperformed the pin-liquid setup in terms of the discharge stability and that the concentration of reactive species was different in the two plasma modes. PLBD can be used as a digestion technique for determining the phosphorus concentration in natural water sources. The method for decomposing phosphorus compounds by employing PLBD exhibited excellent decomposition performance, similar to the performance of thermochemical digestion-an established conventional method for phosphorus detection in water. The PLBD structure can replace the conventional chemical-agent-based digestion method for determining the total dissolved phosphorus concentration using the ascorbic acid reduction method.

A mouse model of naturally occurring age-related cognitive impairment.

Age-related cognitive impairment (ARCI) is a neurological condition that affects millions of older people, but little is known about the increased risk of developing more severe neurodegeneration and dementia. Preclinical research is needed to understand the mechanisms of the impairment and the neuropathology associated with it. We have characterized a model of naturally occurring ARCI in the C57BL/6J mouse strain that shows an age-dependent development of cognitive impairment. As in people, some mice have little cognitive impairment while others have more severe cognitive impairment. Therefore, mice can be categorized as resistant or susceptible and the two groups can be studied for behavioral and neuropathology differences. Preliminary observations show no difference in strength and agility test scores between ARCI resistant and susceptible mice of either sex suggesting the cognitive impairment in ARCI susceptible mice is not accompanied by impairment in daily living activities, similar to ARCI in humans. The hippocampal area of the brain from ARCI susceptible mice shows evidence of an increase in the inflammatory cytokine MCP-1 compared to ARCI resistant mice, suggesting inflammation may be associated with ARCI. These preliminary observations suggest that ARCI in C57BL/6J mice could be a high-impact model to study how resilience to brain aging may predict resilience to dementia associated with Alzheimer's disease and other age-related neurological conditions.

Public interest in the digital transformation accelerated by the COVID-19 pandemic and perception of its future impact.

BACKGROUND/AIMS: The coronavirus disease 2019 (COVID-19) pandemic has accelerated digital transformation (DT). We investigated the trend of the public interest in technologies regarding the DT and Koreans' experiences and their perceptions of the future impact of these technologies. METHODS: Using Google Trends, the relative search volume (RSV) for topics including "coronavirus," "artificial intelligence," "cloud," "big data," and "metaverse" were retrieved for the period from January 2020 to January 2022. A survey was conducted to assess the population's knowledge, experience, and perceptions regarding the DT. RESULTS: The RSV for "metaverse" showed an increasing trend, in contrast to those for "cloud," "big data," and "coronavirus." The RSVs for DT-related keywords had a negative correlation with the number of new weekly COVID-19 cases. In our survey, 78.1% responded that the positive impact of the DT on future lives would outweigh the negative impact. The predictors for this positive perception included experiences with the metaverse (4.0-fold) and virtual reality (VR)/augmented reality (AR) education (3.8-fold). Respondents predicted that the biggest change would occur in the healthcare sector after transportation/ communication. CONCLUSION: Koreans' search interest for "metaverse" showed an increasing trend during the COVID-19 pandemic. Koreans believe that DT will bring about big changes in the healthcare sector. Most of the survey respondents have a positive outlook about the impact of DT on future life, and the predictors for this positive perception include the experiences with the metaverse or VR/AR education. Healthcare professionals need to accelerate the adoption of DT in clinical practice, education and training.

Reduced diversity of intestinal T-cell receptor repertoire in patients with Crohn's disease.

Background: The intestinal microenvironment directly determines the human T-cell receptor (TCR) repertoire. Despite its extreme diversity, TCR repertoire analysis may provide a better understanding of the immune system in patients with inflammatory bowel disease. Methods: To investigate TCR repertoires in the intestinal mucosa, RNA sequencing was performed for inflamed and non-inflamed intestinal mucosa samples obtained from 13 patients with Crohn's disease (CD) and healthy mucosa from nine non-IBD controls. Results: The gene expression frequency of the TCR repertoire showed a clear separation between inflamed mucosa of patients with CD and healthy mucosa of non-IBD controls in the hierarchical clustering heatmap. The richness of TCR repertoires measured by the Chao1 index did not show a significant difference among groups, whereas diversity measured by the D50 diversity index was decreased in the inflamed mucosa of CD patients. Rare/small TCR clonotypes occupied a large proportion of TCR repertoires in healthy mucosa of controls, whereas expanded clonotypes were common in inflamed mucosa of patients with CD. Segment usages of TRAV2, TRAV22, TRAV40, TRJ14, TRAJ51, TRBV1, TRBV21.1, and TRBJ1.5 were significantly decreased in CD patients. KEGG enrichment analysis identified the enrichment of several KEGG pathways, including inflammatory bowel disease (p = 0.0012), Th1 and Th2 cell differentiation (p = 0.0011), and intestinal immune network for IgA production (p = 0.0468). Conclusions: The diversity of the TCR repertoire is reduced in inflamed mucosa of CD patients, which might contribute to intestinal inflammation.

