Preliminary investigation into long-term stress by isolated captivity-related changes of reproduction hormones in Cynomolgus monkey.

BACKGROUND: Stress profoundly affects physical and emotional well-being, extending its physiological influence to the female menstrual cycle, impeding the hypothalamus-pituitary-gonadal (HPG) axis, and affecting fertility by suppressing sex-stimulating hormones. METHODS: In this study, we meticulously analyzed menstrual cycles and corresponding hormonal fluctuations in three female Cynomolgus monkeys. RESULTS: The preliminary findings indicated lower-than-normal levels of cortisol, follicle-stimulating hormone (FSH), and estradiol. Anovulatory bleeding occurred in one monkey, which could be linked to stress. In contrast to cortisol, alkaline phosphatase (ALP), which is correlated to cortisol levels, was consistently elevated in menstruating monkeys, suggesting its potential as a stress indicator. The non-menstruating group exhibited stress-related weight loss, emphasizing the observed ALP trends. CONCLUSIONS: Non-menstruating monkeys may experience more stress than menstruating monkeys. The implications of this study extend beyond the confines of primate studies and offer a valuable method for enhancing the welfare of female Cynomolgus monkeys.

Potential Food Inclination of Crab-Eating Macaques in Laboratory Environments: Enhancing Positive Reinforcement Training and Health Optimization.

Positive reinforcement and training for health optimization are pivotal for successful studies with monkeys. Potential food inclination is important for studies on crab-eating macaques in laboratory environments, but evaluations remain scarce. We explored crab-eating macaques' potential food inclination to establish a reward system for future behavioral assessments. Twelve male and three female monkeys underwent a food inclination assessment in which they were offered four food categories-fruits, vegetables, proteins, and nuts. The monkeys exhibited a higher inclination for plant-based foods, particularly fruits and vegetables, over animal-based proteins like chicken and tuna (p < 0.0001), with a notable inclination for nuts (eaten/provided = 100%). Additionally, the consistency of potential food inclination after repeated offerings was investigated, revealing a time-dependent increase in inclination for protein items. Food consumption ratios correlated positively with caloric intake (r = 0.59, p = 0.02), implying that individuals with a regular high caloric intake and increased body weight are more likely to accept food during positive reinforcement training. Our findings suggest fruits, vegetables, protein-rich foods, and nuts can help with health optimization. However, animal-based protein-rich foods initially had a low preference, which may increase over time. Our study can provide guidelines for positive reinforcement training and health optimization.

Far cortical locking constructs for fixation of distal femur fractures in an Asian population: A prospective observational study.

BACKGROUND: The stiffness of locked plates suppresses healing process, prompting the introduction of far cortical locking to address this issue. This study aimed to demonstrate the clinical efficacy of far cortical locking constructs in treating distal femoral fractures in an Asian population. METHODS: This multicenter prospective observational study was conducted at four university hospitals between February 2018 and February 2021. Demographic data, the presence of metaphyseal comminution, and surgical fixation details were recorded. Clinical outcomes, including single-leg standing, EQ-5D, and EQ-VAS scores, and radiologic outcomes, including the RUST score of each cortex, were evaluated and compared according to the presence of metaphyseal comminution. RESULTS: There were 37 patients (14 men and 23 women) with a mean age of 67.3 ± 11.8 years. Twenty-two patients had metaphyseal comminution (59%), and 15 presented simple fractures in metaphyseal areas. Four patients (13%) could stand on one leg >10s at 6 weeks, and 24 patients (92%) at 1 year. EQ-5D increased from 0.022 ± 0.388 to 0.692 ± 0.347, and the mean EQ-VAS 51.1 ± 13.1 to 74.1 ± 24.1 between discharge (n = 37) and post-operative 1 year (n = 33), respectively. RUST score presented increment for time, from 6.2 ± 1.8 at 6 week to 11.6 ± 1.1 at 1 year. Radiological healing demonstrated rapid increase from week 6 (16/28, 43%) to month 3 (27/31, 87%), with no obvious increase was observed in 6 months (23/26, 89%) or 12 months (25/28, 89%). Simple metaphyseal fractures presented significantly higher RUST scores at 6 weeks and 3 months, but there was no difference in RUST scores at 6 months or 1 year according to metaphyseal comminution. CONCLUSIONS: Plate constructs with far cortical locking screws provided safe and effective fixation for distal femoral fractures, with consistent radiological and clinical results, regardless of metaphyseal comminution.

Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons.

Human induced pluripotent stem cells (iPSCs) can be differentiated into neurons, providing living human neurons to model brain diseases. However, it is unclear how different types of molecules work together to regulate stem cell and neuron biology in healthy and disease states. In this study, we conducted integrated proteomics, lipidomics, and metabolomics analyses with confident identification, accurate quantification, and reproducible measurements to compare the molecular profiles of human iPSCs and iPSC-derived neurons. Proteins, lipids, and metabolites related to mitosis, DNA replication, pluripotency, glycosphingolipids, and energy metabolism were highly enriched in iPSCs, whereas synaptic proteins, neurotransmitters, polyunsaturated fatty acids, cardiolipins, and axon guidance pathways were highly enriched in neurons. Mutations in the GRN gene lead to the deficiency of the progranulin (PGRN) protein, which has been associated with various neurodegenerative diseases. Using this multiomics platform, we evaluated the impact of PGRN deficiency on iPSCs and neurons at the whole-cell level. Proteomics, lipidomics, and metabolomics analyses implicated PGRN's roles in neuroinflammation, purine metabolism, and neurite outgrowth, revealing commonly altered pathways related to neuron projection, synaptic dysfunction, and brain metabolism. Multiomics data sets also pointed toward the same hypothesis that neurons seem to be more susceptible to PGRN loss compared to iPSCs, consistent with the neurological symptoms and cognitive impairment from patients carrying inherited GRN mutations.

Unveiling local and global conformational changes and allosteric communications in SOD1 systems using molecular dynamics simulation and network analyses.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disorder affecting nerve cells in the brain and spinal cord that is caused by mutations in the superoxide dismutase 1 (SOD1) enzyme. ALS-related mutations cause misfolding, dimerisation instability, and increased formation of aggregates. The underlying allosteric mechanisms, however, remain obscure as far as details of their fundamental atomistic structure are concerned. Hence, this gap in knowledge limits the development of novel SOD1 inhibitors and the understanding of how disease-associated mutations in distal sites affect enzyme activity. METHODS: We combined microsecond-scale based unbiased molecular dynamics (MD) simulation with network analysis to elucidate the local and global conformational changes and allosteric communications in SOD1 Apo (unmetallated form), Holo, Apo_CallA (mutant and unmetallated form), and Holo_CallA (mutant form) systems. To identify hotspot residues involved in SOD1 signalling and allosteric communications, we performed network centrality, community network, and path analyses. RESULTS: Structural analyses showed that unmetallated SOD1 systems and cysteine mutations displayed large structural variations in the catalytic sites, affecting structural stability. Inter- and intra H-bond analyses identified several important residues crucial for maintaining interfacial stability, structural stability, and enzyme catalysis. Dynamic motion analysis demonstrated more balanced atomic displacement and highly correlated motions in the Holo system. The rationale for structural disparity observed in the disulfide bond formation and R143 configuration in Apo and Holo systems were elucidated using distance and dihedral probability distribution analyses. CONCLUSION: Our study highlights the efficiency of combining extensive MD simulations with network analyses to unravel the features of protein allostery.

Reduced lysosomal activity and increased amyloid beta accumulation in silica-coated magnetic nanoparticles-treated microglia.

Nanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO2(RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aß) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aß accumulation significantly increased in the 0.1 µg/µl MNPs@SiO2(RITC)-treated BV2 cells compared to the untreated control and 0.01 µg/µl MNPs@SiO2(RITC)-treated BV2 cells. Moreover, the MNPs@SiO2(RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO2(RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO2(RITC)-treated BV2 cells. Aß accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO2(RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aß accumulation.

SurgT challenge: Benchmark of soft-tissue trackers for robotic surgery.

