ABSTRACT
Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hippocampal neuronal cultures showed that lipocalin-2 (LCN2), derived from reactive astrocytes, mediated neuroinflammation and induced cognitive impairment by decreasing the LTP through the reduction of neuronal NMDA receptors. Sustained chemogenetic stimulation of hippocampal astrocytes provided similar results. Conversely, these phenomena were attenuated by a metabolic inhibitor of astrocytes. Fiber photometry using GCaMP revealed a high level of hippocampal astrocyte activation in the neuroinflammation model. Our findings suggest that reactive astrocytes in the hippocampus are sufficient and required to induce cognitive decline through LCN2 release and synaptic modulation. This abnormal glial-neuron interaction may contribute to the pathogenesis of cognitive disturbances in neuroinflammation-associated brain conditions.
Subject(s)
Astrocytes , Cognitive Dysfunction , Hippocampus , Lipocalin-2 , Long-Term Potentiation , Neuroinflammatory Diseases , Neurons , Animals , Astrocytes/metabolism , Astrocytes/pathology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Lipocalin-2/metabolism , Lipocalin-2/genetics , Mice , Hippocampus/metabolism , Hippocampus/pathology , Neuroinflammatory Diseases/pathology , Neuroinflammatory Diseases/metabolism , Neurons/metabolism , Neurons/pathology , Mice, Knockout , Male , Mice, Inbred C57BL , Receptors, N-Methyl-D-Aspartate/metabolism , Optogenetics , CA1 Region, Hippocampal/pathology , CA1 Region, Hippocampal/metabolism , Disease Models, AnimalABSTRACT
BACKGROUND/OBJECTIVES: The objective of this study was to compare dietary habits and mental health among middle school students in urban and rural areas based on bedtime, and to provide evidence supporting appropriate bedtime for Korean middle school students in relation to their healthy dietary habits and mental well-being. SUBJECTS/METHODS: The study population consisted of 25,681 second-year middle school students who participated in the Korea Youth Risk Behavior Survey in 2020-2022. Participants were asked about their bedtime and wake-up time during the past 7 days and were classified into five categories. The study compared the general characteristics, academic factors, dietary habits, and mental health of urban and rural students based on their bedtime. RESULTS: Bedtime was found to be later in the following order: urban female students, rural female students, urban male students, and rural male students. As bedtime got later, the rates of smoking and alcohol consumption increased. Students who went to bed before 11 p.m. had lower academic performance, while rural male students who went to bed after 2 a.m. had lower academic performance. Later bedtime was associated with increased smartphone usage, skipping breakfast, consuming fast food, and drinking carbonated beverages. Later bedtime was also associated with higher perceived stress levels, particularly among students who went to bed after 2 a.m., higher rates of suicidal ideation, experiencing sadness and despair, as well as the prevalence of clinically significant anxiety disorders. CONCLUSION: These results suggest that middle school students who go to bed too late have higher rates of smoking and alcohol drinking, as well as unhealthy eating habits, stress, suicidal ideation, sadness, and anxiety. Therefore, it is necessary to provide educational and social institutional support to promote adequate sleep for the health of adolescents.
ABSTRACT
Carbon nanotubes (CNTs) are increasingly being used in industrial applications, but their toxicological data in animals and humans are still sparse. To assess the toxicological dose-response of CNTs and to evaluate their pulmonary biopersistence, their quantification in tissues, especially lungs, is crucial. There are currently no reference methods or reference materials for low levels of CNTs in organic matter. Among existing analytical methods, few have been fully and properly validated. To remedy this, we undertook an inter-laboratory comparison on samples of freeze-dried pig lung, ground and doped with CNTs. Eight laboratories were enrolled to analyze 3 types of CNTs at 2 concentration levels each in this organic matrix. Associated with the different analysis techniques used (specific to each laboratory), sample preparation may or may not have involved prior digestion of the matrix, depending on the analysis technique and the material being analyzed. Overall, even challenging, laboratories' ability to quantify CNT levels in organic matter is demonstrated. However, CNT quantification is often overestimated. Trueness analysis identified effective methods, but systematic errors persisted for some. Choosing the assigned value proved complex. Indirect analysis methods, despite added steps, outperform direct methods. The study emphasizes the need for reference materials, enhanced precision, and organized comparisons.