Antitumor necrosis factor treatment in patients with inflammatory bowel disease does not promote psoriasis development: A meta-analysis.

BACKGROUND: Recent case reports have suggested that anti-tumor necrosis factor (TNF) agents are associated with an increased risk of developing psoriasis in patients with inflammatory bowel disease (IBD). AIMS: This meta-analysis of published studies aimed to evaluate the association between anti-TNF treatment and psoriasis in patients with IBD. METHODS: An electronic search for original articles published before April 7, 2022, was performed using PubMed, EMBASE, and the Cochrane Library. Independent reviewers conducted the article screening and data extraction. Psoriasis development between anti-TNF-treated and anti-TNF-naïve patients was compared. Patients with ulcerative colitis and Crohn disease were compared with determine the differences in anti-TNF-induced psoriasis. Also, psoriasis development was compared according to the types of anti-TNF agents. Random-effects model meta-analyses, network meta-analysis, funnel plot asymmetry, Begg rank correlation test, and Egger regression test were performed to generate summary estimates and explore the possibility of publication bias. RESULTS: We analyzed a total of 10,778 articles searched and 14 articles were selected to analyze. There was no significant difference in psoriasis development between anti-TNF-treated and anti-TNF-naïve patients (relative risk = 1.14; 95% confidence interval = 0.77-1.68). No differences were found for psoriasis development between anti-TNF-treated ulcerative colitis and Crohn disease patients (relative risk = 1.30; 95% confidence interval = 0.87-1.95). No significant difference was reported with respect to psoriasis development according to the types of anti-TNF agents. We found no definitive publication bias in our analyses. CONCLUSIONS: Anti-TNF treatment did not contribute to the psoriasis development in patients with IBD. Based on our study, anti-TNF agents may be used for IBD treatment without concern for psoriasis development.

Instant inactivation of aerosolized SARS-CoV-2 by dielectric filter discharge.

This study aimed to evaluate the instant inactivation effect of dielectric filter discharge (DFD) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aerosols. The filter consisted of one layer of ZrO2 beads covered by aluminum mesh electrodes; this porous structure of DFD part generates filter-type surface discharge and reactive oxygen species. In a closed cylindrical chamber, DFD treated air flow containing SARS-CoV-2 aerosols, primarily composed of particle diameters of ≤ 1 µm. A polypropylene melt-blown filter collected the treated bioaerosols for inactivation analysis. Plaque and polymerase chain reaction assays showed that the aerosolized SARS-CoV-2 that passed through the filter were more than 99.84% inactivated with degradation of SARS-CoV-2 genes (ORF1ab and E). However, ozone exposure without DFD passage was not found to be effective for bioaerosol inactivation in plaque assay.

Conversational Artificial Intelligence for Spinal Pain Questionnaire: Validation and User Satisfaction.

OBJECTIVE: The purpose of our study is to develop a spoken dialogue system (SDS) for pain questionnaire in patients with spinal disease. We evaluate user satisfaction and validated the performance accuracy of the SDS in medical staff and patients. METHODS: The SDS was developed to investigate pain and related psychological issues in patients with spinal diseases based on the pain questionnaire protocol. We recognized patients' various answers, summarized important information, and documented them. User satisfaction and performance accuracy were evaluated in 30 potential users of SDS, including doctors, nurses, and patients and statistically analyzed. RESULTS: The overall satisfaction score of 30 patients was 5.5 ± 1.4 out of 7 points. Satisfaction scores were 5.3 ± 0.8 for doctors, 6.0 ± 0.6 for nurses, and 5.3 ± 0.5 for patients. In terms of performance accuracy, the number of repetitions of the same question was 13, 16, and 33 (13.5%, 16.8%, and 34.7%) for doctors, nurses, and patients, respectively. The number of errors in the summarized comment by the SDS was 5, 0, and 11 (5.2%, 0.0%, and 11.6 %), respectively. The number of summarization omissions was 7, 5, and 7 (7.3%, 5.3%, and 7.4%), respectively. CONCLUSION: This is the first study in which voice-based conversational artificial intelligence (AI) was developed for a spinal pain questionnaire and validated by medical staff and patients. The conversational AI showed favorable results in terms of user satisfaction and performance accuracy. Conversational AI can be useful for the diagnosis and remote monitoring of various patients as well as for pain questionnaires in the future.