This paper introduces the "SurgT: Surgical Tracking" challenge which was organized in conjunction with the 25th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2022). There were two purposes for the creation of this challenge: (1) the establishment of the first standardized benchmark for the research community to assess soft-tissue trackers; and (2) to encourage the development of unsupervised deep learning methods, given the lack of annotated data in surgery. A dataset of 157 stereo endoscopic videos from 20 clinical cases, along with stereo camera calibration parameters, have been provided. Participants were assigned the task of developing algorithms to track the movement of soft tissues, represented by bounding boxes, in stereo endoscopic videos. At the end of the challenge, the developed methods were assessed on a previously hidden test subset. This assessment uses benchmarking metrics that were purposely developed for this challenge, to verify the efficacy of unsupervised deep learning algorithms in tracking soft-tissue. The metric used for ranking the methods was the Expected Average Overlap (EAO) score, which measures the average overlap between a tracker's and the ground truth bounding boxes. Coming first in the challenge was the deep learning submission by ICVS-2Ai with a superior EAO score of 0.617. This method employs ARFlow to estimate unsupervised dense optical flow from cropped images, using photometric and regularization losses. Second, Jmees with an EAO of 0.583, uses deep learning for surgical tool segmentation on top of a non-deep learning baseline method: CSRT. CSRT by itself scores a similar EAO of 0.563. The results from this challenge show that currently, non-deep learning methods are still competitive. The dataset and benchmarking tool created for this challenge have been made publicly available at https://surgt.grand-challenge.org/. This challenge is expected to contribute to the development of autonomous robotic surgery and other digital surgical technologies.

Recent Advances in Patterning Strategies for Full-Color Perovskite Light-Emitting Diodes.

Metal halide perovskites have emerged as promising light-emitting materials for next-generation displays owing to their remarkable material characteristics including broad color tunability, pure color emission with remarkably narrow bandwidths, high quantum yield, and solution processability. Despite recent advances have pushed the luminance efficiency of monochromic perovskite light-emitting diodes (PeLEDs) to their theoretical limits, their current fabrication using the spin-coating process poses limitations for fabrication of full-color displays. To integrate PeLEDs into full-color display panels, it is crucial to pattern red-green-blue (RGB) perovskite pixels, while mitigating issues such as cross-contamination and reductions in luminous efficiency. Herein, we present state-of-the-art patterning technologies for the development of full-color PeLEDs. First, we highlight recent advances in the development of efficient PeLEDs. Second, we discuss various patterning techniques of MPHs (i.e., photolithography, inkjet printing, electron beam lithography and laser-assisted lithography, electrohydrodynamic jet printing, thermal evaporation, and transfer printing) for fabrication of RGB pixelated displays. These patterning techniques can be classified into two distinct approaches: in situ crystallization patterning using perovskite precursors and patterning of colloidal perovskite nanocrystals. This review highlights advancements and limitations in patterning techniques for PeLEDs, paving the way for integrating PeLEDs into full-color panels.

Modified Outside-In Plus Suture Technique for Repair of the Anterior and Middle Segments of the Meniscus: Technical Note.

Traditionally, an outside-in suture technique is appropriate to repair longitudinal tears of the anterior and middle segments of the meniscus. However, it has a fundamental weakness of not creating a vertical mattress-type suture. To overcome this weakness, the modified outside-in technique was developed using a suture hook to create a vertical mattress-type suture in the inner fragment. However, it still has the disadvantage of requiring an open skin incision to prevent neurovascular damage during knot tying. Thus, we developed the modified outside-in plus technique to make a vertical mattress suture without an open skin incision in the knee joint. With this technique, the use of both vertical and horizontal mattress sutures is possible. Although this technique is similar to the modified outside-in technique, a suture knot is made inside the knee joint. Therefore, it compensates for the disadvantage of the outside-in technique. The modified outside-in plus technique is able to achieve good reduction and sufficient stability through a vertical mattress suture technique without additional skin incisions.

Photosynthetic responses of large old Zelkova serrata (Thunb.) Makino trees to different growth environments.