Subject(s)
Lung , Nanotubes, Carbon , Nanotubes, Carbon/chemistry , Nanotubes, Carbon/toxicity , Animals , Swine , Lung/chemistry , Lung/drug effects , Laboratories/standards , Organic Chemicals/analysis , Organic Chemicals/chemistryABSTRACT
Although studies on terrain identification algorithms to control walking assistive devices have been conducted using sensor fusion, studies on transition classification using only electromyography (EMG) signals have yet to be conducted. Therefore, this study was to suggest an identification algorithm for transitions between walking environments based on the entire EMG signals of selected lower extremity muscles using a deep learning approach. The muscle activations of the rectus femoris, vastus medialis and lateralis, semitendinosus, biceps femoris, tibialis anterior, soleus, medial and lateral gastrocnemius, flexor hallucis longus, and extensor digitorum longus of 27 subjects were measured while walking on flat ground, upstairs, downstairs, uphill, and downhill and transitioning between these walking surfaces. An artificial neural network (ANN) was used to construct the model, taking the entire EMG profile during the stance phase as input, to identify transitions between walking environments. The results show that transitioning between walking environments, including continuously walking on a current terrain, was successfully classified with high accuracy of 95.4 % when using all muscle activations. When using a combination of muscle activations of the knee extensor, ankle extensor, and metatarsophalangeal flexor group as classifying parameters, the classification accuracy was 90.9 %. In conclusion, transitioning between gait environments could be identified with high accuracy with the ANN model using only EMG signals measured during the stance phase.
Subject(s)
Deep Learning , Humans , Electromyography , Walking/physiology , Muscle, Skeletal/physiology , Gait/physiology , AlgorithmsABSTRACT
The purpose of this study was to investigate the relationship between muscular parameters of quadriceps/hamstrings and knee joint kinetics in gait. Muscle architecture (thickness, pennation angle, and fascicle length), and quality (echo intensity) of individual quadriceps and hamstrings of 30 healthy participants (16 males and 14 females) was measured using ultrasound. Peak knee flexion moment (KFM), KFM impulse, peak knee adduction moment (KAM), and KAM impulse during walking were obtained at preferred speed. Pearson's correlation coefficient and multiple regression analyses were performed at significance level of 0.05, and Cohen's f2 values were calculated to examine the effect sizes of multiple regression. The hamstring-to-quadriceps muscle thickness ratio (r = 0.373) and semitendinosus echo intensity (r = - 0.371) were predictors of first peak KFM (R2 = 0.294, P = 0.009, f2 = 0.42), whereas only vastus medialis (VM) echo intensity was a significant predictor of second peak KFM (r = 0.517, R2 = 0.267, P = 0.003, f2 = 0.36). Only the VM thickness was the predictor of first (r = 0.504, R2 = 0.254, P = 0.005, f2 = 0.34) and second peak KAM (r = 0.581, R2 = 0.337, P = 0.001, f2 = 0.51), and KAM impulse (r = 0.693, R2 = 0.480, P < 0.001, f2 = 0.92). In conclusion, the greater hamstring-to-quadriceps muscle thickness ratio and the muscle architecture and quality of medial quadriceps/hamstring play an important role in KFM and KAM, and may have implications in knee osteoarthritis.
Subject(s)
Hamstring Muscles , Osteoarthritis, Knee , Male , Female , Humans , Quadriceps Muscle/diagnostic imaging , Hamstring Muscles/diagnostic imaging , Knee Joint/diagnostic imaging , Knee Joint/physiology , Gait/physiology , Knee , Walking/physiology , Biomechanical PhenomenaABSTRACT
BACKGROUND: Although most elderly patients with acute myeloid leukemia (AML) are ineligible for intensive chemotherapy (ICT), treatment options remain limited. CURRENT (UMIN000037786), a real-world, non-interventional, retrospective chart review, evaluated clinical outcomes, clinicopathologic characteristics, and treatment patterns in these patients. We present results from a subanalysis of Korean patients in this study. METHODS: Patients were aged ≥ 18 years with primary or secondary AML ineligible for ICT who initiated first-line systemic therapy or best supportive care (BSC) between 2015 and 2018 across four centers in Korea. Primary endpoint was overall survival (OS) from diagnosis. Secondary endpoints included progression-free survival (PFS), time to treatment failure, and response rates. Data analyses were primarily descriptive, with time-to-event outcomes estimated using the Kaplan-Meier method, and Cox regression used to determine prognostic factors for survival. RESULTS: Among 194 patients enrolled, 84.0% received systemic therapy and 16.0% received BSC. Median age at diagnosis was 74 and 78 years, and Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 was reported in 73.0% and 48.4% of patients, respectively; poor cytogenetic risk was reported in 30.1% and 16.1% of patients. Median OS was 7.83 vs. 4.50 months, and median PFS was 6.73 vs. 4.50 months in the systemic therapy vs. BSC groups. Prognostic factors affecting OS included secondary AML (hazard ratio, 1.67 [95% confidence interval, 1.13-2.45]), ECOG performance status ≥ 2 (2.41 [1.51-3.83]), poor cytogenetic risk (2.10 [1.36-3.24]), and Charlson comorbidity index ≥ 1 (2.26 [1.43-3.58]). CONCLUSION: Clinical outcomes are poor in Korean patients with AML ineligible for ICT who are prescribed current systemic therapies or BSC. There is a substantial unmet need for novel agents (monotherapy or in combination) to improve clinical outcomes in this patient population.