Sustainable Antibacterial and Antiviral High-Performance Copper-Coated Filter Produced via Ion Beam Treatment.

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), disease prevention has become incredibly important. Consequently, mask and air-purifier use has increased. The filter is the core component of these items. However, most filter materials lack antimicrobial properties. Copper is a sustainable antimicrobial material. When copper is deposited onto the filter's surface, the microorganisms that come into contact with it can be effectively inactivated. In this study, we used an oxygen ion beam with a controlled process temperature to treat filter surfaces with copper. This enabled a strong adhesion of at least 4 N/cm between the copper and the filter fibers without damaging them. Upon exposing the filter to bacteria (Staphylococcus aureus ATCC 6538, Klebsiella pneumoniae ATCC 4352, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853) for one hour, a >99.99% removal rate was attained; when the filter was exposed to SARS-CoV-2 virus for one hour, it inactivated more than 99%. These beneficial properties minimize the risk of secondary infections, which are significantly more likely to occur when a conventional filter is replaced or removed.

Unboxing mathematics: creating a culture of modeling as critic.

From the socio-critical perspective of mathematical modeling, reflexive discussions about the nature, criteria, and consequences of mathematical models are not a natural consequence of modeling in school. This report is part of a larger study focused on stimulating reflexive discussions in practice employing constructivist grounded theory as a research method. Twenty-seven college algebra students engaged in a 3-week modeling project at a community college in the USA. Audio-recorded group discussions and written reflections were collected to determine how reflexive discussions were taking place. Analysis of students' actions and reflexive discussions during the modeling project produced four concepts: voicing mathematics, personalizing mathematics, challenging mathematics, and negotiating mathematics. These concepts are integrated into an overall process for stimulating reflexive discussions and are conceptualized as unboxing mathematics. The overarching concept of unboxing mathematics represents one interpretation of how reflexive discussions may be constituted during modeling activities and identifies classroom mathematical practices specific to the socio-critical modeling context of this study.

In vivo availability of the cytokine IL-7 constrains the survival and homeostasis of peripheral iNKT cells.

Understanding the homeostatic mechanism of invariant natural killer T (iNKT) cells is a critical issue in iNKT cell biology. Because interleukin (IL)-15 is required for the thymic generation of iNKT cells, IL-15 has also been considered necessary for the homeostasis of peripheral iNKT cells. Here, we delineated the in vivo cytokine requirement for iNKT cells, and we came to the surprising conclusion that IL-7, not IL-15, is the homeostatic cytokine for iNKT cells. Employing a series of experimental mouse models where the availability of IL-7 or IL-15 was manipulated in peripheral tissues, either by genetic tools or by adult thymectomy and cytokine pump installation, we demonstrate that the abundance of IL-7, and not IL-15, limits the size of the peripheral iNKT cell pool. These results redefine the cytokine requirement for iNKT cells and indicate competition for IL-7 between iNKT and conventional αß T cells.

Targeting IGF1R signaling for brain aging and Alzheimer's disease.

The role of IGF1R signaling in the brain and its relationship to aging and neurological dysfunction is controversial. Because it was shown that low IGF1R activity consistently improved myocardial bioenergetics and function in hearts from aging mice, but not hearts from young mice, it was of interest to investigate this relationship in brain aging. We used CRISPR technology to develop a mouse model with targeted replacement of mouse IGF1R with the equivalent of the human R407H (IGF1RR407H) variant enriched in centenarians with a reduction in IGF1R protein activity. Middle-aged mice show improved cognitive performance thus possibly modeling IGF1R signaling in the aging brain, similar to what was reported in the aging heart. Because Alzheimer's disease (AD) is an age-related disease, specific IGF1RR407H pathways could be therapeutic targets in mice with AAV vector-based AD as well as for overall brain aging.