Large old trees, which provide ecosystem services and serve as a historical and cultural heritage, are exposed to various environmental threats, such as habitat fragmentation and climate change, necessitating diagnosis of tangible and intangible stresses and their effects on tree growth for effective management. This study investigated the photosynthetic characteristics of 25 large old Zelkova serrata (Thunb.) Makino trees in Chungcheong Province, Korea, and identified the physical environmental factors affecting their physiological responses. Maximum assimilation rate (Amax) was the highest in July (summer), transpiration rate (E) and stomatal conductance (gs) increased from May (spring) to September (fall), and water use efficiency (WUE) was the highest in May (spring) and decreased until September (fall). Amax decreased as tree height increased. Ambient CO2 and vapor pressure deficit (VPD) were negatively correlated with photosynthetic parameters throughout the growth season and in July (summer) and September (fall), respectively. Physical environmental factors exhibited complex effect on physiological activities, which increased with wide growth space and decreased with deep soil covering and high impervious ground surface ratio. Physiological responses differed with surface types within the growth space, with bare land showing higher mean Amax, E, and gs than areas with mulching material or concrete. This study quantitatively determined the physiological activities of large old Z. serrata and proposes appropriate management measures for ensuring their healthy growth in abiotic stress environment.

Evaluation of Lentilactobacillus parafarraginis A6-2 strain for aluminum removal and anti-inflammatory effects: implications for alleviating Al toxicity.

AIM: To assess the effectiveness of Lentilactobacillus parafarraginis A6-2 cell lysate for the removal of aluminum (Al), which induces neurotoxicity, and its protective effect at cellular level. METHODS AND RESULTS: The cell lysate of the selected L. parafarraginis A6-2 strain demonstrated superior Al removal compared to live or dead cells. The Al removal efficiency of L. parafarraginis A6-2 cell lysate increased with decreasing pH and increasing temperature, primarily through adsorption onto peptidoglycan. Neurotoxicity mitigation potential of L. parafarraginis A6-2 was evaluated using C6 glioma cells. C6 cells exposed with increasing concentration of Al led to elevated toxicity and inflammation, which were gradually alleviated upon treatment with L. parafarraginis A6-2. Moreover, Al-induced oxidative stress in C6 cells showed a concentration-dependent reduction upon treatment with L. parafarraginis A6-2. CONCLUSIONS: This study demonstrated that L. parafarraginis A6-2 strain, particularly in its lysate form, exhibited enhanced capability for Al removal. Furthermore, it effectively mitigated Al-induced toxicity, inflammation, and oxidative stress.

Regular medical checkup program (in K-MEDI hub) to enhance the welfare of laboratory dogs and pigs.

BACKGROUND: The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the risk of complications. RESULTS: Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups. CONCLUSIONS: Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.

Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta.

Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

Subway station dust-induced pulmonary inflammation may be due to the dysfunction of alveolar macrophages: Possible contribution of bound elements.

With its increasing value as a means of public transportation, the health effects of the air in subway stations have attracted public concern. In the current study, we investigated the pulmonary toxicity of dust collected from an air purifier installed on the platform of the busiest subway station in Seoul. We found that the dust contained various elements which are attributable to the facilities and equipment used to operate the subway system. Particularly, iron (Fe), chromium (Cr), zirconium (Zr), barium (Ba), and molybdenum (Mo) levels were more notable in comparison with those in dust collected from the ventilation chamber of a subway station. To explore the health effects of inhaled dust, we first instilled via the trachea in ICR mice for 13 weeks. The total number of pulmonary macrophages increased significantly with the dose, accompanying hematological changes. Dust-laden alveolar macrophages and inflammatory cells accumulated in the perivascular regions in the lungs of the treated mice, and pulmonary levels of CXCL-1, TNF-α, and TGF-ß increased clearly compared with the control. The CCR5 and CD54 level expressed on BAL cell membranes was also enhanced following exposure to dust, whereas the CXCR2 level tended to decrease in the same samples. In addition, we treated the dust to alveolar macrophages (known as dust cells), lysosomal and mitochondrial function decreased, accompanied by cell death, and NO production was rapidly elevated with concentration. Moreover, the expression of autophagy- (p62) and anti-oxidant (SOD-2)-related proteins increased, and the expression of inflammation-related genes was dramatically up-regulated in the dust-treated cells. Therefore, we suggest that dysfunction of alveolar macrophages may importantly contribute to dust-induced inflammatory responses and that the exposure concentrations of Cr, Fe, Mo, Zr, and Ba should be considered carefully when assessing the health risks associated with subway dust. We also hypothesize that the bound elements may contribute to dust-induced macrophage dysfunction by inhibiting viability.