Subject(s)
Leukemia, Myeloid, Acute , Aged , Humans , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Proportional Hazards Models , Progression-Free Survival , Republic of Korea , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson's ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 µm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays.
ABSTRACT
BACKGROUND: Nanodiamonds (NDs) have gained a rapidly growing interest in biomedical applications; however, little is known regarding their biokinetics owing to difficulties in measurements and limited synthesis/purification technologies. In this study, we investigated the distribution kinetics of detonation-synthesized NDs in mice via intravenous injection to evaluate the parameters that determine the behavior of the particles. We prepared two distinctive NDs that controlled the sp3/sp2 carbon ratio and particle size by coating them with serum proteins. The four control samples were intravenously injected into mice, and tissue distribution and clearance were evaluated at 30 min and 1, 7, and 28 days post-injection. RESULTS: The sp3/sp2 carbon ratio showed no correlation with the organ distribution of the NDs. However, hydrodynamic size showed an excellent correlation with organ distribution levels: a negative correlation in the liver and positive correlations in the spleen and lungs. Furthermore, the deposition levels of NDs in the lung suggest that particles smaller than 300 nm could avoid lung deposition. Finally, a similar organ distribution pattern was observed in mice injected with carbon black nanoparticles controlled hydrodynamic size. CONCLUSIONS: In conclusion, the tissue distribution of NDs is modulated not by the sp3/sp2 carbon ratio but by the hydrodynamic size, which can provide helpful information for targeting the tissue of NDs. Furthermore, the organ distribution pattern of the NDs may not be specific to NDs but also can apply to other nanoparticles, such as carbon black.
Subject(s)
Hydrodynamics , Nanodiamonds , Animals , Mice , Injections, Intravenous , Kinetics , Soot , Tissue Distribution , CarbonABSTRACT
Expanded polystyrene (EPS), also known as Styrofoam, is a widespread global pollutant, and its lightweight floating property increases its chances of weathering by abrasion and ultraviolet (UV) irradiation, resulting in microplastics. Herein, we investigated the effects of particle size ((1 µm versus 10 µm), UV irradiation (pristine versus UV oxidation), and origin (secondary versus primary) on the toxicity of Styrofoam microplastics. The target cells used in this study were selected based on human exposure-relevant cell lines: differentiated THP-1 cells for macrophages, Caco-2 for enterocytes, HepG2 for hepatocytes, and A549 for alveolar epithelial cells. In the differentiated THP-1 cells, the levels of cytotoxicity and inflammatory cytokines showed size- (1 µm > 10 µm), UV oxidation- (UV > pristine), and origin- (secondary > primary) dependency. Furthermore, the intrinsic oxidative potential of the test particles was positively correlated with cellular oxidative levels and toxicity endpoints, suggesting that the toxicity of Styrofoam microplastics also follows the oxidative stress paradigm. Additionally, all microplastics induced the activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome and the release of interleukin-1ß (IL-1ß). These results imply that weathering process can aggravate the toxicity of Styrofoam microplastics due to the increased oxidative potential and decreased particle size.
Subject(s)
Microplastics , Polystyrenes , Humans , Polystyrenes/toxicity , Microplastics/toxicity , Plastics , Caco-2 Cells , MacrophagesABSTRACT
BACKGROUND: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. OBJECTIVES: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). METHODS: Each EGT concentration (0, 10, 50, and 100 µM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. RESULTS: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 µM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 µM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 µM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. CONCLUSIONS: Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.
Subject(s)
Antioxidants , Ergothioneine , Pregnancy , Female , Swine , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Ergothioneine/pharmacology , Ergothioneine/analysis , Ergothioneine/metabolism , In Vitro Oocyte Maturation Techniques/veterinary , Reactive Oxygen Species/metabolism , Oocytes , Embryonic Development , Glutathione/analysis , Glutathione/metabolism , Glutathione/pharmacology , Fertilization in Vitro/veterinary , Blastocyst/metabolismABSTRACT
BACKGROUND: Muscle thickness can influence the joint kinematics and/or kinetics during dynamic activities. The relationship between the muscle thickness of individual quadriceps and hamstrings or medial-to-lateral thigh muscle thickness ratio and the knee kinematics/kinetics with respect to anterior cruciate ligament (ACL) injury risk remains unclear. HYPOTHESIS: Higher medial-to-lateral thigh muscle thickness ratio would be associated with lower knee valgus angle/moment and lower tibial internal rotation angle/moment during single-leg landing. STUDY DESIGN: Cross-sectional. LEVEL OF EVIDENCE: Level 4. METHODS: Muscle thickness of the vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), and semitendinosus (ST) of 30 healthy participants (16 males and 14 females) were measured using ultrasound. Knee joint kinematics and kinetics during single-leg landing were obtained. Stepwise multiple regression analysis, a follow-up Fisher's r to z test to examine the sex as a moderator, and independent t tests to evaluate sex difference were performed. RESULTS: Both knee valgus moment (R2 = 0.466, P < 0.001) and tibial external rotation moment (R2 = 0.330, P < 0.001) at peak anterior tibial shear force during single-leg landing were negatively correlated with medial-to-lateral (ie, (VM+ST):(VL+BF)) thickness ratio regardless of sex, whereas medial-to-lateral thigh muscle thickness ratio was not correlated with knee valgus and tibial external rotation angles. Male participants exhibited higher (VM+ST):(VL+BF) thickness ratio than female participants (P = 0.005), and lower knee valgus moment (P = 0.04) and tibial external rotation moment (P = 0.05), as well. CONCLUSION: The knee joint moments in frontal and transverse planes during single-leg landing were associated with the medial-to-lateral thigh muscle thickness ratio; thus, the medial-lateral thigh muscle thickness could be a potential contributor to frontal and transverse plane knee joint loading during dynamic movement. CLINICAL RELEVANCE: Strength training that aims to selectively strengthen the medial/lateral thigh muscles might be considered in a new ACL injury prevention training program to alter the biomechanical parameters associated with ACL injuries.
Subject(s)
Anterior Cruciate Ligament Injuries , Hamstring Muscles , Female , Male , Humans , Hamstring Muscles/diagnostic imaging , Hamstring Muscles/physiology , Quadriceps Muscle/diagnostic imaging , Leg , Biomechanical Phenomena , Kinetics , Cross-Sectional Studies , Knee JointABSTRACT
The measurement of nanoparticles (NPs) in a biological matrix is essential in various toxicity studies. However, the current knowledge has limitations in differentiating particulate and ionic forms and further identification of their biotransformation. Herein, we evaluate the biotransformation and differential lung clearance kinetics of particulate and ionic forms using PEGylated silver NPs (AgNP-PEGs; 47.51 nm) and PEGylated gold NPs (AuNP-PEGs; 11.76 nm). At 0, 3, and 6 h and 1, 3, 7, and 14 days after a single pharyngeal aspiration in mice at 25 µg/mouse, half of the lung is digested by proteinase K (PK) to separate particulates and ions, and the other half is subjected to the acid digestion method for comparison. The quantitative and qualitative evaluation of lung clearance kinetics suggests that AgNP-PEGs are quickly dissolved and transformed into insoluble silver sulfide (Ag2S), which shows a fast-clearing early phase (0 -6 h; particle T1/2: 4.8 h) and slow-clearing late phase (1 -14 days; particle T1/2: 13.20 days). In contrast, AuNP-PEGs were scarcely cleared or biotransformed in the lungs for 14 days. The lung clearance kinetics of AgNPs and biotransformation shown in this study can be informed by the PK digestion method and cannot be obtained using the acid digestion method.