ADP-Fuse: A novel two-layer machine learning predictor to identify antidiabetic peptides and diabetes types using multiview information.

Diabetes mellitus has become a major public health concern associated with high mortality and reduced life expectancy and can cause blindness, heart attacks, kidney failure, lower limb amputations, and strokes. A new generation of antidiabetic peptides (ADPs) that act on ß-cells or T-cells to regulate insulin production is being developed to alleviate the effects of diabetes. However, the lack of effective peptide-mining tools has hampered the discovery of these promising drugs. Hence, novel computational tools need to be developed urgently. In this study, we present ADP-Fuse, a novel two-layer prediction framework capable of accurately identifying ADPs or non-ADPs and categorizing them into type 1 and type 2 ADPs. First, we comprehensively evaluated 22 peptide sequence-derived features coupled with eight notable machine learning algorithms. Subsequently, the most suitable feature descriptors and classifiers for both layers were identified. The output of these single-feature models, embedded with multiview information, was trained with an appropriate classifier to provide the final prediction. Comprehensive cross-validation and independent tests substantiate that ADP-Fuse surpasses single-feature models and the feature fusion approach for the prediction of ADPs and their types. In addition, the SHapley Additive exPlanation method was used to elucidate the contributions of individual features to the prediction of ADPs and their types. Finally, a user-friendly web server for ADP-Fuse was developed and made publicly accessible (https://balalab-skku.org/ADP-Fuse), enabling the swift screening and identification of novel ADPs and their types. This framework is expected to contribute significantly to antidiabetic peptide identification.

Chiral LC-MS/MS method for the discrimination of triiodothyronine enantiomers on a crown ether-based chiral stationary phase.

Considering the greater pharmaceutical and clinical interest of triiodothyronine (T3 ) thyroid hormone, an effective D/L-T3 enantiomer separation was performed on a crown ether-based chiral stationary phase by LC-MS/MS. In optimal analytical condition and selected reaction monitoring mode, the two enantiomers of T3 were baseline separated within 10 min. The limit of detection and limit of quantitation were found to be 0.05 and 0.10 ng/µl; 0.20 and 0.50 ng/µl for D- and L-T3 , respectively. During validation, this method proved to be feasible, accurate as well as enantioselective and sensitive for the resolution of T3 enantiomers. For commercial D- and L-T3 chemicals, the enantiomeric impurities as the other enantiomer were 0.11% and 4.61%. On the other hand, the impurity as D-T3 for commercial pharmaceutical products (liothyronine sodium tablets, two suppliers) was 0.68% and 6.57%.

Subchronic pulmonary toxicity of ambient particles containing cement production-related elements.

Chronic respiratory disease is among the most common non-communicable diseases, and particulate materials (PM) are a major risk factor. Meanwhile, evidence of the relationship between the physicochemical characteristics of PM and pulmonary toxicity mechanism is still limited. Here, we collected particles (CPM) from the air of a port city adjacent to a cement factory, and we found that the CPM contained various elements, including heavy metals (such as arsenic, thallium, barium, and zirconium) which are predicted to have originated from a cement plant adjacent to the sampling site. We also delivered the CPM intratracheally to mice for 13 weeks to investigate the pulmonary toxicity of inhaled CPM. CPM-induced chronic inflammatory lesions with an increased total number of cells in the lung of mice. Meanwhile, among inflammatory mediators measured in this study, levels of IL-1ß, TNF-α, CXCL-1, and IFN-γ were elevated in the treated group compared with the controls. Considering that the alveolar macrophage (known as dust cell) is a professional phagocyte that is responsible for the clearance of PM from the respiratory surfaces, we also investigated cellular responses following exposure to CPM in MH-S cells, a mouse alveolar macrophage cell line. CPM inhibited cell proliferation and formed autophagosome-like vacuoles. Intracellular calcium accumulation and oxidative stress, and altered expression of pyrimidine metabolism- and olfactory transduction-related genes were observed in CPM-treated cells. More interestingly, type I-LC3B and full-length PARP proteins were not replenished in CPM-treated cells, and cell cycle changes, apoptotic and necrotic cell death, and caspase-3 cleavage were not significantly detected in cells exposed to CPM. Taken together, we conclude that dysfunction of alveolar macrophages may contribute to CPM-induced pulmonary inflammation. In addition, given the possible transformation of heart tissue observed in CPM-treated mice, we suggest that further study is needed to clarify the systemic pathological changes and the molecular mechanisms following chronic exposure to CPM.