Subject(s)
Metal Nanoparticles , Silver , Mice , Animals , Silver/metabolism , Lung/metabolism , Biotransformation , Ions , Polyethylene Glycols , Particle SizeABSTRACT
The development of digital technology has made our lives more advanced as a society familiar with the Internet of Things (IoT). Solar cells are among the most promising candidates for power supply in IoT sensors. Perovskite photovoltaics (PPVs), which have already attained 25% and 40% power conversion efficiencies for outdoor and indoor light, respectively, are the best candidates for self-powered IoT system integration. In this review, we discuss recent research progress on PPVs under indoor light conditions, with a focus on device engineering to achieve high-performance indoor PPVs (Id-PPVs), including bandgap optimization and defect management. Finally, we discuss the challenges of Id-PPVs development and its interpretation as a potential research direction in the field.
ABSTRACT
The manufacturing process for an ultrawide flexible microwave absorbing meta-surface was developed and optimized experimentally. The developed replication process consists of four main steps to demonstrate double-square loop array meta-structures: (1) mechanical machining of a master mold, (2) soft mold replication and patterned film imprinting, (3) conductive ink blade filling, (4) lamination of a base flexible film to meta sheet. Based on experimental optimization of the individual steps, the manufacturing process for a large-area flexible meta-film was established successfully. The feasibility of a developed process has been demonstrated with a 200 mm × 500 mm fabricated meta-film with a focus on microwave absorbing uniformity in the X-band region.
ABSTRACT
In ultra-precision planing process, the analysis of the critical depth of cut (DOC) is required to reduce the edge blunt and micro burrs produced by size effect which decreases of the effective area for high luminance retroreflector. However, since the machining characteristics are different according to cutting tool shape, machining material, and cutting condition, determine of the critical DOC is difficult without a comparison of machined surfaces under various DOC measured by ultra-high resolution measuring instrument. In this study, the critical DOC was analyzed using cutting force and tool vibration signals. The specific cutting energy was calculated by cutting force and cross-sectional area to analyze the stress variation according to DOC. Also, acceleration signals were converted to frequency spectrum that analyze dominant vibrating direction of the cutting tool by variation of cutting characteristic. It was confirmed that the method of using tool vibration more effective and accurate than specific cutting energy through validation of the comparison between results from analyze of the vibration signals and direction measuring surfaces. The master mold with area of 250 mm2 was manufactured by applying analyzed critical DOC. In addition, the high luminance characteristic of a retroreflection film press formed by the master mold was confirmed.
ABSTRACT
Although ATP and/or adenosine derived from astrocytes are known to regulate sleep, the precise mechanisms underlying the somnogenic effects of ATP and adenosine remain unclear. We selectively expressed channelrhodopsin-2 (ChR2), a light-sensitive ion channel, in astrocytes within the ventrolateral preoptic nucleus (VLPO), which is an essential brain nucleus involved in sleep promotion. We then examined the effects of photostimulation of astrocytic ChR2 on neuronal excitability using whole-cell patch-clamp recordings in two functionally distinct types of VLPO neurons: sleep-promoting GABAergic projection neurons and non-sleep-promoting local GABAergic neurons. Optogenetic stimulation of VLPO astrocytes demonstrated opposite outcomes in the two types of VLPO neurons. It led to the inhibition of non-sleep-promoting neurons and excitation of sleep-promoting neurons. These responses were attenuated by blocking of either adenosine A1 receptors or tissue-nonspecific alkaline phosphatase (TNAP). In contrast, exogenous adenosine decreased the excitability of both VLPO neuron populations. Moreover, TNAP was expressed in galanin-negative VLPO neurons, but not in galanin-positive sleep-promoting projection neurons. Taken together, these results suggest that astrocyte-derived ATP is converted into adenosine by TNAP in non-sleep-promoting neurons. In turn, adenosine decreases the excitability of local GABAergic neurons, thereby increasing the excitability of sleep-promoting GABAergic projection neurons. We propose a novel mechanism involving astrocyte-neuron interactions in sleep regulation, wherein endogenous adenosine derived from astrocytes excites sleep-promoting VLPO neurons, and thus decreases neuronal excitability in arousal-related areas of the brain.
Subject(s)
Galanin , Preoptic Area , Adenosine/pharmacology , Adenosine Triphosphate/pharmacology , Astrocytes , GABAergic Neurons , Galanin/pharmacology , Preoptic Area/physiologyABSTRACT
Cytokine release syndrome (CRS) is a systemic inflammatory response resulting in overexpression of cytokines in serum and tissues, which leads to multiple-organ failure. Due to rapid aggravation of symptoms, timely intervention is paramount; however, current therapies are limited in their capacity to address CRS. Here, we find that the intravenous injection of highly purified detonation-synthesized nanodiamonds (DND) can act as a therapeutic agent for treating CRS by adsorbing inflammatory cytokines. Highly purified DNDs successfully inactivated various key cytokines in plasma from CRS patients with pneumonia, septic shock, and coronavirus disease 2019 pandemic (COVID-19). The intravenous injection of the DND samples in a mouse sepsis model by cecal ligation and puncture significantly improved survival rates and prevented tissue damage by reducing the circulating inflammatory cytokines. The results of this study suggest that the clinical application of highly purified DND can provide survival benefits for CRS patients by adsorbing inflammatory cytokines.