Impaired BCAA catabolism in adipose tissues promotes age-associated metabolic derangement.

Adipose tissues are central in controlling metabolic homeostasis and failure in their preservation is associated with age-related metabolic disorders. The exact role of mature adipocytes in this phenomenon remains elusive. Here we describe the role of adipose branched-chain amino acid (BCAA) catabolism in this process. We found that adipocyte-specific Crtc2 knockout protected mice from age-associated metabolic decline. Multiomics analysis revealed that BCAA catabolism was impaired in aged visceral adipose tissues, leading to the activation of mechanistic target of rapamycin complex (mTORC1) signaling and the resultant cellular senescence, which was restored by Crtc2 knockout in adipocytes. Using single-cell RNA sequencing analysis, we found that age-associated decline in adipogenic potential of visceral adipose tissues was reinstated by Crtc2 knockout, via the reduction of BCAA-mTORC1 senescence-associated secretory phenotype axis. Collectively, we propose that perturbation of BCAA catabolism by CRTC2 is critical in instigating age-associated remodeling of adipose tissue and the resultant metabolic decline in vivo.

Mechanobiological Analysis of Nanoparticle Toxicity.

Nanoparticles (NPs) are commonly used in healthcare and nanotherapy, but their toxicity at high concentrations is well-known. Recent research has shown that NPs can also cause toxicity at low concentrations, disrupting various cellular functions and leading to altered mechanobiological behavior. While researchers have used different methods to investigate the effects of NPs on cells, including gene expression and cell adhesion assays, the use of mechanobiological tools in this context has been underutilized. This review emphasizes the importance of further exploring the mechanobiological effects of NPs, which could reveal valuable insights into the mechanisms behind NP toxicity. To investigate these effects, different methods, including the use of polydimethylsiloxane (PDMS) pillars to study cell motility, traction force production, and rigidity sensing contractions, have been employed. Understanding how NPs affect cell cytoskeletal functions through mechanobiology could have significant implications, such as developing innovative drug delivery systems and tissue engineering techniques, and could improve the safety of NPs for biomedical applications. In summary, this review highlights the significance of incorporating mechanobiology into the study of NP toxicity and demonstrates the potential of this interdisciplinary field to advance our knowledge and practical use of NPs.

Human Bone Marrow-Derived Mesenchymal Stem Cell Applications in Neurodegenerative Disease Treatment and Integrated Omics Analysis for Successful Stem Cell Therapy.

Neurodegenerative diseases (NDDs), which are chronic and progressive diseases, are a growing health concern. Among the therapeutic methods, stem-cell-based therapy is an attractive approach to NDD treatment owing to stem cells' characteristics such as their angiogenic ability, anti-inflammatory, paracrine, and anti-apoptotic effects, and homing ability to the damaged brain region. Human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) are attractive NDD therapeutic agents owing to their widespread availability, easy attainability and in vitro manipulation and the lack of ethical issues. Ex vivo hBM-MSC expansion before transplantation is essential because of the low cell numbers in bone marrow aspirates. However, hBM-MSC quality decreases over time after detachment from culture dishes, and the ability of hBM-MSCs to differentiate after detachment from culture dishes remains poorly understood. Conventional analysis of hBM-MSCs characteristics before transplantation into the brain has several limitations. However, omics analyses provide more comprehensive molecular profiling of multifactorial biological systems. Omics and machine learning approaches can handle big data and provide more detailed characterization of hBM-MSCs. Here, we provide a brief review on the application of hBM-MSCs in the treatment of NDDs and an overview of integrated omics analysis of the quality and differentiation ability of hBM-MSCs detached from culture dishes for successful stem cell therapy.