ABSTRACT
The metatarsophalangeal (MTP) joint is not considered in most current walking assistive devices even though it plays an important role during walking. The purpose of this study was to develop a new MTP assistive device and investigate its effectiveness on the muscle activities of the lower extremities during walking while wearing the device. The MTP assistive device is designed to support MTP flexion by transmitting force through a cable that runs parallel with the plantar fascia. Eight participants were instructed to walk at a constant speed on a treadmill while wearing the device. The muscle activities of their lower extremities and MTP joint kinematics were obtained during walking under both actuated and non-actuated conditions. Paired t-tests were performed to compare the differences in each dependent variable between the two conditions. The muscle activity of the MTP flexor was significantly reduced during walking under actuated conditions (p = 0.013), whereas no differences were found in the muscle activities of other muscles or in the MTP joint angle between actuated and non-actuated conditions (p > 0.05 for all comparisons). In conclusion, the cable-driven MTP assistive device is able to properly assist the MTP flexor without interfering with the action of other muscles in the lower extremities; as such, this MTP assistive device, when integrated into existing exoskeleton designs, has the potential to offer improved walking assistance by reducing the amount of muscle activity needed from the MTP flexor.
Subject(s)
WalkingABSTRACT
The development of a universal, label-free, and reliable in vitro toxicity testing method for nanoparticles is urgent because most nanoparticles can interfere with toxicity assays. In this regard, the colony-forming efficacy (CFE) assay has been suggested as a suitable in vitro toxicity assay for testing nanoparticles without such interference. Recently, the Organisation for Economic Co-operation and Development (OECD) developed a 60 × 15 mm Petri dish-based CFE assay for testing nanoparticles in MDCK-1 cells. However, further investigations are needed, including testing with other cell types, at a smaller scale for greater efficiency, and the application of the co-culture technique. In this study, we selected TiO2, CuO, CeO2, and SiO2 as test nanoparticles and successfully developed a 6-well plate-based CFE assay using HepG2 and A549 cells and a co-culture assay for combinations of HepG2 cells and THP-1 macrophages or A549 cells and THP-1 monocytes. The results suggest that the 6-wellplate-based CFE assay for HepG2 and A549 cells can be applied to nanoparticles, but the co-culture CFE assay has limitations in that it is not different from the single culture study, and it inhibits colony-formation by A549 cells in the presence of macrophages; this warrant further study.
Subject(s)
Metal Nanoparticles/toxicity , Toxicity Tests/methods , Cell Line, Tumor , Coculture Techniques , Dose-Response Relationship, Drug , Humans , Toxicity Tests/standardsABSTRACT
Pulmonary alveolar proteinosis (PAP) has been reported in rodents treated with nanoparticles (NPs). However, little is known about the type of NPs producing PAP and their toxicity mechanisms. Here, we assembled seven PAP-inducing NPs and TiO2 NPs as a negative control. At 1 and 6 months after a single intratracheal instillation in rats, pulmonary inflammation and the gene expression of ATP-binding cassette (ABC) transporters and related genes were evaluated in separated alveolar macrophages (AMs). One month after intratracheal instillation, seven NPs (Eu2O3, In2O3, Pr6O11, Sm2O3, Tb4O7, and NiO) caused PAP, but only In2O3 NPs caused persistent PAP at 6 months after treatment. The levels of phospholipids, indicators of PAP, showed good correlations with the gene expression profile of five transporters (ABCA1, ABCB4, ABCB8, ABCG1, and ABCG4), which effluxing phospholipids in AMs. Among them, ABCG1 and ABCG4 might be key transporters involved in PAP development because both showed a negative correlation with the magnitude of PAP, while others might be compensatory transporters for PAP recovery, as they showed a positive correlation. In conclusion, the identification of seven PAP-producing NPs implies that PAP may be an emerging occupational disease and that ABCG1 and ABCG4 may be therapeutic targets for PAP.